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Three-dimensional (3D) imaging techniques are promising new tools for measuring breast volume, for example in gender-affirming therapy. Transgender individuals can be treated with gender-affirming hormone therapy (GAHT). A robust method for monitoring breast volume changes is critical to be able to study the effects of feminizing GAHT. The primary aim of this study was to compare the accuracy of three 3D devices (Vectra XT, Artec LEO and iPhone XR) for measuring modest breast volume differences using a mannequin. The secondary aim of this study was to evaluate these methods in several performance domains. We used reference prostheses of increasing volumes and compared the volumes using GOM-inspect software. For Vectra XT 3D images, manufacturer-provided software was used to calculate volumes as well. The scanning methods were ranked based on their performance in a total of five categories: volume estimations, costs, user-friendliness, test subject-friendliness and technical aspects. The 3D models analyzed with GOM-inspect showed relative mean estimate differences from the actual volumes of 9.1% for the Vectra XT, 7.3% for the Artec LEO and 14% for the iPhone XR. For the Vectra XT models analyzed with the built-in software this was 6.2%. Root mean squared errors (RMSE) calculated based on the GOM-inspect volume analyses showed mean RMSEs of 2.27, 2.54 and 8.93 for the Vectra XT, Artec LEO and iPhone XR, respectively. The Vectra software had a mean RMSE of 3.00. In the combined performance ranking, the Vectra XT had the most favorable ranking, followed by the Artec LEO and the iPhone XR. The Vectra XT and Artec LEO are the preferred scanners to monitor breast development due to the combination of higher accuracy and overall performance. The current study shows that 3D techniques can be used to adequately measure modest breast volume differences and therefore will be useful to study for example breast changes in transgender individuals using feminizing GAHT. These observations may also be relevant in other fields of 3D imaging research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dijkman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This review provides an overview regarding the abdominal effects of an omentectomy, with or without extra-peritoneal reconstructions. In general, reported complication rates were low. Short-term complications involved ileus, bowel stenosis, abdominal abscess and sepsis (range 0.0%-23%). Donor-site hernia was mainly reported as long-term complication (up to 32%) and negligible gastrointestinal complications were observed. However, the level of evidence and methodological quality are quite low with a maximum of 8.5 years follow-up., (© 2024 The Authors. Journal of Surgical Oncology published by Wiley Periodicals LLC.)

Background: With developments in screening and treatment, survival rates of breast cancer patients are increasing, and so is the number of women opting for breast reconstruction to improve their quality of life. One factor that could play an important role in improving the quality of life is breast sensibility. Therefore, the aim of this study was to explore breast sensibility in participants of the Breast Reconstruction with External Preexpansion and Autologous Fat Transfer versus Standard Therapy trial: an ongoing randomized controlled trial comparing breast reconstruction with autologous fat transfer (AFT) versus implant-based reconstruction (IBR)., Methods: This study was conducted on participants of the Breast Reconstruction with External Preexpansion and Autologous Fat Transfer versus Standard Therapy trial who were at least 12 months after final surgery. Semmes-Weinstein monofilaments were used to measure skin sensibility in breast cancer patients who underwent breast reconstruction with either AFT or IBR following their mastectomy., Results: A total of 46 patients were included in this study, resulting in 62 breast reconstructions (28 AFT breasts and 34 IBR breasts). Significantly higher mean monofilament values were found for skin sensibility after AFT (-0.7; P < 0.001), clinically correlating to "diminished protective function," as opposed to the IBR group, with clinical values indicating "loss of protective function.", Conclusions: In this study, the authors found that breast cancer patients who underwent a mastectomy had a significantly better sensibility of the breast following AFT for total breast reconstruction as compared with IBR. Larger studies that include null measurements are required to further explore these noteworthy results of AFT., Clinical Question/level of Evidence: Therapeutic, II., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

At a time when nature conservation has become essential to ensure the long-term sustainability of our environment, it is widely acknowledged that conservation actions must be implemented within a solid taxonomic framework. In preparation for the upcoming update of the IUCN Red List, we here update the European checklist of the wild bees (sensu the IUCN geographical framework). The original checklist, published in 2014, was revised for the first time in 2017. In the present revision, we add one genus, four subgenera and 67 species recently described, 40 species newly recorded since the latest revision (including two species that are not native to Europe), 26 species overlooked in the previous European checklists and 63 published synonymies. We provide original records for eight species previously unknown to the continent and, as original taxonomic acts, we provide three new synonyms, we consider two names as nomina nuda, ten names as nomina dubia, three as species inquirenda, synonymize three species and exclude 40 species from the previous checklist. Around a hundred other taxonomic changes and clarifications are also included and discussed. The present work revises the total number of genera for IUCN Europe to 77 and the total number of species to 2,138. In addition to specifying the taxonomic changes necessary to update the forthcoming Red List of European bees, we discuss the sampling and taxonomic biases that characterise research on the European bee fauna and highlight the growing importance of range expansions and species invasions.

Purpose: The aim of this prospective cohort study was to estimate the relationship between the course of HRQOL in the first 2 years after diagnosis and treatment of head and neck cancer (HNC) and personal, clinical, psychological, physical, social, lifestyle, HNC-related, and biological factors., Methods: Data were used from 638 HNC patients of the NETherlands QUality of life and BIomedical Cohort study (NET-QUBIC). Linear mixed models were used to investigate factors associated with the course of HRQOL (EORTC QLQ-C30 global quality of life (QL) and summary score (SumSc)) from baseline to 3, 6, 12, and 24 months after treatment., Results: Baseline depressive symptoms, social contacts, and oral pain were significantly associated with the course of QL from baseline to 24 months. Tumor subsite and baseline social eating, stress (hyperarousal), coughing, feeling ill, and IL-10 were associated with the course of SumSc. Post-treatment social contacts and stress (avoidance) were significantly associated with the course of QL from 6 to 24 months, and social contacts and weight loss with the course of SumSc. The course of SumSc from 6 to 24 months was also significantly associated with a change in financial problems, speech problems, weight loss, and shoulder problems between baseline and 6 months., Conclusion: Baseline clinical, psychological, social, lifestyle, HNC-related, and biological factors are associated with the course of HRQOL from baseline to 24 months after treatment. Post-treatment social, lifestyle, and HNC-related factors are associated with the course of HRQOL from 6 to 24 months after treatment., (© 2023. The Author(s).)

Background: Suicidal ideation (SI) is a significant and long-lasting mental health problem, with a third of individuals still experiencing SI after two years. To date, most Ecological Momentary Assessment (EMA) studies of SI have assessed its day-to-day course over one to four consecutive weeks and found no consistent trends in average SI severity over time., Aim: The current proof of concept study assessed daily fluctuations of SI over a time span of 3 to 6 months to explore whether individual trends in SI severity could be detected, and if so, if the trajectory of changes were gradual or sudden. The secondary aim was to explore whether changes in SI severity could be detected at an early stage., Method: Five adult outpatients with depression and SI used an EMA app on their smartphone in addition to their regular treatment for 3 to 6 months, where SI was assessed 3 times a day. To detect trends in SI for each patient, three models were tested: a null model, a gradual change model and a sudden change model. To detect changes in SI before a new plateau was reached, Early Warning Signals and Exponentially Weighted Moving Average control charts were used., Results: In each patient, average SI severity had a unique trajectory of sudden and/or gradual changes. Additionally, in some patients, increases in both sudden and gradual SI could be detected at an early stage., Conclusions: The study presents a first indication of unique individual trends in SI severity over a 3 to 6 months period. Though replication in a larger sample is needed to test how well results generalize, a first proof-of-concept is provided that both sudden and gradual changes in SI severity may be detectable at an early stage using the dynamics of time-series data., Competing Interests: The authors declare that they have no conflict of interests., (© Person-Oriented Research.)

