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The authors review the current status of percutaneous left atrial appendage (LAA) occlusion therapy in patients with atrial fibrillation with the goal to prevent ischemic stroke and systemic embolism and to reduce oral anticoagulation associated bleeding. While we cover the historical and also surgical background, and all tested devices, the main focus rests on the single currently U.S. Food and Drug Administration (FDA) approved LAA occluder, the WATCHMAN device, and its approval process. The authors also give a critical appraisal beyond the review of mere facts, trying to put the current data into perspective.
Background: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.
Methods: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.
Discussion: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.
Trial registration: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).
Different response of Ptch mutant and Ptch wildtype Rhabdomyosarcoma toward SMO and PI3K inhibitors
(2018)
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. RMS frequently show Hedgehog (HH) pathway activity, which is predominantly seen in the embryonal subtype (ERMS). They also show activation of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling. Here we compared the therapeutic effectiveness and the impact on HH target gene expression of Smoothened (SMO) antagonists with those of the PI3K inhibitor pictilisib in ERMS with and without mutations in the HH receptor Patched1 (PTCH). Our data demonstrate that growth of ERMS showing canonical Hh signaling activity due to Ptch germline mutations is efficiently reduced by SMO antagonists. This goes along with strong downregulation of the Hh target Gli1. Likewise Ptch mutant tumors are highly responsive toward the PI3K inhibitor pictilisib, which involves modulation of AKT and caspase activity. Pictilisib also modulates Hh target gene expression, which, however, is rather not correlated with its antitumoral effects. In contrast, sporadic ERMS, which usually express HH target genes without having PTCH mutation, apparently lack canonical HH signaling activity. Thus, stimulation by Sonic HE (SHH) or SAG (Smoothened agonist) or inhibition by SMO antagonists do not modulate HH target gene expression. In addition, SMO antagonists do not provoke efficient anticancer effects and rather exert off-target effects. In contrast, pictilisib and other PI3K/AKT/mTOR inhibitors potently inhibit cellular growth. They also efficiently inhibit HH target gene expression. However, of whether this is correlated with their antitumoral effects it is not clear. Together, these data suggest that PI3K inhibitors are a good and reliable therapeutic option for all ERMS, whereas SMO inhibitors might only be beneficial for ERMS driven by PTCH mutations.
The opportunistic pathogen Acinetobacter baumannii is able to grow on carnitine. The genes encoding the pathway for carnitine degradation to the intermediate malic acid are known but the transporter mediating carnitine uptake remained to be identified. The open reading frame HMPREF0010_01347 (aci01347) of Acinetobacter baumannii is annotated as a gene encoding a potential transporter of the betaine/choline/carnitine transporter (BCCT) family. To study the physiological function of Aci01347, the gene was deleted from A. baumannii ATCC 19606. The mutant was no longer able to grow on carnitine as sole carbon and energy source demonstrating the importance of this transporter for carnitine metabolism. Aci01347 was produced in Escherichia coli MKH13, a strain devoid of any compatible solute transporter, and the recombinant E. coli MKH13 strain was found to take up carnitine in an energy‐dependent fashion. Aci01347 also transported choline, a compound known to be accumulated under osmotic stress. Choline transport was osmolarity‐independent which is consistent with the absence of an extended C‐terminus found in osmo‐activated BCCT. We propose that the Aci01347 is the carnitine transporter mediating the first step in the growth of A. baumannii on carnitine.
Danger signals in trauma
(2018)
This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often pleiotropic effects of a DAMP, it is difficult to describe its “friend or foe” role in post-traumatic inflammation and regeneration, both systemically as well locally in tissues. DAMP can be used as biomarkers to indicate or monitor disease or injury severity, but also may serve as clinically applicable parameters for better indication and timing of surgery. Due to the inflammatory processes at the local tissue level or the systemic level, the precise role of DAMP is not always clear to define. While in vitro and experimental studies allow for the detection of these biomarkers at the different levels of an organism—cellular, tissue, circulation—this is not always easily transferable to the human setting. Increased knowledge exploring the dual role of DAMP after trauma, and concentrating on their nuclear functions, transcriptional targets, release mechanisms, cellular sources, multiple functions, their interactions and potential therapeutic targeting is warranted.
Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished L‐45 in enantiopure form. L‐45 was shown to disrupt PCAF‐Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‐crystal structure of L‐45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‐45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‐permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
Objective. Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.
Measurements and Main Results. Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.
Conclusions. This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.
Species identification of adult African blowflies (Diptera: Calliphoridae) of forensic importance
(2017)
Necrophagous blowflies can provide an excellent source of evidence for forensic entomologists and are also relevant to problems in public health, medicine, and animal health. However, access to useful information about these blowflies is constrained by the need to correctly identify the flies, and the poor availability of reliable, accessible identification tools is a serious obstacle to the development of forensic entomology in the majority of African countries. In response to this need, a high-quality key to the adults of all species of forensically relevant blowflies of Africa has been prepared, drawing on high-quality entomological materials and modern focus-stacking photomicroscopy. This new key can be easily applied by investigators inexperienced in the taxonomy of blowflies and is made available through a highly accessible online platform. Problematic diagnostic characters used in previous keys are discussed.
