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Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: Recent analyses have shown that in health services research in Germany, healthcare organisations are often considered primarily as a study setting, without fully taking their complex organisational nature into account, neither theoretically nor methodologically. Therefore, an initiative was launched to analyse the state of Organisational Health Services Research (OHSR) in Germany and to develop a strategic framework and road map to guide future efforts in the field. This paper summarizes positions that have been jointly developed by consulting experts from the interdisciplinary and international scientific community., Methods: In July 2023, a scoping workshop over the course of three days was held with 32 (inter)national experts from different research fields centred around OHSR topics using interactive workshop methods. Participants discussed their perspectives on OHSR, analysed current challenges in OHSR in Germany and developed key positions for the field's development., Results: The seven agreed-upon key positions addressed conceptual and strategic aspects. There was consensus that the field required the development of a research agenda that can guide future efforts. On a conceptual level, the need to address challenges in terms of interdisciplinarity, terminology, organisation(s) as research subjects, international comparative research and utilisation of organisational theory was recognized. On a strategic level, requirements with regard to teaching, promotion of interdisciplinary and international collaboration, suitable funding opportunities and participatory research were identified., Conclusions: This position paper seeks to serve as a framework to support further development of OHSR in Germany and as a guide for researchers and funding organisations on how to move OHSR forward. Some of the challenges discussed for German OHSR are equally present in other countries. Thus, this position paper can be used to initiate fruitful discussions in other countries., Competing Interests: LA ist Vorstandsmitglied der DGMS und des DNVF. Sie ist Mitglied des Editorial Boards des Journal of Health Care Services and Implementation. JB erhält Fördermittel für mehrere OVF-Projekte in Australien und Europa. ME ist Vorsitzender der Society for Studies in Organizing Healthcare (SHOC). Die Arbeit des Instituts für Arbeitsmedizin, Sozialmedizin und Versorgungsforschung, Universitätsklinikum Tübingen, wird durch einen zweckungebundenen Zuschuss des Arbeitgeberverbands der Metall- und Elektroindustrie Baden-Württemberg (Südwestmetall) unterstützt. Die übrigen Autor*innen erklären, dass keine Interessenkonflikte bestehen., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Numerous studies have demonstrated that low, unstable, or contingent self-esteem negatively affects youth development and is linked to adolescent psychopathology. However, most previous studies have applied variable-oriented approaches, and less is known about the natural combination of self-esteem facets in school-aged adolescents, how parental conditional regard affects self-esteem profiles, and how these profiles relate to self-kindness, self-judgement, and life satisfaction., Methods: By employing a longitudinal person-oriented approach (i.e., latent profile analysis and latent transition analysis) on two-wave longitudinal data from 587 German secondary school students (52.3% female, M age =13.52 years), this study aims to (1) identify adolescents' self-esteem profiles based on the level, stability, and contingency of self-esteem; (2) examine the impact of parental conditional regard on the self-esteem profiles explained using self-determination theory; and (3) examine these profiles' relationship with self-kindness, self-judgement, and life satisfaction., Results: Four self-esteem profiles were derived: optimal-secure (~ 8%), good (~ 18%), average (~ 36%), and low-insecure (~ 38%). The results reveal a concerningly high proportion as well as a high stability of low-insecure self-esteem (~ 98%) and indicate the strong negative influence of parental conditional regard on the development of optimal-secure self-esteem. Furthermore, the results demonstrate strong correlations between optimal-secure self-esteem, highly developed self-kindness, and high life satisfaction., Conclusions: Using a longitudinal person-oriented approach, it was possible to identify a group with highly vulnerable self-esteem, characterised by particularly low self-kindness, strong self-judgment, and lower life satisfaction. The findings of this study support the need for prevention and intervention targeting adolescents with low-insecure self-esteem., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: The high-fidelity ORSIM (Airway Simulation Ltd) and the low-fidelity wooden-block fiber-optic task trainers allow users to familiarize themselves with the psychomotor skills required to manipulate the fiber-optic scope., Methods: This single-center study aimed to compare residents' performance of fiber-optic intubation after 2 different types of task training. Twenty-four residents with experience of <8 fiber-optic intubations were randomized to either the ORSIM or a wooden-block task trainer. In a single teaching session, the resident performed 20 fiber-optic intubations on their assigned task trainer. This implied simulator competence. In the 4 months after this training, all subjects then attempted to perform a fiber-optic intubation on an American Society of Anesthesiologists (ASA) I or II anesthetized patient whose airway was preoperatively assessed as normal. The primary outcome was the cumulative sum (CUSUM) learning curves obtained as the residents trained on their respective task trainers. Secondary outcomes included: the mean time (in seconds) to perform each of the 20 fiber-optic intubations on their assigned task trainer, the total simulator training time, global rating scale score, checklist score, and time to carina when performing fiber-optic intubation on the patient., Results: The CUSUM analysis showed that the ORSIM group achieved simulator competence faster. The mean time to perform fiber-optic intubation was shorter in the ORSIM group. A 2-way analysis of variance (ANOVA) test suggests that the combined effect of group (wooden-block or ORSIM) and time is statistically significant ( P < .05).Total training time (mean, 899 s ± 440 s vs 1358 s ± 405 s; 95% confidence interval [CI], 100.46-818.54; P = .01) was also significantly better in the ORSIM group.No significant difference was found between the 2 groups ( P > 0) in terms of global rating scale, checklist score, and time to reach the carina ( P >.05) when performing the fiber-optic intubation on the patient., Conclusions: ORSIM showed superiority in terms of the CUSUM learning curve in reaching competence faster in fewer attempts. There was no statistically significant difference in residents' performance when translated to clinical practice on a patient. This information should assist course directors when choosing task trainers for fiber-optic intubation training programs., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Previous studies reported that physical activity could buffer the negative association of psychological stress with affective wellbeing. However, the studies that examined this relation in everyday life have assessed physical activity only by self-report but not with objective measures such as accelerometry. We therefore investigated the associations of both subjectively and objectively measured physical activity with stress experiences and affective wellbeing. A total of 90 university students participated in a 10-day experience sampling and diary study during their examination period and reported about stress experiences, physical activity, and affective states. Physical activity was additionally assessed using accelerometry in 50 of the participants. Subjectively assessed physical activity and objectively assessed light physical activity were associated with feeling less stressed in the evening. Also, light physical activity during the day was associated with a smaller increase/higher decrease in feeling stressed from morning to evening. The association of stress experience with negative affect was moderated by objective light physical activity. No interactive effects of stress intensity and physical activity on affective wellbeing were found. On stressful days, physical activity may buffer the negative association between stress and affective wellbeing. Particularly light physical activity as assessed with accelerometry seems to play an important role. It may be beneficial for students' affective wellbeing to increase or at least maintain physical activity during examination periods., (© 2023. The Author(s).)