Background: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics., Methods: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed., Results: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17)., Conclusions: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point., Competing Interests: Conflicts of interest BP has received research funding (not related to the current paper) from Boehringer Ingelheim and Jansen Research., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Internet-based cognitive behavioral therapy (iCBT) services for common mental health disorders have been found to be effective. There is a need for strategies that improve implementation in routine practice. One-size-fits-all strategies are likely to be ineffective. Tailored implementation is considered as a promising approach. The self-guided integrated theory-based Framework for intervention tailoring strategies toolkit (ItFits-toolkit) supports local implementers in developing tailored implementation strategies. Tailoring involves identifying local barriers; matching selected barriers to implementation strategies; developing an actionable work plan; and applying, monitoring, and adapting where necessary., Objective: This study aimed to compare the effectiveness of the ItFits-toolkit with implementation-as-usual (IAU) in implementing iCBT services in 12 routine mental health care organizations in 9 countries in Europe and Australia., Methods: A stepped-wedge cluster randomized trial design with repeated measures was applied. The trial period lasted 30 months. The primary outcome was the normalization of iCBT delivery by service providers (therapists, referrers, IT developers, and administrators), which was measured with the Normalization Measure Development as a proxy for implementation success. A 3-level linear mixed-effects modeling was applied to estimate the effects. iCBT service uptake (referral and treatment completion rates) and implementation effort (hours) were used as secondary outcomes. The perceived satisfaction (Client Satisfaction Questionnaire), usability (System Usability Scale), and impact of the ItFits-toolkit by implementers were used to assess the acceptability of the ItFits-toolkit., Results: In total, 456 mental health service providers were included in this study. Compared with IAU, the ItFits-toolkit had a small positive statistically significant effect on normalization levels in service providers (mean 0.09, SD 0.04; P=.02; Cohen d=0.12). The uptake of iCBT by patients was similar to that of IAU. Implementers did not spend more time on implementation work when using the ItFits-toolkit and generally regarded the ItFits-toolkit as usable and were satisfied with it., Conclusions: The ItFits-toolkit performed better than the usual implementation activities in implementing iCBT services in routine practice. There is practical utility in the ItFits-toolkit for supporting implementers in developing and applying effective tailored implementation strategies. However, the effect on normalization levels among mental health service providers was small. These findings warrant modesty regarding the effectiveness of self-guided tailored implementation of iCBT services in routine practice., Trial Registration: ClinicalTrials.gov NCT03652883; https://clinicaltrials.gov/ct2/show/NCT03652883., International Registered Report Identifier (irrid): RR2-10.1186/s13063-020-04686-4., (©Christiaan Vis, Josien Schuurmans, Bruno Aouizerate, Mette Atipei Craggs, Philip Batterham, Leah Bührmann, Alison Calear, Arlinda Cerga Pashoja, Helen Christensen, Els Dozeman, Claus Duedal Pedersen, David Daniel Ebert, Anne Etzelmueller, Naim Fanaj, Tracy L Finch, Denise Hanssen, Ulrich Hegerl, Adriaan Hoogendoorn, Kim Mathiasen, Carl May, Andia Meksi, Sevim Mustafa, Bridianne O'Dea, Caroline Oehler, Jordi Piera-Jiménez, Sebastian Potthoff, Gentiana Qirjako, Tim Rapley, Judith Rosmalen, Ylenia Sacco, Ludovic Samalin, Mette Maria Skjoth, Kristine Tarp, Ingrid Titzler, Erik Van der Eycken, Claire Rosalie van Genugten, Alexis Whitton, Enrico Zanalda, Jan H Smit, Heleen Riper. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 03.02.2023.)

In 2015, Apple launched an open-source software framework called ResearchKit. ResearchKit provides an infrastructure for conducting remote, smartphone-based research trials through the means of Apple's App Store. Such trials may have several advantages over conventional trial methods including the removal of geographic barriers, frequent assessments of participants in real-life settings, and increased inclusion of seldom-heard communities. The aim of the current study was to explore the feasibility of participant recruitment and the potential for data collection in the non-clinical population in a smartphone-based trial using ResearchKit. As a case example, an app called eMovit, a behavioural activation (BA) app with the aim of helping users to build healthy habits was used. The study was conducted over a 9-month period. Any iPhone user with access to the App Stores of The Netherlands, Belgium, and Germany could download the app and participate in the study. During the study period, the eMovit app was disseminated amongst potential users via social media posts (Twitter, Facebook, LinkedIn), paid social media advertisements (Facebook), digital newsletters and newspaper articles, blogposts and other websites. In total, 1,788 individuals visited the eMovit landing page. A total of 144 visitors subsequently entered Apple's App Store through that landing page. The eMovit product page was viewed 10,327 times on the App Store. With 79 installs, eMovit showed a conversion rate of 0.76% from product view to install of the app. Of those 79 installs, 53 users indicated that they were interested to participate in the research study and 36 subsequently consented and completed the demographics and the participants quiz. Fifteen participants completed the first PHQ-8 assessment and one participant completed the second PHQ-8 assessment. We conclude that from a technological point of view, the means provided by ResearchKit are well suited to be integrated into the app process and thus facilitate conducting smartphone-based studies. However, this study shows that although participant recruitment is technically straightforward, only low recruitment rates were achieved with the dissemination strategies applied. We argue that smartphone-based trials (using ResearchKit) require a well-designed app dissemination process to attain a sufficient sample size. Guidelines for smartphone-based trial designs and recommendations on how to work with challenges of mHealth research will ensure the quality of these trials, facilitate researchers to do more testing of mental health apps and with that enlarge the evidence-base for mHealth., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Bührmann, Van Daele, Rinn, De Witte, Lehr, Aardoom, Loheide-Niesmann, Smit and Riper.)

Myeloid cells, crucial players in antitumoral defense, are affected by tumor-derived factors and treatment. The role of myeloid cells and their progenitors prior to tumor infiltration is poorly understood. Here we show single-cell transcriptomics and functional analyses of the myeloid cell lineage in patients with non-medullary thyroid carcinoma (TC) and multinodular goiter, before and after treatment with radioactive iodine compared to healthy controls. Integrative data analysis indicates that monocytes of TC patients have transcriptional upregulation of antigen presentation, reduced cytokine production capacity, and overproduction of reactive oxygen species. Interestingly, these cancer-related pathological changes are partially removed upon treatment. In bone marrow, TC patients tend to shift from myelopoiesis towards lymphopoiesis, reflected in transcriptional differences. Taken together, distinct transcriptional and functional changes in myeloid cells arise before their infiltration of the tumor and are already initiated in bone marrow, which suggests an active role in forming the tumor immune microenvironment., (© 2022. The Author(s).)

Mental health smartphone apps could increase the safety and self-management of patients at risk of suicide, but it is still unclear whether it is feasible to integrate such apps into routine mental healthcare. This study reports on the feasibility of using a safety planning app (BackUp) and a self-monitoring app (mEMA) as components of the routine treatment of depressed outpatients with suicidal ideation. Clinicians were trained in working with both of the apps, and they invited their eligible patients with suicidal ideation for study participation. Patients used the apps for 3 months and discussed these with their clinician during treatment. Patients completed assessments at baseline (T 0 ), 4 weeks (T 1 ) and post-test (T 2 , 12 weeks after baseline). Both patients and clinicians also participated in telephone interviews. Feasibility was assessed in terms of usability (score > 70 on System Usability Scale, SUS), acceptability (score > 20 on Client Satisfaction Questionnaire-8, CSQ-8), and uptake (sufficient rates of component completion and app usage in treatment). The sample included 17 adult outpatients (52.9% male, age range 20-50 years) diagnosed with a depressive disorder and suicidal ideation at baseline. BackUp was rated by patients at above the cut-off scores for usability (SUS mean score at T 1 75.63 and at T 2 77.71) and acceptability (CSQ-8 mean score at T 1 23.42 and at T 2 23.50). mEMA was similarly rated (SUS mean score at T 1 75.83 and at T 2 76.25; CSQ-8 mean score at T 1 23.92 and at T 2 22.75). Telephone interviews with patients and clinicians confirmed the usability and acceptability. The uptake criteria were not met. Our findings suggest that mobile safety planning and mobile self-monitoring can be considered acceptable and usable as treatment components for depressed suicidal outpatients, but the integration of apps into routine treatment needs to be further explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nuij, van Ballegooijen, de Beurs, de Winter, Gilissen, O’Connor, Smit, Kerkhof and Riper.)