2010 yılında Polonya'nın Varşova kentinde "Vielheit und Einheit der Germanistik" teması ile gerçekleştirilen 12. Uluslararası Germanistik Kongresi’nin ardından 13. Uluslararası Germanistik Kongresi 2015 yılında "Germanistik zwischen Tradition und Innovation" teması ile Çin Halk Cumhuriyeti Şanghay Tongji Üniversitesi'nde 23-30 Ağustos 2015 tarihlerinde düzenlendi. Türkiye'nin de aralarında bulunduğu 96 ülkeden kongreye katılan 1200'ün üzerinde değerli akademisyen ve araştırmacı kongrede bildirilerini sundular.
Der 13. Weltkongress der Internationalen Vereinigung für Germanistik (IVG) fand vom 23.08.2015 bis zum 30.08.2015 unter dem Motto "Germanistik zwischen Tradition und Innovation" in Shanghai/China statt. Gastgeber dieses vielfältigen und reichhaltigen internationalen Kongresses war die Tongji-Universität. Mehr als 1200 Teilnehmerinnen und Teilnehmer aus 69 Ländern haben an diesem Kongress, der alle fünf Jahre organisiert wird, teilgenommen. Auch die Türkei beteiligte sich mit ca. 30 Wissenschaftlerinnen und Wissenschaftlern aus Edirne bis Van an diesem Kongress.
Das wissenschaftliche Interesse auf dem Feld der Germanistik ist in den letzten Jahren in Rumänien, auch dank Herta Müller, die 2009 den Nobelpreis für Literatur bekommen hat, stark gestiegen. Nach dem letzten Kongress der Germanisten Rumäniens 2012 in Bukarest wurde der 10. Kongress der Germanisten Rumäniens vom 01. bis 04. Juni 2015 in der Aula an der Universität Transilvania in Braşov/Kronstadt veranstaltet. Die Tagung wird alle drei Jahre an jeweils wechselnden Hochschulen vom dortigen Germanistik-Fachbereich veranstaltet, was zeigt, dass die Germanistik in Rumänien an vielen Orten durch zum Teil kleine, aber aktive Lehrstühle vertreten ist.
Considering the misunderstanding of the particles used as an adverb by itself in closely related languages, we will try to provide the comprehension of sense of language about this area, which is missing in German. For this purpose, opposite language pairs seeming logical and etimological proofs about language variation will be presented. Firstly, we will try to explain what the sense of language is. We believe that it is more appropriate to say 'language acquisition' which can be acquired and developed by means of activities in foreign language classes. Examples verify this. In the conclusion, some other clarifying questions follow.
Sowohl international als auch national ist erkennbar, dass Länder in Bereichen Wirtschaft, kommunikative und informative Technologien, Politik, Bildung und Gesellschaft in unterschiedlicher Art und Weise mit kulturellen bzw. interkulturellen Tendenzen konfrontiert sind. Diese Tatsachen reflektieren somit, dass Gesellschaften immer mehr mit interkulturellen Herausforderungen in Kontakt kommen. Interkulturelles Lernen, Interkulturalität und interkulturelle Kompetenz enthalten gleichfalls im gegenwärtigen und modernen Fremdsprachenunterricht eine bedeutende Rolle und ein wichtiges Aufgabenfeld.
Present conditions are affecting the educational process and as a result of these changes restructuring these processes is essential. There is no doubt that in teaching foreign languages in general and in particular German as a foreign language, one of the prerequisites to gain for providing a qualified German language teaching is the training of qualified and well equipped German teachers. In this context one of the substantial competences in the training process is the linguistic competence. It is aimed that at the end of their study period, German language teacher candidates should have the ability of using the German language in written and spoken area and creating models for their prospective students.
Despite the new technological developments writing has not lost its importance; on the contrary, ist importance has been increasing day by day. German teacher candidates should be trained to be able to express themself written as well as verbally to respond to their students' writing needs. For this reason students who graduated from the German Language Teaching Department of Hasan Ali Yücel Faculty of Education of Istanbul University in 2013-2014 academic year were asked to evaluate their writing competence.
The self assessments results of the candidate teachers are going to be compared with the results of the writing competence part of the Goethe Zertifikat C1 examination. The aim is to determine proficiency in the duration of 4 years. The results also constitute the scientific basis of curricular discussions in the field of writing courses of the German Language Teaching Department.
In den letzten Jahren ist eine kaum überschaubare Anzahl von Büchern zum Thema Körpermodifikationen erschienen, was aber bisher fehlt, ist ein klares Verständnis und eine kurze überblicksartige Dаrstellung der gängigen Formen der Fachausdrücke im Bereich der ästhetischen Chirurgie, die dem linguistisch-medizinisch Interessierten einen prägnanten Einblick in die Herkunft, die Wоrtbildung und die Häufigkeit und vergleichende Analyse der medizinischen Termini liefert. Deshalb soll in diesem Artikel versucht werden, einen kleinen Beitrag zur Bildung und Entwicklung ästhetisch-medizinischer Terminologie zu leisten. Bei dem vorliegenden Artikel handelt es sich um eine deskriptive Terminоlоgiearbeit, deren Ziel es ist, die verwendete Terminologie eines Fachgebietes zu beschreiben und aufzuzeichnen
This article focuses primarily on three areas: First the article deals with Alfred Döblin's concept of the novel and the function of the montage technique from his perspective. Secondly, the article draws attention to the fact that Alfred Döblin, a neurologist by profession, who later dedicated himself exclusively to his writing, used the montage technique intensively in his great city novel Berlin Alexanderplatz. The technique, which operates at different levels of language, narrative technique and plot, is demonstrated by selected examples from the novel. In each case the intention of the novelist is discussed. The article considers whether individual accumulating elements accord with the wholeness of the novel, and if so, how this interesting synthesis occurs. The final focus is on his efforts to use the montage technique to portray the big city. In the case of Berlin Alexanderplatz, this effort ultimately ends with a big city epic. In this study, we consider how Döblin used the montage technique in Berlin Alexanderplatz, which was central, and new for German literature at that time. Additionally, narrative styles and techniques as parables, paraboles, sound associations, word and rhyme repetition and relevant passages are supported by quotations from the novel.
