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Institute
In recent environmental research, relational values (RVs) have emerged as a new group of values to explain environmental behavior. Although this new concept is attracting attention, empirical studies on the subject are still rare. On this basis, we have conducted three studies to analyze an existing measurement tool for RVs and compared the construct with the concept of connection to nature. In study 1, we confirmed convergent and discriminant validity of the RV scale by comparing it with the Two Factor Model of Environmental Values (2-MEV) model using a sample of n = 350 university students. Additionally, study 1 verified reliability using test–retest reliability on three different groups of students (n1 = 53; n2 = 37; n3 = 48). In study 2, principal component analyses were performed to examine the structure of RVs and to compare it to the concept of connection to nature by reusing the sample 350 university students from study 1. The results show that RVs and connection to nature are not fundamentally distinct constructs, but overlap. However, if the structure of the RV measurement is forced to a single factor, no perfect fit is found, making a multidimensional solution more likely. A third study was conducted to review the results from study 2 using confirmatory factor analysis on a new sample of 878 university and high school students. Study 3 confirmed RVs as a multidimensional construct with three factors: care, community, and connection. It also proved the overlap of the connection to nature and RV concepts to some extent.
A high-precision pressure probe is described which allows non-invasive online-monitoring of the water relations of intact leaves. Real-time recording of the leaf water status occurred by data transfer to an Internet server. The leaf patch clamp pressure probe measures the attenuated pressure, Pp, of a leaf patch in response to a constant clamp pressure, Pclamp. Pp is sensed by a miniaturized silicone pressure sensor integrated into the device. The magnitude of Pp is dictated by the transfer function of the leaf, Tf, which is a function of leaf patch volume and ultimately of cell turgor pressure, Pc, as shown theoretically. The power function Tf=f(Pc) theoretically derived was experimentally confirmed by concomitant Pp and Pc measurements on intact leaflets of the liana Tetrastigma voinierianum under greenhouse conditions. Simultaneous Pp recordings on leaflets up to 10 m height above ground demonstrated that changes in Tf induced by Pc changes due to changes of microclimate and/or of the irrigation regime were sensitively reflected in corresponding changes of Pp. Analysis of the data show that transpirational water loss during the morning hours was associated with a transient rise in turgor pressure gradients within the leaflets. Subsequent recovery of turgescence during the afternoon was much faster than the preceding transpiration-induced water loss if the plants were well irrigated. Our data show the enormous potential of the leaf patch clamp pressure probe for leaf water studies including unravelling of the hydraulic communication between neighbouring leaves and over long distances within tall plants (trees).
Impact of biological education and gender on students' connection to nature and relational values
(2020)
The new concept of relational values (RVs) is gaining more and more attention in environmental research, but empirical analyses are still rare. However, this type of research is necessary because the RVs have an influence on environmental behavior. To evaluate the impact of biological education on attributing higher importance to RVs and connectedness to nature, we compared the connection to nature scores (using the inclusion of nature scale (INS) and connectedness to nature scale (CNS)) and RV scores of biologically interested high school students (n = 417) with first year (n = 593) and advanced biology (n = 223) students. While high school students showed significant lower connection to nature scores than university students, there was no significant difference in RVs between the test groups. These results suggest that there is a lack of factors in the university study of biology that can change RVs. The gender comparison of RVs and connection to nature showed a significant higher RV score for females while INS and CNS did not show a gender difference. Thus, the study makes an important contribution to the research, as it was able to prove that gender has an influence on a person's RVs but not on their connection to nature.
The UN's sustainable development goals (SDGs), which aim to solve important economic, social, and environmental problems of humanity, are to be supported by education for sustainable development (ESD). Empirical studies on the success of the implementation of the SDGs in the field of education are still pending. For this reason, using the loss of global biodiversity as an example, this study examined the extent to which high school students, teacher trainees in biology, and biology bachelor students can identify the causes of the global biodiversity loss. A new questioning tool was developed and tested on 889 participants. In addition, the relationship between connection to nature and the personal assessment about biodiversity threats was examined. The factor analysis of the scale used showed that 11 out of 16 items were assigned to the intended factor. The comparison between high school students, teacher trainees in biology, and biology bachelor students showed no significant difference in overall assessment of the reasons for global biodiversity loss. When comparing the three risk levels in which the risk factors for biodiversity could be divided, across the three student groups, only minor differences were found. Therefore, a specific education of prospective teachers is necessary, as they have to pass on the competence as multipliers to their students. No significant difference could be found when examining the relationship between connection to nature and the overall scores of the assessment scale for the reasons of biodiversity loss. However, it was found that people who felt more connected to nature were more capable of assessing the main causes of risk for global biodiversity, while people who felt less connected to nature achieved better scores for the medium factors
Cardiac rehabilitation (CR) is a multidisciplinary intervention including patient assessment and medical actions to promote stabilization, management of cardiovascular risk factors, vocational support, psychosocial management, physical activity counselling, and prescription of exercise training. Millions of people with cardiac implantable electronic devices live in Europe and their numbers are progressively increasing, therefore, large subsets of patients admitted in CR facilities have a cardiac implantable electronic device. Patients who are cardiac implantable electronic devices recipients are considered eligible for a CR programme. This is not only related to the underlying heart disease but also to specific issues, such as psychological adaptation to living with an implanted device and, in implantable cardioverter-defibrillator patients, the risk of arrhythmia, syncope, and sudden cardiac death. Therefore, these patients should receive special attention, as their needs may differ from other patients participating in CR. As evidence from studies of CR in patients with cardiac implantable electronic devices is sparse, detailed clinical practice guidelines are lacking. Here, we aim to provide practical recommendations for CR in cardiac implantable electronic devices recipients in order to increase CR implementation, efficacy, and safety in this subset of patients.
Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC).
Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m2 doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m2 every 28 days or capecitabine 1250 mg/m2 twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP).
Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31).
Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.
Measles virus (MeV) is an aerosol-borne and one of the most contagious pathogenic viruses known. Almost every MeV infection becomes clinically manifest and can lead to serious and even fatal complications, especially under conditions of malnutrition in developing countries, where still 115,000 to 160,000 patients die from measles every year. There is no specific antiviral treatment. In addition, MeV infections cause long-lasting memory B and T cell impairment, predisposing people susceptible to opportunistic infections for years. A rare, but fatal long-term consequence of measles is subacute sclerosing panencephalitis. Fifteen years ago (2001), WHO has launched a programme to eliminate measles by a worldwide vaccination strategy. This is promising, because MeV is a human-specific morbillivirus (i.e. without relevant animal reservoir), safe and potent vaccine viruses are sufficiently produced since decades for common application, and millions of vaccine doses have been used globally without any indications of safety and efficacy issues. Though the prevalence of wild-type MeV infection has decreased by >90 % in Europe, measles is still not eliminated and has even re-emerged with recurrent outbreaks in developed countries, in which effective vaccination programmes had been installed for decades. Here, we discuss the crucial factors for a worldwide elimination of MeV: (1) efficacy of current vaccines, (2) the extremely high contagiosity of MeV demanding a >95 % vaccination rate based on two doses to avoid primary vaccine failure as well as the installation of catch-up vaccination programmes to fill immunity gaps and to achieve herd immunity, (3) the implications of sporadic cases of secondary vaccine failure, (4) organisation, acceptance and drawbacks of modern vaccination campaigns, (5) waning public attention to measles, but increasing concerns from vaccine-associated adverse reactions in societies with high socio-economic standards and (6) clinical, epidemiological and virological surveillance by the use of modern laboratory diagnostics and reporting systems. By consequent implementation of carefully designed epidemiologic and prophylactic measures, it should be possible to eradicate MeV globally out of mankind, as the closely related morbillivirus of rinderpest could be successfully eliminated out of the cattle on a global scale.