Introduction: This study aimed to evaluate the incidence, severity and presence of symptoms of respiratory tract infections and COVID-19, in patients with pre-existing thyroid dysfunction compared to individuals without thyroid diseases, during the peak month of the COVID-19 pandemic in the Netherlands., Subjects and Methods: In this retrospective observational cohort study, all patients currently under follow-up at the Radboud UMC for thyroid dysfunction received a digital questionnaire. Primary outcomes were incidence of self-reported sickness and cases diagnosed with COVID-19. We compared these primary outcomes between these patients and individuals without thyroid diseases that received the same questionnaire, recruited from the Human Functional Genomics Cohort at the Radboud UMC., Results: In total, 238 patients with pre-existing thyroid dysfunction and 161 controls were included. Patients did not report more sickness (30.7% vs. 29.2%; p = 0.752) or microbiologically confirmed SARS-CoV-2 infections (1.7% vs. 0.6%; p = 0.351). COVID-19 clinical diagnosis was more frequently made in patients with thyroid diseases (4.2% vs. 0.6%; p = 0.032), despite overall lower incidence of self-reported respiratory related symptoms (52.8% vs. 63.8%; p = 0.028), compared to controls. Sub-group analysis between patients with autoimmune and not-autoimmune thyroid dysfunction did not reveal significant associations with respect to any of the outcome measures., Conclusion: This retrospective survey of a cohort of patients with from a tertiary academic hospital suggests that pre-existing thyroid dysfunction, independent from the aetiology, does not lead to an apparent risk to develop respiratory tract infections and COVID-19 related symptoms.

To fully assess the resilience and recovery of life in response to the Cretaceous-Paleogene (K-Pg) boundary mass extinction ~ 66 million years ago, it is paramount to understand biodiversity prior to the Chicxulub impact event. The peak ring of the Chicxulub impact structure offshore the Yucatán Peninsula (México) was recently drilled and extracted a ~ 100 m thick impact-generated, melt-bearing, polymict breccia (crater suevite), which preserved carbonate clasts with common biogenic structures. We pieced this information to reproduce for the first time the macrobenthic tracemaker community and marine paleoenvironment prior to a large impact event at the crater area by combining paleoichnology with micropaleontology. A variable macrobenthic tracemaker community was present prior to the impact (Cenomanian-Maastrichtian), which included soft bodied organisms such as annelids, crustaceans and bivalves, mainly colonizing softgrounds in marine oxygenated, nutrient rich, conditions. Trace fossil assemblage from these upper Cretaceous core lithologies, with dominant Planolites and frequent Chondrites, corresponds well with that in the overlying post-impact Paleogene sediments. This reveals that the K-Pg impact event had no significant effects (i.e., extinction) on the composition of the macroinvertebrate tracemaker community in the Chicxulub region., (© 2022. The Author(s).)

Background: Internet-based Cognitive Behaviour Therapy (iCBT) for depression have been implemented in routine care across Europe in varying ways, at various scales and with varying success. This study aimed to advance our understanding of organisational implementation climate from the perspectives of implementers and mental health service deliverers., Methods: Qualitative and quantitative methods were combined to study the concept of organisational implementation climate in mental health care settings. Based on concept mapping, a qualitative workshop with implementers was used to conceptualise organisational implementation climate for optimizing iCBT use in routine practice. Service deliverers involved in the provision of iCBT were invited to participate in an explorative cross-sectional survey assessing levels of satisfaction and usability of iCBT, and organisational implementation climate in implementing iCBT. The two methods were applied independently to study viewpoints of implementers as well as service deliverers. Corresponding to the explorative nature of the study, inductive reasoning was applied to identify patterns and develop a reasonable explanation of the observations made. Correlative associations between satisfaction, usability and implementation climate were explored., Results: Sixteen implementers representing fourteen service delivery organisations across Europe participated in the workshop. The top-three characteristics of a supportive organisational implementation climate included: (1) clear roles and skills of implementers, (2) feasible implementation targets, and (3) a dedicated implementation team. The top-three tools for creating a supportive implementation climate included: (1) feedback on job performance, (2) progress monitoring in achieving implementation targets, and (3) guidelines for assessing the impact of iCBT. The survey (n=111) indicated that service providers generally regarded their organisational implementation climate as supportive in implementing iCBT services. Organisational implementation climate was weakly associated with perceived usability and moderately with satisfaction with iCBT services., Conclusions: Organisational implementation climate is a relevant factor to implementers and service deliverers in implementing iCBT in routine care. It is not only an inherent characteristic of the context in which implementation takes place, it can also be shaped to improve implementation of iCBT services. Future research should further theorise organisational implementation climate and empirically validate the measurement instruments such as used in this study., (© 2022. The Author(s).)

Fibrodysplasia ossificans progressiva (FOP), sometimes known as myositis ossificans progressiva, is an ultra-rare disease in which bone is formed in muscular tissue, tendons and ligaments. This is known as heterotopic ossification (HO). FOP is caused by a heterozygous mutation in the highly conserved ACVR1/ALK2 gene which affects about 1 in 1.5-2 million individuals. At birth, patients with the predominant R206H mutation only exhibit a bilateral hallux valgus. During childhood, heterotopic bone formation develops in a typical pattern, affecting the axial muscles first before appendicular body parts are involved. HO can start spontaneously but is often elicited by soft tissue trauma or medical procedures. After soft tissue injury, an inflammatory process called a flare-up can start, followed by the formation of HO. HO leads to a limited range of motion, culminating in complete ankylosis of nearly all joints. As a result of HO surrounding the thorax, patients often suffer from thoracic insufficiency syndrome (TIS). TIS is the most common cause of a limited life expectancy for FOP patients, with a median life expectancy of 56 years. Management is focused on preventing soft-tissue injury that can provoke flare-ups. This includes prevention of iatrogenic damage by biopsies, intramuscular injections and surgery. Anti-inflammatory medication is often started when a flare-up occurs but has a poor basis of evidence. Several forms of potential treatment for FOP are being researched in clinical trials. Progression of the disease is monitored using CT and 18F-NaF PET/CT combined with functional assessments. Patients are regularly evaluated for frequently occurring complications such as restrictive lung disease. Here, we review the current management, monitoring and treatment of FOP., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Smilde et al.)

Literature provides a moderate level of evidence for the beneficial effects of incisional negative pressure wound therapy (iNPWT) on scar quality. The purpose of this study was to establish if iNPWT results in improved scar outcomes in comparison to the standard of care. Therefore, a within-patient randomised controlled, open-label trial was conducted in transgender men undergoing gender-affirming mastectomies. A unilateral side was randomised to receive iNPWT (PICO™, Smith&Nephew) without suction drains and contrastingly the standard dressing (Steri-Strips™) with suction drain. Scar quality and questionnaires were bilaterally measured by means of objective assessments and patient-reported outcome measures (PROM) at 1, 3 and 12 months. Objective scar outcomes were scar pliability (Cutometer®), colouration (DSM-II) and scar width (3-D imaging). PROM outcomes were related to scars (POSAS and SCAR-Q) and body satisfaction (BODY-Q). From 85 included patients, 80 were included for analyses. No significant difference between treatments was seen in the quantitative outcomes of scar pliability, colour, and width. For qualitative scar outcomes, several significant findings for iNPWT were found for several subscales of the POSAS, SCAR-Q, and BODY-Q. These effects could not be substantiated with linear mixed-model regression, signifying no statically more favourable outcome for either treatment option. In conclusion, this study demonstrated that some PROM outcomes were more favourable for the iNPWT compared to standard treatment. In contrast, the quantitative outcomes showed no beneficial effects of iNPWT on scar outcomes. This suggests that iNPWT is of little benefit as a scar-improving therapy., (© 2022 The Authors. Wound Repair and Regeneration published by Wiley Periodicals LLC on behalf of The Wound Healing Society.)

