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Simple Summary: Glioblastomas are very malignant and essentially incurable brain tumors. One problem is the extensive penetration of tumor cells into the adjacent normal brain tissue. Thus, the testing of novel drugs requires appropriate tumor models, preferentially avoiding animal studies. This paper describes so-called brain tissue slice tandem-culture systems. They consist of a slice of normal brain tissue and a second layer of tumor tissue. The microscopic analysis of these slice tandem-cultures allows for the simultaneous assessment of single cells invading into the normal brain tissue and the space occupying growth of the total tumor mass. It is shown that the direct application of test drugs onto the slices exerts inhibitory effects on both mechanisms. We thus describe a system mimicking the situation in glioblastoma patients. It reduces animal studies, allows for the direct application of test drugs and the precise quantitation of their inhibitory effects on tumor growth and invasion.
Abstract: Glioblastomas (GBMs) are the most malignant brain tumors and are essentially incurable even after extensive surgery, radiotherapy, and chemotherapy, mainly because of extensive infiltration of tumor cells into the adjacent normal tissue. Thus, the evaluation of novel drugs in malignant glioma treatment requires sophisticated ex vivo models that approach the authentic interplay between tumor and host environment while avoiding extensive in vivo studies in animals. This paper describes the standardized setup of an organotypic brain tissue slice tandem-culture system, comprising of normal brain tissue from adult mice and tumor tissue from human glioblastoma xenografts, and explore its utility for assessing inhibitory effects of test drugs. The microscopic analysis of vertical sections of the slice tandem-cultures allows for the simultaneous assessment of (i) the invasive potential of single cells or cell aggregates and (ii) the space occupying growth of the bulk tumor mass, both contributing to malignant tumor progression. The comparison of tissue slice co-cultures with spheroids vs. tissue slice tandem-cultures using tumor xenograft slices demonstrates advantages of the xenograft tandem approach. The direct and facile application of test drugs is shown to exert inhibitory effects on bulk tumor growth and/or tumor cell invasion, and allows their precise quantitation. In conclusion, we describe a straightforward ex vivo system mimicking the in vivo situation of the tumor mass and the normal brain in GBM patients. It reduces animal studies and allows for the direct and reproducible application of test drugs and the precise quantitation of their effects on the bulk tumor mass and on the tumor’s invasive properties
Background Coronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.
Methods 2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).
Results The completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.
Conclusion Primary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.
Registration Trial registration at the German Clinical Trials Register: DRKS00021231
Risk evaluations for agricultural chemicals are necessary to preserve healthy populations of honey bee colonies. Field studies on whole colonies are limited in behavioural research, while results from lab studies allow only restricted conclusions on whole colony impacts. Methods for automated long-term investigations of behaviours within comb cells, such as brood care, were hitherto missing. In the present study, we demonstrate an innovative video method that enables within-cell analysis in honey bee (Apis mellifera) observation hives to detect chronic sublethal neonicotinoid effects of clothianidin (1 and 10 ppb) and thiacloprid (200 ppb) on worker behaviour and development. In May and June, colonies which were fed 10 ppb clothianidin and 200 ppb thiacloprid in syrup over three weeks showed reduced feeding visits and duration throughout various larval development days (LDDs). On LDD 6 (capping day) total feeding duration did not differ between treatments. Behavioural adaptation was exhibited by nurses in the treatment groups in response to retarded larval development by increasing the overall feeding timespan. Using our machine learning algorithm, we demonstrate a novel method for detecting behaviours in an intact hive that can be applied in a versatile manner to conduct impact analyses of chemicals, pests and other stressors.
Perspectives on participation in continuous vocational education training - an interview study
(2020)
In European industrialized countries, a large number of companies in the healthcare, hotel, and catering sectors, as well as in the technology sector, are affected by demographic, political, and technological developments resulting in a greater need of skilled workers with a simultaneous shortage of skilled workers (CEDEFOP, 2015, 2016). Consequently, employers have to address workers who have not been taken into account such as low-skilled workers, workers returning from a career break, people with a migrant background, older people, and jobseekers and train them, in order to guarantee the professionalization of this workforce (Festing and Harsch, 2018). Continuing vocational education and training (CVET) is seen as an indispensable tool; because CVET has advantages for both employers and employees, it helps to increase the productivity of companies (Barrett and O’Connell, 2001), to prevent the widening of socioeconomic disparities (Dieckhoff, 2007), and to open up career opportunities for the workforce (Rubenson and Desjardins, 2009). However, participation rate on CVET seems to differ, depending on institutional factors (such as sector and size of the company) and individual characteristics (such as qualification level, migration background, age and time of absence from work) (e.g., Rubenson and Desjardins, 2009; Wiseman and Parry, 2017). In contrast to previous research, our study aims to provide a holistic view of reasons for and against CVET, combining the different perspectives of employers and (potential) employees. The analysis of reasons and barriers was carried out based on semi-structured interviews. Fifty-seven employers, 73 employees, and 42 jobseekers (potential employees) from the sectors retail, healthcare and social services, hotels and catering, and technology were interviewed. Results point to considerable differences in the reasons and barriers mentioned by the disadvantaged groups. These differences are particularly significant between employees on the one side and employers, as well as jobseekers, on the other side, while the reasons to attend CVET of jobseekers are more similar to those of employers. The results can be used to tailor CVET more closely to the needs of (potential) employees and thus strengthen both the qualification and career opportunities of (potential) employees and the competitiveness and productivity of companies.
This paper summarizes key elements of the German Federal Constitutional Court’s decision on the European Central Bank’s Public Sector Asset Purchase Programme. It briefly explains how it is possible for the German Court to disagree with the ruling of the Court of Justice of the European Union. Finally, it makes suggestions concerning a practical way forward for the Governing Council of the ECB in light of these developments.
This article studies whether people want to control what information on their own past pro-social behavior is revealed to others. Participants are assigned a color that depends on their past pro-social behavior. They can spend money to manipulate the probability with which their color is revealed to another participant. The data show that participants are more likely to reveal colors with more favorable informational content. This pattern is not found in a control treatment in which colors are randomly assigned, thus revealing nothing about past pro-social behavior. Regression analysis confrms these fndings, also when controlling for past pro-social behavior. These results complement the existing empirical evidence, confrming that people strategically and, therefore, consciously manipulate their social image.
The tremendous diversity of life in the ocean has proven to be a rich source of inspiration for drug discovery, with success rates for marine natural products up to 4 times higher than other naturally derived compounds. Yet the marine biodiscovery pipeline is characterized by chronic underfunding, bottlenecks and, ultimately, untapped potential. For instance, a lack of taxonomic capacity means that, on average, 20 years pass between the discovery of new organisms and the formal publication of scientific names, a prerequisite to proceed with detecting and isolating promising bioactive metabolites. The need for “edge” research that can spur novel lines of discovery and lengthy high-risk drug discovery processes, are poorly matched with research grant cycles. Here we propose five concrete pathways to broaden the biodiscovery pipeline and open the social and economic potential of the ocean genome for global benefit: (1) investing in fundamental research, even when the links to industry are not immediately apparent; (2) cultivating equitable collaborations between academia and industry that share both risks and benefits for these foundational research stages; (3) providing new opportunities for early-career researchers and under-represented groups to engage in high-risk research without risking their careers; (4) sharing data with global networks; and (5) protecting genetic diversity at its source through strong conservation efforts. The treasures of the ocean have provided fundamental breakthroughs in human health and still remain under-utilised for human benefit, yet that potential may be lost if we allow the biodiscovery pipeline to become blocked in a search for quick-fix solutions.
The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.
Safety requirements and the need of low‐migration UV inks have received increasing attention in the packaging industry. Crucial for the development and design of low‐migration UV inkjet inks for migration‐sensitive applications is the polymerization degree. In this study, curing‐behavior of a black, high purity packaging ink (HPP‐ink) was monitored using ATR‐FTIR spectroscopy. UV irradiation of HPP‐ink led to changes in specific absorption bands of the FTIR spectra due to crosslinking reaction of double bonds. Changes in absorptions bands at 1,408 and 1,321 cm−1 permitted the determination of CC conversion of acrylic and vinyl double bond, independently of one another. In addition, a method was developed which allows the investigation of surface‐cure and deep‐cure behavior, separately.
Anna Simon-Sickley zeigt in ihrem Beitrag die historischen Verflechtungen des Begriffs des 'Anthropozäns' mit den Diskursen von Energie und Entropie. Die Gefahren einer semantischen Rückprojektion reflektierend, kann sie deutlich machen, wie die heute 'totalisierende Metapher' des Anthropozäns bis in die Diskurse der Energie und Entropie zurückreicht. Energie erscheint dabei begrifflich als Einheitswährung, mittels deren Natur einzig als auszubeutende Ressource (fossile Brennstoffe) thematisiert wird. Mit der Thermodynamik legt die Umweltforschung den Schwerpunkt auf Effizienz, Produktion und Abfall. Das wachsende Bewusstsein, dass Energie Geschichte strukturiert, erweist sich als eine Perspektive, die für die Geschichtsschreibung des Anthropozäns von entscheidender Bedeutung geworden ist. Mit ihm soll sich das wissenschaftliche Thema des Menschen vom Kontext der Geisteswissenschaften zum Kontext der Wissenschaften verschoben haben. Menschliche Systeme und Kulturen werden im Anthropozändiskurs als geologische Kräfte verstanden und erscheinen als geochronologische Epochen naturwissenschaftlich exakt berechenbar.
Rodrigues Ridge connects the Réunion hotspot track with the Central Indian Ridge (CIR) and has been suggested to represent the surface expression of a sub-lithospheric flow channel. From global earthquake catalogues, the seismicity in the region has been associated mainly with events related to the fracture zones at the CIR. However, some segments of the CIR appear void of seismic events. Here, we report on the seismicity recorded at a temporary array of 10 seismic stations operating on Rodrigues Island from September 2014 to June 2016. The array analysis was performed in the time domain by time shifting and stacking the complete waveforms. Event distances were estimated based on a 1-D velocity model and the travel time differences between S and P wave arrivals. We detected and located 63 new events that were not reported by the global networks. Most of the events (51) are located off the CIR and can be classified as intraplate earthquakes. Local magnitudes varied between 1.6 and 3.7. Four seismic clusters were observed that occurred to the west of the spreading segment of the CIR. The Rodrigues Ridge appeared to be aseismic during the period of operation. The lack of seismic activity along both Rodrigues Ridge and the sections of the CIR to the east of Rodrigues may be explained by partially molten upper-mantle material, possibly in relation to the proposed material flow between the Réunion plume and the CIR.
Omkāra to Ek Onkāra
(2020)
Background: Persistent pain in breast cancer survivors is common. Psychological and sleep-related factors modulate perception, interpretation and coping with pain and may contribute to the clinical phenotype. The present analysis pursued the hypothesis that breast cancer survivors form subgroups, based on psychological and sleep-related parameters that are relevant to the impact of pain on the patients’ life.
Methods: We analysed 337 women treated for breast cancer, in whom psychological and sleep-related parameters as well as parameters related to pain intensity and interference had been acquired. Data were analysed by using supervised and unsupervised machine-learning techniques (i) to detect patient subgroups based on the pattern of psychological or sleep-related parameters, (ii) to interpret the detected cluster structure and (iii) to relate this data structure to pain interference and impact on life.
Results: Artificial intelligence-based detection of data structure, implemented as self-organizing neuronal maps, identified two different clusters of patients. A smaller cluster (11.5% of the patients) had comparatively lower resilience, more depressive symptoms and lower extraversion than the other patients. In these patients, life-satisfaction, mood, and life in general were comparatively more impeded by persistent pain.
Conclusions: The results support the initial hypothesis that psychological and sleep-related parameter patterns are meaningful for subgrouping patients with respect to how persistent pain after breast cancer treatments interferes with their life. This indicates that management of pain should address more complex features than just pain intensity. Artificial intelligence is a useful tool in the identification of subgroups of patients based on psychological factors.
Although immune checkpoint inhibitors such as anti-PD-1 antibodies have shown remarkable clinical success in many different tumor types, the proportion of patients benefiting from this treatment option remains low. Therefore, there is a need to sensitize tumors for immune checkpoint blockade. In this study two approaches were tested, a chemoimmunotherapy approach combining PD-1 checkpoint blockade with doxorubicin (DOX) chemotherapy, and ablation of the sphingosine-1-phosphate (S1P) receptor (S1PR4) based on the following rationale. Chemotherapy was shown to induce immune paralysis which contributes to tumor relapse, while PD-1 signaling was shown to facilitate the acquisition of chemoresistance. Thus, combinatorial chemoimmunotherapy is expected to be beneficial by maintaining or even activating anti-tumor immunity during chemotherapy. S1PR4 is an immune cell specific receptor, whose ablation slowed tumor progression by activating anti-tumor immunity in a mouse model that was previously insensitive to anti-PD-1 monotherapy. This suggested that S1PR4 ablation might pre-activate immunity to sensitize for anti-PD-1 therapy.
To test these combinatorial approaches, two tumor mouse models were employed, namely the MC38 murine adenocarcinoma model as well as the transgenic polyoma middle T oncogene (PyMT) breast cancer model. In the MC38 model, a mild synergistic effect of PD-1 immune checkpoint blockade and S1PR4 ablation was observed, indicated by improved tumor progression and survival as compared to the WT control, and an increased number of tumor-free mice compared to anti-PD-1 therapy alone in WT mice. These observations correlated with an enhanced natural killer (NK) cell infiltrate and increased CXCL9 and CXCL10 production in anti-PD-1 treated S1PR4 KO tumors. As noted before, the PyMT model was largely resistant to anti-PD-1 monotherapy in a therapeutic setting. S1PR4 ablation alone showed significant tumor reduction that was not further enhanced by anti-PD-1 treatment. The same was observed when chemotherapy with DOX was added, where WT tumors relapsed, while S1PR4 KO tumor did not. Addition of anti-PD-1 did only mildly increase tumor control in S1PR4 KO mice, indicating that S1PR4 KO per se very efficiently re-activated anti-tumor immunity. Since S1PR4 KO induces type I 12 interferon (IFN-1) over-production in S1PR4 KO PyMT tumors, a link between high IFN-1 levels and tumor immunity was tested by using mice deficient in the IFN-1 receptor (IFNAR1). Unexpectedly, DOX chemotherapy was most efficient in mice with IFNAR ablation only as compared to WT, S1PR4 KO or S1PR4 and IFNAR1 double KO mice, although deficiency in IFNAR signaling is predominantly regarded as tumor promoting. The underlying mechanisms need to be tested in future studies. Interestingly, chemoimmunotherapy in WT mice prevented tumor relapse to a similar extent than S1PR4 KO and was superior to chemotherapy or immune checkpoint blockade alone. To investigate mechanisms of chemoimmunotherapy success compared to monotherapy, whole transcriptome analysis was used, which identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort.
Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly NK cells. Gene set enrichment analysis and ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 improved NK cell cytotoxicity against PyMT cells in vitro. These data supported recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggested potential underlying mechanisms.
Taken together the present work revealed new strategies to reactivate tumor immunity leading to improved chemotherapy response, namely a combination with immune checkpoint blockade and ablation of S1PR4, which activated different lymphocyte compartments within tumors.
Despite the success of immune checkpoint blockade in cancer, the number of patients that benefit from this revolutionary treatment option remains low. Therefore, efforts are being undertaken to sensitize tumors for immune checkpoint blockade, which includes combining immune checkpoint blocking agents such as anti-PD-1 antibodies with standard of care treatments. Here we report that a combination of chemotherapy (doxorubicin) and immune checkpoint blockade (anti-PD-1 antibodies) induces superior tumor control compared to chemotherapy and immune checkpoint blockade alone in the murine autochthonous polyoma middle T oncogene-driven (PyMT) mammary tumor model. Using whole transcriptome analysis, we identified a set of genes that were upregulated specifically upon chemoimmunotherapy. This gene signature and, more specifically, a condensed four-gene signature predicted favorable survival of human mammary carcinoma patients in the METABRIC cohort. Moreover, PyMT tumors treated with chemoimmunotherapy contained higher levels of cytotoxic lymphocytes, particularly natural killer cells (NK cells). Gene set enrichment analysis and bead-based ELISA measurements revealed increased IL-27 production and signaling in PyMT tumors upon chemoimmunotherapy. Moreover, IL-27 signaling improved NK cell cytotoxicity against PyMT cells in vitro. Taken together, our data support recent clinical observations indicating a benefit of chemoimmunotherapy compared to monotherapy in breast cancer and suggest potential underlying mechanisms.
Antoinettia, new genus (Coleoptera: Erotylidae: Erotylinae: Tritomini), is erected for three species: A. audbala (Skelley), new combination, A. huhnei Skelley, new species, and A. kovariki (Skelley), new combination. A genus complex involving Ischyrus Lacordaire, 1842, and Megischyrus Crotch, 1873, is defined and a preliminary key to neotropical genera of Tritomini with coarsely facetted eyes is presented.
Several taxonomic and nomenclatural issues are reviewed, clarified, and resolved for multiple genera of the Erotylinae (Coleoptera: Erotylidae). Generic-group names discussed: Brachymerus Dejean, 1836, Cypherotylus Crotch, 1873, Cytorea Laporte, 1840, Erotylus Fabricius, 1775, Eudaemonius Lewis, 1887, Eutriplax Lewis,1887, Gibbifer Voet, 1806, Neobarytopus Alvarenga, 1965, Neomorphoides Alvarenga, 1977, Ogcotriplax Heller,1920, Paratritoma Gorham, 1888, Platichna Thomson, 1863, Pseudochrysomela Voet, 1806, Pseudotriplax Heller,1920, Triplax Herbst, 1793, Tritomapara Alvarenga, 1970, Typocephalus Hope,1841, and Xestus Wollaston, 1864. Reviewing these issues resulted in a several nomenclatural actions. Eutriplax Lewis,1887,was found to be an unnecessary replacement name for Eudaemonius Lewis,1887.The genus name is reverted to Eudaemonius,
resulting in one new combination: Eudaemonius quinquepustulatus (Li and Ren, 2006).
The Neotropical Tritomapara Alvarenga,1970,was found to be a new objective synonym of Paratritoma Gorham,1888, which is a synonym of Triplax Herbst,1793,leading to the following eight new combinations:
Triplax atricaudata (Kuhnt,1910),Triplax brasiliensis (Guérin,1946),Triplax bruchi (Kuhnt,1910),Triplax caduca (Gorham,1888),Triplax dimidiata (Gorham,1888),Triplax melanoderes (Kuhnt,1910),Triplax triplacoides
(Crotch,1876), and Triplax vivida (Gorham,1888). Erotylus tibialis Duponchel, 1825, is recognized as the valid type species for Brachymerus Dejean 1836, which moves the name Brachymerus to a different genus-group taxon and renders Neomorphoides Alvarenga, 1977, a new synonym. This revalidates Neobarytopus Alvarenga, 1965, as originally proposed. These genus-group names are presently subgenera in Iphiclus Dejean, 1836, and the move creates 23 new combinations in Iphiclus(Brachymerus) Dejean, 1836: I. (B.) amazonus (Crotch, 1876), I. (B.) atriventris (Mader,1943), I. (B.) bicolor(Lacordaire,1842), I. (B.) clavicornis (Olivier,1792), I. (B.) columbiae (Crotch,1876), I. (B.) costaricensis (Mader,1943), I. (B.) disconigrum (Mader,1942), I. (B.) dorsonotatus (Lacordaire, 1842), I. (B.) fulviventris (Gorham,1888), I. (B.) humeropictus (Mader,1943), I. (B.) lateripunctatus (Crotch,1876), I. (B.) melanopus (Gorham,1888), I. (B.) neglectus (Guérin,1956), I. (B.) nigritarsis (Mader,1942), I. (B.) nigriventris (Crotch, 1876), I. (B.) nigropectus (Mader,1942), I. (B.) posticenigrum (Mader,1942), I. (B.) pyrrhocephalus (Erichson,1847), I. (B.) rubripennis (Lacordaire,1842), I. (B.) signaticollis (Kuhnt,1910), I. (B.) simplex (Lacordaire,1842), I. (B.) spilotus (Gorham,1888), I. (B.) tibialis (Duponchel,1825); and, 75 new combinations in Iphiclus (Neobarytopus) Alvarenga, 1965: I. (N.) adustus (Duponchel,1825), I. (N.) alboniger (Guérin,1956), I. (N.) amictus (Erichson,1847), I. (N.) andicola (Kirsch,1867), I. (N.) assequens (Mader,1942), I. (N.) bajulus (Lacordaire,1842), I. (N.) batesi (Gorham, 1889),I. (N.) bellulus (Lacordaire,1842), I. (N.) bicinctus (Olivier,1807), I. (N.) bistrifoliatus (Gorham,1889), I. (N.) bizonatus (Crotch,1876), I. (N.) bremei (Guérin-Méneville,1841), I. (N.) brongniarti (Lacordaire,1842), I. (N.) brunneostriolatus (Kuhnt, 1910), I. (N.) cerasinus (Lacordaire,1842), I. (N.) conformis (Lacordaire,1842), I. (N.)distinctus (Duponchel, 1825), I. (N.) divisus (Guérin,1956), I. (N.) dorsalis (Olivier,1792), I. (N.) eburneus (Crotch,1876), I. (N.) elegans (Mader,1942), I. (N.) epipleuralis (Crotch,1876), I. (N.) erichsoni (Lacordaire,1842), I. (N.) flavofasciatus (Duponchel,1825), I. (N.) flavosignatus (Duponchel,1825), I. (N.) fragmentatus (Gorham,1888), I.(N.) friedei (Mader,1938), I. (N.) geometra (Lacordaire,1842), I. (N.) hebriacus (Lacordaire,1842), I. (N.) hexastictus (Crotch,1876), I. (N.) incas (Gorham,1889), I. (N.) iris (Guérin,1956), I. (N.) jacinthoi (Alvarenga,1977), I.(N.) laceratus (Mader,1938), I. (N.) lugens (Lacordaire,1842), I. (N.) lunaris (Guérin,1956), I. (N.) luteozonatus (Crotch, 1876), I. (N.) miles (Mader,1942), I. (N.) mirus (Mader,1942), I. (N.) musicalis (Lacordaire,1842), I. (N.) neophyta (Lacordaire, 1842), I. (N.) nigripennis (Demay,1838), I. (N.) nigropictus (Lacordaire,1842), I. (N.) nigrofasciatus (Mader,1942), I. (N.) nitidulus (Oliver,1807), I. (N.) obsoletesignatus (Crotch, 1876), I. (N.) octoguttatus (Olivier,1807), I. (N.) octopustulatus (Guérin,1956), I. (N.) odyneroides (Crotch, 1876), I. (N.) ornatus (Kuhnt,1909), I. (N.) pantherinus (Kuhnt, 1909), I. (N.) pauper (Guérin,1956), I. (N.) peraffinis (Crotch,1876), I. (N.) perplexus (Mader,1942), I. (N.) peruvianus (Mader,1942), I. (N.) planipennis (Kuhnt,1909), I. (N.) puncticollis (Kirsch,1876), I. (N.) quadrifasciatus (Kirsch,1865), I. (N.) quinquefasciatus (Lacordaire,1842), I. (N.) ramosus (Olivier,1807), I. (N.) regularis (Erichson, 1848), I. (N.) rhomboidalis (Guérin,1956), I. (N.) rufipennis (Panzer,1798), I. (N.) salamandra (Erichson,1847), I. (N.) spectabilis (Lacordaire,1842), I. (N.) stramineus (Lacordaire,1842), I. (N.) subsanguineus (Crotch,1876), I. (N.) superbus (Mader,1942), I. (N.) tigrinatus (Guérin,1956), I. (N.) tricinctus (Duponchel,1825), I. (N.) trifasciatus (Olivier,1807), I. (N.) tripartitus (Lacordaire,1842), I. (N.) ucayalensis (Gorham,1889), I. (N.) venezuelae (Crotch, 1876), I. (N.) westwoodi (Guérin-Méneville,1841).
The works of Voet (1766–1778,1806) do not follow binominal nomenclature and are therefore unavailable by the International Code of Zoological Nomenclature, Article 11.4.Thus, Voet’s (1806) generic names “Pseudochrysomela” and “Gibbifer”, and the species names proposed in each, are unavailable. Removing them from nomenclatural considerations resulted in the following nomenclatural acts: the resurrection of Erotylus rufipennis Panzer,1798, now Iphiclus (Neobarytopus) rufipennis (Panzer) new combination; the proposal of a new name, Iphiclus (Brachymerus) fabricii Skelley for Erotylus rufipennis Fabricius, 1801, not Erotylus rufipennis Panzer, 1798; new combinations for the two species, Cypherotylus adrianae (Alvarenga, 1976) and Cypherotylus borgmeieri (Alvarenga, 1976); and revalidated status for the five species names, Erotylus variegatus Fabricius,
1781, Barytopus gronovii (Herbst, 1783), Prepopharus notatus (Olivier, 1792), Iphiclus (Iphiclus) sedecimguttatus (Olivier, 1792), and Cypherotylus duponcheli Arrow, 1937.
We honor the life and accomplishments of Michael C. Thomas with a short narrative of his professional life along with appendices listing his scientific artwork, bibliography and patronyms. This paper is the first of a Festschrift with contributed remembrances and separate papers honoring him with additional patronyms.
Dyslexia Skelley and Gasca-Álvarez, new genus (Coleoptera: Erotylidae: Erotylinae: Erotylini), is described and illustrated. The genus is comprised of four new species, all described by Skelley and Gasca-Álvarez: D. belamyi, D. dathomirria, D. pulcricolor, and D. tomasi. The unique broad head structures of this genus are characterized and compared with other genera. Problems associated with the taxonomy of Erotylini are discussed.
Two species of the early-diverging lineages of Pharaxonotha Reitter (Coleoptera: Erotylidae: Pharaxonothinae) are described: Pharaxonotha taylori Skelley and Tang, new species, and Pharaxonotha thomasi Skelley and Tang, new species. A new key to described species of Pharaxonotha, based on previously unused characters, is presented.
Activations with neutrons in the keV energy range were routinely performed at the Karlsruhe Institute of Technology (KIT) in Germany in order to simulate stellar conditions for neutron-capture cross sections. A quasi-Maxwell-Boltzmann neutron spectrum of kT = 25 keV, being of interest for the astrophysical s-process, was produced by the 7Li(p,n) reaction utilizing a 1912 keV proton beam at the Karlsruhe Van de Graaff accelerator. Activated samples resulting in long-lived nuclear reaction products with half-lives in the order of yr 100 Myr were analyzed by Accelerator Mass Spectrometry (AMS). Comparison of the obtained reaction cross sections to literature data from previous Time-of-Flight (ToF) measurements showed that the selected AMS data are systematically lower than the ToF data. To investigate this discrepancy, 54Fe(n,γ)55Fe and 35Cl(n,γ)36Cl reaction cross sections were newly measured at the Frankfurt Neutron Source (FRANZ) in Germany. To complement the existing data, an additional neutron activation of 54Fe and 35Cl at a proton energy of 2 MeV was performed. The results will give implications for the stellar environment at kT = 90 keV, reaching the not yet experimentally explored high-energy s-process range. AMS measurements of the activated samples are scheduled.
Description of two new genera and a taxonomic key to the world genera of Cybocephalidae (Coleoptera)
(2020)
The sixteen genera of Cybocephalidae (Coleoptera) occurring worldwide are listed and keyed. The genera included are Amedissia Kirejtshuk and Mantič, Apastillus Kirejtshuk and Mantič, Cybocephalus Erichson, Endrodiellus Endrödy-Younga, Eupastillus Lawrence, Hierronius Endrödy-Younga, Horadion Endrödy-Younga, Pacicephalus Kirejtshuk and Mantič, Pastillocenicus Kirejtshuk and Nel, Pastillodes Endrödy-Younga, Pastillus Endrödy-Younga, Pycnocephalus Sharp, Taxicephomerus Kirejtshuk, Theticephalus Kirejtshuk, a description of a new genus, Microthomas T. R. Smith, with one new species, M. brevicornis T. R. Smith, from Bolivia, and a new genus, Conglobatus T. R. Smith, with two new species, C. armatus T. R. Smith from Central and South America and C. fullertoni T. R. Smith from Dominica. A key to genera, illustrations of morphological features, and distributional data are provided. The genus Nodola Bréthes is found to be a new synonym of Cybocephalus Erichson. The transfer of Nodola chilensis Bréthes into Cybocephalus creates a secondary homonymy with C. chilensis Reitter. Nodola chilensis Bréthes is here given a new name, Cybocephalus brethesi T. R. Smith.
