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Virtual environments open up far-reaching possibilities with respect to knowledge impartation. Nevertheless, they have the potential to negatively influence learning behavior. As a possible positive determinant, especially in the digital context, the moment "game" can be listed. Accordingly, previous studies prove an overall positive influence of serious games on learning success and motivation. However, the current state of research only allows for careful and few conclusions in terms of a nuanced differentiation of this influence. Thus, this study differentiates on a deeper level with regard to different parameters of learning success and motivation. The aim of the study is to quantify and evaluate a possible influence of the factor "game" with regard to these parameters. Two versions of the modular software environment Arctic Economy, a game and a nongame version, served as the basis for evaluation. Both versions were compared in a field experiment, with randomized group formation (N = 97) and repeated measures. The data analysis showed the game group having a tendency to demonstrate better learning performance. In the differentiated analysis, a significant effect can be proven: subjects in the game group were able to remember facts more easily than subjects in the nongame group (group difference retention rate [x-bar] = 17%). In addition, participants showed an average of 46% higher motivation and were significantly more capable of linking the application's content with reality. The identified "game effect" can therefore be classified as highly significant in the context of this study.

Abstract Cave carbonates, seemingly growing in defiance of gravity, have attracted the community's interest for more than a century. This paper focusses on ‘helictites’, contorted vermiform speleothems with central capillaries. Petrographic, crystallographic and geochemical data of calcitic and aragonitic helictites (recent to 347 ka) from three caves in Western Germany are placed in context with previous work. Aragonitic helictites from one site, the Windloch Cave, form exceptionally large and complex structures that share similarities with the celebrated helictite arrays in the Asperge Cave in France. Aragonitic and calcitic helictites differ significantly in their crystal fabrics and internal geometry. Calcitic helictites are best described as a composite crystal fabric consisting of fibrous mesocrystals. Aragonite helictites display a complex fabric of acicular to platy crystals, some of which show evidence for growth‐twinning and perhaps crystallisation via a monoclinal precursor stage. The micro‐tomographic characterisation of several orders of channels and their complex architecture raises important questions regarding fluid migration and helictite architecture. In terms of their isotope geochemistry, helictites are depleted in 13C to various degrees, isotope values that are controlled by the mixing of fluids and mineralogy‐related fractionation. Regarding their δ18O values, most helictites overlap with other calcitic and aragonitic speleothems. Previous models explaining the twisted morphology of helictites are discussed from the viewpoint of fluid migration and CO2 degassing rates, mineralogy and helictite petrography. For the complex aragonitic helicities documented here, the most likely mechanisms to explain the contorted growth forms include the internal capillary network combined with localised (sector) growth at the helictite tip. The morphologically simpler calcitic helictites are best explained by capillary and surface flow. Future work should include geomicrobiology to assess the significance of induced mineralisation and transmission electron microscopy analysis to more quantitatively assign crystallographic properties.

Previous research suggests that the conductor's choice of preparatory gesture affects choral singers’ breathing behavior as well as the corresponding loudness and sound quality. As these gestures are in choral practice often combined with instructions on the desired breathing technique, the aim of this study was to explore whether congruent and incongruent combinations of preparatory gestures with breathing instructions affect the breathing behavior and resulting loudness in choral singers. In our within-subjects study design, 18 healthy choral singers were asked to sing a tone in response to 4 different video stimuli, consisting of two congruent and two incongruent gesture-instruction combinations. We recorded chest wall kinematics via three-dimensional motion capture and voice samples. The results show that the used preparatory gesture has an influence on the predetermined inhalation type. Particularly, the most common inward-upward gesture combined with an abdominal inhalation results in a significantly reduced chest wall expansion and loudness of the resulting tone. Furthermore, the moment of maximum inhalation and onset are delayed after inward-upward gestures. Consequently, in choral practice, it is essential to generally consider that the selected preparatory gesture has significant influence on the resulting sound and should therefore be chosen according to the desired type of inhalation.