The Cretaceous-Palaeogene mass extinction around 66 million years ago was triggered by the Chicxulub asteroid impact on the present-day Yucatán Peninsula 1,2 . This event caused the highly selective extinction that eliminated about 76% of species 3,4 , including all non-avian dinosaurs, pterosaurs, ammonites, rudists and most marine reptiles. The timing of the impact and its aftermath have been studied mainly on millennial timescales, leaving the season of the impact unconstrained. Here, by studying fishes that died on the day the Mesozoic era ended, we demonstrate that the impact that caused the Cretaceous-Palaeogene mass extinction took place during boreal spring. Osteohistology together with stable isotope records of exceptionally preserved perichondral and dermal bones in acipenseriform fishes from the Tanis impact-induced seiche deposits 5 reveal annual cyclicity across the final years of the Cretaceous period. Annual life cycles, including seasonal timing and duration of reproduction, feeding, hibernation and aestivation, vary strongly across latest Cretaceous biotic clades. We postulate that the timing of the Chicxulub impact in boreal spring and austral autumn was a major influence on selective biotic survival across the Cretaceous-Palaeogene boundary., (© 2022. The Author(s).)

Background: Longitudinal observational cohort studies in cancer patients are important to move research and clinical practice forward. Continued study participation (study retention) is of importance to maintain the statistical power of research and facilitate representativeness of study findings. This study aimed to investigate study retention and attrition (drop-out) and its associated sociodemographic and clinical factors among head and neck cancer (HNC) patients and informal caregivers included in the Netherlands Quality of Life and Biomedical Cohort Study (NET-QUBIC)., Methods: NET-QUBIC is a longitudinal cohort study among 739 HNC patients and 262 informal caregivers with collection of patient-reported outcome measures (PROMs), fieldwork data (interview, objective tests and medical examination) and biobank materials. Study retention and attrition was described from baseline (before treatment) up to 2-years follow-up (after treatment). Sociodemographic and clinical characteristics associated with retention in NET-QUBIC components at baseline (PROMs, fieldwork and biobank samples) and retention in general (participation in at least one component) were investigated using Chi-square, Fisher exact or independent t-tests (p< 0.05)., Results: Study retention at 2-years follow-up was 80% among patients alive (66% among all patients) and 70% among caregivers of patients who were alive and participating (52% among all caregivers). Attrition was most often caused by mortality, and logistic, physical, or psychological-related reasons. Tumor stage I/II, better physical performance and better (lower) comorbidity score were associated with participation in the PROMs component among patients. No factors associated with participation in the fieldwork component (patients), overall sample collection (patients and caregivers) or PROMs component (caregivers) were identified. A better performance and comorbidity score (among patients) and higher age (among caregivers) were associated with study retention at 2-years follow-up., Conclusions: Retention rates were high at two years follow-up (i.e. 80% among HNC patients alive and 70% among informal caregivers with an active patient). Nevertheless, some selection was shown in terms of tumor stage, physical performance, comorbidity and age, which might limit representativeness of NET-QUBIC data and samples. To facilitate representativeness of study findings future cohort studies might benefit from oversampling specific subgroups, such as patients with poor clinical outcomes or higher comorbidity and younger caregivers., (© 2022. The Author(s).)

Background: Accurate identification of older persons at risk of unplanned hospital visits can facilitate preventive interventions. Several risk scores have been developed to identify older adults at risk of unplanned hospital visits. It is unclear whether risk scores developed in one country, perform as well in another. This study validates seven risk scores to predict unplanned hospital admissions and emergency department (ED) visits in older home care recipients from six countries., Methods: We used the IBenC sample (n = 2446), a cohort of older home care recipients from six countries (Belgium, Finland, Germany, Iceland, Italy and The Netherlands) to validate four specific risk scores (DIVERT, CARS, EARLI and previous acute admissions) and three frailty indicators (CHESS, Fried Frailty Criteria and Frailty Index). Outcome measures were unplanned hospital admissions, ED visits or any unplanned hospital visits after 6 months. Missing data were handled by multiple imputation. Performance was determined by assessing calibration and discrimination (area under receiver operating characteristic curve (AUC))., Results: Risk score performance varied across countries. In Iceland, for any unplanned hospital visits DIVERT and CARS reached a fair predictive value (AUC 0.74 [0.68-0.80] and AUC 0.74 [0.67-0.80]), respectively). In Finland, DIVERT had fair performance predicting ED visits (AUC 0.72 [0.67-0.77]) and any unplanned hospital visits (AUC 0.73 [0.67-0.77]). In other countries, AUCs did not exceed 0.70., Conclusions: Geographical validation of risk scores predicting unplanned hospital visits in home care recipients showed substantial variations of poor to fair performance across countries. Unplanned hospital visits seem considerably dependent on healthcare context. Therefore, risk scores should be validated regionally before applied to practice. Future studies should focus on identification of more discriminative predictors in order to develop more accurate risk scores., (© 2021. The Author(s).)

Introduction: Pioneers have shown that it is possible to reconstruct a full breast using just autologous fat harvested by liposuction or autologous fat transfer (AFT). This study describes the first multicentre randomised study protocol to thoroughly investigate the effectiveness of AFT to reconstruct full breasts following mastectomy procedures (primarily and delayed)., Methods and Analysis: This study is designed as a multicentre, randomised controlled clinical superiority trial with a 1:1 allocation ratio. A total of 196 patients (98 patients per treatment arm) are aimed to be included. Patients who wish to undergo breast reconstruction with either one of the two techniques are randomly allocated into the AFT group (intervention) or the tissue-expander/prosthesis group (control). The primary outcome measure for the quality of life is measured by the validated BREAST-Q questionnaire., Ethics and Dissemination: Approval for this study was obtained from the medical ethics committee of Maastricht University Medical Centre/Maastricht University; the trial has been registered at ClinicalTrials.gov. The results of this randomised controlled trial will be presented at scientific meetings as abstracts for poster or oral presentations and published in peer-reviewed journals., Trial Status: Enrolment into the trial has started in October 2015. Data collection and data analysis are expected to be completed in December 2021., Trial Registration Number: NCT02339779., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Unusual sexual interests are largely intercorrelated, yet not much is known about underlying patterns of clusters between various sexual interests., Aim: To identify underlying clusters of unusual sexual interests using exploratory factor analysis., Methods: We conducted exploratory factor analysis with self-reported interest in a wide variety of unusual sexual acts for an online, international sample (N = 669; 61% female), and for women and men separately. Factor regression weights were correlated to self-reported sex life satisfaction, sexual outlet, and psychiatric symptoms., Outcomes: Participants rated the attractiveness of 50 unusual sexual activities, and reported on their sex life satisfaction (Arizona Sexual Experiences Scale), sexual outlet, and symptoms regarding ADHD (Adult ADHD Self-Report Screening Scale for DSM-5), depression, anxiety, and stress (Depression, Anxiety, and Stress Scale)., Results: We identified 5 factors of unusual sexual interests that were largely comparable for women and men: submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia (attraction to dirtiness or soiled things), and fetishism. For women, unusual sexual interests related to more psychiatric symptoms and higher sexual outlet, whereas this relation was less explicit for men., Clinical Implications: Different factors of unusual sexual interests may serve different underlying functions or motivations, for instance related to sexual, and emotional regulation. A better understanding of the nature of unusual sexual interests is important to be able to influence sexual interests that are unwanted or cause damage to others., Strengths & Limitations: Strength of this study include its anonymity, the avoidance of sexual orientation effects, and the possibility to indicate only a slight endorsement toward sexual items. Limitations include the sample's generalizability and the truthfulness of online responding., Conclusion: Unusual sexual interests could be clustered into 5 factors that were largely comparable for women and men: submission/masochism, forbidden sexual activities, dominance/sadism, mysophilia, and fetishism. Schippers EE, Smid WJ, Huckelba AL, et al. Exploratory Factor Analysis of Unusual Sexual Interests. J Sex Med 2021;18:1615-1631., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Attachment (mal)functioning and a history of childhood trauma (CT) are both considered psychological determinants of personality disorders (PDs). Their interaction, however, remains largely uninvestigated. In this study, the authors assessed adult and childhood attachment style in a sample of patients with diverse PDs ( N = 75) and determined the relation with both occurrence and severity of CT. The authors found that the sample was characterized by severe attachment malfunctioning and high levels of CT. Using cross-tabulations and analysis of variance, the authors showed that patients with a fearful or dismissive attachment style experienced more severe CT than patients with a preoccupied attachment style. Patients reporting an affectionless control bonding style to either parent suffered frequent and severe CT. Although temporal causality cannot be determined, these findings stress the necessity to screen for CT in PDs and suggest that attachment-centered psychotherapy for these patients may benefit from preceding or concurrent trauma treatment.