Background: Pancreatic surgery demands complex multidisciplinary management. Clinical pathways (CPs) are a tool to facilitate this task, but evidence for their utility in pancreatic surgery is scarce. This study evaluated the effect of CPs on quality of care for pancreatoduodenectomy.
Methods: Data of all consecutive patients who underwent pancreatoduodenectomy before (n = 147) or after (n = 148) CP introduction were evaluated regarding catheter and drain management, postoperative mobilization, pancreatic enzyme substitution, resumption of diet and length of stay. Outcome quality was assessed using glycaemia management, morbidity, mortality, reoperation and readmission rates.
Results: Catheters and abdominal drainages were removed significantly earlier in patients treated with CP (p < 0.0001). First intake of liquids, nutritional supplement and solids was significantly earlier in the CP group (p < 0.0001). Exocrine insufficiency was significantly less common after CP implementation (47.3% vs. 69.7%, p < 0.0001). The number of patients receiving intraoperative transfusion dropped significantly after CP implementation (p = 0.0005) and transfusion rate was more frequent in the pre-CP group (p = 0.05). The median number of days with maximum pain level >3 was significantly higher in the CP group (p < 0.0001). There was no significant difference in mortality, morbidity, reoperation and readmission rates.
Conclusions: Following implementation of a CP for pancreatoduodenectomy, several indicators of process and outcome quality improved, while others such as mortality and reoperation rates remained unchanged. CPs are a promising tool to improve quality of care in pancreatic surgery.
Objective: Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone-releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients.
Methods: Patients had FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) III or IV or recurrent EC, LHRH receptor-positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors.
Results: From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%).
Conclusions: AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor-positive EC, supporting the principle of receptor-mediated targeted chemotherapy.
Nerve injury leads to sensitization mechanisms in the peripheral and central nervous system which involve transcriptional and post-transcriptional modifications in sensory nerves. To assess protein regulations in the spinal cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE) technology. Among approximately 2300 protein spots separated on each gel we detected 55 significantly regulated proteins after SNI whereof 41 were successfully identified by MALDI-TOF MS. Out of the proteins which were regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A inhibitor latexin because protease dysfunctions contribute to the development of neuropathic pain. Latexin protein expression was reduced after SNI which could be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ hybridisation. The decrease of latexin was associated with an increase of the activity of carboxypeptidase A indicating that the balance between latexin and carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury due to a loss of latexin expression in spinal cord neurons. This may contribute to the development of cold allodynia because normalization of neuronal latexin expression in the spinal cord by AAV-mediated latexin transduction or administration of a small molecule carboxypeptidase A inhibitor significantly reduced acetone-evoked nociceptive behavior after SNI. Our results show the usefulness of proteomics as a screening tool to identify novel mechanisms of nerve injury evoked hypernociception and suggest that carboxypeptidase A inhibition might be useful to reduce cold allodynia.
We report the transverse energy (ET) measured with ALICE at midrapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV as a function of centrality. The transverse energy was measured using identified single particle tracks. The measurement was cross checked using the electromagnetic calorimeters and the transverse momentum distributions of identified particles previously reported by ALICE. The results are compared to theoretical models as well as to results from other experiments. The mean ET per unit pseudorapidity (η), ⟨dET/dη⟩, in 0-5% central collisions is 1737 ± 6(stat.) ± 97(sys.) GeV. We find a similar centrality dependence of the shape of ⟨dET/dη⟩ as a function of the number of participating nucleons to that seen at lower energies. The growth in ⟨dET/dη⟩ at the LHC sNN−−−√ exceeds extrapolations of low energy data. We observe a nearly linear scaling of ⟨dET/dη⟩ with the number of quark participants. With the canonical assumption of a 1 fm/c formation time, we estimate that the energy density in 0-5% central Pb-Pb collisions at sNN−−−√ = 2.76 TeV is 12.3 ± 1.0 GeV/fm3\xspace and that the energy density at the most central 80 fm2 of the collision is at least 21.5 ± 1.7 GeV/fm3. This is roughly 2.3 times that observed in 0-5% central Au-Au collisions at sNN−−−√ = 200 GeV.
Background The detection of the new Coranavirus (CoV) causing agent of the severe acute respiratory syndrome (SARS) for diagnostic purposes is still a critical step in prevention of secondary hospital infections. In this respect the PCR for SARS diagnostic is the fastest and most sensitive method and was published very early after the description of the new pathogen by different groups. To evaluate the quality and sensitivity of the SARS PCR performed in diagnostic laboratories all over the world an external quality assurance (EQA) for SARS PCR was initiated by the WHO, the European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) and the Robert Koch-Institut. Methods Therefore 10 samples of inactivated SARS CoV strains isolated in Frankfurt and Hong Kong in different dilutions and negative controls were prepared. The freeze dried samples were send by mail to 62 different laboratories, in 37 countries in Europe and Israel (35), Asia (11), The Americas (11), Australia and New Zealand (4) and Africa (1). The results were returned by email or fax 1 week (13), 2 weeks (14), 3 weeks (6) and later (29) after receiving the material which does not mimic at all the possible speed of this fast method. But this was not considered in the evaluation of these first SARS EQA. Results 44 laboratories showed good or excellent results (26 = 100%, 18 = 90%) and even the 14 laboratories which archived only 80% (10) or 70% (4) correct results are mostly lacking sensitivity. The results of the other 4 laboratories show basic problems in regard to sensitivity, specificity and consistency of results and must be overcome as soon as possible. 4 laboratories seem to have problems with the specificity finding a positive signal in negative samples. The different methods used for preparation of the SARS CoV genome and diagnostic PCR test procedure used by the participating laboratories will be discussed in more detail in the presentation. Conclusion However, in contrast to previous EQAs for Ebola, Lassa and Orthopoxviruses the quality of PCR results was rather good which might be caused by the early publication and distribution of well developed PCR methods. An EQA for evaluation of SARS specific serology is still ongoing, first results will be available beginning of April 2004.