Else LaskerSchüler (1869-1945), among the significant expressionist woman writers, did not only suffer from being both a woman and author, but also had to struggle under difficulties of being a hebrew. In this paper, especially the letter novel titled "Der Malik : Eine Kaisergeschichte" has been handled in the light of Homi K. Bhabha's 'Third Space Theory'. In regard to this, the "Third Space", which is defined by postcolonial theoretician Homi K. Bhabha as an extra place where minorities and outcast groups can express themselves in his work "The Location of Culture", is adapted to the literary "Orient" and defined once again in Else Lasker-Schüler's novel as it was never approached and interpreted before. In this sense, this supports the relevance to analyze her mentioned works in terms of the "Third Space Theory". Else Lasker-Schüler constructed a new world for herself through literature; her works were her life and her life was her works.
Black Humor, Brimstone Grotesque and A Terrifying Scenery in the work of Thomas Bernhard named "The Painter". Thomas Bernhard (1931-1989) is one of the most important writers of the Austrian postwar literature. All of his works reflect the characteristics of that period. "Bernhardesque" literature (just as the "Kafkaesque") always shapes the language and brings it out forcing the maximum limits of the semantics and stylistics expression facilities of the language. Bernhard generally figures out the inner world of the modern people psychologically disturbed and represents their wholly technological, noncommunicative and hostile environment in his works, especially features ironic, absurd, and grotesque and a little bit comic elements. Thomas Bernhard, a worldwide famous writer, poet and playwright, wrote a prose novel entitled "Ereignisse" (Events) that includes thirty-one extraordinary stories in 1957. These are the stories can be read both independently from each other and also in coherence. This study is aimed to analyses one of these works, the twelfth one in the light of eclectical way, mostly involves 'black humor' which is named "Der Anstreicher" (The Painter). The term Black Humor is generally defined for the works characterized by a desperate, sardonic humor intended to induce laughter as the appropriate response to the apparent meaninglessness and absurdity of existence. This short story of Bernhard tells about an "Event" derived its theme from the daily life and can be thought as a simple work accident but it brings a death to his main character. Narrator narrates this fatal and ordinary event with a horrific, grotesque and agonizing absurdity and as we try to figure out in this study; The Painter includes 'Black Humor' in this context.
Biological invasions are frequently studied topics in ecological research. Unfortunately, within invasion ecology parasite-associated aspects such as parasite impacts on new environments and on local host populations are less well-studied. Round gobies migrating from the Ponto-Caspian region into the Rhine River system are heavily infested with the Ponto-Caspian acanthocephalan parasite Pomphorhynchus laevis. As shown by experimental infestations the acanthocephalans occur as pre-adults in host-encapsulated cysts within the internal organs of the migrating gobies, but remain infective for their definitive host chub. Recently, we described the occurrence of larvae of another parasite, the invasive eel swim bladder nematode Anguillicola crassus, in these Pomphorhynchus cysts. In the present study, we could prove the infectivity of the nematode larvae for European eels for the first time. After experimental inoculation of Pomphorhynchus cysts occasionally infested with A. crassus larvae, the nematodes grow to maturity and reproduce whereas all P. laevis were unviable. We therefore postulate that the nematode larvae behave like immunological hitchhikers that follow a “Trojan horse strategy” in order to avoid the paratenic host’s immune response. Accordingly, the interaction between both invasive parasites gives first evidence that the invasional meltdown hypothesis may also apply to parasites.
New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called “living drugs”. Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report.
Background: Histological evidence suggests that autism spectrum disorder (ASD) is accompanied by a reduced integrity of the grey-white matter boundary. This has also recently been confirmed by a structural neuroimaging study in vivo reporting significantly reduced grey-white matter tissue contrast (GWC) in adult individuals (18–42 years of age) with ASD relative to typically developing (TD) controls. However, it remains unknown whether the neuroanatomical differences in ASD at the grey-white matter boundary are stable across development or are age-dependent.
Methods: Here, we examined differences in the neurodevelopmental trajectories of GWC in a cross-sectional sample of 77 male ASD individuals and 76 typically developing (TD) controls across childhood and early adulthood (from 7 to 25 years).
Results: Using nested model comparisons, we first established that the developmental trajectory of GWC is complex in many regions across the cortex and includes linear and non-linear effects of age. Second, while ASD individuals have significantly reduced GWC overall, these differences are age-dependent and are most prominent during childhood (< 15 years).
Conclusions: Taken together, our findings suggest that differences in GWC in ASD are unlikely to reflect atypical grey matter cytoarchitecture alone, but may also represent other aspects of the cortical architecture such as age-dependent variability in myelin integrity.