Macrophages acquire anti-inflammatory and proresolving functions to facilitate resolution of inflammation and promote tissue repair. While alternatively activated macrophages (AAMs), also referred to as M2 macrophages, polarized by type 2 (Th2) cytokines IL-4 or IL-13 contribute to the suppression of inflammatory responses and play a pivotal role in wound healing, contemporaneous exposure to apoptotic cells (ACs) potentiates the expression of anti-inflammatory and tissue repair genes. Given that liver X receptors (LXRs), which coordinate sterol metabolism and immune cell function, play an essential role in the clearance of ACs, we investigated whether LXR activation following engulfment of ACs selectively potentiates the expression of Th2 cytokine-dependent genes in primary human AAMs. We show that AC uptake simultaneously upregulates LXR-dependent, but suppresses SREBP-2-dependent gene expression in macrophages, which are both prevented by inhibiting Niemann–Pick C1 (NPC1)-mediated sterol transport from lysosomes. Concurrently, macrophages accumulate sterol biosynthetic intermediates desmosterol, lathosterol, lanosterol, and dihydrolanosterol but not cholesterol-derived oxysterols. Using global transcriptome analysis, we identify anti-inflammatory and proresolving genes including interleukin-1 receptor antagonist (IL1RN) and arachidonate 15-lipoxygenase (ALOX15) whose expression are selectively potentiated in macrophages upon concomitant exposure to ACs or LXR agonist T0901317 (T09) and Th2 cytokines. We show priming macrophages via LXR activation enhances the cellular capacity to synthesize inflammation-suppressing specialized proresolving mediator (SPM) precursors 15-HETE and 17-HDHA as well as resolvin D5. Silencing LXRα and LXRβ in macrophages attenuates the potentiation of ALOX15 expression by concomitant stimulation of ACs or T09 and IL-13. Collectively, we identify a previously unrecognized mechanism of regulation whereby LXR integrates AC uptake to selectively shape Th2-dependent gene expression in AAMs.
We study the influence of the baryon chemical potential μB on the properties of the Quark–Gluon–Plasma (QGP) in and out-of equilibrium. The description of the QGP in equilibrium is based on the effective propagators and couplings from the Dynamical QuasiParticle Model (DQPM) that is matched to reproduce the equation-of-state of the partonic system above the deconfinement temperature Tc from lattice Quantum Chromodynamics (QCD). We study the transport coefficients such as the ratio of shear viscosity η and bulk viscosity ζ over entropy density s, i.e., η/s and ζ/s in the (T,μ) plane and compare to other model results available at μB=0 . The out-of equilibrium study of the QGP is performed within the Parton–Hadron–String Dynamics (PHSD) transport approach extended in the partonic sector by explicitly calculating the total and differential partonic scattering cross sections based on the DQPM and the evaluated at actual temperature T and baryon chemical potential μB in each individual space-time cell where partonic scattering takes place. The traces of their μB dependences are investigated in different observables for symmetric Au + Au and asymmetric Cu + Au collisions such as rapidity and mT -distributions and directed and elliptic flow coefficients v1,v2 in the energy range 7.7 GeV ≤sNN−−−−√≤200 GeV.
Direct nanoscopic observation of plasma waves in the channel of a graphene field-effect transistor
(2020)
Plasma waves play an important role in many solid-state phenomena and devices. They also become significant in electronic device structures as the operation frequencies of these devices increase. A prominent example is field-effect transistors (FETs), that witness increased attention for application as rectifying detectors and mixers of electromagnetic waves at gigahertz and terahertz frequencies, where they exhibit very good sensitivity even high above the cut-off frequency defined by the carrier transit time. Transport theory predicts that the coupling of radiation at THz frequencies into the channel of an antenna-coupled FET leads to the development of a gated plasma wave, collectively involving the charge carriers of both the two-dimensional electron gas and the gate electrode. In this paper, we present the first direct visualization of these waves. Employing graphene FETs containing a buried gate electrode, we utilize near-field THz nanoscopy at room temperature to directly probe the envelope function of the electric field amplitude on the exposed graphene sheet and the neighboring antenna regions. Mapping of the field distribution documents that wave injection is unidirectional from the source side since the oscillating electrical potentials on the gate and drain are equalized by capacitive shunting. The plasma waves, excited at 2 THz, are overdamped, and their decay time lies in the range of 25-70 fs. Despite this short decay time, the decay length is rather long, i.e., 0.3-0.5 μm, because of the rather large propagation speed of the plasma waves, which is found to lie in the range of 3.5-7 × 106 m/s, in good agreement with theory. The propagation speed depends only weakly on the gate voltage swing and is consistent with the theoretically predicted 1/4 power law.
Management of decompensated cirrhosis is currently geared towards the treatment of complications once they occur. To date there is no established disease-modifying therapy aimed at halting progression of the disease and preventing the development of complications in patients with decompensated cirrhosis. The design of clinical trials to investigate new therapies for patients with decompensated cirrhosis is complex. The population of patients with decompensated cirrhosis is heterogeneous (i.e., different etiologies, comorbidities and disease severity), leading to the inclusion of diverse populations in clinical trials. In addition, primary endpoints selected for trials that include patients with decompensated cirrhosis are not homogeneous and at times may not be appropriate. This leads to difficulties in comparing results obtained from different trials. Against this background, the LiverHope Consortium organized a meeting of experts, the goal of which was to develop recommendations for the design of clinical trials and to define appropriate endpoints, both for trials aimed at modifying the natural history and preventing progression of decompensated cirrhosis, as well as for trials aimed at managing the individual complications of cirrhosis.
Many species of plants and a few species of animals are believed to have resulted from hybridization of parental species, and the ability of species to occasionally hybridize in captivity and in nature is even more widespread. In the present study, we describe a hybridization experiment conducted in the laboratory between the sexually dimorphic Automeris io (Fabricius), a widespread, variable species ranging from Canada to Costa Rica, and its congener A. louisiana (Ferguson and Brou), a more local, sexually monomorphic species (Lepidoptera: Saturniidae). The A. louisiana populations occur in a highly specialized habitat—the coastal marshland along the Gulf of Mexico in Louisiana and Texas and is nested inside the broad distribution of A. io, demonstrating strong differences from the latter in its ecology and morphology. No natural hybridization between the two species has been described. While the separate species status of A. io and A. louisiana is supported by morphology and ecology of their populations, we were able to create a hybrid lineage in the laboratory and maintained it for three generations. The hybrids were phenotypically intermediate between the parental species. Under a stricter reading of the biological species concept, such an ability to hybridize would be interpreted by some as a sign of conspecificity. Our experiments once again demonstrate the complexity of ‘species’ as a concept, which may need major redefinition in the popular interpretation of sciences.
Capparis macrantha Souvannakhoummane, Fici & Lanorsavanh sp. nov., a new shrub species characterized by erect or ascending habit, stipular thorns, large lanceolate-elliptic leaves and large flowers in supra-axillary rows, is described and illustrated from the deciduous forest in Nam Kading National Protected Area (central Lao PDR). The new species belongs to Capparis sect. Monostichocalyx Radlk. and is morphologically similar to C. radula Gagnep., a shrub widespread in the Indochinese area, differing in the shorter, straight stipular thorns, larger leaves, larger sepals and petals, higher number of stamens with longer filaments and longer gynophore and ovary. Its affinities with related taxa are discussed and a key is provided for the species of Capparis L. known from Lao PDR. The conservation status of the new species is provisionally assessed as Vulnerable (VU D1).
High-pressure single-crystal to 20 GPa and powder diffraction measurements to 50 GPa, show that the structure of Pb2SnO4 strongly distorts on compression with an elongation of one axis. A structural phase transition occurs between 10 GPa and 12 GPa, with a change of space group from Pbam to Pnam. The resistivity decreases by more than six orders of magnitude when pressure is increased from ambient conditions to 50 GPa. This insulator-to-semiconductor transition is accompanied by a reversible appearance change from transparent to opaque. Density functional theory-based calculations show that at ambient conditions the channels in the structure host the stereochemically-active Pb 6s2 lone electron pairs. On compression the lone electron pairs form bonds between Pb2+ ions. Also provided is an assignment of irreducible representations to the experimentally observed Raman bands.
The recruitment processes and resulting distribution pattern of bird-dispersed Canary Island Date Palm, Phoenix canariensis (family Arecaceae) in a riverine forest setting are described. All palms on a near-urban peninsula of the Murrumbidgee River near Hay, New South Wales were GPS mapped and classified into height-dependent age categories. The distribution of the plants was examined spatially in relation to possible source palms and in relation to elevation with regard to flooding levels. Successful recruitment is subject to a range of environmental parameters, primarily palatability to vectors and seedling mortality due to lack of moisture, frost or grazing by herbivores. If a seedling survives that critical period of the first 18 months, long-term success is (almost) guaranteed, unless catastrophic events (bushfires, prolonged flooding) intervene. Based on the findings, a conceptual model for the recruitment of Phoenix canariensis palms is provided. Even though the palms produce fruit for much of the year (March–December), the time window for successful recruitment is restricted to a period from August to mid-September with short shoulder periods on either side.
Radiating exposures
(2020)
The brief explorations of radiation exposures presented within this essay draw primarily from nuclear art and culture and contribute to the field of nuclear aesthetics, which has long been fixated on the problem of visibility and the representation of nuclear residues. The examples draw primarily from photographic technologies and other aesthetic registers that capture visual residues of radiation. The challenges of nuclear aesthetics are also political and social. This constellation of objects and inquiries is meant to explore the fraught political, environmental, and social relations between radiation, visibility, toxicity, through the concept of exposure. They offer feminist glimpses into other ways of thinking exposure, as it develops in relation to (often imperceptible) toxicity that is not inscribed into a logic that partitions the passive victim of suffering from some pure or unaffected subject. They are examples that are both forms of exposure specific to the nuclear while also, perhaps, helping to expose more nuanced and complex ways of understanding forms of exposure that extend beyond nuclearity.
The issue of data security has become increasingly complex in the age of the internet and artificial intelligence. The developments seem to be almost unmanageable in some areas. Cooperation between jurisprudence and information technology is the only thing that can protect the individual and certain social groups from discrimination.
A new millipede species of the genus Sechelleptus Mauriès, 1980 is described and illustrated from Mayotte Island, Indian Ocean. This new species, S. arborivagus sp. nov., found on trees, looks particularly similar to the sympatric S. variabilis VandenSpiegel & Golovatch, 2007, but is much larger and has a very different ecological behavior. Phylogenetic analyses based on a concatenated dataset of the COI and 16S rRNA genes and including nine species of Spirostreptidae (including Sechelleptus, Doratogonus Attems, 1914, Bicoxidens Attems, 1928 and Spirostreptus Brandt, 1833), strongly support the monophyly of Sechelleptus. Despite the similarity of their genitalia, the molecular analyses also reveal a clear-cut genetic divergence between S. arborivagus sp. nov. and S. variabilis (22.55% for COI and 6.63% for 16SrRNA) and further suggest the presence of a higher diversity within the genus Sechelleptus on Mayotte.
A link between populism and social media is often suspected. This paper spells out a set of possible mechanisms underpinning this link: that social media changes the communication structure of the public sphere, making it harder for citizens to obtain evidence that refutes populist assumptions. By developing a model of the public sphere, four core functions of the public sphere are identified: exposing citizens to diverse information, promoting equality of deliberative opportunity, creating deliberative transparency, and producing common knowledge. A wellworking public sphere allows citizens to learn that there are genuine disagreements among citizens that are held in good faith. Social media makes it harder to gain this insight, opening the door for populist ideology.
We investigate hadronic particle spectra and flow characteristics of heavy-ion reactions in the FAIR/NICA energy range of 1 AGeV ≤ Elab ≤ 10 AGeV within a relativistic ideal hydrodynamic one-fluid approach. The particlization is realized by sampling the Cooper-Frye distribution for a grand canonical hadron gas on a hypersurface of constant energy density. Results of the hydrodynamic calculations for different underlying equations of state are presented and compared with experimental data and microscopic transport simulations. The sensitivity of the approach to physical model inputs concerning the initial state and the particlization is studied.
Virtual reality (VR) headsets offer a large and immersive workspace for displaying visualizations with stereoscopic vision, as compared to traditional environments with monitors or printouts. The controllers for these devices further allow direct three-dimensional interaction with the virtual environment. In this paper, we make use of these advantages to implement a novel multiple and coordinated view (MCV) system in the form of a vertical stack, showing tilted layers of geospatial data. In a formal study based on a use-case from urbanism that requires cross-referencing four layers of geospatial urban data, we compared it against more conventional systems similarly implemented in VR: a simpler grid of layers, and one map that allows for switching between layers. Performance and oculometric analyses showed a slight advantage of the two spatial-multiplexing methods (the grid or the stack) over the temporal multiplexing in blitting. Subgrouping the participants based on their preferences, characteristics, and behavior allowed a more nuanced analysis, allowing us to establish links between e.g., saccadic information, experience with video games, and preferred system. In conclusion, we found that none of the three systems are optimal and a choice of different MCV systems should be provided in order to optimally engage users.
Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories. Within iNEXT (Infrastructure for NMR, EM and X-rays for Translational research), a EU-funded Horizon 2020 program, a collection of 782 fragments were assembled utilizing the concept of “poised fragments” with the aim to facilitate downstream synthesis of ligands with high affinity by fragment ligation. Herein, we describe the analytical procedure to assess the quality of this purchased and assembled fragment library by NMR spectroscopy. This quality assessment requires buffer solubility screening, comparison with LC/MS quality control and is supported by state-of-the-art software for high throughput data acquisition and on-the-fly data analysis. Results from the analysis of the library are presented as a prototype of fragment progression through the quality control process.