Beim Übergang vom Wachstum zur Entwicklung entsteht in Dictyostelium discoideum aus einzelnen vegetativ wachsenden Zellen ein multizellulärer Organismus, der in der Lage ist ausdauernde Sporen zu bilden. Während der im multizellulären Verband stattfindenden morphologischen Veränderungen und Zelldifferenzierung nimmt die Proteinkinase A (PKA) eine Schlüsselfunktion ein. Der C-Modul bindende Faktor A (CbfA), ursprünglich aufgrund seiner spezifischen Bindung an eine regulatorische DNA-Sequenz des Non-LTR Retrotransposons TRE5-A.1 in D. discoideum entdeckt, ist für den Übergang vom Wachstum zur Differenzierungsphase essentiell. Zellen der CbfA-Mangelmutante JH.D2 weisen im Vergleich zu denen des Wildtyp-Stamms AX2 ein verlangsamtes Wachstum und eine verzögerte Einleitung der Aggregation und der Entwicklung auf. Charakteristisch für diese CbfA-Mutante ist die Unterexpression der mRNA für die katalytische Untereinheit der Proteinkinase A (PkaC). Da die Expression der PkaC sowohl auf der Transkriptions- als auch auf der Translationsebene reguliert ist, wurde in dieser Arbeit ein monoklonaler Antikörper gegen die katalytische Untereinheit hergestellt, um den Proteingehalt an PkaC in Zellen der CbfA-Mutante zu untersuchen. Dabei konnte eine starke Unterexpression der PkaC in den CbfA-depletierten Zellen nachgewiesen werden. Demnach scheint es einen mittelbaren Zusammenhang zwischen der Menge an CbfA und dem sich selbst verstärkenden cAMP-abhängigen Signaltransduktionssystem der Zellen zu geben, da ein Mangel an cAMP eine fehlende Aktivierung der sich selbst induzierenden PKA nach sich zieht. Für D. discoideum konnte erstmals eine reproduzierbare 2D-gelelektrophoretische Trennmethode etabliert werden, mit der es gelang, differentiell exprimierte Proteine im Stadium der frühen Entwicklung zwischen den untersuchten D. discoideum-Stämmen AX2 und JH.D2 aufzufinden. Die Anwendung der DIGE-Technologie ermöglichte dabei die Detektion von ca. 30-40 differentiell exprimierten Proteinen. Durch die massenspektrometrische Untersuchung dieser Proteine unter Verwendung der MALDI-TOF Methode in Kombination mit dem Peptid-Massen-Fingerabdruck konnten insgesamt ca. 30% der differentiell exprimierten Proteine identifiziert werden. Dabei stellte sich heraus, daß vor allem Proteine mit essentiellen Funktionen im zellulären Stoffwechsel in der CbfA-Mangelmutante JH.D2 auf geringerem Niveau exprimiert wurden als im Wildtyp-Stamm AX2. Dies könnte eine Erklärung für die letalen Auswirkungen eines vollständigen knockouts von CbfA in D. discoideum liefern. Zusätzlich wurde mit Hilfe der DIGE-Technologie die Funktion der C-terminalen Domäne des CbfA-Proteins untersucht. Für diese Experimente wurde eine CbfA-Mutante verwendet, die den C-Terminus konstitutiv überexprimiert. Die daraus resultierenden Proteinmuster haben gezeigt, daß die C-terminale Domäne unabhängig vom Rest des Proteins sowohl induzierenden als auch reprimierenden Einfluß auf die Proteinexpression nimmt. Diese Ergebnisse zeigen eine unerwartet komplexe Funktion des Proteins CbfA in der Regulation von Genen während der untersuchten Lebensphasen von D. discoideum.
Out-of-school laboratories, also called student labs, are an advantageous opportunity to teach biological subjects. Particularly in the case of complex fields such as neurobiology, student labs offer the opportunity to learn about difficult topics in a practical way. Due to numerous advantages, digital student labs are becoming increasingly popular nowadays. In this study, we investigated the effect of an electrophysiological setup for a virtual experiment with and without hands-on elements on participant motivation and technology acceptance. For this purpose, 235 students were questioned during a student laboratory day. The surveyed students showed high motivation and technology acceptance for the virtual experiment. In the comparison, the electrophysiological setup with hands-on elements performs better in the intrinsic components than the setup without hands-on elements: Thus, the hands-on approach is rated as more interesting and the perceived enjoyment scores higher. Nevertheless, both experimental groups show high values, so that the results of the study support the positive influence of digital laboratory as well as a positive influence of hands-on elements.
In recent decades, zoos have been increasingly transformed into education centers with the goal of raising awareness about environmental issues and providing environmental education. Probably the simplest and most widespread environmental education program in the zoo is the guided tour. This study therefore aims to test whether a one hour zoo tour has an influence on the participants’ connection to nature and attitude towards species conservation. For this purpose, 269 people who had voluntarily registered for a zoo tour were surveyed before and after the tour. In addition to the regular zoo tour, special themed tours and tours with animal feedings were included. The results show a positive increase in connection to nature and a strengthening of positive attitudes towards species conservation for all tour types. For nature connectedness, in particular, people with an initial high connection to nature benefitted from the special themed tours and the tours, including animal feedings. For attitudes towards species conservation, no difference was found between the tour types. The results prove the positive influence of a very simple environmental education program, even for people with a preexisting high level of connection to nature and positive attitude towards species conservation.
In order to effectively address global environmental problems, it is important that future decision-makers in society are aware of the safe operation space for humans, which is limited by the planetary boundaries. Until now, however, there has been a lack of international studies examining how the planet's boundaries are perceived. In this study, we investigated how students of environmental and sustainability studies in 35 countries (n = 4140) assess the planetary boundaries. Based on the rating, using spectral clustering, the 35 countries were assigned to five different clusters. Four indicators (Human Development Index, Legatum Prosperity Index, Natural Resources Income and Forest Area) were used to provide explanations for the clustering result. The indices allow a distinction between the clusters and provide initial explanations for the clustering. The results provide important insights for today's decision-makers, as possible measures for action in the individual countries can be derived from the findings.
Measuring connection to nature - a illustrated extension of the inclusion of nature in self scale
(2021)
The human-nature connection is an important factor that is frequently the subject of environmental education research and environmental psychology. Therefore, over the years, numerous measuring instruments have been established to quantitatively record a person’s connection to nature. However, there is no instrument specifically for children with cognitive limitations. For this reason, in this study, an established scale for connection to nature, the inclusion of nature in self scale (INS), was modified especially for the needs of this group. Study 1 investigated what students understand by the term “nature” in order to create an illustrated version of the INS. In study 2, the new instrument was tested on university students and compared with the original INS and the connectedness to nature scale (CNS). No significant differences between the original INS and the new developed scale were found (p = 0.247), from which it can be concluded that the illustrated INS (IINS) measures the connection to nature with similar accuracy as the original INS. In study 3, the instrument was tested together with other established nature connection instruments on the actual target group, students with disabilities. The correlation between the IINS, the CNS, and nature connectedness scale (NR) were in accordance with the expected literature values (rIINS-CNS = 0.570 & rIINS-NR = 0.605). The results of this study also prove effectiveness of the developed illustrated scale. This research thus provides a suitable measuring instrument for people with learning difficulties and can make a contribution to the investigation of human-nature connections and conservation education.