IntroductionChildren and youth at risk for mental health disorders, such as eating disorders (ED), were particularly affected by the COVID-19 pandemic, yet evidence for the most seriously affected and thus hospitalized youth in Germany is scarce.MethodsThis crosssectional study investigated anonymized routine hospital data (demographic information, diagnoses, treatment modalities) of patients admitted (n = 2,849) to the Department of Child and Adolescence Psychiatry, Psychosomatics and Psychotherapy (DCAPPP) of a German University Hospital between 01/2016 and 02/2022. Absolute and relative number of inpatients with or without ED prior to (01/2016–02/2020) and during the COVID-19 pandemic (03/2020–02/2022) were compared. The effect of school closures as part of social lockdown measures for COVID-19 mitigation on inpatient admission rate was explored as it has been discussed as a potential risk factor for mental health problems in youth.ResultsDuring the COVID-19 pandemic, ED inpatient admission rate increased from 10.5 to 16.7%, primarily driven by Anorexia Nervosa (AN). In contrast to previous reports, we found no change in somatic and mental disorder comorbidity, age or sexratio for hospitalized youth with ED. However, we did observe a shortened length of hospital stay (LOS) for hospitalized youth with and without ED. In addition, non-ED admissions presented with an increased number of mental disorder comorbidities. In contrast to our hypothesis, school closures were not related to the observed increase in ED.DiscussionIn summary, the COVID-19 pandemic was associated with an increased rate of inpatient treatment for youth suffering from AN, and of youth affected by multiple mental disorders. Accordingly, we assume that inpatient admission was prioritized for individuals with a higher burden of disease during the COVID-19 pandemic. Our findings pinpoint the need for adequate inpatient mental health treatment capacities during environmental crises, and a further strengthening of child and adolescence psychiatry services in Germany.

Numerous publications showing that robust prediction models for microorganisms based on Raman micro-spectroscopy in combination with chemometric methods are feasible, often with very precise predictions. Advances in machine learning and easier accessibility to software make it increasingly easy for users to generate predictive models from complex data. However, the question regarding why those predictions are so accurate receives much less attention. In our work, we use Raman spectroscopic data of fungal spores and carotenoid-containing microorganisms to show that it is often not the position of the peaks or the subtle differences in the band ratios of the spectra, due to small differences in the chemical composition of the organisms, that allow accurate classification. Rather, it can be characteristic effects on the baselines of Raman spectra in biochemically similar microorganisms that can be enhanced by certain data pretreatment methods or even neutral-looking spectral regions can be of great importance for a convolutional neural network. Using a method called Gradient-weighted Class Activation Mapping, we attempt to peer into the black box of convolutional neural networks in microbiological applications and show which Raman spectral regions are responsible for accurate classification.

Purpose: The present study examined the joint impact of coping and rumination after trauma on posttraumatic growth (PTG) and posttraumatic depreciation (PTD) based on the PTG model. Methods: A cross-sectional study was conducted between October 2017 and May 2018. A sample of 253 individuals who had experienced a traumatic event in the last two years, was included. Participants completed an online self-reported survey, including demographic variables, trauma characteristics, the German Posttraumatic Growth and Depreciation Inventory – Expanded, the Brief COPE Inventory, and the Event Related Rumination Inventory. An analysis of correlation, a principal component analysis and hierarchical regression analyses were conducted. Statistical analyses were undertaken on SPSS (version 25.0; IBM, New York, USA). Results: After controlling for the effects of personal and trauma characteristics, self-sufficient coping and socially supported coping were found to favor the emergence of PTG. Event-related and recent deliberate rumination were positively related to PTG. Avoidant-focused coping and recent intrusive rumination were positively associated with PTD. Overall, the final models accounted for 46% and 58% of the variance in PTG and PTD. Conclusion: Our findings confirm the PTG model and support the central role of deliberate rumination, self-sufficient coping and socially supported coping in the development of PTG. Our results indicate that a similar model of PTD with comparable influencing factors can be assumed: if the individual is stuck in ongoing intrusive rumination and uses more avoidance-focused coping, it might lead to more reports of PTD.

BackgroundBRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs).MethodsWe characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database.ResultsAmong BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)).ConclusionsOn the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

Background and Objectives: Outcome data from wearable devices are increasingly used in both research and clinics. Traditionally, a dedicated device is chosen for a given study or clinical application to collect outcome data as soon as the patient is included in a study or undergoes a procedure. The current study introduces a new measurement strategy, whereby patients’ own devices are utilized, allowing for both a pre-injury baseline measure and ability to show achievable results. Materials and Methods: Patients with a pre-existing musculoskeletal injury of the upper and lower extremity were included in this exploratory, proof-of-concept study. They were followed up for a minimum of 6 weeks after injury, and their wearable outcome data (from a smartphone and/or a body-worn sensor) were continuously acquired during this period. A descriptive analysis of the screening characteristics and the observed and achievable outcome patterns was performed. Results: A total of 432 patients was continuously screened for the study, and their screening was analyzed. The highest success rate for successful inclusion was in younger patients. Forty-eight patients were included in the analysis. The most prevalent outcome was step count. Three distinctive activity data patterns were observed: patients recovering, patients with slow or no recovery, and patients needing additional measures to determine treatment outcomes. Conclusions: Measuring outcomes in trauma patients with the Bring Your Own Device (BYOD) strategy is feasible. With this approach, patients were able to provide continuous activity data without any dedicated equipment given to them. The measurement technique is especially suited to particular patient groups. Our study’s screening log and inclusion characteristics can help inform future studies wishing to employ the BYOD design.

IntroductionIndividuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers.MethodsWe genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals.ResultsWe discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk.ConclusionsThis study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.

Pressure sensors are frequently used for dynamic pressure measurements but are mostly calibrated by static methods. This is done due to the insufficient availability of dynamic calibration methods. One approach to overcome this lack is shown in this paper. The developed calibration device is a pistonphone based exciter to calibrate the frequency response of common pressure sensors. The first section disuses the principle of operation of the exciter. The following chapters show the evaluation of the uncertainty of measurement. First all effects are named while few effects are highlighted in detail. The paper closes with the final outcome of the uncertainty of measurement.

ImportanceLimited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists.ObjectiveTo identify mutation-specific cancer risks for carriers of BRCA1/2.Design, setting, and participantsObservational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19,581 carriers of BRCA1 mutations and 11,900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents. We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position. We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk.ExposuresMutations of BRCA1 or BRCA2.Main outcomes and measuresBreast and ovarian cancer risks.ResultsAmong BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95% CI, 1.22-1.74; P = 2 × 10(-6)), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95% CI, 1.22-1.55; P = 6 × 10(-9)). We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95% CI, 0.56-0.70; P = 9 × 10(-17)). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95% CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69-3.16; P = .00002). We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95% CI, 0.44-0.60; P = 6 × 10(-17)). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers.Conclusions and relevanceBreast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.

BackgroundBRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants in many candidate modifier genes.MethodsGenotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysis was performed within a retrospective cohort approach.ResultsThe observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments.ConclusionThere is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers.ImpactGenome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

IntroductionMore than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers.MethodsWe used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement.ResultsThe estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive associations in the general population (intraclass correlation (ICC) = 0.61, 95% confidence interval (CI): 0.45 to 0.74), and the same was true when considering ER-negative associations in both groups (ICC = 0.59, 95% CI: 0.42 to 0.72). Similarly, there was strong correlation between the ER-positive associations for BRCA1 and BRCA2 carriers (ICC = 0.67, 95% CI: 0.52 to 0.78), whereas ER-positive associations in any one of the groups were generally inconsistent with ER-negative associations in any of the others. After stratifying by ER status in mutation carriers, additional significant associations were observed. Several previously unreported variants exhibited associations at P

IntroductionThe distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling.MethodsSelection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach.ResultsER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)).ConclusionsThese results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.

The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the likelihood of mutation status by histopathological markers were derived using a Mantel-Haenszel approach. ER-positive phenotype negatively predicted BRCA1 mutation status, irrespective of grade (LRs from 0.08 to 0.90). ER-negative grade 3 histopathology was more predictive of positive BRCA1 mutation status in women 50 years or older (LR = 4.13 (3.70 to 4.62)) versus younger than 50 years (LR = 3.16 (2.96 to 3.37)). For BRCA2, ER-positive grade 3 phenotype modestly predicted positive mutation status irrespective of age (LR = 1.7-fold), whereas ER-negative grade 3 features modestly predicted positive mutation status at 50 years or older (LR = 1.54 (1.27 to 1.88)). Triple-negative tumor status was highly predictive of BRCA1 mutation status for women younger than 50 years (LR = 3.73 (3.43 to 4.05)) and 50 years or older (LR = 4.41 (3.86 to 5.04)), and modestly predictive of positive BRCA2 mutation status in women 50 years or older (LR = 1.79 (1.42 to 2.24)). These results refine likelihood-ratio estimates for predicting BRCA1 and BRCA2 mutation status by using commonly measured histopathological features. Age at diagnosis is an important variable for most analyses, and grade is more informative than ER status for BRCA2 mutation carrier prediction. The estimates will improve BRCA1 and BRCA2 variant classification and inform patient mutation testing and clinical management.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p