Neutron-induced fission cross sections of isotopes involved in the nuclear fuel cycle are vital for the design and safe operation of advanced nuclear systems. Such experimental data can also provide additional constraints for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of fission models. In the present work, the 237Np(n,f) cross section was studied at the EAR2 vertical beam-line at CERN's n_TOF facility, over a wide range of neutron energies, from meV to MeV, using the time-of-flight technique and a set-up based on Micromegas detectors, in an attempt to provide accurate experimental data. Preliminary results in the 200 keV – 14 MeV neutron energy range as well as the experimental procedure, including a description of the facility and the data handling and analysis, will be presented.
Under the Kigali Amendment to the Montreal Protocol, new controls are being implemented to reduce emissions of HFC-23 (CHF3), a by-product during the manufacture of HCFC-22 (CHClF2). Starting in 2015, China and India, who dominate global HCFC-22 production (75% in 2017), set out ambitious programs to reduce HFC-23 emissions. Here, we estimate that these measures should have seen global emissions drop by 87% between 2014 and 2017. Instead, atmospheric observations show that emissions have increased and in 2018 were higher than at any point in history (15.9 ± 0.9 Gg yr−1). Given the magnitude of the discrepancy between expected and observation-inferred emissions, it is likely that the reported reductions have not fully materialized or there may be substantial unreported production of HCFC-22, resulting in unaccounted-for HFC-23 by-product emissions. The difference between reported and observation-inferred estimates suggests that an additional ~309 Tg CO2-equivalent emissions were added to the atmosphere between 2015 and 2017.
Recent research has identified significant correlations between traumatic events and depression in refugees. However, few studies have addressed the role of acculturation strategies in this relationship. This study explored the relationship between cultural orientation, traumatic events and depression in female refugees from Syria, Afghanistan, Eritrea, Iran, Iraq, and Somalia living in Germany. We expected acculturation strategies to moderate the effect of traumatic experiences on depression. The sample included 98 female refugees in Germany. The depression scale of the Hopkins Symptom Checklist (HSCL) represented the dependent measure. The trauma checklists derived from the Post-traumatic Diagnostic Scale (PDS) and the Harvard Trauma Questionnaire (HTQ) as well as the Frankfurt Acculturation Scale (FRACC) were used as independent measures for traumatic events and orientation toward the host culture as well as orientation toward the culture of origin, respectively. A moderation analysis was conducted to examine whether the relationship between the number of traumatic events and depression was influenced by the women’s orientation toward the culture of origin and the host culture. We identified a significant model explaining 26.85% of the variance in depressive symptoms (Cohen’s f2 = 0.37). The number of traumatic events and the orientation toward the host culture exerted significant effects on depressive symptoms. The moderating effect was not significant, indicating that the effect of the number of traumatic events was not influenced by cultural orientation. Based on our results, orientation toward the host culture as well as traumatic experiences exert independent effects on depressive symptoms in refugees.
Chronic inflammation is considered to be a cause of the autoimmune diseases such as rheumatoid arthritis, Alzheimer’s disease, multiple sclerosis, etc. The search for effective compounds with anti-inflammatory properties to combat these diseases is still ongoing. Natural compound narciclasine, derived from plants of Narcissus species, demonstrated its anti-inflammatory activity in in vivo arthritis models. Further investigation of narciclasine’s anti-inflammatory activity together with its impact on the interaction between leukocytes and endothelial cells was the main focus of this PhD thesis.
Narciclasine reduced the infiltration of monocytes and neutrophils to the abdomen and the concentration of the pro-inflammatory cytokines TNF, IL-6 and IL-1β. Together with this, it reduced acute visceral pain caused by zymosan injection. Narciclasine interfered with leukocyte-endothelial cell interaction in both in vivo and in vitro models. In vivo microscopy revealed that the compound reduced rolling, adhesion and transmigration of leukocytes in the vessels of an injured murine cremaster muscle. This observation was confirmed in the in vitro models for adhesion and transmigration where narciclasine reduced the level of leukocyte’s interaction with HUVECs. Narciclasine demonstrated profound anti-inflammatory properties based on its interference with leukocyte-endothelium interaction by downregulation of endothelial cell adhesion molecules expression (ICAM-1, VCAM-1, E-selectin, CX3CL1) and shutdown of NF-κB pathway. All these effects were a result of the TNF receptor 1 protein translation blocking by narciclasine.
In this work the ability of the compound to reduce visceral pain, downregulate the expression of the endothelial cell adhesion molecules and to interfere with the interaction between leukocytes and endothelial cells was demonstrated for narciclasine for the first time. Obtained results open a promising insight into the understanding of narciclasine’s anti-inflammatory properties and justify further investigation of its potential for treatment of inflammatory diseases.
In this paper we describe Macrobiotus engbergi sp. nov. and Tenuibiotus zandrae sp. nov. from Greenland. Our study has involved both classical taxonomic methods, which include morphological and morphometric analyses conducted with the use of light and scanning electron microscopy, and genetic analysis based on four molecular markers (three nuclear: 18S rRNA, 28S rRNA, ITS-2, and one mitochondrial: COI). Moreover, we re-examined the type series of Tenuibiotus voronkovi (Tumanov, 2007) as well as the original sample where the species was found and we provide new morphological data from light and scanning electron microscopy which enabled us to amend its description. Finally, we also analysed slides with animals and egg of two populations from Nordaustlandet and Edgeøya (archipelago of Svalbard, Norway) designated as T. voronkovi within its recent redescription. The results and comparisons presented in our study question the validity of this designation.
Objective: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving.
Methods: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan–Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data.
Results: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59–66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39–0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011–2017), being on a multi-tablet regimen (MTR).
Conclusions: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.
The first Oriental species of the genus Trichopsomyia Williston, 1888, Trichopsomyia pilosa sp. nov. (Java), has been discovered and is now described. This Oriental species of Trichopsomyia has several characters strongly differing from the other species within this genus. It is hypothesized that it forms a separate group within Trichopsomyia. One species, Trichopsomyia formiciphila Downes, Skevington & Thompson, 2017, from Australia, is similar to the Oriental species described here, and the group is named after this first described species, hence the formiciphila group. The characters for a future phylogenetic analysis are discussed. The character states of the pilosity of the katepisternum and the shape of the metasternum hitherto used in a phylogenetic analysis of Syrphidae Latreille, 1802 are discussed too.
Purpose: Perfusion-weighted MRI (PWI) and O-(2-[18F]fluoroethyl-)-l-tyrosine ([18F]FET) PET are both applied to discriminate tumor progression (TP) from treatment-related changes (TRC) in patients with suspected recurrent glioma. While the combination of both methods has been reported to improve the diagnostic accuracy, the performance of a sequential implementation has not been further investigated. Therefore, we retrospectively analyzed the diagnostic value of consecutive PWI and [18F]FET PET.
Methods: We evaluated 104 patients with WHO grade II–IV glioma and suspected TP on conventional MRI using PWI and dynamic [18F]FET PET. Leakage corrected maximum relative cerebral blood volumes (rCBVmax) were obtained from dynamic susceptibility contrast PWI. Furthermore, we calculated static (i.e., maximum tumor to brain ratios; TBRmax) and dynamic [18F]FET PET parameters (i.e., Slope). Definitive diagnoses were based on histopathology (n = 42) or clinico-radiological follow-up (n = 62). The diagnostic performance of PWI and [18F]FET PET parameters to differentiate TP from TRC was evaluated by analyzing receiver operating characteristic and area under the curve (AUC).
Results: Across all patients, the differentiation of TP from TRC using rCBVmax or [18F]FET PET parameters was moderate (AUC = 0.69–0.75; p < 0.01). A rCBVmax cutoff > 2.85 had a positive predictive value for TP of 100%, enabling a correct TP diagnosis in 44 patients. In the remaining 60 patients, combined static and dynamic [18F]FET PET parameters (TBRmax, Slope) correctly discriminated TP and TRC in a significant 78% of patients, increasing the overall accuracy to 87%. A subgroup analysis of isocitrate dehydrogenase (IDH) mutant tumors indicated a superior performance of PWI to [18F]FET PET (AUC = 0.8/< 0.62, p < 0.01/≥ 0.3).
Conclusion: While marked hyperperfusion on PWI indicated TP, [18F]FET PET proved beneficial to discriminate TP from TRC when PWI remained inconclusive. Thus, our results highlight the clinical value of sequential use of PWI and [18F]FET PET, allowing an economical use of diagnostic methods. The impact of an IDH mutation needs further investigation.
DeriMo is an international meeting dealing with derivational morphology from the perspective of data analysis. Its second edition DeriMo 2019 was held at the Faculty of Mathematics and Physics, Charles University in Prague. The local organizers are researchers of the Institute of Formal and Applied Linguistics (ÚFAL = Ústav Formální a Aplikované Linguistiky) at the Computer Science School of the Faculty of Mathematics and Physics. Chairs of the program committee were Magda Ševčíková (ÚFAL), Zdeněk Žabokrtský (ÚFAL), Eleonora Litta Modignani Picozzi (CIRCSE, Università Cattolica del Sacro Cuore, Milan), and Marco Passarotti (CIRCSE, Università Cattolica del Sacro Cuore, Milan).
Objective: To determine the impact of an exercise-based prehabilitation (EBPrehab) program on preand postoperative exercise capacity, functional capacity (FC) and quality of life (QoL) in patients awaiting elective coronary artery bypass graft surgery (CABG).
Design: A two-group randomized controlled trail.
Setting: Ambulatory prehabilitation.
Subjects: Overall 230 preoperative elective CABG-surgery patients were randomly assigned to an intervention (IG, n=88; n=27 withdrew after randomization) or control group (CG, n=115).
Intervention: IG: two-week EBPrehab including supervised aerobic exercise. CG: usual care.
Main measures: At baseline (T1), one day before surgery (T2), at the beginning (T3) and at the end of cardiac rehabilitation (T4) the following measurements were performed: cardiopulmonary exercise test, six-minute walk test (6MWT), Timed-Up-and-Go Test (TUG) and QoL (MacNew questionnaire).
Results: A total of 171 patients (IG, n=81; CG, n=90) completed the study. During EBPrehab no complications occurred. Preoperatively FC (6MWTIG: 443.0±80.1m to 493.5±75.5m, P=0.003; TUGIG: 6.9±2.0 s to 6.1±1.8 s, P=0.018) and QoL (IG: 5.1±0.9 to 5.4±0.9, P<0.001) improved significantly more in IG compared to CG. Similar effects were observed postoperatively in FC (6MWDIG: Δ-64.7m, pT1–T3=0.013; Δ+47.2m, pT1–T4<0.001; TUGIG: Δ+1.4s, pT1–T3=0.003).
Conclusions: A short-term EBPrehab is effective to improve perioperative FC and preoperative QoL in patients with stable coronary artery disease awaiting CABG-surgery.
A survey for myxomycetes (plasmodial slime moulds or myxogastrids) was carried out on Norfolk Island in June 2019. The overall objective was to collect both specimens that had fruited in the field under natural conditions as well as specimens appearing in moist chamber cultures prepared with samples of dead plant material collected on the island. However, only three species were recorded as field collections over a period of almost two weeks, so the primary focus of the survey was redirected to collecting samples for moist chamber cultures. Approxmately 120 samples of dead plant material collected from 21 different sampling sites on the island and used to prepare 356 moist chamber cultures yielded a total of 497 specimens. These specimens included at least 48 species in 18 genera. This brings the total number of species and genera now known from Norfolk Island to 55 and 19, respectively.
Purpose: Diffuse cortical damage in relapsing–remitting multiple sclerosis (RRMS) is clinically relevant but cannot be directly assessed with conventional MRI. In this study, it was aimed to use diffusion tensor imaging (DTI) techniques with optimized intrinsic eddy current compensation to quantify and characterize cortical mean diffusivity (MD) and fractional anisotropy (FA) changes in RRMS and to analyze the distribution of these changes across the cortex.
Materials and Methods: Three-Tesla MRI acquisition, mapping of the MD providing information about the integrity of microstructural barriers and of the FA reflecting axonal density and surface-based analysis with Freesurfer were performed for 24 RRMS patients and 25 control subjects.
Results: Across the whole cortex, MD was increased in patients (p < 0.001), while surface-based analysis revealed focal cortical FA decreases. MD and FA changes were distributed inhomogeneously across the cortex, the MD increase being more widespread than the FA decrease. Cortical MD correlated with the Expanded Disability Status Scale (EDSS, r = 0.38, p = 0.03).
Conclusion: Damage of microstructural barriers occurs inhomogeneously across the cortex in RRMS and might be spatially more widespread than axonal degeneration. The results and, in particular, the correlation with the clinical status indicate that DTI might be a promising technique for the monitoring of cortical damage under treatment in larger clinical studies.
Background: Current literature is inconsistent regarding the risk of severe side effects using accelerated induction protocols in Hymenoptera venom immunotherapy (VIT). In addition, several data indicate the influence of purity grade of venom preparation on tolerability. We evaluated the safety and tolerability of ultra-rush and rush build-up protocols using purified and non-purified venom preparations. Methods: Retrospective single-center study of 581 VIT inductions (325 ultra-rush and 256 rush protocols) from 2005 to 2018 in 559 patients with bee and vespid venom allergy using aqueous purified (ALK SQ®) for ultra-rush protocol and aqueous non-purified (ALK Reless®) venom preparations for rush protocol. Results: Urticaria (8% vs. 3.1%, p = 0,013) and dose reductions (4.3% vs. 1.2%, p = 0,026) were significantly more frequent in the ultra-rush group. Overall rate of moderate-to-severe side effects (anaphylaxis ≥grade 2 according to Ring and Meβmer) was low and did not differ significantly between protocols (p = 0.105). Severe events (grade 4 anaphylaxis) were not reported. Discontinuation rate was very low in both cohorts (0.6% vs 1.2%). The higher purity grade of venom preparations in the ultra-rush cohort did not improve tolerability. The bee venom group showed a non-significant trend towards higher incidence of mild reactions (urticaria), resulting in more frequent dose reductions and antiallergic therapy. Conclusion: Rush and ultra-rush protocols show an excellent safety profile with only infrequent and mild anaphylactic reactions in bee and vespid venom allergy. Ultra-rush immunotherapy reduces the duration of the inpatient build-up phase setting and thus is viewed by the authors as preferred treatment in Hymenoptera venom allergic patients.