Interest is an important factor for successful learning that has been the subject of intensive research for decades. Although interest in nature is of great importance for environmental education, to date there is no valid and reliable measurement tool. Therefore, the purpose of this study was to develop and test a scale for interest in nature, the Nature Interest Scale (NIS). In study 1, nine items were selected based on the three dimensions of the psychological interest construct to represent interest in nature. The factor structure of this new measurement instrument, was tested using confirmatory factor analyses. The results show that the instrument represents the three dimensions of the interest construct well. In study 2 the validity (discriminant and convergent validity) as well as the reliability (internal consistency, composite reliability, test-retest reliability) of the NIS were demonstrated. In study 3, the applicability of the NIS was tested with a different target group, students with learning disabilities. The results of this factor analysis also confirm the factor structure of the scale. Thus, this study provides a valid and reliable measurement tool for individual interest in nature that can be used for future research.
Measurements of charged jet production as a function of centrality are presented for p-Pb collisions recorded at sNN−−−√=5.02 TeV with the ALICE detector. Centrality classes are determined via the energy deposit in neutron calorimeters at zero degree, close to the beam direction, to minimise dynamical biases of the selection. The corresponding number of participants or binary nucleon-nucleon collisions is determined based on the particle production in the Pb-going rapidity region. Jets have been reconstructed in the central rapidity region from charged particles with the anti-kT algorithm for resolution parameters R=0.2 and R=0.4 in the transverse momentum range 20 to 120 GeV/c. The reconstructed jet momentum and yields have been corrected for detector effects and underlying-event background. In the five centrality bins considered, the charged jet production in p-Pb collisions is consistent with the production expected from binary scaling from pp collisions. The ratio of jet yields reconstructed with the two different resolution parameters is also independent of the centrality selection, demonstrating the absence of major modifications of the radial jet structure in the reported centrality classes.
We present a Bayesian approach to particle identification (PID) within the ALICE experiment. The aim is to more effectively combine the particle identification capabilities of its various detectors. After a brief explanation of the adopted methodology and formalism, the performance of the Bayesian PID approach for charged pions, kaons and protons in the central barrel of ALICE is studied. PID is performed via measurements of specific energy loss (dE/dx) and time-of-flight. PID efficiencies and misidentification probabilities are extracted and compared with Monte Carlo simulations using high-purity samples of identified particles in the decay channels K0S→π−π+, ϕ→K−K+, and Λ→pπ− in p-Pb collisions at sNN−−−√=5.02 TeV. In order to thoroughly assess the validity of the Bayesian approach, this methodology was used to obtain corrected pT spectra of pions, kaons, protons, and D0 mesons in pp collisions at s√=7 TeV. In all cases, the results using Bayesian PID were found to be consistent with previous measurements performed by ALICE using a standard PID approach. For the measurement of D0→K−π+, it was found that a Bayesian PID approach gave a higher signal-to-background ratio and a similar or larger statistical significance when compared with standard PID selections, despite a reduced identification efficiency. Finally, we present an exploratory study of the measurement of Λ+c→pK−π+ in pp collisions at s√=7 TeV, using the Bayesian approach for the identification of its decay products.
Measurements of charged jet production as a function of centrality are presented for p-Pb collisions recorded at sNN−−−√=5.02 TeV with the ALICE detector. Centrality classes are determined via the energy deposit in neutron calorimeters at zero degree, close to the beam direction, to minimise dynamical biases of the selection. The corresponding number of participants or binary nucleon-nucleon collisions is determined based on the particle production in the Pb-going rapidity region. Jets have been reconstructed in the central rapidity region from charged particles with the anti-kT algorithm for resolution parameters R=0.2 and R=0.4 in the transverse momentum range 20 to 120 GeV/c. The reconstructed jet momentum and yields have been corrected for detector effects and underlying-event background. In the five centrality bins considered, the charged jet production in p-Pb collisions is consistent with the production expected from binary scaling from pp collisions. The ratio of jet yields reconstructed with the two different resolution parameters is also independent of the centrality selection, demonstrating the absence of major modifications of the radial jet structure in the reported centrality classes.
We report the first results of elliptic (v2), triangular (v3) and quadrangular flow (v4) of charged particles in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurements are performed in the central pseudorapidity region |η|<0.8 and for the transverse momentum range 0.2<pT<5 GeV/c. The anisotropic flow is measured using two-particle correlations with a pseudorapidity gap greater than one unit and with the multi-particle cumulant method. Compared to results from Pb-Pb collisions at sNN−−−√=2.76 TeV, the anisotropic flow coefficients v2, v3 and v4 are found to increase by (3.0±0.6)%, (4.3±1.4)% and (10.2±3.8)%, respectively, in the centrality range 0-50%. This increase can be attributed mostly to an increase of the average transverse momentum between the two energies. The measurements are found to be compatible with hydrodynamic model calculations. This comparison provides a unique opportunity to test the validity of the hydrodynamic picture and the power to further discriminate between various possibilities for the temperature dependence of shear viscosity to entropy density ratio of the produced matter in heavy-ion collisions at the highest energies.
We report the first results of elliptic (v2), triangular (v3) and quadrangular flow (v4) of charged particles in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurements are performed in the central pseudorapidity region |η|<0.8 and for the transverse momentum range 0.2<pT<5 GeV/c. The anisotropic flow is measured using two-particle correlations with a pseudorapidity gap greater than one unit and with the multi-particle cumulant method. Compared to results from Pb-Pb collisions at sNN−−−√=2.76 TeV, the anisotropic flow coefficients v2, v3 and v4 are found to increase by (3.0±0.6)%, (4.3±1.4)% and (10.2±3.8)%, respectively, in the centrality range 0-50%. This increase can be attributed mostly to an increase of the average transverse momentum between the two energies. The measurements are found to be compatible with hydrodynamic model calculations. This comparison provides a unique opportunity to test the validity of the hydrodynamic picture and the power to further discriminate between various possibilities for the temperature dependence of shear viscosity to entropy density ratio of the produced matter in heavy-ion collisions at the highest energies.
The inclusive production of the ψ(2S) charmonium state was studied as a function of centrality in p-Pb collisions at the nucleon-nucleon center of mass energy sNN−−−√ = 5.02 TeV at the CERN LHC. The measurement was performed with the ALICE detector in the center of mass rapidity ranges −4.46<ycms<−2.96 and 2.03<ycms<3.53, down to zero transverse momentum, by reconstructing the ψ(2S) decay to a muon pair. The ψ(2S) production cross section σψ(2S) is presented as a function of the collision centrality, which is estimated through the energy deposited in forward rapidity calorimeters. The relative strength of nuclear effects on the ψ(2S) and on the corresponding 1S charmonium state J/ψ is then studied by means of the double ratio of cross sections [σψ(2S)/σJ/ψ]pPb/[σψ(2S)/σJ/ψ]pp between p-Pb and pp collisions, and by the values of the nuclear modification factors for the two charmonium states. The results show a large suppression of ψ(2S) production relative to the J/ψ at backward (negative) rapidity, corresponding to the flight direction of the Pb-nucleus, while at forward (positive) rapidity the suppressions of the two states are comparable. Finally, comparisons to results from lower energy experiments and to available theoretical models are presented.