Background: The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC).
Methods: First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization.
Results: Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR).
Conclusion: Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.
The challenges posed by climate and land use change are increasingly complex, with ever-increasing and accelerating impacts on the global environmental system. The establishment of an internationally harmonized, integrated, and long-term operated environmental monitoring infrastructure is one of the major challenges of modern environmental research. Increased efforts are currently being made in Europe to establish such a harmonized pan-European observation infrastructure, and the European network of Long-Term Ecological Research sites – LTER-Europe – is of particular importance. By evaluating 477 formally accredited LTER-Europe sites, this study gives an overview of the current distribution of these infrastructures and the present condition of long-term environmental research in Europe. We compiled information on long-term biotic and abiotic observations and measurements and examined the representativeness in terms of continental biogeographical and socio-ecological gradients. The results were used to identify gaps in both measurements and coverage of the aforementioned gradients. Furthermore, an overview of the current state of the LTER-Europe observation strategies is given. The latter forms the basis for investigating the comparability of existing LTER-Europe monitoring concepts both in terms of observational design as well as in terms of the scope of the environmental compartments, variables and properties covered.
We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64–90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.
Background: This study assessed the impact of medical students’ emotion recognition ability and extraversion on their empathic communication, as perceived by simulated patients in a training context.
Methods: This study used a crossed-effect data structure and examined 245 students in their fourth year of medical school. The students’ personality traits were assessed based on a self-assessment questionnaire of the short form of the Big Five Inventory; their emotion recognition ability was measured using a performance test (Diagnostic Analysis of Nonverbal Accuracy-2, Adult Facial Expressions). Simulated patients evaluated the medical students’ empathic communication.
Results: Students with a combination of high emotion recognition ability and extraversion received more positive ratings from simulated patients than their fellow students with a combination of emotion recognition ability and low extraversion. The main effects of emotion recognition or extraversion were not sufficient to yield similar effects. There were no other effects related to the remaining Big Five variables.
Conclusions: The results support the hypothesis that to build rapport with patients, medical staff need to combine emotional capabilities with a dispositional interest in interpersonal encounters.
Most studies in the life sciences and other disciplines involve generating and analyzing numerical data of some type as the foundation for scientific findings. Working with numerical data involves multiple challenges. These include reproducible data acquisition, appropriate data storage, computationally correct data analysis, appropriate reporting and presentation of the results, and suitable data interpretation.
Finding and correcting mistakes when analyzing and interpreting data can be frustrating and time-consuming. Presenting or publishing incorrect results is embarrassing but not uncommon. Particular sources of errors are inappropriate use of statistical methods and incorrect interpretation of data by software. To detect mistakes as early as possible, one should frequently check intermediate and final results for plausibility. Clearly documenting how quantities and results were obtained facilitates correcting mistakes. Properly understanding data is indispensable for reaching well-founded conclusions from experimental results. Units are needed to make sense of numbers, and uncertainty should be estimated to know how meaningful results are. Descriptive statistics and significance testing are useful tools for interpreting numerical results if applied correctly. However, blindly trusting in computed numbers can also be misleading, so it is worth thinking about how data should be summarized quantitatively to properly answer the question at hand. Finally, a suitable form of presentation is needed so that the data can properly support the interpretation and findings. By additionally sharing the relevant data, others can access, understand, and ultimately make use of the results.
These quick tips are intended to provide guidelines for correctly interpreting, efficiently analyzing, and presenting numerical data in a useful way.
Perception of irony has been observed to be impaired in adults with autism spectrum disorder. In typically developed adults, the mismatch of verbal and nonverbal emotional cues can be perceived as an expression of irony even in the absence of any further contextual information. In this study, we evaluate to what extent high functioning autists perceive this incongruence as expressing irony. Our results show that incongruent verbal and nonverbal signals create an impression of irony significantly less often in participants with high-functioning autism than in typically developed control subjects. The extent of overall autistic symptomatology as measured with the autism-spectrum questionnaire (AQ), however, does not correlate with the reduced tendency to attribute incongruent stimuli as expressing irony. Therefore, the attenuation in irony attribution might rather be related to specific subdomains of autistic traits, such as a reduced tendency to interpret communicative signals in terms of complex intentional mental states. The observed differences in irony attribution support the assumption that a less pronounced tendency to engage in higher order mentalization processes might underlie the impairment of pragmatic language understanding in high functioning autism.
Invasive species provide a unique opportunity to evaluate factors controlling biogeographic distributions; we can consider introduction success as an experiment testing suitability of environmental conditions. Predicting potential distributions of spreading species is not easy, and forecasting potential distributions with changing climate is even more difficult. Using the globally invasive coypu (Myocastor coypus [Molina, 1782]), we evaluate and compare the utility of a simplistic ecophysiological based model and a correlative model to predict current and future distribution. The ecophysiological model was based on winter temperature relationships with nutria survival. We developed correlative statistical models using the Software for Assisted Habitat Modeling and biologically relevant climate data with a global extent. We applied the ecophysiological based model to several global circulation model (GCM) predictions for mid-century. We used global coypu introduction data to evaluate these models and to explore a hypothesized physiological limitation, finding general agreement with known coypu distribution locally and globally and support for an upper thermal tolerance threshold. Global circulation model based model results showed variability in coypu predicted distribution among GCMs, but had general agreement of increasing suitable area in the USA. Our methods highlighted the dynamic nature of the edges of the coypu distribution due to climate non-equilibrium, and uncertainty associated with forecasting future distributions. Areas deemed suitable habitat, especially those on the edge of the current known range, could be used for early detection of the spread of coypu populations for management purposes. Combining approaches can be beneficial to predicting potential distributions of invasive species now and in the future and in exploring hypotheses of factors controlling distributions.
