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BACKGROUND: In the Netherlands, the turnover of midwives of relatively young age is high. This is concerning since a lack of midwifery experience can negatively affect the quality of maternity care.AIM: To study the rate and the reasons for intending to leave, and to explore the reasons for leaving midwifery jobs in the Netherlands.METHODS: We used a mixed-methods design including a quantitative survey (N = 726) followed by qualitative interviews (N = 17) with community midwives.FINDINGS: Almost one third of the respondents considered leaving the profession. The decision to actually leave the job was the result of a process in which midwives first tried to adapt to their working conditions, followed by feelings of frustration and finally feelings of decreased engagement with the work. The reasons for leaving midwifery practice are an accumulation of job demands, lack of social resources and family responsibilities.DISCUSSION: Compared to international figures, we found a lower rate of midwives who considered leaving the profession. This could be explained by the differences in the organisation of midwifery care and the relatively high job autonomy of midwives in the Netherlands. Nevertheless, changes must be made in terms of decreasing the demands of the job and creating more job resources.CONCLUSION: Innovations in the organisational structure that focus on continuity of care for pregnant individuals, job satisfaction for midwives and building a sustainable workforce may result in an increase in the retention of midwives. These innovations would ensure that women and their babies receive the best care possible.

International audience; Counseling for familial breast cancer focuses on communicating the gene test result (GENE) to counselees, but risk prediction models have become more complex by including non-genetic risk factors (NGRF) and polygenic risk scores (PRS). We examined genetic clinicians' confidence in counseling and counselees' psychosocial outcomes, using the BOADICEA risk prediction tool with different categories of risk factors as input. A prospective observational study in Dutch, French and German genetic clinics was performed including 22 clinicians, and 406 of 460 (88.3%) eligible cancer-unaffected women at high breast cancer risk assessed at pre-test and 350 (76.1%) at post-test. We performed multilevel analyses accounting for the clinician, and counselees' characteristics. Overall, risk estimates category by GENE versus GENE+ NGRF, or GENE+NGRF+PRS differed in 11% and 25% of counselees, respectively. In multilevel analyses, clinicians felt less confident in counseling when the full model provided lower breast cancer risks than GENE (i.e., in 8% of cases). Older counselees expressed higher breast cancer risk perception and worries about the hereditary predisposition when the full model provided higher breast cancer risks than GENE only. Genetic clinicians appear confident with breast cancer risk comprehensive models, which seem only to affect perceptions of older counselees.

Hereditary papillary renal cell carcinoma (HPRC) is a rare inherited renal cancer syndrome characterized by bilateral and multifocal papillary type 1 renal tumors (PRCC1). Activating germline pathogenic variants of the MET gene were identified in HPRC families. We reviewed the medical and molecular records of a large French series of 158 patients screened for MET oncogenic variants. MET pathogenic and likely pathogenic variants rate was 12.4% with 40.6% among patients with familial PRCC1 and 5% among patients with sporadic PRCC1. The phenotype in cases with MET pathogenic and likely pathogenic variants was characteristic: PRCC1 tumors were mainly bilateral (84.3%) and multifocal (87.5%). Histologically, six out of seven patients with MET pathogenic variant harbored biphasic squamoid alveolar PRCC. Genetic screening identified one novel pathogenic variant MET c.3389TC, p.(Leu1130Ser) and three novel likely pathogenic variants: MET c.3257AT, p.(His1086Leu); MET c.3305TC, p.(Ile1102Thr) and MET c.3373TG, p.(Cys1125Gly). Functional assay confirmed their oncogenic effect as they induced an abnormal focus formation. The genotype-phenotype correlation between MET pathogenic variants and PRCC1 presentation should encourage to widen the screening, especially toward nonfamilial PRCC1. This precise phenotype also constitutes a strong argument for the classification of novel missense variants within the tyrosine kinase domain when functional assays are not accessible.

Predicció de risc de càncer de mama; Dones europees; Variant patògena heterozigota Predicción del riesgo de cáncer de mama; Mujeres europeas; Variante patógena heterocigota Breast cancer risk prediction; European women; Heterozygous pathogenic variant Purpose To evaluate the association between a previously published 313 variant–based breast cancer (BC) polygenic risk score (PRS313) and contralateral breast cancer (CBC) risk, in BRCA1 and BRCA2 pathogenic variant heterozygotes. Methods We included women of European ancestry with a prevalent first primary invasive BC (BRCA1 = 6,591 with 1,402 prevalent CBC cases; BRCA2 = 4,208 with 647 prevalent CBC cases) from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), a large international retrospective series. Cox regression analysis was performed to assess the association between overall and ER-specific PRS313 and CBC risk. Results For BRCA1 heterozygotes the estrogen receptor (ER)-negative PRS313 showed the largest association with CBC risk, hazard ratio (HR) per SD = 1.12, 95% confidence interval (CI) (1.06–1.18), C-index = 0.53; for BRCA2 heterozygotes, this was the ER-positive PRS313, HR = 1.15, 95% CI (1.07–1.25), C-index = 0.57. Adjusting for family history, age at diagnosis, treatment, or pathological characteristics for the first BC did not change association effect sizes. For women developing first BC

Objectives Comprehensive breast cancer (BC) risk models integrating effects of genetic (GRF) and non-genetic risk factors (NGRF) may refine BC prevention recommendations. We explored the perceived information received on BC risk factors, and related characteristics, in female relatives of women with a BRCA1/2 or PALB2 pathogenic variant, undergoing BC risk assessment using the CanRisk© prediction tool. Methods Of 200 consecutive cancer-free women approached after the initial genetic consultation, 161 (80.5%) filled in questionnaires on their perception of information received and wished further information on BC risk factors (e.g., being a carrier of a moderate risk altered gene, personal genetic profile, lifestyles). Multilevel multivariate linear models were performed accounting for the clinician who met the counselee and exploring the effect of counselees’ socio-demographic, familial and psychological characteristics on the perceived extent of information received. Results Perceived no/little information received and wish for further information were more frequent for NGRF (>50%) than for GRF, especially high-risk genes (, Highlights • Comprehensive breast cancer (BC) risk assessment may integrate genetic and non-genetic risk factors, providing more accurate BC risk estimates and nuanced clinical recommendations. • Standard BC genetic counseling focuses on major genetic risks. • Female relatives of women with a BRCA1/2 or PALB2 pathogenic variant perceived a lack of information about non-genetic risk factors. • As these factors may affect health prevention, enhancing the provision of information about them appears necessary. • Further research should focus on modalities of information delivery about overall BC risk factors such as by which health care professionals provide this information and at which time-point in the BC risk counseling journey.