The inclusive production of the ψ(2S) charmonium state was studied as a function of centrality in p-Pb collisions at the nucleon-nucleon center of mass energy sNN−−−√ = 5.02 TeV at the CERN LHC. The measurement was performed with the ALICE detector in the center of mass rapidity ranges −4.46<ycms<−2.96 and 2.03<ycms<3.53, down to zero transverse momentum, by reconstructing the ψ(2S) decay to a muon pair. The ψ(2S) production cross section σψ(2S) is presented as a function of the collision centrality, which is estimated through the energy deposited in forward rapidity calorimeters. The relative strength of nuclear effects on the ψ(2S) and on the corresponding 1S charmonium state J/ψ is then studied by means of the double ratio of cross sections [σψ(2S)/σJ/ψ]pPb/[σψ(2S)/σJ/ψ]pp between p-Pb and pp collisions, and by the values of the nuclear modification factors for the two charmonium states. The results show a large suppression of ψ(2S) production relative to the J/ψ at backward rapidity, corresponding to the flight direction of the Pb-nucleus, while at forward rapidity the suppressions of the two states are comparable. Finally, comparisons to results from lower energy experiments and to available theoretical models are presented.
Measurements of charged jet production as a function of centrality are presented for p-Pb collisions recorded at sNN−−−√=5.02 TeV with the ALICE detector. Centrality classes are determined via the energy deposit in neutron calorimeters at zero degree, close to the beam direction, to minimise dynamical biases of the selection. The corresponding number of participants or binary nucleon-nucleon collisions is determined based on the particle production in the Pb-going rapidity region. Jets have been reconstructed in the central rapidity region from charged particles with the anti-kT algorithm for resolution parameters R=0.2 and R=0.4 in the transverse momentum range 20 to 120 GeV/c. The reconstructed jet momentum and yields have been corrected for detector effects and underlying-event background. In the five centrality bins considered, the charged jet production in p-Pb collisions is consistent with the production expected from binary scaling from pp collisions. The ratio of jet yields reconstructed with the two different resolution parameters is also independent of the centrality selection, demonstrating the absence of major modifications of the radial jet structure in the reported centrality classes.
We report the transverse energy (ET) measured with ALICE at midrapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV as a function of centrality. The transverse energy was measured using identified single particle tracks. The measurement was cross checked using the electromagnetic calorimeters and the transverse momentum distributions of identified particles previously reported by ALICE. The results are compared to theoretical models as well as to results from other experiments. The mean ET per unit pseudorapidity (η), ⟨dET/dη⟩, in 0-5% central collisions is 1737 ± 6(stat.) ± 97(sys.) GeV. We find a similar centrality dependence of the shape of ⟨dET/dη⟩ as a function of the number of participating nucleons to that seen at lower energies. The growth in ⟨dET/dη⟩ at the LHC sNN−−−√ exceeds extrapolations of low energy data. We observe a nearly linear scaling of ⟨dET/dη⟩ with the number of quark participants. With the canonical assumption of a 1 fm/c formation time, we estimate that the energy density in 0-5% central Pb-Pb collisions at sNN−−−√ = 2.76 TeV is 12.3 ± 1.0 GeV/fm3\xspace and that the energy density at the most central 80 fm2 of the collision is at least 21.5 ± 1.7 GeV/fm3. This is roughly 2.3 times that observed in 0-5% central Au-Au collisions at sNN−−−√ = 200 GeV.
Correlated event-by-event fluctuations of flow harmonics in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
We report the measurements of correlations between event-by-event fluctuations of amplitudes of anisotropic flow harmonics in nucleus-nucleus collisions, obtained for the first time using a new analysis method based on multiparticle cumulants in mixed harmonics. This novel method is robust against systematic biases originating from non-flow effects and by construction any dependence on symmetry planes is eliminated. We demonstrate that correlations of flow harmonics exhibit a better sensitivity to medium properties than the individual flow harmonics. The new measurements are performed in Pb-Pb collisions at the centre-of-mass energy per nucleon pair of sNN−−−√=2.76 TeV by the ALICE experiment at the Large Hadron Collider (LHC). The centrality dependence of correlation between event-by-event fluctuations of the elliptic, v2, and quadrangular, v4, flow harmonics, as well as of anti-correlation between v2 and triangular, v3, flow harmonics are presented. The results cover two different regimes of the initial state configurations: geometry-dominated (in mid-central collisions) and fluctuation-dominated (in the most central collisions). Comparisons are made to predictions from MC-Glauber, viscous hydrodynamics, AMPT and HIJING models. Together with the existing measurements of individual flow harmonics the presented results provide further constraints on initial conditions and the transport properties of the system produced in heavy-ion collisions.
Correlated event-by-event fluctuations of flow harmonics in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
We report the measurements of correlations between event-by-event fluctuations of amplitudes of anisotropic flow harmonics in nucleus-nucleus collisions, obtained for the first time using a new analysis method based on multiparticle cumulants in mixed harmonics. This novel method is robust against systematic biases originating from non-flow effects and by construction any dependence on symmetry planes is eliminated. We demonstrate that correlations of flow harmonics exhibit a better sensitivity to medium properties than the individual flow harmonics. The new measurements are performed in Pb-Pb collisions at the centre-of-mass energy per nucleon pair of sNN−−−√=2.76 TeV by the ALICE experiment at the Large Hadron Collider (LHC). The centrality dependence of correlation between event-by-event fluctuations of the elliptic, v2, and quadrangular, v4, flow harmonics, as well as of anti-correlation between v2 and triangular, v3, flow harmonics are presented. The results cover two different regimes of the initial state configurations: geometry-dominated (in mid-central collisions) and fluctuation-dominated (in the most central collisions). Comparisons are made to predictions from MC-Glauber, viscous hydrodynamics, AMPT and HIJING models. Together with the existing measurements of individual flow harmonics the presented results provide further constraints on initial conditions and the transport properties of the system produced in heavy-ion collisions.
Correlated event-by-event fluctuations of flow harmonics in Pb–Pb collisions at √sNN = 2.76 TeV
(2016)
We report the measurements of correlations between event-by-event fluctuations of amplitudes of anisotropic flow harmonics in nucleus-nucleus collisions, obtained for the first time using a new analysis method based on multiparticle cumulants in mixed harmonics. This novel method is robust against systematic biases originating from non-flow effects and by construction any dependence on symmetry planes is eliminated. We demonstrate that correlations of flow harmonics exhibit a better sensitivity to medium properties than the individual flow harmonics. The new measurements are performed in Pb-Pb collisions at the centre-of-mass energy per nucleon pair of sNN−−−√=2.76 TeV by the ALICE experiment at the Large Hadron Collider (LHC). The centrality dependence of correlation between event-by-event fluctuations of the elliptic, v2, and quadrangular, v4, flow harmonics, as well as of anti-correlation between v2 and triangular, v3, flow harmonics are presented. The results cover two different regimes of the initial state configurations: geometry-dominated (in mid-central collisions) and fluctuation-dominated (in the most central collisions). Comparisons are made to predictions from MC-Glauber, viscous hydrodynamics, AMPT and HIJING models. Together with the existing measurements of individual flow harmonics the presented results provide further constraints on initial conditions and the transport properties of the system produced in heavy-ion collisions.