Soil frequently occurs as a contaminant on numerous sea, land and air transport pathways. It can carry unwanted invasive species, is widely recognized as a biosecurity risk, and is usually strictly regulated by biosecurity authorities. However, little is known about relative risk levels between pathways, thus authorities have limited capability to identify and target the riskiest soil pathways for management. We conducted a an experiment to test the hypotheses that biosecurity risks from soil organisms will increase both with declining transport duration and with increasing protection from environmental extremes. Soil was collected from two sites, a native forest remnant and an orchard, and stored on, in and under sea containers, or in cupboards, and assayed after 0, 3, 6 and 12 months for bacteria, fungi, nematodes and seeds. Results showed that viability of Pseudomonas spp., bacteria, nematodes and plants declined over 12 months, irrespective of soil source. Also, mortality of most biota was higher when exposed to sunlight, moisture and desiccation than when protected. However, bacterial and fungal numbers were higher in exposed environments, possibly due to ongoing colonization of exposed soil by airborne propagules. The results were consistent with our observations of organisms in soil intercepted from airports and sea ports, and indicated there is potential to rank risks from transported soils based partly on transport duration and environmental exposure. This would help authorities to optimally allocate management resources according to pathway-specific risks.
Introduced species lists provide essential background information for biological invasions research and management. The compilation of these lists is, however, prone to a variety of errors. We highlight the frequency and consequences of such errors using introduced Melaleuca (sensu lato, including Callistemon) species in South Africa as a case study. We examined 111 herbarium specimens from South Africa and noted the categories and sub-categories of errors that occurred in identification. We also used information from herbarium specimens and distribution data collected in the field to determine whether a species was introduced, naturalized and invasive. We found that 72% of the specimens were not named correctly. These were due to human error (70%) (misidentification, and improved identifications) and species identification problems (30%) (synonyms arising from inclusion of Callistemon, and unresolved taxonomy). At least 36 Melaleuca species have been introduced to South Africa, and field observations indicate that ten of these have naturalized, including five that are invasive. While most of the errors likely have negligible impact on management, we highlight one case where incorrect identification lead to an inappropriate management approach and some instances of errors in published lists. Invasive species lists need to be carefully reviewed to minimise errors, and herbarium specimens supported by DNA identification are required where identification using morphological features is particularly challenging.
Biological invasions are occurring frequently and with great impact to agricultural production and other ecosystem services. In response to this, the Australian Weed Risk Assessment (AWRA) was created to assess the potential 'weediness' of plants based on answers to questions related to biogeography, undesirable attributes, and biology or ecology. This basic model has been expanded and adapted for use on other taxa, often without adequate validation. Since invasive insect crop pests are a major economic cost to agricultural production, there is interest in using an expanded model for insects. Here, we review traits related to invasiveness of insects based on a systematic review of the literature. We then compare the identified invasive traits of insects with those identified for plants in the AWRA. Using insects as a case study, we illustrate that although there is some overlap in invasive traits, there are many unique traits related to invasion for both insects and plants. For insects, these traits relate largely to social behaviour. This lack of congruence may also be the case for other taxa. To increase predictive power, a taxon-specific risk assessment tool and deliberate verification are required.
Islands are particularly noteworthy for global conservation because of the high number of species they host, the high levels of species endemism, and the large number and proportion of species at risk of extinction. Much of the conservation threat on islands is from invasive species. Whilst biosecurity is an increasing focus of attention for authorities globally, species are continuing to establish in new locations outside of their native ranges. Among invasive species, ants are a prominent taxon, especially on islands. Over the past decade, following the detection of one of the world’s worst invasive ant species, African big-headed ant Pheidole megacephala, the environmental management authority on world-heritage-listed Lord Howe Island has focused attention on invasive ants. This detection influenced the creation of biosecurity measures to prevent further incursions of exotic species, particularly ants. Despite these efforts, over the following decade numerous ant species were collected on the island for the first time, indicating a serious biosecurity problem. Here, we investigate the chronosequence of ant introductions to Lord Howe Island to quantify the extent and nature of the island’s ant biosecurity problem. A total of 45 species have been collected on the island and of these, 12 are considered to be endemic, and a further seven are possibly native. Nineteen of the 26 introduced species (42% of the total fauna and 73% of the introduced fauna) were only found for the first time in the last 15 years. All but two of the species that are not native to Lord Howe Island are native to the Australian mainland, indicating that the biosecurity threat comes from the transport of goods from the Australian mainland. We suggest that the pattern of accelerating ant species accumulation on Lord Howe Island is probably not an isolated phenomenon, and that it is probably occurring on most islands globally that are habitable by ants and visited by people.