Background Overweight and obesity are one of the most significant risk factors of the twenty-first century related to an increased risk in the occurrence of non-communicable diseases and associated increased healthcare costs. To estimate the future impact of overweight, the current study aimed to project the prevalence of overweight and obesity to the year 2030 in Belgium using a Bayesian age-period-cohort (APC) model, supporting policy planning. Methods Height and weight of 58,369 adults aged 18+ years, collected in six consecutive cross-sectional health interview surveys between 1997 and 2018, were evaluated. Criteria used for overweight and obesity were defined as body mass index (BMI) ≥ 25, and BMI ≥ 30. Past trends and projections were estimated with a Bayesian hierarchical APC model. Results The prevalence of overweight and obesity has increased between 1997 and 2018 in both men and women, whereby the highest prevalence was observed in the middle-aged group. It is likely that a further increase in the prevalence of obesity will be seen by 2030 with a probability of 84.1% for an increase in cases among men and 56.0% for an increase in cases among women. For overweight, it is likely to see an increase in cases in women (57.4%), while a steady state in cases among men is likely. A prevalence of 52.3% [21.2%; 83.2%] for overweight, and 27.6% [9.9%; 57.4%] for obesity will likely be achieved in 2030 among men. Among women, a prevalence of 49,1% [7,3%; 90,9%] for overweight, and 17,2% [2,5%; 61,8%] for obesity is most likely. Conclusions Our projections show that the WHO target to halt obesity by 2025 will most likely not be achieved. There is an urgent necessity for policy makers to implement effective prevent policies and other strategies in people who are at risk for developing overweight and/or obesity.

PURPOSE: Knowledge regarding risk factors for pain in the long term after surgery for breast cancer may be of great value in preventing this prevalent and debilitating side effect. Despite the biopsychosocial nature of pain, the predictive value of both pre- and postoperative biopsychosocial functioning for long-term pain intensity and pain-related disability has not yet been studied. METHODS: One hundred sixty-six women planned for unilateral breast cancer surgery were included in this prospective cohort study. Pre- and postoperative outcomes related to pain, psychosocial, and somatosensory functioning (questionnaires and quantitative sensory testing) were evaluated as risk factors for pain intensity (visual analog scale) and pain-related disability (pain disability index) 1 year after surgery for breast cancer. Both bivariable and stepwise linear regression analyses were performed. RESULTS: The most consistent biopsychosocial risk factors were symptoms related to altered central somatosensory functioning (central sensitization inventory), psychological symptoms, and social support (psychological symptoms and support subscale of McGill Quality of Life Questionnaire). Results also showed that a pre- and postoperative disturbed functioning of the somatosensory nervous system in the surgical area could provide additional information regarding pain intensity or pain-related disability in the long term after surgery for breast cancer. CONCLUSION: This study revealed several biopsychosocial characteristics that might be used to identify women more vulnerable to have pain and pain-related disability in the long term after surgery for breast cancer, allowing for more effective pain management and prevention. ispartof: SUPPORTIVE CARE IN CANCER vol:30 issue:5 pages:4465-4475 ispartof: location:Germany status: published

Objective The reactive balance test (RBT) is a recently developed neurocognitive balance test. The aim of this study was to determine test-retest, intra- and inter-rater reliability of the RBT in healthy recreational athletes. Design Reliability study design. Setting Primary. Participants Twenty-one volunteers (age = 22 ± 1 years, height = 175 ± 9 cm, weight = 69 ± 7 kg) participated. Interventions The two experimental trials were separated by an average of 33 ± 15 days. During experimental trials participants performed the Y-balance test (to determine maximal reach distances), and RBT once. Main outcome measures Visuomotor response time and accuracy. Test-retest, intra- and inter-rater reliability were estimated for both these RBT outcome measures. Results Excellent intra- and inter-rater reliability was observed for visuomotor response time and accuracy. Test-retest reliability for visuomotor response time was considered good, while moderate test-retest reliability was found for accuracy. Conclusions Our results indicate that overall test-retest, intra- and inter-rater reliability of the RBT was moderate to excellent. Thus, the RBT possesses acceptable reliability to use in group level analyses. Future research should further determine the clinimetric properties of the RBT in specific populations and research the RBT along the sport injury continuum.

BACKGROUND: BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors. METHODS: BOADICEA was extended to further incorporate the associations of pathogenic variants in BARD1, RAD51C and RAD51D with breast cancer risk. The EOC model was extended to include the association of PALB2 pathogenic variants with EOC risk. Age-specific distributions of oestrogen-receptor-negative and triple-negative breast cancer status for pathogenic variant carriers in these genes and CHEK2 and ATM were also incorporated. A novel method to include continuous risk factors was developed, exemplified by including adult height as continuous. RESULTS: BARD1, RAD51C and RAD51D explain 0.31% of the breast cancer polygenic variance. When incorporated into the multifactorial model, 34%-44% of these carriers would be reclassified to the near-population and 15%-22% to the high-risk categories based on the UK National Institute for Health and Care Excellence guidelines. Under the EOC multifactorial model, 62%, 35% and 3% of PALB2 carriers have lifetime EOC risks of 10%, respectively. Including height as continuous, increased the breast cancer relative risk variance from 0.002 to 0.010. CONCLUSIONS: These extensions will allow for better personalised risks for BARD1, RAD51C, RAD51D and PALB2 pathogenic variant carriers and more informed choices on screening, prevention, risk factor modification or other risk-reducing options.

Altres ajuts: Institut Curie INCa-DGOS-Inserm_12554 We examined how often genetic clinicians correctly identify psychosocial difficulties in women at high breast cancer risk and explored effects of this assessment and the genetic test result on counselees' distress. A prospective observational study of counselee-clinician dyads was performed in three French, German and Spanish genetic clinics, involving 709 counselees (participation rate, 83.4%) and 31 clinicians (participation rate, 100%). Counselee-clinician agreement in perceived psychosocial difficulties was measured after the pre-test genetic consultation. Multivariate mixed linear models accounting for clinicians were tested. Predicted distress levels were assessed after the pre- (T1) and post-test result disclosure consultations (T2). Depending on the difficulty domain, clinicians adequately assessed the presence or absence of difficulties in 51% ("familial issues") to 59% ("emotions") of counselees. When counselees' and clinicians' perceptions disagreed, difficulties were generally underestimated by clinicians. Counselees' distress levels remained stable from T1 to T2, irrespective of clinicians' appraisal adequacy, and the genetic test result disclosure. Psychological referral need were found in 20-42% of counselees, more frequently observed for difficulties in the "emotions" domain. Our findings suggest that the genetic test result is a suboptimal indicator for psychological referral. Instead, clinicians should focus on emotions expressed by counselees to appraise their needs for psychological support.