We report the first results of elliptic (v2), triangular (v3) and quadrangular flow (v4) of charged particles in Pb-Pb collisions at sNN−−−√=5.02 TeV with the ALICE detector at the CERN Large Hadron Collider. The measurements are performed in the central pseudorapidity region |η|<0.8 and for the transverse momentum range 0.2<pT<5 GeV/c. The anisotropic flow is measured using two-particle correlations with a pseudorapidity gap greater than one unit and with the multi-particle cumulant method. Compared to results from Pb-Pb collisions at sNN−−−√=2.76 TeV, the anisotropic flow coefficients v2, v3 and v4 are found to increase by (3.0±0.6)%, (4.3±1.4)% and (10.2±3.8)%, respectively, in the centrality range 0-50%. This increase can be attributed mostly to an increase of the average transverse momentum between the two energies. The measurements are found to be compatible with hydrodynamic model calculations. This comparison provides a unique opportunity to test the validity of the hydrodynamic picture and the power to further discriminate between various possibilities for the temperature dependence of shear viscosity to entropy density ratio of the produced matter in heavy-ion collisions at the highest energies.
In the past two decades, an increasing body of studies has been published on the intersex phenomenon in separate-sexed crustaceans from marine and freshwater ecosystems. Various causes are being considered that could have an influence on the occurrence of intersex. Besides genetic factors, environmental conditions such as photoperiodicity, temperature, salinity and parasitism, but also environmental pollution with endocrine disrupting chemicals (EDCs) are discussed. As part of a long-term monitoring (2012 – 2020) in north-west Brittany, we recorded the occurrence of intersex in the marine amphipod Echinogammarus marinus. We quantified the intersex incidence at marine and estuarine sites and analyzed the incidence in relation to the endocrine potential of the sediments. Intersex occurred with mean frequencies between 0.87% and 12%. It was striking that the incidence of intersex increased with increasing distance from the sea. Since the highest incidence was observed at the range boundary of this stenohaline species, we assume that intersex is triggered by endocrine potential and increasing stress due to increasing freshwater content − and thus an interplay of different environmental factors.
We present a Bayesian approach to particle identification (PID) within the ALICE experiment. The aim is to more effectively combine the particle identification capabilities of its various detectors. After a brief explanation of the adopted methodology and formalism, the performance of the Bayesian PID approach for charged pions, kaons and protons in the central barrel of ALICE is studied. PID is performed via measurements of specific energy loss (dE/dx) and time-of-flight. PID efficiencies and misidentification probabilities are extracted and compared with Monte Carlo simulations using high-purity samples of identified particles in the decay channels K0S→π−π+, ϕ→K−K+, and Λ→pπ− in p-Pb collisions at sNN−−−√=5.02 TeV. In order to thoroughly assess the validity of the Bayesian approach, this methodology was used to obtain corrected pT spectra of pions, kaons, protons, and D0 mesons in pp collisions at s√=7 TeV. In all cases, the results using Bayesian PID were found to be consistent with previous measurements performed by ALICE using a standard PID approach. For the measurement of D0→K−π+, it was found that a Bayesian PID approach gave a higher signal-to-background ratio and a similar or larger statistical significance when compared with standard PID selections, despite a reduced identification efficiency. Finally, we present an exploratory study of the measurement of Λ+c→pK−π+ in pp collisions at s√=7 TeV, using the Bayesian approach for the identification of its decay products.
This paper investigates the semantic underpinnings of the distinction between two syntactic types of "manner of movement" verbs in Levin (1993), namely the RUN and ROLL classes. According to Levin's (1993) and Levin & Rappaport's (1995) work on unaccusativity, a semantic factor of "internal causation" should be the trigger for the classification of a movement verb as intransitive (=not-unaccusative), and hence for its belonging to the RUN class. We point out empirical problems for this characterisation, mainly coming from the different readings of the German verb fliegen (fly). From a comparison with other semantically similar verbs, we conclude that the semantic description which underlies the class distinction should be refined: instead of "internal causation", the crucial semantic factor is described here as "inherent specification for a momentum of movement". This result indicates that forces, and relations between forces, have to be part of the semantic description of the manner component in movement verbs.
We present a Bayesian approach to particle identification (PID) within the ALICE experiment. The aim is to more effectively combine the particle identification capabilities of its various detectors. After a brief explanation of the adopted methodology and formalism, the performance of the Bayesian PID approach for charged pions, kaons and protons in the central barrel of ALICE is studied. PID is performed via measurements of specific energy loss (dE/dx) and time-of-flight. PID efficiencies and misidentification probabilities are extracted and compared with Monte Carlo simulations using high-purity samples of identified particles in the decay channels K0S→π−π+, ϕ→K−K+, and Λ→pπ− in p-Pb collisions at sNN−−−√=5.02 TeV. In order to thoroughly assess the validity of the Bayesian approach, this methodology was used to obtain corrected pT spectra of pions, kaons, protons, and D0 mesons in pp collisions at s√=7 TeV. In all cases, the results using Bayesian PID were found to be consistent with previous measurements performed by ALICE using a standard PID approach. For the measurement of D0→K−π+, it was found that a Bayesian PID approach gave a higher signal-to-background ratio and a similar or larger statistical significance when compared with standard PID selections, despite a reduced identification efficiency. Finally, we present an exploratory study of the measurement of Λ+c→pK−π+ in pp collisions at s√=7 TeV, using the Bayesian approach for the identification of its decay products.
The inclusive production of the ψ(2S) charmonium state was studied as a function of centrality in p-Pb collisions at the nucleon-nucleon center of mass energy sNN−−−√ = 5.02 TeV at the CERN LHC. The measurement was performed with the ALICE detector in the center of mass rapidity ranges −4.46<ycms<−2.96 and 2.03<ycms<3.53, down to zero transverse momentum, by reconstructing the ψ(2S) decay to a muon pair. The ψ(2S) production cross section σψ(2S) is presented as a function of the collision centrality, which is estimated through the energy deposited in forward rapidity calorimeters. The relative strength of nuclear effects on the ψ(2S) and on the corresponding 1S charmonium state J/ψ is then studied by means of the double ratio of cross sections [σψ(2S)/σJ/ψ]pPb/[σψ(2S)/σJ/ψ]pp between p-Pb and pp collisions, and by the values of the nuclear modification factors for the two charmonium states. The results show a large suppression of ψ(2S) production relative to the J/ψ at backward (negative) rapidity, corresponding to the flight direction of the Pb-nucleus, while at forward (positive) rapidity the suppressions of the two states are comparable. Finally, comparisons to results from lower energy experiments and to available theoretical models are presented.