Despite the great importance of the Latin language in the past, there are relatively few resources available today to develop modern NLP tools for this language. Therefore, the EvaLatin Shared Task for Lemmatization and Part-of-Speech (POS) tagging was published in the LT4HALA workshop. In our work, we dealt with the second EvaLatin task, that is, POS tagging. Since most of the available Latin word embeddings were trained on either few or inaccurate data, we trained several embeddings on better data in the first step. Based on these embeddings, we trained several state-of-the-art taggers and used them as input for an ensemble classifier called LSTMVoter. We were able to achieve the best results for both the cross-genre and the cross-time task (90.64% and 87.00%) without using additional annotated data (closed modality). In the meantime, we further improved the system and achieved even better results (96.91% on classical, 90.87% on cross-genre and 87.35% on cross-time).
We report on fourteen species and four genera of Tischeriidae recorded from Las Cuevas, a single tropical forest locality in Belize, Central America. This is the highest number of species of Tischeriidae recorded from a single locality worldwide, exceeding the species and generic diversity of the entire Tischeriidae fauna of Europe and accounting for about 9% of the documented global fauna for this family. We describe and name six new species: Astrotischeria papilloma Diškus & Stonis sp. nov., mining on Lasianthaea fruticosa (L.) K.M.Becker (Asteraceae); A. scutifera Diškus & Stonis sp. nov., mining on Sida glabra Mill. (Malvaceae); A. basilobata Remeikis & Stonis sp. nov., mining on Lasianthaea fruticosa; Paratischeria robinsoni Diškus & Stonis sp. nov., mining on Otopappus verbesinoides Benth. (Asteraceae); P. tubifex Diškus & Stonis sp. nov., mining on Lasianthaea fruticosa; and P. belizensis Remeikis & Stonis sp. nov. (host plant unknown). Additionally, we review eight previously described species from the same period of collecting at Las Cuevas in 1997–1998: A. selvica Diškus, Carvalho-Filho & Stonis, 2018, mining on Sphagneticola trilobata (L.) Pruski and Synedrella nodiflora (L.) Gaertn. (Asteraceae); A. casila Diškus & Stonis, 2018, mining on Montanoa atriplicifolia (Pers.) Sch.Bip. (Asteraceae); A. furcata Diškus & Stonis, 2018 (host plant unknown); Paratischeria neotropicana (Diškus & Stonis, 2015), mining on Sida L. (Malvaceae), including S. rhombifolia L.; Dishkeya gouaniae (Stonis & Diškus, 2007), mining on Gouania polygama (Jacq.) Urb. (Rhamnaceae); Coptotriche pulverea (Walsingham, 1897), mining on Terminalia amazonia (J.F.Gmel.) Exell (Combretaceae); C. forsteroniae Stonis & Diškus, 2008, mining on Forsteronia myriantha Donn Sm. (Apocynaceae); and C. singularis Stonis & Diškus, 2008 (host plant unknown). All taxa, except for C. singularis, are illustrated with photographs of the adults and their genitalia. We also briefly discuss the discovery of some novel characters for Astrotischeria Puplesis & Diškus, 2003 and Paratischeria Diškus & Stonis, 2017, Tischeriidae, and provide the first photographic documentation of Coptotriche pulverea and C. forsteroniae.
Background: Breast cancer is the leading cause of cancer-related deaths in women, demanding new treatment options. With the advent of immune checkpoint blockade, immunotherapy emerged as a treatment option. In addition to lymphocytes, tumor-associated macrophages exert a significant, albeit controversial, impact on tumor development. Pro-inflammatory macrophages are thought to hinder, whereas anti-inflammatory macrophages promote tumor growth. However, molecular markers to identify prognostic macrophage populations remain elusive. Methods: We isolated two macrophage subsets, from 48 primary human breast tumors, distinguished by the expression of CD206. Their transcriptomes were analyzed via RNA-Seq, and potential prognostic macrophage markers were validated by PhenOptics in tissue microarrays of patients with invasive breast cancer. Results: Normal human breast tissue contained mainly CD206+ macrophages, while increased relative amounts of CD206− macrophages were observed in tumors. The presence of CD206+ macrophages correlated with a pronounced lymphocyte infiltrate and subsets of CD206+ macrophages, expressing SERPINH1 and collagen 1, or MORC4, were unexpectedly associated with improved survival of breast cancer patients. In contrast, MHCIIhi CD206− macrophages were linked with a poor survival prognosis. Conclusion: Our data highlight the heterogeneity of tumor-infiltrating macrophages and suggest the use of multiple phenotypic markers to predict the impact of macrophage subpopulations on cancer prognosis. We identified novel macrophage markers that correlate with the survival of patients with invasive mammary carcinoma.
Objectives: Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections.
Materials and methods: Patients who were screened for MDRO colonization within a 90-day period after NSCLC diagnosis of all stages were included in this single-center retrospective study.
Results: Two hundred and ninety-five patients were included of whom 24 patients (8.1%) were screened positive for MDRO colonization (MDROpos) at first diagnosis. Enterobacterales were by far the most frequent MDRO detected with a proportion of 79.2% (19/24). MDRO colonization was present across all disease stages and more present in patients with concomitant diabetes mellitus. Median overall survival was significantly inferior in the MDROpos study group with a median OS of 7.8 months (95% CI, 0.0–19.9 months) compared to a median OS of 23.9 months (95% CI, 17.6–30.1 months) in the MDROneg group in univariate (p = 0.036) and multivariate analysis (P = 0.02). Exploratory analyses suggest a higher rate of non-cancer-related-mortality in MDROpos patients compared to MDROneg patients (p = 0.002) with an increased rate of fatal infections in MDROpos patients (p = 0.0002).
Conclusions: MDRO colonization is an independent risk factor for inferior OS in patients diagnosed with NSCLC due to a higher rate of fatal infections. Empirical antibiotic treatment approaches should cover formerly detected MDR commensals in cases of (suspected) invasive infections.
Evaluation of a rapid turn-over, fully-automated ADAMTS13 activity assay: a method comparison study
(2020)
Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy caused by severely reduced activity of the von-Willebrand factor-cleaving protease ADAMTS13, mainly caused by anti-ADAMTS-13 antibodies. Although several test systems for ADAMTS13 measurement exist, long turn-around times hamper the usability in daily practice. We performed a method comparison study for two commercially available ADAMTS13 assays and evaluated the agreement between the fully-automated rapid turn-over HemosIL AcuStar ADAMTS13 Activity assay and the manually performed TECHNOZYM ADAMTS-13 Activity assay. Twenty-four paired test samples derived from 10 consecutively recruited patients (n = 8, acquired TTP; n = 1, atypical hemolytic uremic syndrome; n = 1, control), of which nine test samples were collected in case of clinically apparent TTP and 13 samples were collected from TTP patients in clinical remission were included. Overall correlation between the TECHNOZYM and AcuStar assay was good with a Pearson R of 0.93 (p < 0.001). Agreement between the assays assessed with the Passing–Bablok analysis showed high agreement with an Intercept of − 2.56 (95% confidence interval [CI], − 5.07 to − 0.86) and Slope of 1.04 (95% CI 0.84–1.17). The absolute mean bias was 2.54% (standard difference [SD], 6.38%; 95% CI to 10.0–15.05%). Intra-method reliability was high with an absolute mean bias of − 0.13% (SD 3.21%; 95% CI to 6.42–6.16%). The observer agreement for categorial thresholds (> or < 10% ADAMTS3 activity) was kappa = 0.82 (95% CI 0.59–1.0). Conclusively, overall agreement between the testing methods was sufficient and we support previously published data suggesting the AcuStar assay being a valuable and accurate tool for ADAMTS13 activity testing and TTP diagnostics.
Ribosome biogenesis is one cell function-defining process. It depends on efficient transcription of rDNAs in the nucleolus as well as on the cytosolic synthesis of ribosomal proteins. For newly transcribed rRNA modification and ribosomal protein assembly, so-called small nucleolar RNAs (snoRNAs) and ribosome biogenesis factors (RBFs) are required. For both, an inventory was established for model systems like yeast and humans. For plants, many assignments are based on predictions. Here, RNA deep sequencing after nuclei enrichment was combined with single molecule species detection by northern blot and in vivo fluorescence in situ hybridization (FISH)-based localization studies. In addition, the occurrence and abundance of selected snoRNAs in different tissues were determined. These approaches confirm the presence of most of the database-deposited snoRNAs in cell cultures, but some of them are localized in the cytosol rather than in the nucleus. Further, for the explored snoRNA examples, differences in their abundance in different tissues were observed, suggesting a tissue-specific function of some snoRNAs. Thus, based on prediction and experimental confirmation, many plant snoRNAs can be proposed, while it cannot be excluded that some of the proposed snoRNAs perform alternative functions than are involved in rRNA modification
Complexome profiling is an emerging ‘omics approach that systematically interrogates the composition of protein complexes (the complexome) of a sample, by combining biochemical separation of native protein complexes with mass-spectrometry based quantitation proteomics. The resulting fractionation profiles hold comprehensive information on the abundance and composition of the complexome, and have a high potential for reuse by experimental and computational researchers. However, the lack of a central resource that provides access to these data, reported with adequate descriptions and an analysis tool, has limited their reuse. Therefore, we established the ComplexomE profiling DAta Resource (CEDAR, www3.cmbi.umcn.nl/cedar/), an openly accessible database for depositing and exploring mass spectrometry data from complexome profiling studies. Compatibility and reusability of the data is ensured by a standardized data and reporting format containing the “minimum information required for a complexome profiling experiment” (MIACE). The data can be accessed through a user-friendly web interface, as well as programmatically using the REST API portal. Additionally, all complexome profiles available on CEDAR can be inspected directly on the website with the profile viewer tool that allows the detection of correlated profiles and inference of potential complexes. In conclusion, CEDAR is a unique, growing and invaluable resource for the study of protein complex composition and dynamics across biological systems.
Background: Culture-derived mesenchymal stromal cells (MSCs) exhibit variable characteristics when manufactured using different methods and different source materials. The purpose of this study was to assess the impact on MSC characteristics when different laboratories propagated MSCs from cultures initiated with BM aliquots derived from the same donor source material.
Methods and Methods: Five aliquots from each of three different BM donors were distributed to five independent laboratories. Three laboratories plated whole BM and two laboratories a mononuclear BM cell fraction. Four laboratories cultured in media supplemented with fetal bovine serum (FBS) and one laboratory used human platelet lysate (hPL). Initial cell seeding densities (i.e., P0) ranged from 19.7 × 103/cm2–282 × 103/cm2 and for second seeding (i.e., P1) 0.05 × 103–5.1 × 103 cells/cm2. Post-thawed MSCs from each laboratory were analyzed for cell viability, immunophenotype, tri-lineage differentiation, fibroblast colony-forming units (CFU-F), gene expression, and immunosuppressive activity.
Results: Transit times from BM collection to receipt by laboratories located in the United States ranged from 16.0–30.0 h and from 41.5–71.5 h for a laboratory in Asia. Post-thaw culture derived MSCs rom BM #1, #2, and #3 exhibited viabilities that ranged from 74–92%, 61–96%, and 23–90%, respectively. CFU activity from BM #1, #2, and #3 per 200 MSCs plated averaged 45.1 ± 21.4, 49.3 ± 26.8 and 14.9 ± 13.3, respectively. No substantial differences were observed in immunophenotype, and immunosuppressive activities. Global gene expression profiles of MSCs revealed transcriptome differences due to different inter-laboratory methods and to donor source material with the center effects showing greater molecular differences than source material.
Conclusion: Functional and molecular differences exist among MSCs produced by different centers even when the same BM starting material is used to initiate cultures. These results indicated that manufacturing of MSCs by five independent centers contributed more to MSC variability than did the source material of the BM used in this study. Thus, emphasizing the importance of establishing worldwide standards to propagate MSCs for clinical use.
100 Jahre Dieter Janz
(2020)
The 20 April 2020 marks the centenary of Dieter Janz’s birth. This issue of Zeitschrift für Epileptologie is published in his honor with the aim of tracing the work of Dieter Janz over the last five decades and summarizing new findings on the Janz syndrome (Juvenile Myoclonic Epilepsy), which is named after him.
Introduction: Dravet syndrome (DS), a prototypic developmental and genetic epileptic encephalopathy (DEE), is characterized by an early onset of treatment-refractory seizures, together with impairments in motor control, behavior, and cognition. Even with multiple conventional anti-epileptic drugs, seizures remain poorly controlled, and there has been a considerable unmet need for effective and tolerable treatments. Areas covered: This targeted literature review aims to highlight recent changes to the therapeutic landscape for DS by summarizing the most up-to-date, evidence-based research, including pivotal data from the clinical development of stiripentol, cannabidiol, and fenfluramine, which are important milestones for DS treatment, together with the latest findings of other pharmacotherapies in development. In phase III, double-blind, placebo-controlled randomized controlled trials stiripentol, cannabidiol, and fenfluramine have shown clinically relevant reductions in convulsive seizure frequency, and are generally well tolerated. Stiripentol was associated with responder rates (greater than 50% reduction in convulsive seizure frequency) of 67%-71%, when added to valproic acid and clobazam; cannabidiol was associated with responder rates of 43%-49% (48%-63% in conjunction with clobazam), and fenfluramine of 54%-68% across studies. Therapies in development include soticlestat, ataluren, verapamil, and clemizole, with strategies to treat the underlying cause of DS, including gene therapy and antisense oligonucleotides beginning to emerge from preclinical studies. Expert opinion: Despite the challenges of drug development in rare diseases, this is an exciting time for the treatment of DS, with the promise of new efficacious and well-tolerated therapies, which may pave the way for treatment advances in other DEEs.
Highlights
• German patients with LGS identified using most specific algorithm to date.
• Prevalence of probable LGS with epilepsy diagnosis before age 6 was 6.5 per 100,000.