Background Patient-centeredness, respect for patient autonomy, and shared decision-making have now made it to center stage in discussions on quality of care. Knowing what actually counts in care and how it should be accomplished from the patients’ and nurses’ perspective seems crucial. Aim To explore how patients and their nurses perceive the importance and enactment of values in their healthcare. Research design An observational, cross-sectional study using a self-developed questionnaire, consisting of 15 items related to seven values (e.g. uniqueness, autonomy, professionalism, compassion, responsiveness, partnership, and empowerment) as described in the taxonomy of Bastemeijer et al. Participants and research context The survey was completed by 384 patients and 81 nurses. Participants were recruited on eight internal medicine wards of a 1000-bed university hospital in Belgium. Ethical considerations This study was approved by the ethical committee of the Ghent University Hospital (B670201836799). Findings (1) Patients and nurses prioritize values of care differently; (2) nurses report not being able to enact the values they prioritize in actual practice as much as one would like to; and (3) there is a gap in experienced delivery of a comprehensible explanation of all treatment options, a conversation based on equality, making shared decisions, and being non-judgmental between nurses and patients. Discussion Our findings challenge nurses’ overemphasis on professional compassion and uniqueness while arguing for increased attention on authentic shared decision-making and empowerment. The first step to a patient-centered culture truly involving patients in their healthcare is communication and information provision, rather than focusing on tangible and normative constructs. Conclusion Our findings revealed differences in prioritization and actual enactment of values in care between patients and nurses. This was especially so for values related to communication, provision of complete unbiased information, and shared decision-making. Nurses should prioritize providing comprehensible information and using conversations based on equality to make decision together with patients.

Our goal was to conduct international comparisons of emotion regulation using the 9-item Emotionally Reactive (ER) syndrome of the Child Behavior Checklist for Ages 1½–5. We analyzed parent ratings for 17,964 preschoolers from 21 societies, which were grouped into 8 GLOBE study culture clusters (e.g., Nordic, Confucian Asian). Omnicultural broad base rates for ER items ranged from 8.0% to 38.8%. Rank ordering for mean item ratings varied widely across societies (omnicultural Q = .50) but less so across culture clusters (M Q = .66). Societal similarity in mean item rank ordering varied by culture cluster, with large within-cluster similarity for Anglo (Q = .96), Latin Europe (Q = .74), Germanic (Q = .77), and Latin American (Q = .76) clusters, but smaller within-cluster similarity for Nordic, Eastern Europe, and Confucian Asian clusters (Qs = .52, .23, and .44, respectively). Confirmatory factor analyses of the ER syndrome supported configural invariance for all 21 societies. All 9 items showed full to approximate metric invariance, but only 3 items showed approximate scalar invariance. The ER syndrome correlated . 65 with the Anxious/Depressed (A/D) syndrome and .63 with the Aggressive Behavior syndrome. ER items varied in base rates and factor loadings, and societies varied in rank ordering of items as low, medium, or high in mean ratings. Item rank order similarity among societies in the same culture cluster varied widely across culture clusters, suggesting the importance of cultural factors in the assessment of emotion regulation in preschoolers.

To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) inWe used data from 3,184In addition to female breast and ovarian cancers

BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) for breast cancer and the epithelial tubo-ovarian cancer (EOC) models included in the CanRisk tool (www.canrisk.org) provide future cancer risks based on pathogenic variants in cancer-susceptibility genes, polygenic risk scores, breast density, questionnaire-based risk factors and family history. Here, we extend the models to include the effects of pathogenic variants in recently established breast cancer and EOC susceptibility genes, up-to-date age-specific pathology distributions and continuous risk factors.BOADICEA was extended to further incorporate the associations of pathogenic variants inThese extensions will allow for better personalised risks for

Summary Background Facial attractiveness has social, psychological, and economic repercussions. Class II malocclusions are associated with a retroposition of the mandible, facial convexity, protruded upper lip, retruded lower lip, and pronounced mentolabial fold. Functional appliances (FA) try to increase mandibular length and normalize lip position, thereby decreasing the facial profile convexity and aesthetics. Objectives The aim of this review and meta-analysis is to investigate the effects of FA on the soft tissues in a non-cephalometric two-dimensional manner. Search methods Medline (via PubMed), Embase (via Ovid), Web of Science, and Cochrane Central were used to identify studies describing the soft tissue results of FA in a non-cephalometric way. The search was conducted up to July 2021. Selection criteria Prospective and retrospective studies investigating the effects of FA appliances on the soft tissues, with non-ionizing, two-dimensional imaging, including an attractiveness assessment based on Visual Analogue Scale or Likert scale, were considered eligible. Data collection and analysis Data extraction was performed separately by two authors. Risk of bias was assessed using the ROBINS-I tool. Results From the eight eligible studies, four were included in the meta-analysis to investigate the influence of assessors on facial attractiveness scores. Age range of the included studies varied from 8 to 21 years old including 313 Caucasian patients whereof 64% females. Six out of eight studies used growing patients as treatment group and only two studies reported follow-up after the end of treatment. Overall facial attractiveness increased after treatment with FA, resulting from a decrease in facial convexity and a normalization of the lip relationship. Orthodontists score higher aesthetic improvements after FA treatment as compared to laypeople. Conclusions Current evidence suggests the positive effects of FA on the facial attractiveness in growing and non-growing patients. FA normalize the lip relationship. Furthermore, they tend to decrease facial convexity and advance the chin point. More pleasing results can be expected in growing patients. Orthodontists are more generous when assessing treatment changes as compared to laypeople. Registration PROSPERO registration (CRD42021254835).

Background The importance of assessing and monitoring the health status of a population has grown in the last decades. Consistent and high quality data on the morbidity and mortality impact of a disease represent the key element for this assessment. Being increasingly used in global and national burden of diseases (BoD) studies, the Disability-Adjusted Life Year (DALY) is an indicator that combines healthy life years lost due to living with disease (Years Lived with Disability; YLD) and due to dying prematurely (Years of Life Lost; YLL). As a step towards a comprehensive national burden of disease study, this study aims to estimate the non-fatal burden of cancer in Belgium using national data. Methods We estimated the Belgian cancer burden from 2004 to 2019 in terms of YLD, using national population-based cancer registry data and international disease models. We developed a microsimulation model to translate incidence- into prevalence-based estimates, and used expert elicitation to integrate the long-term impact of increased disability due to surgical treatment. Results The age-standardized non-fatal burden of cancer increased from 2004 to 2019 by 6 and 3% respectively for incidence- and prevalence-based YLDs. In 2019, in Belgium, breast cancer had the highest morbidity impact among women, followed by colorectal and non-melanoma skin cancer. Among men, prostate cancer had the highest morbidity impact, followed by colorectal and non-melanoma skin cancer. Between 2004 and 2019, non-melanoma skin cancer significantly increased for both sexes in terms of age-standardized incidence-based YLD per 100,000, from 49 to 111 for men and from 15 to 44 for women. Important decreases were seen for colorectal cancer for both sexes in terms of age-standardized incidence-based YLD per 100,000, from 105 to 84 for men and from 66 to 58 for women. Conclusions Breast and prostate cancers represent the greatest proportion of cancer morbidity, while for both sexes the morbidity burden of skin cancer has shown an important increase from 2004 onwards. Integrating the current study in the Belgian national burden of disease study will allow monitoring of the burden of cancer over time, highlighting new trends and assessing the impact of public health policies.