We report the transverse energy (ET) measured with ALICE at midrapidity in Pb-Pb collisions at sNN−−−√ = 2.76 TeV as a function of centrality. The transverse energy was measured using identified single particle tracks. The measurement was cross checked using the electromagnetic calorimeters and the transverse momentum distributions of identified particles previously reported by ALICE. The results are compared to theoretical models as well as to results from other experiments. The mean ET per unit pseudorapidity (η), ⟨dET/dη⟩, in 0-5% central collisions is 1737 ± 6(stat.) ± 97(sys.) GeV. We find a similar centrality dependence of the shape of ⟨dET/dη⟩ as a function of the number of participating nucleons to that seen at lower energies. The growth in ⟨dET/dη⟩ at the LHC sNN−−−√ exceeds extrapolations of low energy data. We observe a nearly linear scaling of ⟨dET/dη⟩ with the number of quark participants. With the canonical assumption of a 1 fm/c formation time, we estimate that the energy density in 0-5% central Pb-Pb collisions at sNN−−−√ = 2.76 TeV is 12.3 ± 1.0 GeV/fm3\xspace and that the energy density at the most central 80 fm2 of the collision is at least 21.5 ± 1.7 GeV/fm3. This is roughly 2.3 times that observed in 0-5% central Au-Au collisions at sNN−−−√ = 200 GeV.
Zoos attract millions of visitors every year, many of whom are schoolchildren. For this reason, zoos are important institutions for the environmental education of future generations. Empirical studies on the educational impact of environmental education programs in zoos are still rare. To address this issue, we conducted two studies: In study 1, we investigated students’ interests in different biological topics, including zoos (n = 1,587). Data analysis of individual topics revealed large differences of interest, with advanced students showing less interest in zoos. In study 2, we invited school classes of this age group to visit different guided tours at the zoo and tested connection to nature before and after each educational intervention (n = 608). The results showed that the guided tours are an effective tool to raise students’ connection to nature. Add-on components have the potential to further promote connection to nature. The education programs are most effective with students with a low initial nature connection.
Update Mammakarzinom 2018 (Teil 2) – fortgeschrittenes Mammakarzinom, Lebensqualität und Prävention
(2018)
Die Behandlung des metastasierten Mammakarzinoms hat bei immer neu zu testenden Therapien deutlich an Komplexität zugenommen. Therapien werden nunmehr nur noch für spezielle klinische oder molekulare Subgruppen entwickelt. Hierbei spielen die intrinsischen, molekularen Subtypen zwar immer noch die größte Rolle, jedoch gibt es zunehmend auch Therapien, die subgruppen- oder sogar histologieübergreifend entwickelt werden, wie z. B. der PARP-Inhibitor bei BRCA-mutierten Patientinnen (Mamma- und Ovarialkarzinom). Aber auch Supportivtherapien entwickeln sich weiter, sodass Probleme wie die Alopezie besser behandelt werden können und neue Therapiearten von Übelkeit und Erbrechen etabliert werden. In einem engen Zusammenhang mit den Supportivtherapien stehen die Nebenwirkungen, welche bei Patientinnen mit einem metastasierten Mammakarzinom einen direkten Einfluss auf die Prognose haben. Hier könnten digitale Werkzeuge helfen, um ein besseres Patientinnenmanagement zu etablieren. Diese Übersichtsarbeit soll diese Aspekte vor dem Hintergrund neuer, aktuell publizierter Studien beleuchten und einen Einblick geben, wie sich diese Studien zu etablierten Routinetherapien verhalten. Zusätzlich werden aktuelle Aspekte der Mammakarzinomprävention beleuchtet.
Background: Efficacy of treatment after failure of check point inhibitors (ICI) therapy remains ill-defined in metastatic renal cell carcinoma (mRCC).
Objective: To evaluate the safety and effectiveness of cabozantinib after failure of ICI-based therapies.
Design, setting and participants: Patients with mRCC who concluded cabozantinib treatment directly after an ICI-based therapy were eligible. Data was collected retrospectively from participating sites in Germany.
Interventions: Cabozantinib was administered as a standard of care.
Outcome measurements and statistical analysis
Adverse events (AE) were reported according to CTCAE v5.0. Objective response rate according to RECIST 1.1 and Progression Free Survival (PFS) were collected from medical records. Descriptive statistics and Kaplan-Meyer-plots were utilized.
Results and limitations: About 56 eligible patients (71.4% male) with median age of 66 years and clear cell histology in 66.1% (n = 37) were analyzed. 87.5% (n = 49) had ≥ 2 previous lines. IMDC risk was intermediate or poor in 17 patients (30.4%) and missing in 66.1%. 20 patients (35.7%) started with 60 mg. 55.4% (n = 31) required dose reductions, 26.8% (n = 15) treatment delays and 1.8% (n = 1) treatment discontinuation. Partial response was reported in 10.7% (n = 6), stable and progressive disease were reported in 19.6% (n = 11) and in 12.5% (n = 7). 32 patients were not evaluable (57.1%). Median treatment duration was 6.1 months. Treatment related AE were reported in 76.8% (n = 43) and 19.6% (n = 11) had grade 3-5. Fatigue (26.8%), diarrhea (26.8%) and hand-foot-syndrome (25.0%) were the 3 most frequent AEs of any grade and causality. SAE were reported in 21.4% (n = 12), 2 were fatal. Major limitation was the retrospective data capture in our study.
Conclusions: Cabozantinib followed directly after ICI-based therapy was safe and feasible. No new safety signals were reported. A lower starting dose was frequently utilized in this real-world cohort, which was associated with a favorable tolerability profile. Our data supports the use of cabozantinib after ICI treatment.
The success of the increasing use of technology in education is highly dependent on learner acceptance. Although the Technology Acceptance Model (TAM) is dominant in research for surveying acceptance of technology, it does not allow the prediction of a successful first time use of technology. The successful first time use can be determined with the survey of technology affinity, as it corresponds to the expression of certain personality traits of users and is thus detached from the specific technology. Since there are no measurement instruments for the educational sector so far and existing instruments for measuring technology affinity do not meet the specific requirements for use in the educational context (e.g., limited time for questioning), we present the single item Inclusion of Technology Affinity in Self-Scale (ITAS). In study 1 we provide evidence of convergent and discriminant validity within the general population so that a generalization of its applicability is possible. In study 2 we subsequently tested ITAS in the actual target group, the educational sector. The high correlations of the ITAS with the ATI and the control instrument TA-EG (ranging from rs = 0.679 to rs = 0.440) show that ITAS is suitable for use in research. Furthermore, the newly developed instrument convinces with its low complexity, the graphical component, which requires little text understanding and the high time saving. This research thus can contribute to the investigation of technology affinity in the educational sector helping educators to conduct technical activities with their learning group, to predict possible difficulties and adjust their planning accordingly.
The treatment of metastatic breast cancer has become more complicated due to increasing numbers of new therapies which need to be tested. Therapies are now being developed to treat special clinical or molecular subgroups. Even though intrinsic molecular subtypes play a major role, more and more new therapies for subgroups and histological subtypes are being developed, such as the use of PARP inhibitors to treat patients with BRCA mutations (breast and ovarian cancer). Supportive therapies are also evolving, allowing problems such as alopecia or nausea and vomiting to be treated more effectively. Treatment-related side effects have a direct impact on the prognosis of patients with metastatic breast cancer, and supportive therapy can improve compliance. Digital tools could be useful to establish better patient management systems. This overview provides an insight into recent trials and how the findings could affect routine treatment. Current aspects of breast cancer prevention are also presented.