Differentiated thyroid cancer (DTC) is the most frequent endocrine tumor with a good prognosis after primary treatment in most cases. By contrast, 30-40% of patients with metastatic DTC are unresponsive to 131 I radioactive iodide (RAI) treatment due to tumor dedifferentiation. Currently, underlying molecular mechanisms of dedifferentiation remain elusive and predictive biomarkers are lacking. Therefore, the present study aimed to identify molecular biomarkers in primary tumors associated with RAI refractoriness. A retrospective cohort was gathered consisting of RAI-sensitive patients with DTC and RAI-refractory patients with poorly DTC. In all patients, extensive intratumoral mutation profiling, gene fusions analysis, telomerase reverse transcriptase (TERT) promoter mutation analysis and formalin-fixed paraffin-embedded-compatible RNA sequencing were performed. Genetic analyses revealed an increased mutational load in RAI-refractory DTC, including mutations in AKT1, PTEN, TP53 and TERT promoter. Transcriptomic analyses revealed profound differential expression of insulin-like growth factor 2 ( IGF2 ), with up to 100-fold higher expression in RAI-refractory DTC compared with in RAI-sensitive DTC cases. ELISA revealed significant lower IGF2 plasma concentrations after surgery and subsequent 131 I RAI therapy in patients with DTC compared with pretreatment baseline. Overall, the current findings suggested that the tumor-promoting growth factor IGF2 may have a potential role in acquiring RAI refractoriness., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Crezee et al.)

Background: Although depression is typically characterized by a persistent depressed mood, mood dynamics do seem to vary across a depressed population. Heterogeneity of mood variability (magnitude of changes) and emotional inertia (speed at which mood shifts) is seen in clinical practice. However, studies investigating the heterogeneity of these mood dynamics are still scarce. The aim of the present study is to explore different distinctive profiles in real-time monitored mood dynamics among depressed persons., Methods: After completing baseline measures, mildly-to-moderately depressed persons ( n  = 37) were prompted to rate their current mood (1-10 scale) on their smartphones, 3 times a day for 7 consecutive days. Latent profile analyses were applied to identify profiles based on average mood, variability of mood and emotional inertia as reported by the participants., Results: Two profiles were identified in this sample. The overwhelming majority of the sample belonged to profile 1 ( n  = 31). Persons in profile 1 were characterized by a mood just above the cutoff for positive mood (M = 6.27), with smaller mood shifts (lower variability [SD = 1.05]) than those in profile 2 ( n  = 6), who displayed an overall negative mood (M = 4.72) and larger mood shifts (higher variability [SD = 1.95]) but at similar speed (emotional inertia) (AC = 0.19, AC = 0.26, respectively)., Conclusions: The present study provides preliminary indications for patterns of average mood and mood variability, but not emotional inertia, among mildly-to-moderately depressed persons., Competing Interests: None., (© 2021 The Authors.)

Context: Lymphopenia is a key feature of immune dysfunction in patients with bacterial sepsis and coronavirus disease 2019 (COVID-19) and is associated with poor clinical outcomes, but the cause is largely unknown. Severely ill patients may present with thyroid function abnormalities, so-called nonthyroidal illness syndrome, and several studies have linked thyrotropin (thyroid stimulating hormone, TSH) and the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3) to homeostatic regulation and function of lymphocyte populations., Objective: This work aimed to test the hypothesis that abnormal thyroid function correlates with lymphopenia in patients with severe infections., Methods: A retrospective analysis of absolute lymphocyte counts, circulating TSH, T4, free T4 (FT4), T3, albumin, and inflammatory biomarkers was performed in 2 independent hospitalized study populations: bacterial sepsis (n = 224) and COVID-19 patients (n = 161). A subgroup analysis was performed in patients with severe lymphopenia and normal lymphocyte counts., Results: Only T3 significantly correlated (ρ = 0.252) with lymphocyte counts in patients with bacterial sepsis, and lower concentrations were found in severe lymphopenic compared to nonlymphopenic patients (n = 56 per group). Severe lymphopenic COVID-19 patients (n = 17) showed significantly lower plasma concentrations of TSH, T4, FT4, and T3 compared to patients without lymphopenia (n = 18), and demonstrated significantly increased values of the inflammatory markers interleukin-6, C-reactive protein, and ferritin. Remarkably, after 1 week of follow-up, the majority (12 of 15) of COVID-19 patients showed quantitative recovery of their lymphocyte numbers, whereas TSH and thyroid hormones remained mainly disturbed., Conclusion: Abnormal thyroid function correlates with lymphopenia in patients with severe infections, like bacterial sepsis and COVID-19, but future studies need to establish whether a causal relationship is involved., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Non-medullary thyroid cancer (NMTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). However, in a subset of NMTC patients tumor dedifferentiation occurs, leading to RAI resistance. Digoxin has been demonstrated to restore iodide uptake capacity in vitro in poorly differentiated and anaplastic NMTC cells, termed redifferentiation. The aim of the present study was to investigate the in vivo effects of digoxin in TPO-Cre/LSL-Braf V600E mice and digoxin-treated NMTC patients., Methods: Mice with thyroid cancer were subjected to 3D ultrasound for monitoring tumor growth and 124 I PET/CT for measurement of intratumoral iodide uptake. Post-mortem analyses on tumor tissues comprised gene expression profiling and measurement of intratumoral autophagy activity. Through PALGA (Dutch Pathology Registry), archived tumor material was obtained from 11 non-anaplastic NMTC patients who were using digoxin. Clinical characteristics and tumor material of these patients were compared to 11 matched control NMTC patients never treated with digoxin., Results: We found that in mice, tumor growth was inhibited and 124 I accumulation was sustainably increased after short-course digoxin treatment. Post-mortem analyses revealed that digoxin treatment increased autophagy activity and enhanced expression of thyroid-specific genes in mouse tumors compared to vehicle-treated mice. Digoxin-treated NMTC patients exhibited significantly higher autophagy activity and a higher differentiation status as compared to matched control NMTC patients, and were associated with favourable clinical outcome., Conclusions: These in vivo data support the hypothesis that digoxin may represent a repositioned adjunctive treatment modality that suppresses tumor growth and improves RAI sensitivity in patients with RAI-refractory NMTC.

The Cretaceous-Paleogene (K-Pg) mass extinction is marked globally by elevated concentrations of iridium, emplaced by a hypervelocity impact event 66 million years ago. Here, we report new data from four independent laboratories that reveal a positive iridium anomaly within the peak-ring sequence of the Chicxulub impact structure, in drill core recovered by IODP-ICDP Expedition 364. The highest concentration of ultrafine meteoritic matter occurs in the post-impact sediments that cover the crater peak ring, just below the lowermost Danian pelagic limestone. Within years to decades after the impact event, this part of the Chicxulub impact basin returned to a relatively low-energy depositional environment, recording in unprecedented detail the recovery of life during the succeeding millennia. The iridium layer provides a key temporal horizon precisely linking Chicxulub to K-Pg boundary sections worldwide., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Context: Breast development is important for most trans women. An important limitation of current breast development measurement methods is that these do not allow for 3D volume analyses., Objectives: To examine breast development and change in anthropometry during the first 3 years of gender-affirming hormone treatment using 3D imaging. Associations with clinical or laboratory parameters and satisfaction with the gained breast development were also studied., Design: Prospective cohort study., Setting: Specialized tertiary gender identity clinic in Amsterdam, the Netherlands., Participants: Participants were 69 adult trans women with a median age of 26 years (interquartile range, 21-38)., Interventions: Gender-affirming hormone treatment., Main Outcome Measures: Volumetric and anthropometric breast development and satisfaction., Results: Breast volume increased by 72 cc (95% confidence interval [CI], 48-97) to 100 cc (standard deviation 48). This resulted in a cup-size