Ambrosia artemisiifolia (common ragweed) is an invasive species native to North America and was accidentally introduced to Europe in the 19th century. Widespread in disturbed habitats, it is a major weed in spring-sown crops and it causes serious allergic rhinitis and asthma due to its allergenic pollen. The aim of this research was to analyse the effects of both competitive vegetation and herbivory by Ophraella communa to control A. artemisiifolia in an agricultural area of north-western Italy. Hayseed mixtures, both over-seeded over the resident plant community or after ploughing, when seeded before the winter season, were able to suppress the establishment of A. artemisiifolia as well as to reduce its growth in terms of plant height and inflorescence size. Defoliation of A. artemisiifolia by O. communa at the end of the growing season was conspicuous but most of the plants still produced flowers and seeds. However, significant O. communa attack was recorded for reproductive structures. As for non-target species, O. communa was mainly recorded on Asteraceae, with low density and low degree of damage. Reduction of inflorescence size due to competitive vegetation and damage to male flowers by O. communa may diminish the amount of available pollen. The results of this study may be useful for the implementation of management measures to control A. artemisiifolia in agricultural areas using mixtures of native species.
Biosecurity measures are commonly used to prevent the introduction of non-native species to natural environments globally, yet the efficacy of practices is rarely tested under operational conditions. A voluntary biosecurity measure was trialled in the Norwegian high Arctic following concern that non-native species might be transferred to the region on the footwear of travellers. Passengers aboard an expedition cruise ship disinfected their footwear with the broad spectrum disinfectant Virkon S prior to and in-between landing at sites around the remote Svalbard archipelago. The authors evaluated the efficacy of simply stepping through a disinfectant foot bath, which is the most common practice of footwear disinfection aboard expedition cruise ships in the Arctic. This was compared to a more time consuming and little-used method involving drying disinfected footwear, as proposed by other studies. The two practices were evaluated by measuring microbial growth on paired footwear samples before and after disinfection under both conditions. Step-through disinfection did not substantially reduce microbial growth on the footwear. Allowing disinfected footwear to dry, however, reduced the microbial burden significantly to lower levels. Thus, the currently adopted procedures used aboard ships are ineffective at removing microbial burden and are only effective when footwear is given more time to dry than currently granted under operational conditions. These findings underscore results from empirical research performed elsewhere and suggest the need to better relay this information to practitioners. It is suggested that footwear should minimally be wiped dry after step-through disinfection as a reasonable compromise between biosecurity and practicability.
Vom 14. bis zum 16. September 2017 fanden am Institut für Germanistik der Universität Wrocław die VI. Linguistischen Treffen unter dem Titel 'Grenzen der Sprache, Grenzen der Sprachwissenschaft' statt. Die Treffen wurden vom Lehrstuhl für Deutsche Sprache und Lehrstuhl für Angewandte Linguistik veranstaltet
Im Folgenden werden für das östliche Ruhrgebiet bemerkenswerte Funde aufgeführt. Das Gebiet umfasst die Städte Gelsenkirchen, Essen, Herne, Bochum, Dortmund, Hagen und Hamm sowie die Kreise Recklinghausen, Unna und den Ennepe-Ruhr-Kreis. Zur besseren Auswertung sind hinter den Fundorten die MTB-Angaben (Topographische Karte 1:25.000) und ggf. eine Bewertung des Fundes für den hiesigen Raum und der floristische Status hinzugefügt. Funde aus dem östlichen Ruhrgebiet, die von nordrhein-westfälischer Bedeutung sind, sind im Beitrag BOCHUMER BOTANISCHER VEREIN (2018) aufgeführt. Die Zuordnung der Arten zu Pflanzenfamilien richtet sich nach PAROLLY & ROHWER (2016).
Factors that cause differential establishment among naturalized, invasive, and native species are inadequately documented, much less often quantified among different communities. We evaluated the effects of seed addition and disturbance (i.e., understory canopy removal) on the establishment and seedling biomass among two naturalized, two invasive, and two native species (1 forb, 1 grass in each group) within steppe and low elevation forest communities in eastern Washington, USA. Establishment within each plant immigrant class was enhanced by seed addition: naturalized species showed the greatest difference in establishment between seed addition and no seed addition plots, native and invasive species establishment also increased following seed addition but not to the same magnitude as naturalized species. Within seed addition plots, understory canopy disturbance resulted in significant increases in plant establishment (regardless of plant immigration class) relative to undisturbed plots and the magnitude of this effect was comparable between steppe and adjacent forest. However, regardless of disturbance treatment fewer invasive plants established in the forest than in the steppe, whereas native and naturalized plant establishment did not differ between the habitats. Individual biomass of naturalized species were consistently greater in disturbed (canopy removed) versus undisturbed control plots and naturalized species were also larger in the steppe than in the forest at the time of harvest. Similar trends in plant size were observed for the native and invasive species, but the differences in biomass for these two immigration classes between disturbance treatments and between habitats were not significant. We found that strong limitations of non-native species is correlated with intact canopy cover within the forest understory, likely driven by the direct or indirect consequences of low light transmittance through the arboreal and understory canopy. Considered collectively, our results demonstrate how seed limitation and intact plant ground cover can limit the abundance and performance of naturalized species in Pacific Northwest steppe and low elevation forest, suggesting that local disturbance in both habitats creates microsites for these species to establish and survive. Future studies evaluating interactions between multiple barriers to establishment using more representatives from each immigration class will further reveal how biotic interactions ultimately influence the demography and distribution of non-native plants within these communities.