Moist/hydrated biofilms have been well-studied in the medical area, and their association with infections is widely recognized. In contrast, dry-surface biofilms (DSBs) on environmental surfaces in healthcare settings have received less attention. DSBs have been shown to be widespread on commonly used items in hospitals and to harbor bacterial pathogens that are known to cause healthcare-acquired infections (HAI). DSBs cannot be detected by routine surface swabbing or contact plates, and studies have shown DSBs to be less susceptible to cleaning/disinfection products. As DSBs are increasingly reported in the medical field, and there is a likelihood they also occur in food production and manufacturing areas, there is a growing demand for the rapid in situ detection of DSBs and the identification of pathogens within DSBs. Raman microspectroscopy allows users to obtain spatially resolved information about the chemical composition of biofilms, and to identify microbial species. In this study, we investigated Staphylococcus aureus mono-species DSB on polyvinylchloride blanks and stainless steel coupons, and dual-species (S. aureus/Bacillus licheniformis) DSB on steel coupons. We demonstrated that Raman microspectroscopy is not only suitable for identifying specific species, but it also enables the differentiation of vegetative cells from their sporulated form. Our findings provide the first step towards the rapid identification and characterization of the distribution and composition of DSBs on different surface areas.

Die praxeologisch-rekonstruktiv ausgerichtete Erforschung des Bildungskontextes inklusiver Hochschule steht, anders als dies für den Bereich der rekonstruktiven Schul- und Unterrichts­forschung gesagt werden kann, noch am Anfang. Das in diesem Artikel vorgestellte Verbundprojekt erweitert den Blick auf Inklusionsbedingungen auf der Ebene der Lehre von Bildungsfachkräften. Damit löst es sich von einer sonst dominierenden Adressat*innenlogik, welche die Inklusionsfrage fast ausschließlich für die Lernenden stellt. Die im Projekt durchgeführten Videografien und Gruppendiskussionen wurden auf Grundlage der Dokumen­tarischen Methode analysiert. Der vorliegende Artikel geht auf das Forschungsdesign und erste Forschungsergebnisse ein. Hierbei spielt das rekonstruierte Anerkennungserleben der Bildungsfachkräfte eine zentrale Rolle. Abstract Compared with the fast growing amount of reconstructive studies on inclusion in school research, reconstructive studies on inclusive teaching at universities are rare. First results of a reconstructive research project about inclusive teaching in higher and adult education widens the perspective on conditions of inclusion: It focusses on the teaching-praxis of so called ‘Bildungsfachkräfte’, people with learning disabilities who accomplished a training program lasting three years to qualify for teaching in various academic settings. Our analysis considers the layer of inclusive teaching instead of conditions of inclusive learning. The videographies and group discussions conducted in the project are analysed on the basis of the documentary method. The experiences of recognition will be analysed empirically as a pattern of orientation among the so called ‘Bildungsfachkräfte’ which guides their teaching approach towards inclusion.

An easy, inexpensive, and rapid method to identify microorganisms is in great demand in various areas such as medical diagnostics or in the food industry. In our study, we show the development of several predictive models based on Raman spectroscopy combined with support vector machines (SVM) for 21 species of microorganisms. The microorganisms, grown under standardized conditions, were placed on a silver mirror slide to record the data for model development. Additional data was obtained from microorganisms on a polished stainless-steel slide in order to validate the models in general and to assess possible negative influences of the material change on the predictions. The theoretical prediction accuracies for the most accurate models, based on a five-fold cross-validation, are 98.4%. For practical validation, new spectra (from stainless-steel surfaces) have been used, which were not included in the calibration data set. The overall prediction accuracy in practice was about 80% and the inaccurate predictions were only due to a few species. The development of a database provides the basis for further investigations such as the application and extension to single-cell analytics and for the characterization of biofilms.

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 × 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 × 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 × 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2×10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.

AbstractIntroductionSeveral common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). MethodsTo evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12599 BRCA1 and 7132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. ResultsOnly SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele Hazard Ratio (HR)= 0.87, 95%CI:0.81-0.94, P-trend=3x10^-4). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR=0.82, 95%CI:0.74-0.90, P-trend=3.1x10^-5, P-difference=0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend=0.015; rs1011970, P-trend=0.048; rs865686, 2df-P=0.007; rs1292011 2df-P=0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR=0.81, 95%CI: 0.74-0.90, P-trend=4x10^-5) and there was marginal evidence of association with ER-negative breast cancer for BRCA2 mutation carriers (HR=0.78, 95%CI:0.62-1.00, P-trend=0.049). ConclusionsThe present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.