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Introduction: Psychotherapy may reduce suicidal thoughts and behaviour, but its effectiveness is not well examined. Furthermore, conventional meta-analyses are unable to test possible effects of moderators affecting this relationship. This protocol outlines the building of a comprehensive database of the literature in this research field. In addition, we will conduct an individual patient data meta-analysis (IPD-MA) to establish the effectiveness of psychotherapy in reducing suicidality, and to examine which factors moderate the efficacy of these interventions., Methods and Analysis: To build a comprehensive database, randomised controlled trials examining the effect of any psychotherapy targeting any psychiatric disorder on suicidal thoughts or behaviour will be identified by running a systematic search in PubMed, Embase, PsycINFO, Web of Science, Scopus and The Cochrane Central Register of Controlled Trials from data inception to 12 August 2019. For the IPD-MA, we will focus on adult outpatients with suicidal ideation or behaviour. In addition, as a comparison group we will focus on a control group (waiting-list, care as usual or placebo). A 1-stage IPD-MA will be used to determine the effectiveness of psychotherapy on suicidal ideation, suicide attempts and/or suicide deaths, and to investigate potential patient-related and intervention-related moderators. Subgroup and sensitivity analyses will be conducted to test the robustness of the findings. Additionally, a conventional MA will be conducted to determine the differences between studies that provided IPD and those that did not. IPD-MA may determine the effectiveness of psychotherapy in reducing suicidality and provide insights into the moderating factors influencing the efficacy of psychotherapy. Answering these questions will inform mental healthcare practitioners about optimal treatments for different groups of individuals with suicidal ideation and/or behaviour and consequently help to reduce suicide risk., Ethics and Dissemination: An ethical approval is not required for this study. The results will be published in a peer-review journal., Prospero Registration Number: CRD42020140573., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Breast implants are frequently used in cosmetic and reconstructive breast surgery. Capsular contracture, the most common long-term complication, is usually graded using the Baker classification. Despite its widespread use, the reliability of the Baker classification has never been established. The aim of this study was to determine the interobserver reliability and agreement of the Baker classification., Methods: Sixty women who had undergone cosmetic breast augmentation were included. They were examined independently by two plastic surgeons from an observer pool. The Baker score was determined, along with firmness, dislocation, symmetry, and pain using four-point scales. Patients were asked to complete the BREAST-Q postaugmentation module. The interobserver reliability and agreement were calculated for all variables with a quadratic weighted kappa., Results: The interobserver reliability of the Baker classification was poor (kappa, 0.55; 95 percent CI, 0.37 to 0.72). Interobserver reliability of the clinical parameters firmness (0.64; 95 percent CI, 0.49 to 0.79), dislocation (0.49; 95 percent CI, 0.26 to 0.73), and symmetry (0.61; 95 percent CI, 0.34 to 0.88) was also poor. Pain scores seemed more reliable (0.72; 95 percent CI, 0.56 to 0.89); however, most patients had no pain. The interobserver agreement for the Baker score was 48 percent; in 43 percent, the observers differed one category; and in 12 percent, the difference was more than one category., Conclusions: Interobserver reliability and observer agreement of the Baker classification for capsular contracture were poor. Consensus about how to adequately rate the symptoms of capsular complaints is lacking. A more reliable method of measurement or description is needed, especially for scientific research purposes, to assess the long-term problems associated with breast implants., Clinical Question/level of Evidence: Diagnostic, IV.

The PI3K-Akt-mTOR pathway plays a central role in the development of non-medullary thyroid carcinoma (NMTC). Although somatic mutations have been identified in these genes in NMTC patients, the role of germline variants has not been investigated. Here, we selected frequently occurring genetic variants in AKT1, AKT2, AKT3, PIK3CA and MTOR and have assessed their effect on NMTC susceptibility, progression and clinical outcome in a Dutch discovery cohort (154 patients, 188 controls) and a Romanian validation cohort (159 patients, 260 controls). Significant associations with NMTC susceptibility were observed for AKT1 polymorphisms rs3803304, rs2494732 and rs2498804 in the Dutch discovery cohort, of which the AKT1 rs3803304 association was confirmed in the Romanian validation cohort. No associations were observed between PI3K-Akt-mTOR polymorphisms and clinical parameters including histology, TNM staging, treatment response and clinical outcome. Functionally, cells bearing the associated AKT1 rs3803304 risk allele exhibit increased levels of phosphorylated Akt protein, potentially leading to elevated signaling activity of the oncogenic Akt pathway. All together, germline encoded polymorphisms in the PI3K-Akt-mTOR pathway could represent important risk factors in development of NMTC.

In the field of rare bone diseases in particular, a broad care team of specialists embedded in multidisciplinary clinical and research environment is essential to generate new therapeutic solutions and approaches to care. Collaboration among clinical and research departments within a University Medical Center is often difficult to establish, and may be hindered by competition and non-equivalent cooperation inherent in a hierarchical structure. Here we describe the "collaborative organizational model" of the Amsterdam Bone Center (ABC), which emerged from and benefited the rare bone disease team. This team is often confronted with pathologically complex and under-investigated diseases. We describe the benefits of this model that still guarantees the autonomy of each team member, but combines and focuses our collective expertise on a clear shared goal, enabling us to capture synergistic and innovative opportunities for the patient, while avoiding self-interest and possible harmful competition., (Copyright © 2020 Eekhoff, Micha, Forouzanfar, de Vries, Netelenbos, Klein-Nulend, van Loon, Lubbers, Schwarte, Schober, Raijmakers, Teunissen, de Graaf, Lammertsma, Yaqub, Botman, Treurniet, Smilde, Bökenkamp, Boonstra, Kamp, Nieuwenhuijzen, Visser, Baayen, Dahele, Eeckhout, Goderie, Smits, Gilijamse, Karagozoglu, van de Valk, Dickhoff, Moll, Verbraak, Curro-Tafili, Ghyczy, Rustemeyer, Saeed, Maugeri, Pals, Ridwan-Pramana, Pekel, Schoenmaker, Lems, Winters, Botman, Giannakópoulos, Koolwijk, Janssen, Kloen, Bravenboer, Smit and Helder.)

Background: Penile inversion vaginoplasty is the surgical gold standard for genital gender-affirmative surgery in transgender women. However, there is an increase of attention for gender-confirming vulvoplasty (GCV), in which no neovaginal cavity is created., Aim: To describe underlying motives and surgical outcomes of GCV in transgender women., Methods: All transgender women who underwent GCV were retrospectively identified from a departmental database. A retrospective chart study was conducted, recording underlying motives, demographics, perioperative complications, and reoperations., Outcomes: Underlying motives and perioperative complication rate., Results: In the period January 1990 to January 2020, 17 transgender women underwent GCV at our center. Most women reported that their motivation to undergo GCV was because they had no wish for postoperative neovaginal penetration (n = 10, 59%). This was due to a sexual preference toward women without the wish for neovaginal penetrative intercourse (n = 6, 35%) or due to a negative sexual experience in the past (n = 4, 24%). Some women desired vaginoplasty with neovaginal cavity creation but were ineligible for this because of their medical history (n = 4, 24%), for example, due to locoregional radiotherapy. The median clinical follow-up was 34 months (range 3-190). The postoperative course was uncomplicated in 11 (65%) women. Postoperative complications comprised the following: meatal stenosis (n = 2, for which surgical correction), remnant corpus spongiosum tissue (n = 1, for which surgical correction), minor wound dehiscence (n = 3, for which conservative management), and postoperative urinary tract infection (n = 1, successfully treated with oral antibiotics). One woman, who developed meatal stenosis, had a history of radiotherapy because of rectal carcinoma and needed 2 surgical procedures under general anesthesia to correct this. Information on self-reported satisfaction was available for 12 women. All were satisfied with the postoperative result and they graded their neovagina an 8.2 ± 0.9 out of 10., Clinical Implications: GCV may be added to the surgical repertoire of the gender surgeon. Transgender women with a desire for genital gender-affirmative surgery should be counseled on surgical options and its (dis)advantages., Strengths & Limitations: Strengths of this study comprise that it is from a high-volume center. A weakness of this study is the retrospective design. The absence of a self-reported outcome measure validated for the transgender persons is a well-known problem., Conclusion: An increase is observed in transgender women who opt for GCV; however, the absolute number undergoing this surgery remains small in our center. Postoperative complications do occur but are generally minor and treatable. van der Sluis WB, Steensma TD, Timmermans FW, et al. Gender-Confirming Vulvoplasty in Transgender Women in the Netherlands: Incidence, Motivation Analysis, and Surgical Outcomes. J Sex Med 2020;17:1566-1573., (Copyright © 2020 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: The level of daily physical activity in patients with cancer is frequently assessed by questionnaires, such as the Physical Activity Scale for the Elderly (PASE). Objective assessments, with for example accelerometers, may be a good alternative. The aim of this study was to investigate the agreement between the PASE questionnaire and accelerometer-assessed physical activity in a large group of patients with different types of cancer., Methods: Baseline accelerometer and PASE questionnaire data of 403 participants from the REACT (Resistance and Endurance Exercise After Chemotherapy, n = 227), the EXIST (Exercise Intervention After Stem-Cell Transplantation, n = 74), and NET-QUBIC (NEtherlands QUality of Life And Biomedical Cohort Studies In Cancer, n = 102) studies were available for the current analyses. Physical activity was assessed by the PASE questionnaire (total score) and accelerometers (total minutes per day > 100 counts). Linear mixed models regression analysis was used to assess the agreement between the PASE questionnaire and accelerometer-assessed physical activity., Results: The mean (SD) PASE score was 95.9 (75.1) points and mean (SD) time in physical activity measured with the accelerometer was 256.6 (78.8) min per day. The agreement between the PASE score and the accelerometer data was significant, but poor (standardized regression coefficient (B) = 0.36, 95%CI = 0.27; 0.44, p < 0.01)., Conclusion: Agreement between the PASE questionnaire and accelerometer-assessed physical activity was poor. The poor agreement indicates that they measure different physical activity constructs and cannot be used interchangeably to assess the level of daily physical activity in patients with cancer.