Although abundant research has demonstrated associations between psychologically controlling parenting and adolescent problem behavior, little is known about the moderating role of adolescent personality herein. This study examined whether adolescent personality moderates the associations between parental psychological control and internalizing and externalizing problems at the level of within-person change. A 3-wave longitudinal design (N = 198 families, Mage adolescent = 14.89 years, Mage mother = 45.14 years, Mage father = 46.79 years), with 1-year intervals between waves, and using multi-informant assessment was conducted. Multilevel analyses demonstrated that changes in parental psychological control related positively to changes in multi-informant scores of both internalizing and externalizing problems. Evidence for the moderating role of personality was found for only 1 out of 25 interactions in a variable-centered approach and for 2 out of 8 interactions in a person-centered approach. The interactions obtained indicated that a mature personality (i.e., higher scores on emotional stability or membership in a resilient profile in comparison to an overcontrolled profile) buffered against the detrimental effects of psychologically controlling parenting on problem behaviors. Overall, the number of interactions was limited, suggesting only a modest moderating effect of adolescent personality. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Animal Welfare Attitudes (AWA) are defined as human attitudes towards the welfare of animals in different dimensions and settings. Demographic factors, such as age and gender are associated with AWA. The aim of this study was to assess gender differences among university students in a large convenience sample from twenty-two nations in AWA. A total of 7914 people participated in the study (5155 women, 2711 men, 48 diverse). Participants completed a questionnaire that collected demographic data, typical diet and responses to the Composite Respect for Animals Scale Short version (CRAS-S). In addition, we used a measure of gender empowerment from the Human Development Report. The largest variance in AWA was explained by diet, followed by country and gender. In terms of diet, 6385 participants reported to be omnivores, 296 as pescatarian, 637 ate a vegetarian diet and 434 were vegans (n = 162 without answer). Diet was related with CRAS-S scores, people with a vegan diet scored higher in AWA than omnivores. Women scored significantly higher on AWA than men. Furthermore, gender differences in AWA increased as gender inequality decreased.

Introduction: Ovarian clear cell carcinoma (OCCC) is a less common subtype accounting for approximately 5% of all epithelial ovarian cancers (EOCs). Clinical experience and research findings confirm the remarkable differences in clinical behavior, molecular alterations and pathogenesis of OCCC. The diagnosis of OCCC is typically set at a younger age, and earlier stage and in a background of endometriosis.Results: Molecularly, OCCCs rarely harbor BRCA1/BRCA2 mutations and have fewer copy number variants (CNVs). The most common molecular changes occur in the SWI/SNF chromatin remodeling complex genes, the PI3K/AKT signaling pathway and the receptor tyrosine kinase (RTK)/Ras signaling pathway.Five-year disease-specific survival of patients with OCCC is worse compared to high grade serous carcinomas (HGSOC). The current treatment options for OCCC are based on studies that included patients with predominantly HGSOC and only a minor proportion of cancers with clear cell histology. In order to improve outcomes for patients with OCCC, research should be specific for this subtype.Discussion: As the available information about the specific characteristics of OCCC is increasing, especially at a molecular level, it should be possible to continuously improve the specific diagnostics and treatment. Since OCCC is so rare, it is essential to collect new evidence at an international level. To avoid extrapolation from EOC trials with possible erroneous conclusions, patients should always be encouraged to participate in specific histological trials and basket trials, while paying extra attention to OCCC-like subtypes.

Up to 80% of BRCA1 and BRCA2 genetic variants remain of uncertain clinical significance (VUSs). Only variants classified as pathogenic or likely pathogenic can guide breast and ovarian cancer prevention measures and treatment by PARP inhibitors. We report the first results of the ongoing French national COVAR (cosegregation variant) study, the aim of which is to classify BRCA1/2 VUSs. The classification method was a multifactorial model combining different associations between VUSs and cancer, including cosegregation data. At this time, among the 653 variants selected, 101 (15%) distinct variants shared by 1,624 families were classified as pathogenic/likely pathogenic or benign/likely benign by the COVAR study. Sixty-six of the 101 (65%) variants classified by COVAR would have remained VUSs without cosegregation data. Of note, among the 34 variants classified as pathogenic by COVAR, 16 remained VUSs or likely pathogenic when following the ACMG/AMP variant classification guidelines. Although the initiation and organization of cosegregation analyses require a considerable effort, the growing number of available genetic tests results in an increasing number of families sharing a particular variant, and thereby increases the power of such analyses. Here we demonstrate that variant cosegregation analyses are a powerful tool for the classification of variants in the BRCA1/2 breast-ovarian cancer predisposition genes.

This study examined the family emotional climate as assessed by Five Minute Speech Samples and the relation with parenting stress and parenting behaviors among parents of children (6-17 years, 64.7% boys) with autism spectrum disorder, cerebral palsy, Down syndrome, and without any known disability (n = 447). The large majority of parents (79%) showed low levels of Expressed Emotion, an indicator of a positive family climate. In all groups, more Emotional Over-involvement, more Criticism and fewer expressions of Warmth were associated with higher levels of parenting stress. Across groups, Emotional Over-involvement was related to more autonomy-supportive parenting, Criticism to more psychologically controlling and overreactive parenting, and Warmth was associated with more responsive and less psychologically controlling and overreactive parenting.

Previous research supports the CBCL/1½-5's DSM-ASD scale (and its precursor, the DSM-PDP scale) as a Level 1 ASD screener. Confirmatory factor analyses (CFAs) with data from population samples in 24 societies (N = 19,850) indicated good measurement invariance across societies, especially for configural and metric invariance. Items 4. 25, 67, 80, and 98 may be especially good discriminators of ASD because they have tend to have low base rates, strong loadings on the ASD latent construct, and the best measurement invariance across societies. Further research is needed to test the discriminative power of these items in predicting ASD, but our strong measurement findings support the international psychometric robustness of the CBCL/1½-5's DSM-ASD scale.

Exposure to cold causes disturbances in cognitive performance that can have a profound impact on the safety, performance, and success of populations that frequent cold environments. It has recently been suggested that repeated cold stress, resulting in cold acclimation, may be a potential strategy to mitigate the cognitive impairments frequently seen upon exposure to cold temperatures. The purpose of this study, therefore, was to examine cognitive and neurophysiological function during repeated cold water immersion. Twelve healthy participants consisting of 8 males and 4 females (mean ± SD age: 26 ± 5 years, height: 174.0 ± 8.9 cm, weight: 75.6 ± 13.1 kg) completed seven 90-minute immersions in 10 °C water, each separated by 24 h. During immersions 1, 4, and 7, a double-digit addition task and a computer-based psychomotor vigilance task (PVT) were administered to assess cognitive performance, while neurophysiological function was assessed using electroencephalography (EEG) measurements collected during the PVT. Findings suggest that participants experienced an insulative type of cold acclimation, evidenced by greater heat retention and less shivering, with possible improvements in cognitive performance. Participants had more correct responses on the double-digit addition task on Immersion 7 (39 ± 5) compared with Immersion 1 (33 ± 6); p