BackgroundA recent genome-wide association study identified single-nucleotide polymorphism (SNP) 2q35-rs13387042 as a marker of susceptibility to estrogen receptor (ER)-positive breast cancer. We attempted to confirm this association using the Breast Cancer Association Consortium.Methods2q35-rs13387042 SNP was genotyped for 31 510 women with invasive breast cancer, 1101 women with ductal carcinoma in situ, and 35 969 female control subjects from 25 studies. Odds ratios (ORs) were estimated by logistic regression, adjusted for study. Heterogeneity in odds ratios by each of age, ethnicity, and study was assessed by fitting interaction terms. Heterogeneity by each of invasiveness, family history, bilaterality, and hormone receptor status was assessed by subclassifying case patients and applying polytomous logistic regression. All statistical tests were two-sided.ResultsWe found strong evidence of association between rs13387042 and breast cancer in white women of European origin (per-allele OR = 1.12, 95% confidence interval [CI] = 1.09 to 1.15; P(trend) = 1.0 x 10(-19)). The odds ratio was lower than that previously reported (P = .02) and did not vary by age or ethnicity (all P > or = .2). However, it was higher when the analysis was restricted to case patients who were selected for a strong family history (P = .02). An association was observed for both ER-positive (OR = 1.14, 95% CI = 1.10 to 1.17; P = 10(-15)) and ER-negative disease (OR = 1.10, 95% CI = 1.04 to 1.15; P = .0003) and both progesterone receptor (PR)-positive (OR = 1.15, 95% CI = 1.11 to 1.19; P = 5 x 10(-14)) and PR-negative disease (OR = 1.10, 95% CI = 1.06 to 1.15; P = .00002).ConclusionThe rs13387042 is associated with both ER-positive and ER-negative breast cancer in European women.

The breathing technique is a determining factor for the sound quality of the singers' vocal production and thus crucial for the choral sound. The aim of this study was to examine choral singers' awareness of breathing techniques and habits while singing and to identify potential correlations between the breathing technique and the preparatory gestures of the conductor. In our prospective, quasi-experimental study, 720 choral singers answered a 25-item anonymous online survey which focused on demographic information, musical and choral experience, information on choir (size, type, repertoire) and conductor (age, gender, level of expertise). As the central issue we examined the subjects' general knowledge of breathing techniques and habits and their own use thereof in choral practice. Finally, subjects were asked to watch videos showing two different preparatory conducting gestures and to assess the meaning of these gestures. The results of the study show that the majority of choral singers (68.1%) inhale not before and not after, but during the conductor's preparatory gesture. The most well-known (94.7%) and allegedly most frequently (81.8%) used type of inhalation is abdominal breathing. Six times more singers associate abdominal breathing with an outward gesture rather than with the more frequently occurring inward-upward gesture. The conducting literature does not discriminate between out- and inward preparatory gestures and describe them as equivalent. However, according to our data, a vast majority of singers assign these gestures to different types of inhalation which influences singing technique and sound quality. This might lead to ambiguous action-reaction expectations from singers and conductors in rehearsals and concerts. [ABSTRACT FROM AUTHOR]

Polyharmonic spline (PHS) radial basis functions (RBFs) have been used in conjunction with polynomials to create RBF finite-difference (RBF-FD) methods. In 2D, these methods are usually implemented with Cartesian nodes, hexagonal nodes, or most commonly, quasi-uniformly distributed nodes generated through fast algorithms. We explore novel strategies for computing the placement of sampling points for RBF-FD methods in both 1D and 2D while investigating the benefits of using these points. The optimality of sampling points is determined by a novel piecewise-defined Lebesgue constant. Points are then sampled by modifying a simple, robust, column-pivoting QR algorithm previously implemented to find sets of near-optimal sampling points for polynomial approximation. Using the newly computed sampling points for these methods preserves accuracy while reducing computational costs by mitigating stencil size restrictions for RBF-FD methods. The novel algorithm can also be used to select boundary points to be used in conjunction with fast algorithms that provide quasi-uniformly distributed nodes.