The ~180-km-diameter Chicxulub peak-ring crater and ~240-km multiring basin, produced by the impact that terminated the Cretaceous, is the largest remaining intact impact basin on Earth. International Ocean Discovery Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drilled to a depth of 1335 m below the sea floor into the peak ring, providing a unique opportunity to study the thermal and chemical modification of Earth's crust caused by the impact. The recovered core shows the crater hosted a spatially extensive hydrothermal system that chemically and mineralogically modified ~1.4 × 10 5 km 3 of Earth's crust, a volume more than nine times that of the Yellowstone Caldera system. Initially, high temperatures of 300° to 400°C and an independent geomagnetic polarity clock indicate the hydrothermal system was long lived, in excess of 10 6 years., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background: The System Usability Scale (SUS) is used to measure usability of internet-based Cognitive Behavioural Therapy (iCBT). However, whether the SUS is a valid instrument to measure usability in this context is unclear. The aim of this study is to assess the factor structure of the SUS, measuring usability of iCBT for depression in a sample of professionals. In addition, the psychometric properties (reliability, convergent validity) of the SUS were tested., Methods: A sample of 242 professionals using iCBT for depression from 6 European countries completed the SUS. Confirmatory Factor Analysis (CFA) was conducted to test whether a one-factor, two-factor, tone-model or bi-direct model would fit the data best. Reliability was assessed using complementary statistical indices (e.g. omega). To assess convergent validity, the SUS total score was correlated with an adapted Client Satisfaction Questionnaire (CSQ-3)., Results: CFA supported the one-factor, two-factor and tone-model, but the bi-factor model fitted the data best (Comparative Fit Index = 0.992, Tucker Lewis Index = 0.985, Root Mean Square Error of Approximation = 0.055, Standardized Root Mean Square Residual = 0.042 (respectively χ 2 diff (9) = 69.82, p < 0.001; χ 2 diff (8) = 33.04, p < 0.001). Reliability of the SUS was good (ω = 0.91). The total SUS score correlated moderately with the CSQ-3 (CSQ1 r s  = .49, p < 0.001; CSQ2 r s  = .46, p < 0.001; CSQ3 r s  = .38, p < 0.001), indicating convergent validity., Conclusions: Although the SUS seems to have a multidimensional structure, the best model showed that the total sumscore of the SUS appears to be a valid and interpretable measure to assess the usability of internet-based interventions when used by professionals in mental healthcare.

Background : There is substantial comorbidity between trauma-related disorders (TRDs), dissociative disorders (DDs) and personality disorders (PDs), especially in patients who report childhood trauma and emotional neglect. However, little is known about the course of these comorbid disorders, despite the fact that this could be of great clinical importance in guiding treatment. Objective : This study describes the two-year course of a cohort of patients with (comorbid) TRDs, DDs and PDs and aims to identify possible predictors of course. Possible gender differences will be described, as well as features of non-respondents. Method : Patients (N = 150) referred to either a trauma treatment program or a PD treatment program were assessed using five structured clinical interviews for diagnosing TRDs, DDs, PDs and trauma histories. Three self-report questionnaires were used to assess general psychopathology, dissociative symptoms and personality pathology in a more dimensional way. Data on demographics and received treatment were obtained using psychiatric records. We described the cohort after a two-year follow-up and used t-tests or chi-square to test possible differences between respondents and non-respondents and between women and men. We used regression analysis to identify possible course predictors. Results : A total of 85 (56.7%) of the original 150 patients participated in the follow-up measurement. Female respondents reported more sexual abuse than female non-respondents. Six patients (4.0%; all women) died because of suicide. Levels of psychopathology significantly declined during the follow-up period, but only among women. Gender was the only significant predictor of change. Conclusions : Comorbidity between TRDs, DDs and PDs was more the rule than the exception, pleading for a more dimensional and integrative view on pathology following childhood trauma and emotional neglect. Courses significantly differed between men and women, advocating more attention to gender in treatment and future research., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Online forums that enable peer-to-peer interaction are widespread and readily available. Aim: This study aimed to identify the reach, benefits, and potential harmful effects for visitors to an online forum embedded in a suicide prevention platform in The Netherlands. Method: The study collected web-based questionnaires from online forum users and moderated posts. Descriptive quantitative and qualitative analyses were performed. Results: The online forum had 330 members in 2017, of whom 130 were active users (posting at least one message). Respondents ( n = 106) experienced from a high severity of suicidal ideation (78%). A minority (12%) visited the forum to find suicide methods and 3% to find a suicide partner. Among respondents who had visited the forum more than once ( n = 49), 53% reported no changes in feelings directly after forum use, 35% felt better and 12% felt worse. Peer support and anonymity were the most mentioned benefits, whereas no personal contacts and few reactions to postings were perceived as limitations. Suicide threats and the search for methods were the main reasons for moderating posts. Limitations: Usage habits and user experiences were available from a relatively small group that visited the forum more than once. Conclusion: In its current form, the forum has a low reach with few benefits and a potential for harm for its users. With a questionable benefit-to-risk ratio, the added value of the online forum appears to be small.

Background: Although major improvements are achieved after cure of Cushing syndrome (CS), fatigue and decreased quality of life persist. This is the first study to measure aerobic exercise capacity in patients in remission of CS for more than 4 years in comparison with matched controls, and to investigate whether the reduction in exercise capacity is related to alterations in muscle tissue., Methods: Seventeen patients were included. A control individual, matched for sex, estrogen status, age, body mass index, smoking, ethnicity, and physical activity level was recruited for each patient. Maximal aerobic capacity (VO2peak) was assessed during incremental bicycle exercise to exhaustion. In 8 individually matched patients and controls, a percutaneous muscle biopsy was obtained and measures were made of cross-sectional areas, capillarization, and oxphos complex IV (COXIV) protein content as an indicator of mitochondrial content. Furthermore, protein content of endothelial nitric oxide synthase (eNOS) and eNOS phosphorylated on serine1177 and of the NAD(P)H-oxidase subunits NOX2, p47phox, and p67phox were measured in the microvascular endothelial layer., Findings: Patients showed a lower mean VO2peak (SD) (28.0 [7.0] vs 34.8 [7.9] ml O2/kg bw/min, P < .01), maximal workload (SD) (176 [49] vs 212 [67] watt, P = .01), and oxygen pulse (SD) (12.0 [3.7] vs 14.8 [4.2] ml/beat, P < .01) at VO2peak. No differences were seen in muscle fiber type-specific cross-sectional area, capillarization measures, mitochondrial content, and protein content of eNOS, eNOS-P-ser1177, NOX2, p47phox, and p67phox., Interpretation: Because differences in muscle fiber and microvascular outcome measures are not statistically significant, we hypothesize that cardiac dysfunction, seen in active CS, persists during remission and limits blood supply to muscles., (© Endocrine Society 2019.)