Managing the complex care needs of seriously ill patients transitioning from hospital to home can have detrimental effects on family caregivers (FCG). Multi-component interventions tailored to FCG needs are most effective at reducing caregiver burden, distress, and depression. However, gaps exist in determining best methods to assess, document, and analyze intervention components for FCGs. Common methods used to capture patient data during transitions in care may not be appropriate or allowed for FCG needs. As such, we present a methodological approach for electronically capturing, reporting, and analyzing multiple intervention components. This approach uses a standardized terminology and pathway for tailoring intervention components in real time while evaluating intervention effects across time. We use examples from a randomized controlled trial to illustrate the benefits of the current approach for analyzing the effectiveness of multi-component interventions in the context of caregiving research.

Background: The relation between parental involvement and student achievement has been of research interest for many decades. Although the idea of reciprocal processes between parent and child was proposed 40 years ago, very few efforts have been made to investigate reciprocal relations between parental involvement and student achievement., Aims: Using self-determination theory, this study investigated the longitudinal associations of the manner of parental involvement (i.e., autonomy-supportive or controlling) in children's academic problems with children's academic achievement. This study further addressed the recently intensely debated methodological issue of examining reciprocal relations by comparing a random-intercept cross-lagged panel model (RI-CLPM) with the traditional cross-lagged panel model (CLPM)., Sample and Methods: A RI-CLPM and a traditional CLPM were applied to 5-year longitudinal data including 1465 secondary school students (M age at T1 = 10.82 years, SD = 0.62). In both models, we controlled for students' gender, school type, socioeconomic status and cognitive ability., Results: The results show that the RI-CLPM fitted the data better than the CLPM. Trait-like stability was found for both forms of parental involvement and academic achievement. At the between-person level, controlling involvement related to lower achievement, whereas no correlation between autonomy-supportive involvement and achievement was found. At the within-person level, there were positive reciprocal relations between autonomy-supportive involvement and achievement, whereas controlling involvement was not associated with achievement., Conclusions: This study contributes substantially to the understanding of the relations between parental involvement in children's academic problems and children's academic achievement by simultaneously taking between-person differences and within-person processes into consideration., (© 2022 The Authors. British Journal of Educational Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.)