Introduction: Lower urinary tract symptoms (LUTS) and gastrointestinal (GI) problems are common in Duchenne muscular dystrophy (DMD), but not systematically assessed in regular care. We aimed to determine the prevalence of bladder and bowel dysfunction (BBD) in DMD patients compared with healthy controls (HC). Methods: The Childhood Bladder and Bowel Dysfunction Questionnaire (CBBDQ) based on the International Rome III criteria and the International Children’s Continence Society was filled out by 57 DMD patients and 56 HC. Additionally, possible associations of BBD with, for example, medication use or quality of life were evaluated in an additional questionnaire developed by experts. Results: In 74% of patients versus 56% of HC ≥ 1 LUTS (n.s.) were reported, 68% of patients versus 39% of HC reported ≥1 bowel symptom (p = 0.002) and 53% of patients versus 30% of HC reported combined LUTS and bowel symptoms (p = 0.019). A negative impact of BBD on daily life functioning was reported by 42% of patients. Conclusions: These data underscore that standard screening for BBD is needed and that the CBBDQ could be of added value to optimize DMD care.

One of the most prominent applications of terahertz time-domain spectroscopy is the spectral investigation of materials covered by visibly opaque objects. Therefore, terahertz waves are well suited to inspect the content of mail. We report on our work on mail inspection in this spectral range including machine design, optical layouts, data analysis, and implementations.

Die C/O-Isotopenzusammensetzung von Speläothemen der Makkaronihalle der Hüttenbläserschachthöhle in Iserlohn belegt eine klare Trennung zwischen kalt- und warmzeitlichen Calciten. Rhomboederkristalle und sphärolithische Speläopartikel weisen mit δ18O-Werten zwischen –8.9 und –17.9 ‰ (VPDB) sowie mit δ13C-Werten zwischen +0.7 und –6.1 ‰ eine von normalen Speläothemen (Stalagmiten, Excentriques, Mikrobecken - Kristalle, Sinterfahnen; δ18O: –4.0 bis –6.1 ‰; δ13C: –4.9 bis –10.9 ‰) deutlich abweichende C/O-Signatur auf. Die kaltzeitlichen Calcite zeigen in der C/O-Isotopenzusammensetzung einen Trend zu leichteren O- bei schwereren C-Werten. Dabei entsprechen die Partikel mit schwereren O- bei leichteren C-Werten einer kaltzeitlichen Genese in Wasserbecken auf Eis, während die Partikel mit leichteren O- bei schwereren C-Werten eine für Ausfrieren karbonathaltiger Wässer typische Zusammensetzung widerspiegeln. Mit 230Th/U-Datierungen werden mehrere Ausfrierzeiten von Eisseen zwischen 28.6 und 33.0 ka für die jüngere Weichselkaltzeit im nordwestdeutschen Raum belegt. Die Ausfrierzeiten in der Makkaronihalle belegen eine Mindestdicke von 34 m für den Permafrostboden dieser Zeiten im nördlichen Sauerland.

This contribution deals with the topic of the consistent further development of a wheel hub motor for battery electric vehicles (BEV) based on the principle of an outer rotor switched reluctance machine (SRM). The research work presented in this paper was founded by the ERDF.NRW program, Investment for Growth and Employment and the European Regional Development Fund. The R&D project was named Switched-Reluctance fo(u)r wheel (SR4Wheel). Based on the experience made by first prototype Evolution 0 (EVO 0), developed in the Laboratory for Automation Engineering, Power Electronics and Electrical Drives of the Cologne University of Applied Sciences (CUAS), the test results of EVO 1, as well as the redesign, EVO 2 is presented in this paper. The prototype EVO 0, a first proof of concept leads to several optimizations and lessons learned for the predecessor model EVO 1. The overall target of developing such a gearless outer rotor wheel hub motor is the full integration of the complete machine including its power electronics into the given space between the original friction brake and the rim. Furthermore, due to the additional integration of the power electronics, great opportunities in terms of new vehicle design as well as retrofitting capabilities of already existing vehicle platforms can be achieved. Thereby, further drive train assembly space like the engine compartment is no longer necessary. The SRM does not require magnets for torque production which leads to independence from the changeable commodity prices on the rare earth element markets. This paper presents the developing process, testing, and verification of the innovative drive train concept starting with the final CAD of EVO 1. During the testing and verification process a machine characteristic mapping is performed on a drive train test bench and subsequently the results of a finite element analysis (FEA) are plausibility checked by the test bench results. The process continues with energy conversion test scenarios of the project demonstrator vehicle on a roller test bench focused on noise vibration harshness (NVH) behavior and efficiency. As a conclusion, the gained knowledge by evaluating two EVO 1 prototypes on the rear axle of the test vehicle, and the design for the front axle drive train EVO 2 will be presented. As a major task on the front axle, the limited space due to the large disc brake can be identified and solved.