In the face of increasing invasions and limited resources, appropriate management of invasive species requires prioritisation of species for management action. This process often relies on knowledge of species specific impacts. However, as studies explicitly measuring impact of marine alien species are rare, prioritisation of management actions is often based on studies from outside the geographic area of interest. Further, few impact studies account for context dependency (e.g. seasonal variability or distinct environmental regimes), raising the question of how transferrable knowledge about the impact of a species is between invaded ranges. This study addressed this question by using the widespread invasive solitary ascidian Ciona robusta as a case study for assessing impacts across two invaded regions: South Africa and California, USA. We replicated a previously conducted experiment from California that showed that C. robusta depresses local species richness in San Francisco Bay. Our South African experiment showed no effect of C. robusta on species richness, the Shannon-Weiner diversity index or community composition, despite experiments being carried out over two years and at two depths. While these results may reflect strong density dependency in the impact of C. robusta, they serve to highlight context dependency in invasive species impacts. This suggests that until studies of impact in marine systems become common place, context dependency should be explicitly addressed as a source of uncertainty during the prioritisation of species for management action.
Carbon mass of the non-indigenous predatory fishhook water flea Cercopagis pengoi (Ostroumov, 1891) from the eastern Gulf of Finland, the Baltic Sea, was for the first time measured using the high temperature combustion method. Prior to the analysis, individual dry weight of Cercopagis was determined; altogether ca. 500 organisms were examined. Mean individual dry weight of C. pengoi for July-September was estimated as 34.0 μg; carbon mass averaged 15.8 μg; carbon content, calculated as percent of dry weight, averaged 43.4%. Those values varied over months, mainly because of different population structure of C. pengoi and variation in their diet due to seasonal dynamics of the food objects. However, relations between carbon mass and dry weight for different months did not differ statistically (p<0.001). Therefore, the general polynomial regressions (k=2), describing carbon mass-to-dry weight and carbon content-to-dry weight relationships, were calculated for the entire dataset of individual measurements of C. pengoi body metrics. These data will contribute to adequate evaluation of food web structure and ecosystem alterations in various water bodies invaded by C. pengoi which has got a strong potential to pelagic food web transformations that may impact the overall energy balance and decrease the size of fish stocks.
Prioritization of introduction pathways is seen as an important component of the management of biological invasions. We address whether established alien plants, mammals, freshwater fish and terrestrial invertebrates with known ecological impacts are associated with particular introduction pathways (release, escape, contaminant, stowaway, corridor and unaided). We used the information from the European alien species database DAISIE (www.europe-aliens.org) supplemented by the EASIN catalogue (European Alien Species Information Network), and expert knowledge. Plants introduced by the pathways release, corridor and unaided were disproportionately more likely to have ecological impacts than those introduced as contaminants. In contrast, impacts were not associated with particular introduction pathways for invertebrates, mammals or fish. Thus, while for plants management strategies should be targeted towards the appropriate pathways, for animals, management should focus on reducing the total number of taxa introduced, targeting those pathways responsible for high numbers of introductions. However, regardless of taxonomic group, having multiple introduction pathways increases the likelihood of the species having an ecological impact. This may simply reflect that species introduced by multiple pathways have high propagule pressure and so have a high probability of establishment. Clearly, patterns of invasion are determined by many interacting factors and management strategies should reflect this complexity.
Humans have an extremely long history of transporting and introducing mammal species outside their native geographic ranges. The characteristics of the species introduced (taxonomy, life-history, ecology, environment) can all influence which traits are available (and selected) for establishment, and subsequent invasive spread. Understanding the non-randomness in species introductions is therefore key to understanding invasions by alien species. Here, we test for selectivity in the identities and traits of mammal species introduced worldwide. We compiled and analysed a comprehensive database of introduced mammal species, including information on a broad range of life history, ecological, distributional and environmental variables that we predicted to differ between introduced and non-introduced mammal species. Certain mammal taxa are much more likely to have been introduced than expected, such as Artiodactyls in the families Bovidae and Cervidae. Rodents and bats were much less likely to have been introduced than expected. Introduced mammal species have significantly larger body masses, longer lifespans and larger litter sizes than a random sample of all mammal species. They also have much larger native geographic ranges than expected, originate from significantly further north, from cooler areas, and from areas with higher human population densities, than mammal species with no recorded introductions. The traits and distributions of species help determine which have been introduced, and reflect how the evolutionary history of mammals has resulted in certain species with certain traits being located in the way of human histories of movement and demands for goods and services. The large amount of unexplained variation is likely to relate to the intrinsically stochastic nature of this human-driven process.
The fluvial systems in the north-east of the Iberian Peninsula are highly disturbed habitats, with widespread occurrence of alien species. Previous studies have shown that alien species have a major impact on native freshwater fauna, but it is not known what effect they have on semi-aquatic reptiles. Here the author investigated the factors that influence the occurrence of three species of semi-aquatic reptiles, one turtle (Mauremys leprosa) and two snakes (Natrix astreptophora and Natrix maura), at 261 sites in seven rivers/streams in Girona (north-eastern Spain). The studied semi-aquatic reptiles are habitat generalists which can occupy sections of rivers with altered regimes. The relationships of reptile presence to abiotic niche parameters and the presence of alien species were evaluated, as well as the patterns of pairwise co-occurrence between the reptiles. The presence of alien species did impact one out of three reptiles in this community. The association between both species of natricines was weakly negative, suggesting that interspecific competition does not structure their co-occurrences. The removal of alien species is the most appropriate strategy to preserve the complete diversity of native semi-aquatic reptiles.