• High healthcare costs of €22,787 PPY; mostly due to inpatient and home nursing care.
• Costs were greater in patients prescribed rescue medications.
• Over 10 years, LGS patients had significant mortality vs. controls (2.88 vs. 0.01%).
Abstract
Objective: This retrospective study examined patients with probable Lennox-Gastaut syndrome (LGS) identified from German healthcare data.
Methods: This 10-year study (2007–2016) assessed healthcare insurance claims information from the Vilua Healthcare research database. A selection algorithm considering diagnoses and drug prescriptions identified patients with probable LGS. To increase the sensitivity of the identification algorithm, two populations were defined: all patients with probable LGS (broadly defined) and only those with a documented epilepsy diagnosis before 6 years of age (narrowly defined). This specific criterion was used as LGS typically has a peak seizure onset between age 3 and 5 years. Primary analyses were prevalence and demographics; secondary analyses included healthcare costs, hospitalization rate and length of stay (LOS), medication use, and mortality.
Results: In the final year of the study, 545 patients with broadly defined probable LGS (mean [range] age: 31.4 [2–89] years; male: 53%) were identified. Using the narrowly defined probable LGS definition, the number of patients was reduced to 102 (mean [range] age: 7.4 [2–14] years; male: 52%). Prevalence of broadly defined and narrowly defined probable LGS was 39.2 and 6.5 per 100,000 people. During the 10-year study, 208 patients with narrowly defined probable LGS were identified and followed up for 1379 patient-years. The mean annual cost of healthcare was €22,787 per patient-year (PPY); greatest costs were attributable to inpatient care (33%), home nursing care (13%), and medication (10%). Mean annual healthcare costs were significantly greater for those with prescribed rescue medication (45% of patient-years) versus those without (€33,872 vs. €13,785 PPY, p < 0.001). Mean (standard deviation [SD]) annual hospitalization rate was 1.6 (2.0) PPY with mean (SD) annual LOS of 22.7 (46.0) days. Annual hospitalization rate was significantly greater in those who were prescribed rescue medication versus those who were not (2.2 [2.3] vs. 1.1 [1.6] PPY, p < 0.001). The mean (SD) number of different medications prescribed was 11.3 (7.3) PPY and 33.8 (17.0) over the entire observable time per patient (OET); antiepileptic drugs only accounted for 2.1 (1.1) of the medications prescribed PPY and 3.8 (2.0) OET. Over the 10-year study period, mortality in patients with narrowly defined probable LGS was significantly higher than the matched control population (six events [2.88%] vs. one event [0.01%], p < 0.001).
Conclusion: Annual healthcare costs incurred by patients with probable LGS in Germany were substantial, and mostly attributable to inpatient care, home nursing care, and medication. Patients prescribed with rescue medication incurred significantly greater costs than those who were not. Patients with narrowly defined probable LGS had a higher mortality rate versus control populations.
Objective: Severely injured patients frequently develop an immunological imbalance following the traumatic insult, which might result in infectious complications evoked by a persisting immunosuppression. Regulatory T cells (Tregs) maintain the immune homeostasis by suppressing proinflammatory responses, however, their functionality after trauma is unclear. Here, we characterized the role of Tregs in regulating the proliferation of CD4+ lymphocytes in traumatized patients (TP). Methods: Peripheral blood was obtained daily from 29 severely injured TP (Injury Severity Score, ISS ≥16) for ten days following admission to the emergency department (ED). Ten healthy volunteers (HV) served as controls. The frequency and activity of Tregs were assessed by flow cytometry. Proliferation of CD4+ cells was analyzed either in presence or absence of Tregs, or after blocking of either IL-10 or IL-10R1. Results: The frequencies of CD4+CD25high and CD4+CD25+CD127− Tregs were significantly decreased immediately upon admission of TP to the ED and during the following 10 post-injury days. Compared with HV CD4+ T cell proliferation in TP increased significantly upon their admission and on the following days. As expected, CD4+CD25+CD127− Tregs reduced the proliferation of CD4+ cells in HV, nevertheless, CD4+ proliferation in TP was increased by Tregs. Neutralization of IL-10 as well as blocking the IL-10R1 increased further CD4+ T cell proliferation in Tregs-depleted cultures, thereby confirming an IL-10-mediated mechanism of IL-10-regulated CD4+ T cell proliferation. Neutralization of IL-10 in TP decreased CD4+ T cell proliferation in Tregs-depleted cultures, whereas blocking of the IL-10R1 receptor had no significant effects. Conclusions: The frequency of Tregs in the CD4+ T lymphocyte population is reduced after trauma; however, their inductiveness is increased. The mechanisms of deregulated influence of Tregs on CD4+ T cell proliferation are mediated via IL-10 but not via the IL-10R1.
CO2 has been electrochemically reduced to the intermediate formate, which was subsequently used as sole substrate for the production of the polymer polyhydroxybutyrate (PHB) by the microorganism Cupriavidus necator. Faradaic efficiencies (FE) up to 54 % have been reached with Sn‐based gas‐diffusion electrodes in physiological electrolyte. The formate containing electrolyte can be used directly as drop‐in solution in the following biological polymer production by resting cells. 56 mg PHB L−1 and a ratio of 34 % PHB per cell dry weight were achieved. The calculated overall FE for the process was as high as 4 %. The direct use of the electrolyte as drop‐in media in the bioconversion enables simplified processes with a minimum of intermediate purification effort. Thus, an optimal coupling between electrochemical and biotechnological processes can be realized.
The conspicuous Mediterranean brittle star Ophioderma longicauda (Bruzelius, 1805) has been discovered to represent a cryptic species complex, consisting of six nuclear clusters with contrasting reproductive modes (broadcast spawners and brooders). Here, O. longicauda is re-described. It is distinguished by a dark reddish-brown colouration both dorsally and on the ventral disc, and multiple tumid dorsal arm plates. One eastern Mediterranean brooding cluster is described as O. zibrowii sp. nov., characterized by a dark olive-green colour both dorsally and on the ventral disc, and single dorsal arm plates. Another brooder is described from Tunisia as O. hybrida sp. nov., with a highly variable morphology that reflects its origin by hybridization of O. longicauda and a brooder (possibly O. zibrowii sp. nov.), leaving the third brooding cluster as morphologically indistinguishable at this point and possibly conspecific with one of the others. The West-African O. guineense Greef, 1882 is resurrected as a valid species, differing morphologically from O. longicauda by predominantly single dorsal arm plates and light green or creamy white ventral side. Also from West Africa, O. africana sp. nov. is described, characterized by a dark brown colour, dorsally and ventrally, and single dorsal arm plates.
So far, personal feedback in the case of lectures with hundreds of students still seems utopic – even after the digitalization boom in times of the coronavirus. Tools from the research field of »learning analytics« could in future give students feedback and at the same time provide their supervisors with clues about where help is still needed.
Since the introduction of rental E-scooters in Germany in mid-June 2019, the safety of this new means of transport has been the subject of extensive public debate. However, valid data on injuries and usage habits are not yet available. This retrospective two-center study included a total of 76 patients who presented to the emergency department following E-scooter-related accidents. The mean age was 34.3 ± 12.4 years and 69.7% of the patients were male. About half of the patients were admitted by ambulance (42.1%). Fractures were found in 48.6% of patients, and 27.6% required surgical treatment due to a fracture. The upper extremities were the most commonly affected body region, followed by injuries to the lower extremity and to the head and face. Only one patient had worn a helmet. In-hospital treatment was necessary for 26.3% of the cases. Patients presented to the emergency department mainly during the weekend and on-call times. This is the first report on E-scooter-related injuries in Germany. Accidents with E-scooters can cause serious injuries and, therefore, represent a further burden to emergency departments. The use of E-scooters appears to be mostly recreational, and the rate of use of protective gear is low.
Dendrites display a striking variety of neuronal type-specific morphologies, but the mechanisms and principles underlying such diversity remain elusive. A major player in defining the morphology of dendrites is the neuronal cytoskeleton, including evolutionarily conserved actin-modulatory proteins (AMPs). Still, we lack a clear understanding of how AMPs might support developmental phenomena such as neuron-type specific dendrite dynamics. To address precisely this level of in vivo specificity, we concentrated on a defined neuronal type, the class III dendritic arborisation (c3da) neuron of Drosophila larvae, displaying actin-enriched short terminal branchlets (STBs). Computational modelling reveals that the main branches of c3da neurons follow a general growth model based on optimal wiring, but the STBs do not. Instead, model STBs are defined by a short reach and a high affinity to grow towards the main branches. We thus concentrated on c3da STBs and developed new methods to quantitatively describe dendrite morphology and dynamics based on in vivo time-lapse imaging of mutants lacking individual AMPs. In this way, we extrapolated the role of these AMPs in defining STB properties. We propose that dendrite diversity is supported by the combination of a common step, refined by a neuron type-specific second level. For c3da neurons, we present a molecular model of how the combined action of multiple AMPs in vivo define the properties of these second level specialisations, the STBs.
p53 regulates the cellular response to genotoxic damage and prevents carcinogenic events. Theoretical and experimental studies state that the p53-Mdm2 network constitutes the core module of regulatory interactions activated by cellular stress induced by a variety of signaling pathways. In this paper, a strategy to control the p53-Mdm2 network regulated by p14ARF is developed, based on the pinning control technique, which consists into applying local feedback controllers to a small number of nodes (pinned ones) in the network. Pinned nodes are selected on the basis of their importance level in a topological hierarchy, their degree of connectivity within the network, and the biological role they perform. In this paper, two cases are considered. For the first case, the oscillatory pattern under gamma-radiation is recovered; afterward, as the second case, increased expression of p53 level is taken into account. For both cases, the control law is applied to p14ARF (pinned node based on a virtual leader methodology), and overexpressed Mdm2-mediated p53 degradation condition is considered as carcinogenic initial behavior. The approach in this paper uses a computational algorithm, which opens an alternative path to understand the cellular responses to stress, doing it possible to model and control the gene regulatory network dynamics in two different biological contexts. As the main result of the proposed control technique, the two mentioned desired behaviors are obtained.
Reliable and efficient recording of the error-related negativity with a speeded Eriksen Flanker task
(2020)
There is accumulating evidence that the error-related negativity (ERN), an event-related potential elicited after erroneous actions, is altered in different psychiatric disorders and may help to guide treatment options. Thus, the ERN is a promising candidate as a psychiatric biomarker. Basic methodological requirements for a biomarker are standardized and reliable measurements. Additional psychiatry specific requirements are time efficiency and patient-friendliness.
The aim of the present study is to establish ERN acquisition in a reliable, time-efficient and patient-friendly way for use in clinical practice.
Healthy subjects (N=27) performed a modified Eriksen Flanker Task with adaptive reaction time window and only incongruent stimuli that maximizes the number of errors. All participants were tested for mental health by the Mini International Neuropsychiatric Interview (M.I.N.I.). The first N=12 subjects were part of a pilot study and further N=14 subjects were included for analysis (one subject was excluded due to technical problems). In a test-retest design with two sessions separated by 28 days the reliability of the ERN has been assessed. To ensure external validity, we aimed to replicate previously reported correlation patterns of ERN amplitude with (1) number of errors and (2) negative affect. State affect of each subject was measured by the Positive and Negative Affect Schedule. In order to optimize the clinical use of the task, we determined to which extent the task can be shortened while keeping reliability >0.80.
We found excellent reliability of the ERN (intraclass correlation coefficient =0.806-0.947) and replicated specific correlation patterns (ERN amplitude with relative number of errors: r=0.394; p=0.082; ERN amplitude with negative affect: r=-0.583, p=0.014). The task can be shortened to a patient-friendly and clinically feasible length of only 8 minutes keeping reliability >0.80.
To conclude, the present modified task provides reliable and efficient recording of the ERN, facilitating its use as a psychiatric biomarker.
The scale insects (Hemiptera: Coccomorpha) are one of the most successful groups of plant-feeding arthropods. Most species of shade trees, fruit trees and ornamental shrubs are subject to scale insect attacks. Based on the review of the literature and survey results, the host plant list of the scale insects in South Korea was developed and updated. Herein, an updated list of 253 species of host plants in 71 families associated with scale insects is provided and 162 species in 15 scale insect families are listed.
Quick and accurate identification of intercepted psyllids (Hemiptera: Psylloidea) is an essential requirement for effective pest management and phytosanitary procedures. However, due to lack of morphological characters in the immature stages that can be used to distinguish species, other molecular methods, such as DNA barcoding are proving to be useful. The current study was to designed to generate comprehensive information on the identification of all developmental stages of eight species of psyllids intercepted on consignments of infested fresh cut flowers at the ports of entry in South Korea using DNA barcoding. It is considered that DNA barcoding is a reliable technique for identification of intercepted psyllids for immature stages and will be helpful in the development of more effective pest management options for regulating pest species.
This study was performed to identify Peronosclerospora species found in Indonesia based on sequence analysis of the cox2 gene. In addition, sequence data in total, 26 isolates of Peronosclerospora were investigated in this study. They were obtained from 7 provinces in Indonesia, namely Lampung, Jawa Timur, Jawa Barat, Sumatera Utara, Jawa Tengah, Yogyakarta, and Sulawesi Selatan. Sequence analysis of cox2 and phylogenetic inference were performed on all the 26 isolates. A set of primers developed in this study, PCOX2F and PCOX2R, was used for PCR amplification. Phylogenetic analyses showed that all the Indonesian isolates were divided into two groups. Group I contained 13 isolates; 9 isolates obtained from Lampung, 3 isolates from Sumatera Utara, and 1 isolate from Jawa Barat. Group II consisted of 13 isolates; 7 isolates from Jawa Timur, 2 isolates from Jawa Tengah, 1 isolate from Yogyakarta, and 3 isolates from Sulawesi Selatan. All the members of group I clustered with the ex-type sequence of P. australiensis. Meanwhile, all members of Group II formed the sister clade of isolates obtained from Timor-Leste and may represent P. maydis.