Are personality disorders (PDs) associated with emotional neglect? Draijer (2003) developed a dimensional model of trauma-related disorders and PD. The first dimension consists of the severity of the trauma endured. The second dimension consists of emotional neglect, which is assumed to be related primarily to personality pathology. In this article, we investigate whether an association between retrospective reports of emotional neglect and the presence and severity of PD exists. A sample of 150 patients was systematically assessed. Results indicate that there is little evidence to support a link between emotional neglect and problematic personality functioning at the disorder level; however, there might be a link between emotional neglect and problematic personality functioning in a dimensional way. Findings indicate a relationship between lack of parental warmth and problematic personality functioning, supporting the existence of the emotional neglectaxis of the proposed model in a dimensional framework of viewing personality pathology.

Background: Metastatic disease is the main cause of cancer-related mortality in thyroid carcinoma (TC) patients. Clinical studies have suggested differences in metastatic patterns between the different subtypes of TC. This study systematically evaluates the metastatic patterns of different subtypes in TC patients., Methods: A nationwide review of pathological records of all 650 patients diagnosed with a primary malignancy in the thyroid who underwent an autopsy between 1991 and 2010 was performed. Patients were selected from the Dutch pathology registry (PALGA)., Results: Metastatic disease was present in 228 (35.1%) patients and was found in 38.7%, 17.3%, 75.4%, and 47.8% of patients with follicular, papillary, anaplastic, and medullary types of TC, respectively (P < .0001). The majority of patients had more than 1 metastasis. The most common site of metastatic disease was the lung for papillary (79.7%), follicular (72.9%), and anaplastic (92.1%) carcinoma but not for medullary carcinoma (56.3%), P < .0001. Medullary carcinoma patients most frequently had metastases to the liver (81.3%). The combination of metastases also differed between subtypes., Conclusion: There are major differences in metastatic patterns between different subtypes of TC. The patterns and frequencies identified in this autopsy study may reflect the underlying biology of metastatic thyroid cancer and have potential to influence future monitoring and treatment strategies depending on clinical correlations., (© Endocrine Society 2019.)

Background: Major depressive disorder (MDD) is a common mood disorder, with a heritability of around 34%. Molecular genetic studies made significant progress and identified genetic markers associated with the risk of MDD; however, progress is slowed down by substantial heterogeneity as MDD is assessed differently across international cohorts. Here, we used a standardized online approach to measure MDD in multiple cohorts in the Netherlands and evaluated whether this approach can be used in epidemiological and genetic association studies of depression., Methods: Within the Biobank Netherlands Internet Collaboration (BIONIC) project, we collected MDD data in eight cohorts involving 31 936 participants, using the online Lifetime Depression Assessment Self-report (LIDAS), and estimated the prevalence of current and lifetime MDD in 22 623 unrelated individuals. In a large Netherlands Twin Register (NTR) twin-family dataset (n ≈ 18 000), we estimated the heritability of MDD, and the prediction of MDD in a subset (n = 4782) through Polygenic Risk Score (PRS)., Results: Estimates of current and lifetime MDD prevalence were 6.7% and 18.1%, respectively, in line with population estimates based on validated psychiatric interviews. In the NTR heritability estimates were 0.34/0.30 (s.e. = 0.02/0.02) for current/lifetime MDD, respectively, showing that the LIDAS gives similar heritability rates for MDD as reported in the literature. The PRS predicted risk of MDD (OR 1.23, 95% CI 1.15-1.32, R2 = 1.47%)., Conclusions: By assessing MDD status in the Netherlands using the LIDAS instrument, we were able to confirm previously reported MDD prevalence and heritability estimates, which suggests that this instrument can be used in epidemiological and genetic association studies of depression.

Introduction: As breast development in trans women (male sex assigned at birth, female gender identity) who receive gender-affirming hormone treatment is often moderate, they may choose breast augmentation as part of their treatment., Aim: The aim of the study was to investigate the frequency, determinants, and satisfaction of breast augmentation among trans women receiving hormone treatment., Methods: Trans women who started hormone treatment between 1972 and 2018 at our center received an anonymous questionnaire., Main Outcome Measure: The questionnaire contained questions about the start date of hormone treatment, the current age of the respondent, whether or not she underwent breast augmentation, what her considerations in this decision were, and, if the respondent did have breast implants, whether she was satisfied with the result and/or experienced health complaints she attributed to her breast implants., Results: A total of 3,073 questionnaires were distributed, of which 773 were retrieved back (median age of the respondents: 50 years, interquartile range: 35-59). Age and year of start of hormone treatment was comparable between responders and nonresponders. The frequency of breast augmentation varied from 70% in trans women who started hormone treatment between 1980 and 2000 to 20% in those who started between 2010 and 2015. Trans women underwent breast augmentation median 2 years after the start of hormone treatment (interquartile range: 2-4), and 80% was satisfied with the result. Approximately one-third experienced health complaints they attributed to their breast implants. People who considered breast augmentation reported financial limitations as an important reason not to undergo breast augmentation., Clinical Implications: This study shows that it is important to discuss pros and cons of breast augmentation to support trans women in making a well-informed decision., Strengths & Limitations: This is the largest study performed on the frequency and satisfaction of breast augmentation among trans women, which also includes health complaints and considerations in the decision whether or not to undergo breast augmentation. One of the limitations was that we were unable to link other clinical data., Conclusion: 4 of 5 trans women either chose or considered breast augmentation as part of their gender-affirming treatment. Most of the trans women who underwent breast augmentation were satisfied with the result, although approximately one-third experienced health complaints they attributed to their breast implants. Reasons not to undergo breast augmentation included financial limitations. This study shows that it is important to discuss with trans women the positive effects and possible side-effects of breast augmentation to help them make a well-informed decision whether or not to undergo breast augmentation. de Blok CJM, Staphorsius AS, Wiepjes CM, et al. Frequency, Determinants, and Satisfaction of Breast Augmentation in Trans Women Receiving Hormone Treatment. J Sex Med 2020;17:342-348., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 2013) introduced a dissociative subtype for patients with posttraumatic stress disorder (PTSD) and depersonalization and/or derealization symptoms. Despite high comorbidity rates between PTSD and dissociative disorders (DDs), research has not paid attention to the differentiation or overlap between the dissociative subtype of PTSD and DDs. This raises a question: To what extent do patients with dissociative PTSD differ from patients with PTSD and comorbid DDs?, Method: We compared three groups of complex patients with trauma-related disorders and/or personality disorders (n = 150): a dissociative PTSD, a nondissociative PTSD, and a non-PTSD group of patients with mainly personality disorders. We used structured clinical interviews and self-administered questionnaires on dissociative symptoms and disorders, personality disorders, trauma histories, depression, anxiety, and general psychopathology. The Dissociative Experiences Scale (DES; ≥20) and the depersonalization/derealization subscale of the DES were used for differentiating dissociative PTSD from nondissociative PTSD., Results: Of all patients, 33% met criteria for dissociative PTSD. More than half of the dissociative PTSD patients (54%) met criteria for one or more DDs; using the depersonalization/derealization subscale of the DES, even 66% had a comorbid DD. But also of the non-PTSD patients, 24% had a mean DES score of ≥20. There were no symptomatic differences (e.g., depression and anxiety) between dissociative PTSD with and without comorbid DDs., Conclusion: Overlap between dissociative PTSD and DD is large and we recommend replication of previous studies, using structured clinical assessment of DDs. (PsycINFO Database Record (c) 2020 APA, all rights reserved).