Introduction: Although studies suggest a potential link between COVID-19 and thyroid dysfunction in adults, there are insufficient data to confirm that association in children, and whether there is any effect on presentation to healthcare services., Aims: To identify whether presentations of thyroid dysfunction in children to a tertiary paediatric hospital changed as a result of the COVID-19 pandemic., Methods: A retrospective case note review was conducted of all children with abnormal thyroid function tests between 1 st January 2016 and 31 st December 2021 at a tertiary paediatric endocrine centre in the United Kingdom., Results: Overall, 244 children whose first presentation was within the timeframe of interest were included in this study, with a median age (range) of 11.5 (6.1, 16.8) years. Of these, 43 (18%) were hyperthyroid and 201 (82%) were hypothyroid. The greatest number of thyroid presentations occurred in 2021 (n=60, 25% of total over time period) and the fewest in 2020 (n=10, 4% of total over time period). Prior to this, the median (range) number of presentations per year was 34 (28, 39). There were no statistically significant differences in biochemistry, antibody status or other clinical characteristics between those who presented with hyperthyroidism prior to the pandemic or after. In those with hypothyroidism, baseline biochemistry was similar between the 2 groups, but the presence of other autoimmune conditions was greater pre-pandemic (17.2% vs 15.0%, p=0.03). In addition, patients were more likely to have transient thyroid dysfunction, which did not require treatment post-pandemic (70.0% vs 49.6%, p=0.0086)., Conclusions: Although overall rates of presentation with thyroid dysfunction have not altered since the first wave of the COVID-19 pandemic, presentations with transient thyroid dysfunction, not requiring ongoing treatment have increased. Further research regarding the relationship between COVID-19 and thyroid function in children and young people, is needed., 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 McCowan, Wild, Lucas-Herald, McNeilly, Mason, Wong, Ahmed and Shaikh.)

The important role of parenting is widely acknowledged, but as most studies have understood and examined it as a stable attribute (e.g., parenting style), the stability of and changes in parenting are less well understood. Using longitudinal person-oriented approaches (i.e., latent profile analyses and latent transition analyses), this study aimed to examine the stability of and changes in autonomy-related parenting profiles and their effects on adolescents' academic and psychological development. Four autonomy-related dimensions (i.e., autonomy support, warmth, psychological control, conditional regard) were chosen to identify parenting profiles on the basis of Self-Determination Theory. Using five-year longitudinal data from 789 German secondary school students (50.06% female, M age at T1 = 10.82 years, age span = 10-17), four autonomy-related parenting profiles were found: Supportive (~17%), Controlling (~31%), Unsupportive-Uncontrolling (~17%), and Limited Supportive (~35%). The results suggest that the Supportive profile contributes to adolescents' positive academic and psychological development, whereas the Controlling profile, which thwarts autonomy development, exacerbates the development of psychopathology, and impairs academic achievement. More importantly, the Limited Supportive profile is as maladaptive as the Unsupportive-Uncontrolling profile. Regarding parenting profiles' stability and changes, the results showed that about half of each profile stayed in the same group. Overall, it could be observed that parents became more supportive and less controlling over time. However, the findings also indicate that parenting profiles are less stable than expected and can still change during early-to-mid adolescence., (© 2021. The Author(s).)

Numerous studies have reported substantive correlations between anger socialization, children's anger regulation, and internalizing/externalizing problems. However, substantially less is known about the interplay among these constructs during the developmental stage of adolescence, and longitudinal studies on causal relations (i.e., parent-directed, adolescent-directed, or reciprocal effects) are rare. It is also unclear whether the development of internalizing and externalizing problems have similar causal relations. We collected three waves of longitudinal data (Grade 6, Grade 7, Grade 9) from multiple informants. A sample of N = 634 adolescents (mostly 11-12 years at Time 1; 50.6% male) and their parents (predominantly Caucasian with German nationality) completed questionnaires assessing parents' responses to anger, adolescents' anger regulation, and adolescents' internalizing/externalizing problems at each wave. Comparisons of different cross-lagged models revealed reciprocal rather than unidirectional effects. However, we found more parent-directed effects with respect to the development of internalizing problems, whereas relations regarding externalizing problems were more adolescent-directed, i.e., adolescents' externalizing problems and their anger regulation predicted changes in their parents' responses to anger across time. Adolescent anger regulation was an important maintaining factor of parents' responses to anger in later adolescence. Our findings suggest that assumptions regarding bidirectional relations should be emphasized much more in emotion socialization frameworks, particularly for the period of adolescence. Moreover, our study emphasizes the transdiagnostic importance of parents' responses to anger for both externalizing and internalizing problems and also suggests different underlying mechanisms., (© 2021. The Author(s).)