Ten species of Campodorus Förster, 1869 are reported from China and five species are new to science: C. albilineatus Sheng, Sun & Li sp. nov. from Guangxi Zhuang Autonomous Region in the Oriental part of China, C. punctatus Sheng, Sun & Li sp. nov. and C. rasilis Sheng, Sun & Li sp. nov. from Beijing, C. shandongicus Sheng, Sun & Li sp. nov. from Shandong Province and C. truncatus Sheng, Sun & Li, sp. nov. from Liaoning Province. Three species, C. ciliatus (Holmgren, 1857) and C. dauricus Kasparyan, 2005 collected from Liaoning Province and Mesoleius faciator Kasparyan, 2001 from Beijing, are new records for China. A key to species of Campodorus and a related genus known in China is provided.
Introduction: Recommendations for venous thromboembolism and deep venous thrombosis (DVT) prophylaxis using graduated compression stockings (GCS) is historically based and has been critically examined in current publications. Existing guidelines are inconclusive as to recommend the general use of GCS.
Patients/Methods: 24 273 in-patients (general surgery and orthopedic patients) undergoing surgery between 2006 and 2016 were included in a retrospectively analysis from a single center. From January 2006 to January 2011 perioperative GCS was employed additionally to drug prophylaxis and from February 2011 to March 2016 patients received drug prophylaxis alone. According to german guidelines all patients received venous thromboembolism prophylaxis with weight-adapted LMWH. Risk stratification (low risk, moderate risk, high risk) was based on the guideline of the American College of Chest Physicians. Data analysis was performed before and after propensity matching (PM). The defined primary endpoint was the incidence of symptomatic or fatal pulmonary embolism (PE). A secondary endpoint was the incidence of deep venous thromboembolism (DVT).
Results: After risk stratification (low risk n = 16 483; moderate risk n = 4464; high risk n = 3326) a total of 24 273 patient were analyzed. Before to PM the relative risk for the occurrence of a PE or DVT was not increased by abstaining from GCS. After PM two groups of 11 312 patients each, one with and one without GCS application, were formed. When comparing the two groups, the relative risk (RR) for the occurrence of a pulmonary embolism was: Low Risk 0.99 [CI95% 0.998–1.000]; Moderate Risk 0.999 [CI95% 0.95–1.003]; High Risk 0.996 [CI95% 0.992–1.000] (p > 0.05). The incidence of PE in the total group LMWH alone was 0.1% (n = 16). In the total group using LMWH + GCS, the incidence was 0.3% (n = 29). RR after PM was 0.999 [CI95% 0.998–1.00].
Conclusion: In comparison to prior studies with only small numbers of patients our trial shows in a large group of patients with moderate and high risk developing VTE we can support the view that abstaining from GCS-use does not increase the incidence of symptomatic or fatal PE and symptomatic DVT.
A myriad of signaling molecules in a heuristic network of the tumor microenvironment (TME) pose a challenge and an opportunity for novel therapeutic target identification in human cancers. MicroRNAs (miRs), due to their ability to affect signaling pathways at various levels, take a prominent space in the quest of novel cancer therapeutics. The role of miRs in cancer initiation, progression, as well as in chemoresistance, is being increasingly investigated. The canonical function of miRs is to target mRNAs for post-transcriptional gene silencing, which has a great implication in first-order regulation of signaling pathways. However, several reports suggest that miRs also perform non-canonical functions, partly due to their characteristic non-coding small RNA nature. Examples emerge when they act as ligands for toll-like receptors or perform second-order functions, e.g., to regulate protein translation and interactions. This review is a compendium of recent advancements in understanding the role of miRs in cancer signaling and focuses on the role of miRs as novel regulators of the signaling pathway in the TME.
Recent studies suggested an important contribution of sphingosine-1-phospate (S1P) signaling via its specific receptors (S1PRs) in the production of pro-inflammatory mediators such as Interleukin (IL)-1β in cancer and inflammation. In an inflammation-driven cancer setting, we previously reported that myeloid S1PR1 signaling induces IL-1β production by enhancing NLRP3 (NOD-, LRR- and Pyrin Domain-Containing Protein 3) inflammasome activity. However, the autocrine role of S1P and enzymes acting on the S1P rheostat in myeloid cells are unknown. Using human and mouse macrophages with pharmacological or genetic intervention we explored the relative contribution of sphingosine kinases (SPHKs) in NLRP3 inflammasome activity regulation. We noticed redundancy in SPHK1 and SPHK2 activities towards macrophage NLRP3 inflammasome transcriptional induction and IL-1β secretion. However, pharmacological blockade of both kinases in unison completely abrogated NLRP3 inflammasome induction and IL-1β secretion. Interestingly, human and mouse macrophages demonstrate varied responses towards SPHKs inhibition and IL-1β secretion. Clinical datasets of renal cell carcinoma and psoriasis patients showed a positive correlation between enzymes affecting the S1P rheostat with NLRP3 inflammasome components expression, which corroborates our finding. Our data provide a better understanding on the role of SPHKs and de novo synthesized S1P in macrophage NLRP3 inflammasome activation
The evolution of the traditional nuclear magic numbers away from the valley of stability is an active field of research. Experimental efforts focus on providing key spectroscopic information that will shed light into the structure of exotic nuclei and understanding the driving mechanism behind the shell evolution. In this work, we investigate the spin-orbit shell gap towards the neutron dripline. To do so, we employed (p,2p) quasi-free scattering reactions to measure the proton component of the state of 16,18,20C. The experimental findings support the notion of a moderate reduction of the proton spin-orbit splitting, at variance to recent claims for a prevalent magic number towards the neutron dripline.
ABC transporters fulfill diverse physiological functions in different cellularlocalizations ranging from the plasma membrane to intracellular membranouscompartments. Several ABC transporters have been spotted in the endolyso-somal system, which consists of endosomes, autophagosomes, lysosomes, andlysosome-related organelles. In this review, we present an overview of lysoso-mal ABC transporters including ABCA2, ABCA3, ABCA5, ABCB6,ABCB9, and ABCD4, discussing their trafficking routes, putative substrates,potential physiological functions, and associated diseases. In addition, weoffer a critical evaluation of the literature linking ABC transporters to lyso-somal drug sequestration, examining pitfalls associated with in vitro modelsof drug resistance.
Respiratory chain signalling is essential for adaptive remodelling following cardiac ischaemia
(2020)
Cardiac ischaemia‐reperfusion (I/R) injury has been attributed to stress signals arising from an impaired mitochondrial electron transport chain (ETC), which include redox imbalance, metabolic stalling and excessive production of reactive oxygen species (ROS). The alternative oxidase (AOX) is a respiratory enzyme, absent in mammals, that accepts electrons from a reduced quinone pool to reduce oxygen to water, thereby restoring electron flux when impaired and, in the process, blunting ROS production. Hence, AOX represents a natural rescue mechanism from respiratory stress. This study aimed to determine how respiratory restoration through xenotopically expressed AOX affects the re‐perfused post‐ischaemic mouse heart. As expected, AOX supports ETC function and attenuates the ROS load in post‐anoxic heart mitochondria. However, post‐ischaemic cardiac remodelling over 3 and 9 weeks was not improved. AOX blunted transcript levels of factors known to be up‐regulated upon I/R such as the atrial natriuretic peptide (Anp) whilst expression of pro‐fibrotic and pro‐apoptotic transcripts were increased. Ex vivo analysis revealed contractile failure at nine but not 3 weeks after ischaemia whilst label‐free quantitative proteomics identified an increase in proteins promoting adverse extracellular matrix remodelling. Together, this indicates an essential role for ETC‐derived signals during cardiac adaptive remodelling and identified ROS as a possible effector.
Cryo electron tomography (cryo-ET) combined with subtomogram averaging (StA) enables structural determination of macromolecules in their native context. A few structures were reported by StA at resolution higher than 4.5 Å, however all of these are from viral structural proteins or vesicle coats. Reaching high resolution for a broader range of samples is uncommon due to beam-induced sample drift, poor signal-to-noise ratio (SNR) of images, challenges in CTF correction, limited number of particles. Here we propose a strategy to address these issues, which consists of a tomographic data collection scheme and a processing workflow. Tilt series are collected with higher electron dose at zero-degree tilt in order to increase SNR. Next, after performing StA conventionally, we extract 2D projections of the particles of interest from the higher SNR images and use the single particle analysis tools to refine the particle alignment and generate a reconstruction. We benchmarked our proposed hybrid StA (hStA) workflow and improved the resolution for tobacco mosaic virus from 7.2 to 5.2 Å and the resolution for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. We demonstrate that hStA can improve the resolution obtained by conventional StA and promises to be a useful tool for StA projects aiming at subnanometer resolution or higher.
Cryo-electron tomography combined with subtomogram averaging (StA) has yielded high-resolution structures of macromolecules in their native context. However, high-resolution StA is not commonplace due to beam-induced sample drift, images with poor signal-to-noise ratios (SNR), challenges in CTF correction, and limited particle number. Here we address these issues by collecting tilt series with a higher electron dose at the zero-degree tilt. Particles of interest are then located within reconstructed tomograms, processed by conventional StA, and then re-extracted from the high-dose images in 2D. Single particle analysis tools are then applied to refine the 2D particle alignment and generate a reconstruction. Use of our hybrid StA (hStA) workflow improved the resolution for tobacco mosaic virus from 7.2 to 4.4 Å and for the ion channel RyR1 in crowded native membranes from 12.9 to 9.1 Å. These resolution gains make hStA a promising approach for other StA projects aimed at achieving subnanometer resolution.
Treatment of large bone defects is one of the great challenges in contemporary orthopedic and traumatic surgery. Grafts are necessary to support bone healing. A well-established allograft is demineralized bone matrix (DBM) prepared from donated human bone tissue. In this study, a fibrous demineralized bone matrix (f-DBM) with a high surface-to-volume ratio has been analyzed for toxicity and immunogenicity. f-DBM was transplanted to a 5-mm, plate-stabilized, femoral critical-size-bone-defect in Sprague-Dawley (SD)-rats. Healthy animals were used as controls. After two months histology, hematological analyses, immunogenicity as well as serum biochemistry were performed. Evaluation of free radical release and hematological and biochemical analyses showed no significant differences between the control group and recipients of f-DBM. Histologically, there was no evidence of damage to liver and kidney and good bone healing was observed in the f-DBM group. Reactivity against human HLA class I and class II antigens was detected with mostly low fluorescence values both in the serum of untreated and treated animals, reflecting rather a background reaction. Taken together, these results provide evidence for no systemic toxicity and the first proof of no basic immunogenic reaction to bone allograft and no sensitization of the recipient.
In Bone Tissue Engineering (BTE), autologous bone-regenerative cells are combined with a scaffold for large bone defect treatment (LBDT). Microporous, polylactic acid (PLA) scaffolds showed good healing results in small animals. However, transfer to large animal models is not easily achieved simply by upscaling the design. Increasing diffusion distances have a negative impact on cell survival and nutrition supply, leading to cell death and ultimately implant failure. Here, a novel scaffold architecture was designed to meet all requirements for an advanced bone substitute. Biofunctional, porous subunits in a load-bearing, compression-resistant frame structure characterize this approach. An open, macro- and microporous internal architecture (100 µm–2 mm pores) optimizes conditions for oxygen and nutrient supply to the implant’s inner areas by diffusion. A prototype was 3D-printed applying Fused Filament Fabrication using PLA. After incubation with Saos-2 (Sarcoma osteogenic) cells for 14 days, cell morphology, cell distribution, cell survival (fluorescence microscopy and LDH-based cytotoxicity assay), metabolic activity (MTT test), and osteogenic gene expression were determined. The adherent cells showed colonization properties, proliferation potential, and osteogenic differentiation. The innovative design, with its porous structure, is a promising matrix for cell settlement and proliferation. The modular design allows easy upscaling and offers a solution for LBDT.
Thirteen species of Echinoderes with nearly identical spine/tube patterns, and apparently similar tergal extensions were re-examined and compared. Based on this, redescriptions and/or emended species diagnoses are provided for Echinoderes aureus, E. dujardinii, E. gerardi, E. imperforatus, E. pacificus, E. pilosus, E. sensibilis, E. sublicarum and E. worthingi, and new details about cuticular structures are added for E. kozloffi and E. gizoensis. The new information derived from the redescriptions, and the subsequent comparative studies revealed that: 1) the holotype of Echinoderes lanceolatus is identical with the types of Echinoderes aureus, and E. lanceolatus is thus a junior synonym of E. aureus; other potentially synonymous species that should be addressed further in the future include: E. dujardinii + E. gerardi; E. imperforatus + E. sensibilis, and E. pacificus + E. sublicarum; 2) the paratypes of E. lanceolatus represented a different yet undescribed species, here described as E. songae Sørensen & Chang sp. nov.; 3) a comparison with literature information about E. ehlersi showed that the species is so insufficiently described that a redescription of topotype material is required before the species should be considered for taxonomic comparison; 4) specimens from the Andaman Islands, India, that previously have been reported as Echinoderes cf. ehlersi represent two different undescribed species, of which one is described as E. chandrasekharai Sørensen & Chatterjee sp. nov. and the other is left undescribed due to the limited material available; 5) out of a total of fifteen addressed species, it is proposed that eleven represent a putatively monophyletic group that is named the Echinoderes dujardinii group. The group includes following species: E. dujardinii, E. ehlersi, E. gerardi, E. imperforatus, E. kozloffi, E. sensibilis, E. pacificus, E. sublicarum, E. songae Sørensen & Chang sp. nov., E. chandrasekharai Sørensen & Chatterjee sp. nov., and Echinoderes sp. from the Andaman Islands, and is supported by a similar spine/tube pattern (except for variation regarding the presence of lateral accessory tubes on segment 8); generally short middorsal spines, especially on segments 4 to 6; glandular cell outlets type 1 always present in middorsal positions on segments 1 to 3, and in subdorsal positions on segments 4 to 9; glandular cell outlets type 2 always present in laterodorsal or midlateral positions on segment 8, and sometimes in same positions on segment 9 but never at any other segments or positions; female papillae always present on sternal plates of segments 7 and 8, and occasionally also on segment 6; tergal extensions well-spaced, triangular, gradually tapered cones, and pectinate fringes of sternal extensions are differentiated into seta-like tufts. The comparisons furthermore showed potential taxonomic significance of two echinoderid character traits that previously have been slightly neglected as diagnostic traits, namely the presence and appearance of female papillae, and the dorsal pattern of glandular cell outlets type 1. Female papillae may occur on the sternal plates of segments 6 to 8, but the positions may differ from ventrolateral to ventromedial, and the morphology of the intracuticular substructure also differ at species level. Information about position and morphology of female papillae proved helpful for species recognition, but it might also provide information of phylogenetic importance. Analyses of glandular cell outlet type 1 patterns on the dorsal sides of segments 1 to 9 in species of Echinoderidae, revealed several apparently unique or rare patterns, but also three distinct patterns that applied to larger groups of species. One pattern is the one present in all species of the E. dujardinii group, whereas the other two common patterns included 1) middorsal outlets on segments 1 to 3, and paradorsal outlets on segments 4 to 9 (found in 27 species), and 2) middorsal outlets on segments 1 to 3, 5 and 7, and paradorsal outlets on segments 4, 6 and 8 to 9 (found in 27 species).