Mass spectrometry imaging (MSI) is an analytical technique for the unlabeled and multiplex imaging of molecules in biological tissue sections. It therefore enables the spatial and molecular annotations of tissues complementary to histology. It has already been shown that MSI can guide subsequent material isolation technologies such as laser microdissection (LMD) to enable a more in-depth molecular characterization of MSI-highlighted tissue regions. However, with MSI now reaching spatial resolutions at the single-cell scale, there is a need for a precise co-registration between MSI and the LMD. As proof-of-principle, MSI of lipids was performed on a breast cancer tissue followed by a segmentation of the data to detect molecularly distinct segments within its tumor areas. After image processing of the segmentation results, the coordinates of the MSI-detected segments were passed to the LMD system by three co-registration steps. The errors of each co-registration step were quantified and the total error was found to be less than 13 μm. With this link established, MSI data can now accurately guide LMD to excise MSI-defined regions of interest for subsequent extract-based analyses. In our example, the excised tissue material was then subjected to ultrasensitive microproteomics in order to determine predominant molecular mechanisms in each of the MSI-highlighted intratumor segments. This work shows how the strengths of MSI, histology, and extract-based omics can be combined to enable a more comprehensive molecular characterization of in situ biological processes. Electronic supplementary material The online version of this article (10.1007/s00216-019-01983-z) contains supplementary material, which is available to authorized users.

Background Conventional rigid laparoscopic instruments offer five degrees of freedom (DOF). Robotic instruments add two independent DOFs allowing unconstrained directional steering. Several nonrobotic instruments have been developed with the additional DOFs, but with these devices, surgeon's wrist movements are not intuitively transmitted into tip movements. In this study, a new articulated instrument has been evaluated. The aim of the study was to compare learning curves and performances of conventional laparoscopic instruments, the da Vinci system and Steerable devices in a crossover study. Materials and methods A total of 16 medical students without any laparoscopic experience were trained for 27 h to operate all of a rigid, a robotic, and a new Steerable instrument in a random order. Learning curves and ultimate experience scores were determined for each instrument. Strain in wrist and shoulders was assessed with a visual analog score. Results Performing the suturing task with rigid and robot instruments required 4 h of training, compared with 6 h to master the Steerable instrument. After 9 h of training with each instrument, completing the complex suturing pattern required 662 ± 308 s with rigid instruments, 279 ± 90 s with the da Vinci system, and 279 ± 53 s with the Steerable instrument. Pain scores were significantly higher after using the rigid instruments compared with the Steerable instruments. Conclusions Transmission of torque and the presence of additional two DOFs in combination with reduced crosstalk significantly improved the instrument dexterity where the Steerable platform is concerned. Although the learning curve is longer, once mastered, it provides enhanced surgical freedom.

The brown planthopper, Nilaparvata lugens, is a model species for hemimetabolous development and the most important pest insect in rice, which is the major staple crop for about half of the world population. Despite its importance, little is known of the N-glycosylation process in this insect. Here we report on the N-glycome for the post-embryonic stages of N. lugens, revealing unique features that are different from the holometabolous insect models, as the fruit fly Drosophila melanogaster and the beetle Tribolium castaneum. Analysis of the N-glycan fingerprint for male and female adults showed sex-specific N-glycosylation in insects. Specifically, the female adults progress towards a unique glycan profile with a striking increase in high mannose N-glycans. The N-glycome of N. lugens contributes to study pathways differentiating between sexes, and the results shed light on the evolution and differences in development between primitive hemimetabolous insects and more advanced holometabolous insects. The data are discussed in relation to potential function(s) in development and sex specificity.

Objective. The introduction of advanced endoscopic systems, such as the Storz Image1S and the Olympus Endoeye, heralds a new era of 3-dimensional (3D) visualization. The aim of this report is to provide a comprehensive overview of the neurophysiology of 3D view, its relevance in videoscopy, and to quantify the benefit of the new 3D technologies for both rigid and articulated instruments. Method. Sixteen medical students without any laparoscopic experience were trained each for a total of 27 hours. Proficiency scores were determined for rigid and articulated instruments under 2D and 3D visualization conditions. Results. A reduction in execution time of 14%, 28%, and 36% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. A reduction in errors of 84%, 92%, and 87% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. Conclusion. 3D visualization greatly augments endoscopic procedures. The advanced endoscopic systems employed in the recent study caused no visual fatigue or discomfort. The benefit of 3D was most distinct with articulated instruments.

This study aimed to gain more insight in the sources of daily parenting among mothers of children with autism spectrum disorder (ASD). Specifically, we examined associations between daily variations in child behavior, mothers’ psychological needs, and mothers’ controlling and autonomy-supportive parenting. Moreover, the study examined the potential mediating role of daily vitality and stress within these associations. In total 41 mothers (Mage = 41.84 years) of children with ASD (Mage = 10.92 years, range 7–15) participated in a 7-day diary study. Multilevel structural equation modeling revealed that both daily child behavior (i.e., externalizing problems and prosocial behavior) and mothers’ psychological needs relate to day-to-day variation in parenting behavior. Daily stress and vitality played an intervening role in most of these associations.

When in emotional distress, people often turn to others for support. Paradoxically, even when people perceive social support to be beneficial, it often does not result in emotional recovery. This paradox may be explained by the fact that the sharing process disproportionately centres on support that is not helpful in the long run. A distinction has been made between two types of support that are differentially effective: Whereas socio-affective support alleviates momentary emotional distress, cognitive support fosters long-term recovery. But can listeners tell what support the sharer needs? The present study examines the hypothesis that sharers communicate their support goals by sharing in such a way that it allows listeners to infer the sharer's needs. In Experiment 1, we manipulated participants' support goals, and showed that socio-affective support goals led participants to express more emotions, whereas cognitive support goals resulted in greater use of appraisals. In Experiments 2 and 3, we tested whether these differential expressions would affect the support goals that listeners inferred. We found no evidence for such an effect: Listeners consistently perceived the sharer to predominantly want socio-affective support. These findings help explain why many social sharing instances revolve around socio-affective support, leading to subjectively experienced benefits, but not to genuine recovery.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P, Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Study design Population-based cross-sectional study. Objective The aim of this study was to gain a better understanding of changes in muscle morphology in patients with chronic idiopathic neck pain (CINP) and chronic whiplash-associated disorder (CWAD). Summary of background data Worldwide, neck pain (NP) is a common health problem with high socioeconomic burden. A high percentage of these patients evolves toward chronic symptoms. Efficacy of treatments for these complaints remains variable. In current literature, changes in muscle morphology (muscle fat infiltration and cross-sectional area) have been reported in patients with NP, both CWAD and CINP. However, no strong conclusions could be made. Methods In this study, magnetic resonance imaging was used to obtain data on muscle morphology from 14 cervical flexor and extensor muscles in 117 female subjects with NP (CWAD = 37; CINP = 45) and healthy controls (HC = 35). Results The CWAD group had a significantly larger muscle fat infiltration in some extensor (semispinalis and splenius capitis, trapezius, obliquus capitis inferior) and flexor (sternocleidomastoid) muscles compared to the CINP and/or HC group. A significantly larger (muscle) cross-sectional area was found in some extensor (levator scapulae, semispinalis capitis, trapezius) and flexor (longus colli, longus capitis, sternocleidomastoid) muscles in the HC group compared to the CINP and/or CWAD group. No clear associations were found between group differences and factors as pain duration, kinesiophobia, and disability. Conclusion The results in this study suggest changes in muscle morphology in both NP cohorts. These results show some similarities with earlier findings in this research domain. Further studies based on controlled longitudinal designs are needed to facilitate data compilation, to draw stronger conclusions, and to integrate them into the treatment of patients with chronic NP.Level of Evidence: 4.