Background: Decision-making deficits in airway emergencies have led to adverse patient outcomes. A cognitive aid would assist clinicians through critical decision-making steps, preventing key action omission., Objective: We aimed to investigate the effects of a visual airway cognitive aid on decision-making in a simulated airway emergency scenario., Design: Randomised controlled study., Setting: Single-institution, tertiary-level hospital in Toronto, Canada from September 2017 to March 2019., Participants: Teams consisting of a participant anaesthesia resident, nurse and respiratory therapist were randomised to intervention (N = 20 teams) and control groups (N = 20 teams)., Intervention: Participants in both groups received a 15-min didactic session on crisis resource management which included teamwork communication and the concepts of cognitive aids for the management of nonairway and airway critical events. Only participants in the intervention group were familiarised, oriented and instructed on a visual airway cognitive aid that was developed for this study. Within 1 to 4 weeks after the teaching session, teams were video-recorded managing a simulated 'cannot intubate-cannot oxygenate' scenario with the aid displayed in the simulation centre., Main Outcome Measures: Decision-making time to perform a front-of-neck access (FONA), airway checklist actions, teamwork performances and a postscenario questionnaire., Results: Both groups performed similar key airway actions; however, the intervention group took a shorter decision-making time than the control group to perform a FONA after a last action [mean ± SD, 80.9 ± 54.5 vs. 122.2 ± 55.7 s; difference (95% CI) -41.2 (-76.5 to -6.0) s, P = 0.023]. Furthermore, the intervention group used the aid more than the control group (63.0 vs. 28.1%, P < 0.001). Total time of scenario completion, action checklist and teamwork performances scores were similar between groups., Conclusions: Prior exposure and teaching of a visual airway cognitive aid improved decision-making time to perform a FONA during a simulated airway emergency., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

This study contributes to understanding students' emotional responses to academic stressors by integrating grit into the well-established Job Demands-Resources Model and by examining the relationship between academic demands, grit (consistency of interests, perseverance of effort), burnout, engagement, academic achievement, depression, and life satisfaction in Chinese students. We conducted a self-report study with N = 1527 Chinese high school students (M age  = 16.38 years, SD = 1.04). The results of structural equation modeling showed that after controlling for gender, socio-economic status, and school types, demands positively related to burnout and negatively related to engagement. Both facets of grit negatively related to exhaustion, whereas only perseverance of effort positively related to engagement. Burnout positively related to depression and negatively related to life satisfaction, whereas engagement positively related to life satisfaction. However, neither burnout nor engagement was related to academic achievement. Our findings indicate that grit may be protective against school burnout.

Competing Interests: The authors report no conflicts of interest.

The schoolwork engagement inventory: Energy, Dedication, and Absorption (EDA) is a measure of students' engagement in schoolwork and has been demonstrated valid in Western student populations. In this study, we adapted this inventory to and tested its psychometric appropriates in Chinese upper secondary school students (CEDA). Participants were 1,527 general high school students and 850 vocational high school students. The mean age of the total sample was 16.21 years (54.4% females, age span: 15-19 years). The results of confirmatory factor analyses (CFA) showed that a modified one-factor model fitted the data best. The results of the multigroup CFA showed that the factor structure was metrically invariant across school tracks (i.e., general or vocational high school) and scalarly invariant across gender and school types (i.e., ordinary or key school). Moreover, schoolwork engagement was negatively related to emotional exhaustion and positively related to self-efficacy, perseverance of effort, teacher-student relationships, and life satisfaction. Overall, the CEDA can be regarded as a valid measure for the assessment of student engagement in the Chinese upper secondary school context., 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 © 2021 Teuber, Tang, Salmela-Aro and Wild.)

Next-generation genetic sequencing (NGS) technologies facilitate the screening of multiple genes linked to neurodegenerative dementia, but there are few reports about their use in clinical practice. Which patients would most profit from testing, and information on the likelihood of discovery of a causal variant in a clinical syndrome, are conspicuously absent from the literature, mostly for a lack of large-scale studies. We applied a validated NGS dementia panel to 3241 patients with dementia and healthy aged controls; 13,152 variants were classified by likelihood of pathogenicity. We identified 354 deleterious variants (DV, 12.6% of patients); 39 were novel DVs. Age at clinical onset, clinical syndrome and family history each strongly predict the likelihood of finding a DV, but healthcare setting and gender did not. DVs were frequently found in genes not usually associated with the clinical syndrome. Patients recruited from primary referral centres were compared with those seen at higher-level research centres and a national clinical neurogenetic laboratory; rates of discovery were comparable, making selection bias unlikely and the results generalisable to clinical practice. We estimated penetrance of DVs using large-scale online genomic population databases and found 71 with evidence of reduced penetrance. Two DVs in the same patient were found more frequently than expected. These data should provide a basis for more informed counselling and clinical decision making.