Three groups of beetles inhabit cones of cycads (Cycadales) in the northern hemisphere and are believed to be involved in their pollination. The primitive weevil subtribe Allocorynina (Coleoptera: Belidae) is restricted to the New World cycad genera Dioon Lindl. and Zamia L. One group of weevils (Curculionidae), found only in Cycas L., appears to be a relatively recent colonizer of northern hemisphere cycads. Members of the beetle subfamily Pharaxonothinae (Erotylidae) occur in all Asian and New World cycad genera. Phylogenetic trees of these beetles, based on DNA analysis and supported with morphological studies, are compared to patterns of continental drift and cycad phylogenies. Laurasian origins are suggested for these beetle groups with high latitude dispersal for at least one of these groups during periods of global warm climates.
Objectives: The aim of the present study was to characterize the cellular reaction to a xenogeneic resorbable collagen membrane of porcine origin using a subcutaneous implantation model in Wistar rats over 30 days.
Materials and methods: Ex vivo, liquid platelet-rich fibrin (PRF), a leukocyte and platelet-rich cell suspension, was used to evaluate the blood cell membrane interaction. The material was implanted subcutaneously in rats. Sham-operated rats without biomaterial displayed physiological wound healing (control group). Histological, immunohistological, and histomorphometric analyses were focused on the inflammatory pattern, vascularization rate, and degradation pattern.
Results: The membrane induced a large number of mononuclear cells over the observation period, including lymphocytes, macrophages, and fibroblasts. After 15 days, multinucleated giant cells (MNGCs) were observed on the biomaterial surface. Their number increased significantly, and they proceeded to the center of the biomaterial on day 30. These cells highly expressed CD-68, calcitonin receptor, and MMP-9, but not TRAP or integrin-ß3. Thus, the membrane lost its integrity and underwent disintegration as a consequence of the induction of MNGCs. The significant increase in MNGC number correlated with a high rate of vascularization, which was significantly higher than the control group. Physiological wound healing in the control group did not induce any MNGCs at any time point. Ex vivo blood cells from liquid-PRF did not penetrate the membrane.
Conclusion: The present study suggests a potential role for MNGCs in biomaterial degradation and questions whether it is beneficial to accept them in clinically approved biomaterials or focus on biomaterials that induce only mononuclear cells. Thus, further studies are necessary to identify the function of biomaterial-induced MNGCs.
Clinical relevance: Understanding the cellular reaction to biomaterials is essential to assess their suitability for specific clinical indications and outline the potential benefit of specific group of biomaterials in the respective clinical indications.
Background: Anemia is the most important complication during major surgery and transfusion of red blood cells is the mainstay to compensate for life threating blood loss. Therefore, accurate measurement of hemoglobin (Hb) concentration should be provided in real-time. Blood Gas Analysis (BGA) provides rapid point-of-care assessment using smaller sampling tubes compared to central laboratory (CL) services. Objective: This study aimed to investigate the accuracy of BGA hemoglobin testing as compared to CL services. Methods: Data of the ongoing LIBERAL-Trial (Liberal transfusion strategy to prevent mortality and anemia-associated ischemic events in elderly non-cardiac surgical patients, LIBERAL) was used to assess the bias for Hb level measured by BGA devices (ABL800 Flex analyzer®, GEM series® and RapidPoint 500®) and CL as the reference method. For that, we analyzed pairs of Hb level measured by CL and BGA within two hours. Furthermore, the impact of various confounding factors including age, gender, BMI, smoker status, transfusion of RBC, intraoperative hemodilution, and co-medication was elucidated. In order to ensure adequate statistical analysis, only data of participating centers providing more than 200 Hb pairs were used. Results: In total, three centers including 963 patients with 1,814 pairs of Hb measurements were analyzed. Mean bias was comparable between ABL800 Flex analyzer® and GEM series®: - 0.38 ± 0.15 g/dl whereas RapidPoint 500® showed a smaller bias (-0.09 g/dl) but greater median absolute deviation (± 0.45 g/dl). In order to avoid interference with different standard deviations caused by the different analytic devices, we focused on two centers using the same BGA technique (309 patients and 1,570 Hb pairs). A Bland-Altman analysis and LOWESS curve showed that bias decreased with smaller Hb values in absolute numbers but increased relatively. The smoker status showed the greatest reduction in bias (0.1 g/dl, p<0.001) whereas BMI (0.07 g/dl, p = 0.0178), RBC transfusion (0.06 g/dl, p<0.001), statins (0.04 g/dl, p<0.05) and beta blocker (0.03 g/dl, p = 0.02) showed a slight effect on bias. Intraoperative substitution of volume and other co-medications did not influence the bias significantly. Conclusion: Many interventions like substitution of fluids, coagulating factors or RBC units rely on the accuracy of laboratory measurement devices. Although BGA Hb testing showed a consistently stable difference to CL, our data confirm that BGA devices are associated with different bias. Therefore, we suggest that hospitals assess their individual bias before implementing BGA as valid and stable supplement to CL. However, based on the finding that bias decreased with smaller Hb values, which in turn are used for transfusion decision, we expect no unnecessary or delayed RBC transfusion, and no major impact on the LIBERAL trial performance.
One limitation of mechanical thrombectomy (MT) is clot migration during procedure. This might be caused by abruption of the trapped thrombus at the distal access catheter (DAC) tip during stent-retriever retraction due to the cylindrical shaped tip of the DAC. Aiming to solve this problem, this study evaluates the proof-of-concept of a new designed funnel-shaped tip, in an experimental in vitro setting. Two catheter models, one with a funnel-shaped tip and one with a cylindrical-shaped tip, were compared in an experimental setup. For MT a self-made vessel model and thrombi generated from pig’s blood were used. MT was performed 20 times for each device using two different stent-retrievers, 10 times respectively. For the funnel-shaped model: for both stent-retrievers (Trevo XP ProVue 3/20 mm; Trevo XP ProVue 4/20 mm) MT was successful at first pass in 9/10 (90%), respectively. For the cylindrical-shaped model: MT was successful at first pass in 5/10 (50%) with the smaller stent-retriever and in 6/10 (60%) with the larger stent-retriever. The experiments show a better recanalization rate for funnel-shaped tips, than for cylindrical-shaped tips. These results are indicating a good feasibility for this new approach, thus the development of a prototype catheter seems reasonable.
Radar technology in the millimeter-wave frequency band offers many interesting features for wind park surveillance, such as structural monitoring of rotor blades or the detection of bats and birds in the vicinity of wind turbines (WTs). Currently, the majority of WTs are affected by shutdown algorithms to minimize animal fatalities via direct collision with the rotor blades or barotrauma effects. The presence of rain is an important parameter in the definition of those algorithms together with wind speed, temperature, time of the day, and season of the year. A Ka-band frequency-modulated continuous-wave radar (33.4-36.0 GHz) installed at the tower of a 2-MW WT was used during a field study. We have observed characteristic rain-induced patterns, based on the range-Doppler algorithm. To better understand those signatures, we have developed a laboratory experiment and implemented a numerical modeling framework. Experimental and numerical results for rain detection and classification are presented and discussed here. Based on this article, a bat- and bird-friendly adaptive WT control can be developed for improved WT efficiency in periods of rain and, at the same time, reduced animal mortality.
Potassium homeostasis is vital for all organisms, but is challenging in single-celled organisms like bacteria and yeast and immobile organisms like plants that constantly need to adapt to changing external conditions. KUP transporters facilitate potassium uptake by the co-transport of protons. Here, we uncover the molecular basis for transport in this widely distributed family. We identify the potassium importer KimA from Bacillus subtilis as a member of the KUP family, demonstrate that it functions as a K+/H+ symporter and report a 3.7 Å cryo-EM structure of the KimA homodimer in an inward-occluded, trans-inhibited conformation. By introducing point mutations, we identify key residues for potassium and proton binding, which are conserved among other KUP proteins.
Features of the Maechidiini (Scarabaeidae: Melolonthinae) genera Maechidius Macleay, 1819, Epholcis Waterhouse, 1875 and Paramaechidius Frey, 1969 are critically revised and a new synonymy is proposed: Maechidius = Epholcis syn. nov. = Paramaechidius syn. nov. A key to and an annotated checklist of Maechidiini from the Indo-Australian transition zone are presented for the first time. Thirty-five new species are described, namely Maechidius aiyura sp. nov., M. alesbezdeki sp. nov., M. awu sp. nov., M. babyrousa sp. nov., M. bintang sp. nov., M. boessnecki sp. nov., M. brocki sp. nov., M. caperatus sp. nov., M. ciliatus sp. nov., M. crypticus sp. nov., M. dani sp. nov., M. deltouri sp. nov., M. dendrolagus sp. nov., M. hamatus sp. nov., M. kazantsevi sp. nov., M. konjo sp. nov., M. lapsus sp. nov., M. legalovi sp. nov., M. leucopsar sp. nov., M. longipes sp. nov., M. mailu sp. nov., M. maleo sp. nov., M. merdeka sp. nov., M. miklouhomaclayi sp. nov., M. nepenthephilus sp. nov., M. owenstanleyi sp. nov., M. riedeli sp. nov., M. similis sp. nov., M. skalei sp. nov., M. sougb sp. nov., M. suwawa sp. nov., M. trivialis sp. nov., M. ursus sp. nov., M. weigeli sp. nov. and M. yamdena sp. nov. Six new synonyms are proposed: Maechidius Macleay, 1819 = Epholcis Waterhouse, 1875 syn. nov. = Paramaechidius Frey, 1969 syn. nov., Maechidius esau Heller, 1914 = M. setosus Moser, 1920 syn. nov. = M. setosellus Frey, 1969 syn. nov., Maechidius heterosquamosus Heller, 1910 comb. rest. = Paramaechidius clypeatus Frey, 1969 syn. nov. and Maechidius paupianus Heller, 1910 = M. arrowi Frey, 1969 syn. nov. The first records of Maechidiini from the Tanimbar Islands (Yamdena), Sangihe Islands (Sangir) and Lesser Sunda Islands (Bali) are documented, of which the latter two are the northern- and westernmost known records of Maechidius and of the tribe Maechidiini. Lectotypes are designated for 23 species. Fifteen new combinations are proposed and the original combination to Maechidius is restored for four species. Ecological data are presented for the first time for selected Papuan and Wallacean species. Type material of Wallacean and Papuan Maechidiini is depicted for the first time. A key to species is given. In total, 78 species of Maechidiini are confirmed for the Indo-Australian transition zone.
Monte Carlo simulations and n-p differential scattering data measured with Proton Recoil Telescopes
(2020)
The neutron-induced fission cross section of 235U, a standard at thermal energy and between 0.15 MeV and 200 MeV, plays a crucial role in nuclear technology applications. The long-standing need of improving cross section data above 20 MeV and the lack of experimental data above 200 MeV motivated a new experimental campaign at the n_TOF facility at CERN. The measurement has been performed in 2018 at the experimental area 1 (EAR1), located at 185 m from the neutron-producing target (the experiment is presented by A. Manna et al. in a contribution to this conference). The 235U(n,f) cross section from 20 MeV up to about 1 GeV has been measured relative to the 1H(n,n)1H reaction, which is considered the primary reference in this energy region. The neutron flux impinging on the 235U sample (a key quantity for determining the fission events) has been obtained by detecting recoil protons originating from n-p scattering in a C2H4 sample. Two Proton Recoil Telescopes (PRT), consisting of several layers of solid-state detectors and fast plastic scintillators, have been located at proton scattering angles of 25.07° and 20.32°, out of the neutron beam. The PRTs exploit the ΔE-E technique for particle identification, a basic requirement for the rejection of charged particles from neutron-induced reactions in carbon. Extensive Monte Carlo simulations were performed to characterize proton transport through the different slabs of silicon and scintillation detectors, to optimize the experimental set-up and to deduce the efficiency of the whole PRT detector. In this work we compare measured data collected with the PRTs with a full Monte Carlo simulation based on the Geant-4 toolkit.
Background: A large number of idiosyncratic drug induced liver injury (iDILI) and herb induced liver injury(HILI) cases of variable quality has been published but some are a matter of concern if the cases were not evaluated for causality using a robust causality assessment method (CAM) such as RUCAM (Roussel Uclaf Causality Assessment Method) as diagnostiinjuryc algorithm. The purpose of this analysis was to evaluate the worldwide use of RUCAM in iDILI and HILI cases. Methods: The PubMed database (1993–30 June 2020) was searched for articles by using the following key terms: Roussel Uclaf Causality Assessment Method; RUCAM; Idiosyncratic drug induced liver injury; iDILI; Herb induced liver injury; HILI. Results: Considering reports published worldwide since 1993, our analysis showed the use of RUCAM for causality assessment in 95,885 cases of liver injury including 81,856 cases of idiosyncratic DILI and 14,029 cases of HILI. Among the top countries providing RUCAM based DILI cases were, in decreasing order, China, the US, Germany, Korea, and Italy, with China, Korea, Germany, India, and the US as the top countries for HILI. Conclusion: Since 1993 RUCAM is certainly the most widely used method to assess causality in IDILI and HILI. This should encourage practitioner, experts, and regulatory agencies to use it in order to reinforce their diagnosis and to take sound decisions.