Highlights • Amygdala-ventral frontal connectivity is enhanced in chronic neck pain. • Enhanced amydala-frontal operculum coupling is related to decreased pain inhibition. • Local hyperalgesia is associated with superior parietal-motor cortex connectivity. • Symptoms and connectivity findings are most pronounced in traumatic neck pain., Background Chronic neck pain is a leading cause of disability worldwide, affecting the lives of millions of people. Research investigating functional brain alterations in relation to somatosensory function is necessary to better understand mechanisms underlying pain development and maintenance in individuals with chronic neck pain, yet remains scarce. This case-control study aimed to examine resting-state functional connectivity alterations and associations with pain outcomes, self-reported central sensitization-related symptoms and quantitative sensory testing (QST) measures in patients with chronic non-traumatic (idiopathic/CINP) neck pain and chronic traumatic (whiplash associated/CWAD) neck pain compared to pain-free controls. Methods Resting-state functional magnetic resonance images were acquired in 107 female participants (38 CINP, 37 CWAD, 32 healthy controls). After data pre-processing, seed-to-seed analyses were conducted focusing on resting-state functional connectivity involving pre-defined regions of interest that have previously been observed to be structurally or functionally altered and/or associated with pain-related measures in this patient population. Results Findings demonstrate enhanced left amygdala functional coupling during rest with the left frontal operculum in women with CINP and CWAD compared to controls. This increased resting-state functional connectivity was associated with more self-reported symptoms related to central sensitization and decreased efficacy of conditioned pain modulation. Furthermore, enhanced connectivity between the left amygdala and left frontal orbital cortex, and between the left pallidum and the left frontal operculum was observed only in patients with CWAD compared to healthy controls. In patients, additional associations between local hyperalgesia and enhanced connectivity between the left superior parietal cortex and the left and right precentral gyrus were found. Conclusions In line with our hypotheses, patients with CWAD showed the most pronounced alterations in resting-state functional connectivity, encompassing subcortical limbic (amygdala) and basal ganglia (pallidum), and ventral frontal regions (frontal operculum, orbitofrontal cortex) when compared to CINP and controls. Findings are generally in line with the idea of a continuum, in absence of significant group differences across CINP and CWAD. Enhanced amygdala-frontal operculum functional connectivity was the most robust and only connectivity pair in the cluster that was associated with QST (i.e., dynamic QST; endogenous pain inhibition), and that was observed in both patient groups. In addition, independent of group differences, enhanced resting-state functional connectivity between superior parietal cortex (involved in attention) and primary motor cortex was associated with static QST (i.e., greater local hyperalgesia). Taken together, our findings show a key role for enhanced amygdala-ventral frontal circuitry in chronic neck pain, and its association with diminished endogenous pain inhibition further emphasizes the link between cognitive-affective and sensory modulations of pain in women with chronic non-traumatic and traumatic neck pain.

International audience; With advances in breast cancer (BC) gene panel testing, risk counseling has become increasingly complex, potentially leading to unmet psychosocial needs. We assessed psychosocial needs and correlates in women initiating testing for high genetic BC risk in clinics in France and Germany, and compared these results with data from a literature review. Among the 442 counselees consecutively approached, 212 (83%) in France and 180 (97%) in Germany, mostly BC patients (81% and 92%, respectively), returned the 'Psychosocial Assessment in Hereditary Cancer' questionnaire. Based on the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) BC risk estimation model, the mean BC lifetime risk estimates were 19% and 18% in France and Germany, respectively. In both countries, the most prevalent needs clustered around the "living with cancer" and "children-related issues" domains. In multivariate analyses, a higher number of psychosocial needs were significantly associated with younger age (b = −0.05), higher anxiety (b = 0.78), and having children (b = 1.51), but not with country, educational level, marital status, depression, or loss of a family member due to hereditary cancer. These results are in line with the literature review data. However, this review identified only seven studies that quantitatively addressed psychosocial needs in the BC genetic counseling setting. Current data lack understandings of how cancer risk counseling affects psychosocial needs, and improves patient-centered care in that setting.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

This two-year longitudinal study addressed the joint contribution of parent-rated parenting behaviors and child personality on psychosocial outcomes in 118 families of children with Cerebral Palsy (M age Time 1 = 10.9 years old, 64.4% boys). Latent change modeling revealed intra-individual changes in children's psychosocial development as internalizing and externalizing behaviors increased from the first to the second assessment and psychosocial strengths increased from the second to the third assessment, whereas externally controlling and autonomy-supportive parenting behavior remained stable over time. Externally controlling parenting related to higher levels of, and increases in behavioral problems, with these associations being most pronounced among children low on Extraversion, Conscientiousness, or Imagination. Autonomy-supportive parenting related to higher levels of psychosocial strengths, with this association being most pronounced among children high on Emotional Stability.

This nine-year longitudinal study addresses the joint contribution of parent-rated negative controlling parenting and child personality on psychosocial outcomes in 141 families of children with autism spectrum disorder (83% boys, mean age Time 1 = 10.1). Latent change modeling revealed substantial variation in within-person change in parenting and psychosocial outcomes across a six- and three-year-interval. Over time, negative controlling parenting and child personality were consistently related to externalizing problems, whereas child personality was differentially related to internalizing problems and psychosocial strengths. Three personality-by-parenting interactions were significant, suggesting that children with less mature personality traits show more externalizing behaviors in the presence of controlling parenting. This study identified both parenting and child personality as important modifiers of developmental outcomes in youth with autism.