The relevance of using various scoring schemes revealed by an impact assessment of feral mammals
(2018)
Impact scoring schemes are useful for identifying to what extent alien species cause damage. Quantifying the similarity and differences between impact scoring schemes can help determine how to optimally use these tools for policy decisions. Using feral mammals (including rats and mice) as a case study, environmental and socio-economic impacts were assessed using three schemes, namely the Generic Impact Scoring System (GISS), Environmental Impact Classification for Alien Taxa (EICAT) and Socio-Economic Impact Classification for Alien Taxa (SEICAT). The results show that socio-economic impacts scores differ between the respective schemes (GISS and SEICAT) possibly because they assess different aspects of social life and economy. This suggests that both scoring schemes should ideally be applied in concert to get a complete picture of socio-economic impacts. In contrast, environmental impact scores are correlated between GISS and EICAT assessments and this similarity is consistent over most mechanisms except for predation and ecosystems, suggesting that one scoring scheme is sufficient to capture all the environmental impacts. Furthermore, we present evidence for the island susceptibility hypothesis as impacts of feral mammals were found to be higher on islands compared to mainlands.
Impact assessment with different scoring tools: How well do alien amphibian assessments match?
(2017)
Classification of alien species' impacts can aid policy making through evidence based listing and management recommendations. We highlight differences and a number of potential difficulties with two scoring tools, the Environmental Impact Classification of Alien Taxa (EICAT) and the Generic Impact Scoring System (GISS) using amphibians as a case study. Generally, GISS and EICAT assessments lead to very similar impact levels, but scores from the schemes are not equivalent. Small differences are attributable to discrepancies in the verbal descriptions for scores. Differences were found in several impact categories. While the issue of disease appears to be related to uncertainties in both schemes, hybridisation might be inflated in EICAT. We conclude that GISS scores cannot directly be translated into EICAT classifications, but they give very similar outcomes and the same literature base can be used for both schemes.
Range expansion drives the evolution of alternate reproductive strategies in invasive fire ants
(2017)
Many species are expanding their ranges in response to climate changes or species introductions. Expansion-related selection likely drives the evolution of dispersal and reproductive traits, especially in invasive species introduced into novel habitats. We used an agent-based model to investigate these relationships in the red imported fire ant, Solenopsis invicta, by tracking simulated populations over 25 years. Most colonies of this invasive species produce two types of queens practicing alternate reproductive strategies. Claustral queens found new colonies in vacant habitats, while parasitic queens take over existing colonies whose queens have died. We investigated how relative investment in the two queen types affects population demography, habitat occupancy, and range expansion. We found that parasitic queens extend the ecological lifespan of colonies, thereby increasing a population’s overall habitat occupancy as well as average colony size (number of workers) and territory size. At the same time, investment in parasitic queens slowed the rate of range expansion by diverting investment from claustral queens. Divergent selection regimes caused edge and interior populations to evolve different levels of reproductive investment, such that interior populations invested heavily in parasitic queens whereas those at the edge invested almost entirely in claustral queens. Our results highlight factors shaping ant life histories, including the evolution of social parasitism, and have implications for the response of species to range shifts.
Plant traits are critical for understanding invasion success of introduced species, yet attempts to identify universal traits that explain invasion success and impact have been unsuccessful because environmenttrait- fitness relationships are complex, potentially context dependent, and variation in traits is often unaccounted for. As introduced species encounter novel environments, their traits and trait variability can determine their ability to grow and reproduce, yet invasion biologists do not often have an understanding of how novel environments might shape traits. To uncover which combination of traits are most effective for predicting invasion success, we studied three different urban habitat types along the Nile Delta in Egypt invaded by the Pink Morning Glory, Ipomoea carnea Jacq. (Family: Convolvulaceae). Over two years, we measured ten plant traits at monthly intervals along an invasion gradient in each habitat. No single trait sufficiently explained survival probability and that traits linked to invasion success were better predicted by the characteristics of the invaded habitat. While the measured traits did influence survival of I. carnea, the importance of specific traits was contingent on the local environment, meaning that local trait-environment interactions need to be understood in order to predict invasion.
The adoption of a consistent alien species pathways categorization, hierarchy and terminology is crucial for increasing the interoperability of different online databases. In the present paper the European Alien Species Information Network (EASIN) classification system of pathways is compared and discussed with the classification scheme recently published by the Convention on Biological Diversity (CBD). Although the main pathway categories of the two classifications overall match, there are substantial differences in their subcategorization, with EASIN including 20 pathway subcategories while CBD considers 44 subcategories. In most cases, each EASIN subcategory pathway can correspond to two or more CBD subcategories. About 5,500 species listed in EASIN do not match directly with the CBD pathway subcategories, most of which are terrestrial invertebrates. Aiming at achieving synchronization between the two classification systems and at facilitating the access to information to researchers and policy makers, EASIN is trying to align with the CBD pathway classification scheme. This alignment process requires the involvement of a large number of experts, especially from the terrestrial realm, and the adoption of commonly accepted definitions of the CBD pathways.