In dieser Übersichtsarbeit wird dargestellt, wie neue Therapien oder neue Aspekte etablierter Therapien in Zusammenhang mit neuesten, aktuellen Erkenntnissen stehen. Neoadjuvanz, Lokaltherapie, neue Aspekte der Systemtherapie und Prognose- sowie Prädiktivfaktoren werden beleuchtet. In der Neoadjuvanz ist nach wie vor der Zusammenhang zwischen pCR und Prognose von Interesse, ebenso wie neue molekulare Prädiktoren für neue Therapien wie CDK4/6-Inhibitoren zu identifizieren. Bei der operativen Behandlung wird weiter nach einer Reduktion der Aggressivität gestrebt. Insbesondere das duktale Carcinoma in situ muss dafür noch besser verstanden werden. Bei den Systemtherapien wächst die Datenlage zum Verständnis der besten Kombinationen und Therapieabläufe für bestehende Therapieverfahren. Letztendlich muss mithilfe von Prognose- und Prädiktivfaktoren vermieden werden, dass Übertherapien stattfinden und nur die Patientin spezifische Therapien erhält, welche bei dieser individuellen Patientin eine nachgewiesene Wirksamkeit mit wenig Nebenwirkungen haben.
This summary provides an overview of how new therapies or new aspects of established therapies relate to the latest findings. Neoadjuvant therapy, local therapy, new aspects of systemic therapy, and prognostic and predictive factors are presented. In the neoadjuvant setting, the association between pathological complete response (pCR) and prognosis is still of interest as is the identification of new molecular predictors for new therapies such as CDK4/6 inhibitors. As regards surgical treatment, the target is still to reduce the aggressiveness of surgery. To achieve this, a better understanding particularly of ductal carcinoma in situ is required. With regard to systemic therapy, more data on the best combinations and therapy sequences for existing therapies is available. Finally, the use of prognostic and predictive factors may help to avoid overtreatment and ensure that patients only receive therapies which have been shown to be effective for their specific condition and have fewer side effects.
Einleitung: Die konventionelle Galaktografie stellte jahrzehntelang das einzige bildgebende Verfahren zur Darstellung von Milchgängen in der Brust dar. Heute verfügen wir in der Diagnostik über ein multimodales Konzept aus hochauflösendem Ultraschall, der Magnetresonanz-(MR-)Mammografie und der Duktoskopie/Galaktoskopie mit Sensitivitäten und Spezifitäten bis zu 95%. Ziel unserer Untersuchung war es, erstmalig die Tomosynthesetechnik in der Galaktografie einzusetzen und die daraus generierten synthetischen digitalen 2-D-Vollfeld-Mammografien mit der etablierten Methode der duktusorientierten Sonografie zu vergleichen. Es sollen mit beiden Methoden invasive Mammakarzinome und deren Vorstufen wie duktale Carcinoma in situ (DCIS) sowie benigne Befunde erkannt werden. Material und Methoden: Wir führten bei 5 Patientinnen mit pathologischer Mamillensekretion sowohl eine duktusorientierte Sonografie, eine kontrastmittelunterstützte Galaktografie mithilfe der Tomosynthese in 3-D sowie auch den daraus generierten synthetischen digitalen 2-D-Vollfeld-Mammografien durch. Die Auswertung der unterschiedlichen Untersuchungsmodalitäten erfolgte durch 3 in der komplementären Mammadiagnostik erfahrene Untersucher (1, 5 und 15 Jahre) und wurde mit der endgültigen Histologie korreliert. Ergebnisse: Alle 3 Untersucher beurteilten unabhängig voneinander die Bilder des duktusorientierten Ultraschalls und der kontrastmittelunterstützten Galaktografie in Tomosynthesetechnik in 3-D und den daraus generierten, synthetischen digitalen 2-D-Vollfeld-Mammografien. Die Ergebnisse wurden mit den histopathologischen Befunden der Operationspräparate korreliert, wobei sich bei den 5 Patientinnen 1 invasives Mammakarzinom, 2-mal ein duktales Carcinoma in situ (DCIS) und 2 benigne Befunde ergaben. Alle drei Untersucher lagen bei der Verdachtsdiagnose in der Standardbildgebung der duktusorientierten Sonografie seltener richtig als bei der erstmalig durchgeführten, kontrastmittelunterstützten Galaktografie in Tomosynthesetechnik und den daraus generierten, synthetischen digitalen 2-D-Vollfeld-Mammografien. Schlussfolgerung: Erstmalig wurde die Brusttomosynthese in der Galaktografie (Galaktomosynthese) eingesetzt und ermöglichte eine digitale, 3-dimensionale Darstellung von suspekten Befunden. Zusammen mit den daraus synthetisierten, digitalen 2-D-Vollfeld-Mammografien könnte dies in Zukunft eine sinnvolle Ergänzung der komplementären Mammadiagnostik sein – und eine Renaissance dieser Methode. Im Vergleich mit dem duktusorientierten Ultraschall in Hochauflösung erzielten die Untersucher mit der kontrastmittelunterstützten Galaktografie in Tomosynthesetechnik und den daraus generierten, synthetischen digitalen 2-D-Vollfeld-Mammografien bessere Ergebnisse in Korrelation mit den histopathologischen Befunden.
Introduction: For decades, conventional galactography was the only imaging technique capable of showing the mammary ducts. Today, diagnosis is based on a multimodal concept which combines high-resolution ultrasound with magnetic resonance (MR) mammography and ductoscopy/galactoscopy and has a sensitivity and specificity of up to 95%. This study used tomosynthesis in galactography for the first time and compared the synthetic digital 2D full-field mammograms generated with this technique with the images created using the established method of ductal sonography. Both methods should be able to detect invasive breast cancers and their precursors such as ductal carcinoma in situ (DCIS) as well as being able to identify benign findings.
Material and Methods: Five patients with pathological nipple discharge were examined using ductal sonography, contrast-enhanced 3D galactography with tomosynthesis and the synthetic digital 2D full-field mammograms generated with the latter method. Evaluation of the images created with the different imaging modalities was done by three investigators with varying levels of experience with complementary breast diagnostics (1, 5 and 15 years), and their evaluations were compared with the histological findings.
Results: All 3 investigators independently evaluated the images created with ductal sonography, contrast-enhanced 3D galactography with tomosynthesis, and generated synthetic digital 2D full-field mammograms. Their evaluations were compared with the histopathological assessment of the surgical specimens resected from the 5 patients. There was 1 case of invasive breast cancer, 2 cases with ductal carcinoma in situ and 2 cases with benign findings. All 3 investigators made more mistakes when they used the standard imaging technique of ductal sonography to diagnose suspicious lesions than when they used contrast-enhanced galactography with tomosynthesis and the generated synthetic digital 2D full-field mammograms.
Conclusion: This is the first time breast tomosynthesis was used in galactography (galactomosynthesis) to create digital 3-dimensional images of suspicious findings. When used together with the generated synthetic digital 2D full-field mammograms, it could be a useful complementary procedure for the diagnosis of breast anomalies and could herald a renaissance of this method. Compared with high-resolution ductal ultrasound, the investigators achieved better results with contrast-enhanced galactography using tomosynthesis and the generated synthetic digital 2D full-field mammograms, as confirmed by histopathological findings.