ObjectiveTo compare the prevalence of work-related potential traumatic events (PTEs), support protocols and mental health symptoms across Dutch gynaecologists, orthopaedic surgeons and paediatricians.DesignCross-sectional study, supplementary analysis of combined data.SettingNationwide survey between 2014 and 2017.ParticipantsAn online questionnaire was sent to all Dutch gynaecologists, orthopaedic surgeons and paediatricians, including resident physicians (4959 physicians). 1374 questionnaires were eligible for analysis, corresponding with a response rate of 27.7%.Outcome measuresPrimary outcome measures were the prevalence of work-related PTEs, depression, anxiety, psychological distress and traumatic stress, measured with validated screening instruments (Hospital Anxiety and Depression Scale, Trauma Screening Questionnaire). Secondary outcomes were the association of mental health and defensive practice to traumatic events and support protocols.ResultsOf the respondents, 20.8% experienced a work-related PTE at least 4 weeks ago. Prevalence rates indicative of depression, anxiety or post-traumatic stress disorder (PTSD) were 6.4%, 13.6% and 1.5%, respectively. Depression (9.2% vs 5.2%, p=0.019), anxiety (18.2% vs 8.2%, pConclusionPhysicians are frequently exposed to PTEs with high emotional impact over the course of their career. Lacking a support protocol after adverse events was associated with more post-traumatic stress. Adverse events were associated with considering to quit medical practice and a more defensive practice. More awareness must be created for the mental health of physicians as well as for the implementation of a well-organised support system after PTEs.

Venous thromboembolism (VTE) is common in cancer patients and is an important cause of morbidity and mortality. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE (ClinicalTrials.gov: NCT02155491) is a prospective, observational study of 10,684 patients with objectively diagnosed VTE from 415 sites in 28 countries. We compared baseline characteristics, VTE treatment patterns, and 1-year outcomes (mortality, recurrent VTE and major bleeding) in 1075 patients with active cancer, 674 patients with a history of cancer, and 8935 patients without cancer. Patients with active cancer and history of cancer were older than cancer-free patients, with median ages of 64.8, 68.9, and 58.4 years, respectively. The most common sites of active cancer were lung (14.5%), colorectal (11.0%), breast (10.6%), and gynaecological (10.3%). Active cancer patients had a higher incidence of upper limb and vena cava thrombosis than cancer-free patients (9.0% vs 4.8% and 5.1% vs 1.4%, respectively), and were more likely to receive parenteral anticoagulation as monotherapy than cancer-free patients (57.8% vs 12.1%), and less likely to receive DOACs (14.2% vs 50.6%). Rates of death, recurrent VTE, and major bleeding were higher in active cancer patients than in cancer-free patients, with hazard ratios (95% confidence intervals) of 14.2 (12.1-16.6), 1.6 (1.2-2.0) and 3.8 (2.9-5.0), respectively. VTE was the second most common cause of death in patients with active cancer or history of cancer. In patients with VTE, those with active cancer are at higher risk of death, recurrence, and major bleeding than those without cancer.

This study tested the effectiveness of HeartMan—a mobile personal health system offering decisional support for management of congestive heart failure (CHF)—on health-related quality of life (HRQoL), self-management, exercise capacity, illness perception, mental and sexual health. A randomized controlled proof-of-concept trial (1:2 ratio of control:intervention) was set up with ambulatory CHF patients in stable condition in Belgium and Italy. Data were collected by means of a 6-min walking test and a number of standardized questionnaire instruments. A total of 56 (34 intervention and 22 control group) participants completed the study (77% male; mean age 63 years, sd 10.5). All depression and anxiety dimensions decreased in the intervention group (p p p p

Malignant cardiac tamponade is a life-threatening condition that requires prompt treatment and effective management to prevent recurrence. This paper describes safety and efficacy outcomes after intrapericardial instillation of bleomycin as well as possible predictors of survival.We performed a 10-year retrospective, single-center study to evaluate the safety and efficacy of intrapericardial instillation of bleomycin in patients with suspected malignant cardiac tamponade.Intrapericardial instillation of bleomycin was performed in 31 cancer patients (9 men, 22 women) presenting with cardiac tamponade. Non-fatal complications occurred in 3 patients and relapse occurred in 1 patient. Overall survival was less than 10% at the end of the study. Median survival was 104 days (95% CI, 0-251 days). Survival was compared between different groups (defined by primary tumor, type of tumor, TNM stage and results of cytological analysis) with median survival being considerably higher when oncologic therapy was altered afterwards.The use of intrapericardial bleomycin instillation following pericardiocentesis for malignant cardiac tamponade is a safe procedure with a high success rate. Survival rates depend on further oncological treatment options available.

Background In the context of interventions aimed at reducing pain, disability, and maladaptive pain cognitions in chronic neck pain, it is hypothesized that patients who have greater symptom reduction possibly also demonstrate greater improvement in cervical motor output. Therefore, the aim of this study was to examine the effect of pain neuroscience education plus cognition‐targeted motor control training on cervical motor output. Methods Impairments in cervical motor output were measured in 64 subjects with chronic neck pain using standardized tests. Cervical muscle strength, cervical mobility, balance, and cervical neuromuscular control were derived. To assess the differences between groups in response to treatment, a random‐intercept linear mixed‐models analysis, applying a diagonal covariance matrix, was used. Results A significant treatment × time interaction effect was found for neuromuscular control of the deep cervical flexors, favoring the experimental treatment at 3 months’ follow‐up (mean group difference: 1.982; 95% confidence interval 0.779, 3.185; large effect size d = 0.82). Significant main effects of time were found for the neuromuscular capacity of scapulothoracic muscles and for cervical mobility. No significant effects were found for balance, cervical muscle strength, or endurance of cervical flexors. Conclusion Pain neuroscience education combined with cognition‐targeted motor control training is not more effective than biomedically focused education and exercise therapy for improving cervical motor output in people with chronic neck pain. Our findings question the relative importance of factors such as pain, disability, and maladaptive pain cognitions on cervical motor output and the need to address it in treatment.

BACKGROUND: The therapeutic success in patients with congenital heart disease (CHD) leads to a growing number of adults with CHD (adult CHD [ACHD]) who develop end-stage heart failure. We aimed to determine patient characteristics and outcomes of ACHD listed for heart transplantation. METHODS: Using data from all the patients with ACHD in 20 transplant centers in the Eurotransplant region from 1999 to 2015, we analyzed patient characteristics, waiting list, and post-transplantation outcomes. RESULTS: A total of 204 patients with ACHD were listed during the study period. The median age was 38 years, and 62.3% of the patients were listed in high urgency (HU), and 37.7% of the patients were in transplantable (T)-listing status. A total of 23.5% of the patients died or were delisted owing to clinical worsening, and 75% of the patients underwent transplantation. Median waiting time for patients with HU-listing status was 4.18 months and with T-listing status 9.07 months. There was no difference in crude mortality or delisting between patients who were HU status listed and T status listed (p = 0.65). In multivariable regression analysis, markers for respiratory failure (mechanical ventilation, hazard ratio [HR]: 1.41, 95% CI: 1.11-1.81, p = 0.006) and arrhythmias (anti-arrhythmic medication, HR: 1.42, 95% CI: 1.01-2.01, p = 0.044) were associated with a higher risk of death or delisting. In the overall cohort, post-transplantation mortality was 26.8% after 1 year and 33.4% after 5 years. CONCLUSIONS: Listed patients are at high risk of death without differences in the urgency of listing. Respiratory failure requiring invasive ventilation and possibly arrhythmias requiring anti-arrhythmic medication indicate worse outcomes on waiting list. (C) 2020 International Society for Heart and Lung Transplantation. All rights reserved.

Background Cancer patients have been reported to be at higher risk of COVID-19 complications and deaths. We report the characteristics and outcome of patients diagnosed with COVID-19 during breast cancer treatment at Institut Curie hospitals (ICH, Paris area, France). Methods An IRB-approved prospective registry was set up at ICH on March 13, 2020, for all breast cancer patients with COVID-19 symptoms or radiologic signs. Registered data included patient history, tumor characteristics and treatments, COVID-19 symptoms, radiological features, and outcome. Data extraction was done on April 25, 2020. COVID-19 patients were defined as those with either a positive RNA test or typical, newly appeared lung CT scan abnormalities. Results Among 15,600 patients actively treated for early or metastatic breast cancer during the last 4 months at ICH, 76 patients with suspected COVID-19 infection were included in the registry and followed. Fifty-nine of these patients were diagnosed with COVID-19 based on viral RNA testing (N = 41) or typical radiologic signs: 37/59 (63%) COVID-19 patients were treated for metastatic breast cancer, and 13/59 (22%) of them were taking corticosteroids daily. Common clinical features mostly consisted of fever and/or cough, while ground-glass opacities were the most common radiologic sign at diagnosis. We found no association between prior radiation therapy fields or extent of radiation therapy sequelae and extent of COVID-19 lung lesions. Twenty-eight of these 59 patients (47%) were hospitalized, and 6 (10%) were transferred to an intensive care unit. At the time of analysis, 45/59 (76%) patients were recovering or had been cured, 10/59 (17%) were still followed, and 4/59 (7%) had died from COVID-19. All 4 patients who died had significant non-cancer comorbidities. In univariate analysis, hypertension and age (> 70) were the two factors associated with a higher risk of intensive care unit admission and/or death. Conclusions This prospective registry analysis suggests that the COVID-19 mortality rate in breast cancer patients depends more on comorbidities than prior radiation therapy or current anti-cancer treatment. Special attention must be paid to comorbidities when estimating the risk of severe COVID-19 in breast cancer patients.

Research has shown that healthcare providers lack confidence in having the knowledge needed to have conversations about body image with their patients. No research to date has explicitly explored how providers in primary healthcare understand body image, including its definition and how it impacts plans for care. Accordingly, the current study explored how primary healthcare providers define body image and how they see the concept of body image manifest in their practice. A total of 21 participants were interviewed, including 3 registered dietitians, 6 occupational therapists, 4 physiotherapists, 1 registered massage therapist, 1 kinesiologist, 4 family physicians, 1 nurse, and 1 social worker. Using thematic analysis, it was found that gaps in knowledge about body image were quite apparent as participants' understanding of body image was slippery (e.g., they struggled to articulate specifics about the concept within care and recognized body image is not something associated with a clinical guideline that would bring form to the concept). However, healthcare providers believed in the importance of body image in their patients' care in broad and far reaching ways. Future directions for bridging the knowledge gap with respect to body image among primary healthcare providers are discussed.

Objective The aim of this study is to test the unified theory of acceptance and use of technology (UTAUT) model for explaining the intention to use exoskeletons among industrial workers. Background Exoskeletons could help reduce physical workload and risk for injuries among industrial workers. Therefore, it is crucial to understand which factors play a role in workers’ intention to use such exoskeletons. Method Industrial workers ( N = 124) completed a survey on their attitudes regarding the use of exoskeletons at their workplace. Using partial least squares (PLS) path modeling, the UTAUT model and a revised version of the UTAUT model were fitted to these data. Results The adapted UTAUT model of Dwivedi et al. (2017) was able to explain up to 75.6% of the variance in intention to use exoskeletons, suggesting a reasonable model fit. Conclusion The model fit suggests that effort expectancy (how easy it seems to use an exoskeleton) plays an important role in predicting the intention to use exoskeletons. Social influence (whether others think workers should use exoskeletons) and performance expectancy (how useful exoskeletons seem to be for work) play a smaller role in predicting the intention to use. Applications This research informs companies about the optimal implementation of exoskeletons by improving the determinants of acceptance among their workers.

Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes., This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant agreement number 656144. Genotyping of the OncoArray was principally funded from three sources: the PERSPECTIVE project (funded by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the ‘Ministère de l’Économie de la Science et de l’Innovation du Québec’ (through Genome Québec) and the Quebec Breast Cancer Foundation); the NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative and the Discovery, Biology and Risk of Inherited Variants in Breast Cancer (DRIVE) project (NIH grants U19 CA148065 and X01HG007492); and Cancer Research UK (C1287/A10118, C8197/A16565 and C1287/A16563). BCAC is funded by Cancer Research UK (C1287/A16563), by the European Community’s Seventh Framework Programme under grant agreement 223175 (HEALTH-F2-2009-223175) (COGS) and by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreements 633784 (B-CAST) and 634935 (BRIDGES). Genotyping of the iCOGS array was funded by the European Union (HEALTH-F2-2009-223175), Cancer Research UK (C1287/A10710), the Canadian Institutes of Health Research for the ‘CIHR Team in Familial Risks of Breast Cancer’ program, and the Ministry of Economic Development, Innovation and Export Trade of Quebec (grant PSR-SIIRI-701). Combining of the GWAS data was supported in part by NIH Cancer Post-Cancer GWAS initiative grant U19 CA 148065 (DRIVE; part of the GAME-ON initiative).

Background. A patent foramen ovale (PFO) is a rare cause of hypoxemia and clinical symptoms of dyspnea. Due to a right-to-left shunt, desaturated blood enters the systemic circulation in a subset of patients resulting in dyspnea and a subsequent reduction in quality of life (QoL). Percutaneous closure of PFO is the treatment of choice. Objectives. This retrospective multicentre study evaluates short- and long-term results of percutaneous closure of PFO in patients with dyspnea and/or reduced oxygen saturation. Methods. Patients with respiratory symptoms were selected from databases containing all patients percutaneously closed between January 2000 and September 2018. Improvement in dyspnea, oxygenation, and QoL was investigated using pre- and postprocedural lung function parameters and two postprocedural questionnaires (SF-36 and PFSDQ-M). Results. The average follow-up period was 36 [12–43] months, ranging from 0 months to 14 years. Percutaneous closure was successful in 15 of the 16 patients. All patients reported subjective improvement in dyspnea immediately after device deployment, consistent with their improvement in oxygen saturation (from 90 ± 6% to 94 [92–97%] on room air and in upright position) (p<0.05). Both questionnaires also indicated an improvement of dyspnea and QoL after closure. The two early and two late deaths were unrelated to the procedure. Conclusion. PFO-related dyspnea and/or hypoxemia can be treated successfully with a percutaneous intervention with long-lasting benefits on oxygen saturation, dyspnea, and QoL.