The concept of spinal cord injury has existed since the earliest human civilizations, with the earliest documented cases dating back to 3000 BC under the Egyptian Empire. Howevr, an understanding of this field developed slowly, with real advancements not emerging until the 20th century. Technological advancements including the dawn of modern warfare producing mass human casualties instigated revolutionary advancement in the field of spine injury and its management. Spine surgeons today encounter "Chance" and "Holdsworth" fractures commonly; however, neurosurgical literature has not explored the history of these physicians and their groundbreaking contributions to the modern understanding of spine injury. A literature search using a historical database, Cochrane, Google Scholar, and PubMed was performed. As needed, hospitals and native universities were contacted to add their original contributions to the literature. George Quentin Chance, a Manchester-based British physician, is well known to many as an eminent radiologist of his time who described the eponymous fracture in 1948. Sir Frank Wild Holdsworth (1904-1969), a renowned British orthopedic surgeon who laid a solid foundation for rehabilitation of spinal injuries under the aegis of the Miners' Welfare Commission, described in detail the management of thoraco-lumbar junctional rotational fracture. The work of these 2 men laid the foundation for today's understanding of spinal instability, which is central to modern spine injury classification and management algorithms. This historical vignette will explore the academic legacies of Sir Frank Wild Holdsworth and George Quentin Chance, and the evolution of spinal instability and spine injury classification systems that ensued from their work., (Copyright © 2020 by the Congress of Neurological Surgeons.)

Objectives : Stress fractures (SFx) occur as the result of repetitive loads over short periods of time, which leads to micro-damage of the bone through cortical resorption, ultimately leading to fracture. They are a common injury in female athletes and often cause significant morbidity. The goal of this study is to review the presentation, diagnosis, classification, treatment, and prevention of SFx in female athletes. Results : A thorough history, physical exam, and appropriate imaging can facilitate early diagnosis of stress fracture (SFx) and faster resolution of symptoms with more conservative management. The female athlete triad is an especially important factor that contributes to the increased risk of SFx in females. The continuum of stress injuries ranges from mild microfailure to complete fracture, which has resulted in the development of newer grading schemas through MRI and radiographic findings. Stress fractures are also classified as low- or high-risk according to anatomic location, as blood supply and applied forces at different locations affect the likelihood of fracture propagation, displacement, delayed union, or non-union. Conclusions : The ability to screen for at-risk athletes is paramount in preventing SFx. Recognition and prompt treatment of the female athlete triad requires a multidisciplinary approach in order to restore energy balance, correct menstrual irregularities, and improve bone health. This review provides a basis for understanding how to identify and treat stress fractures, which may allow treating physicians to diagnose this condition earlier and minimize any associated morbidity.

Objectives : Stress fractures (SFx) are a common athletic injury, occurring in up to 40% of athletes at some point in their career. These injuries can cause pain, permanent disability, financial burden, and loss of playing time. This review presents updated epidemiology and comprehensive analysis of risk factors for stress fractures, especially as it pertains to female athletes. Results : Stress fractures (SFx) account for up to 10% of all orthopedic injuries and up to 20% of injuries seen in sports medicine clinics, with an incidence among female athletes as high as 13%. Lower extremity SFx represent 80-95% of SFx, and the increased popularity of endurance running has contributed to the tibia (49% prevalence) replacing the metatarsals (9%) as the most common location for lower extremity SFx. Studies have demonstrated that 50% of peak bone mass is acquired during adolescence, a 'peak time' for eating disorder and female athlete triad development; furthermore, catch-up growth cannot be expected in athletes with diminished bone growth in this critical period. The female athlete triad (low energy availability with or without disordered eating, menstrual dysfunction, and low bone mineral density) are well-known risk factors for SFx; the risk of SFx for female athletes presenting with a single aspect of the triad is 15-20%, and this risk increases to 30-50% for female athletes presenting with multiple aspects of the triad. Conclusion : This review provides a basis for how to identify populations at greatest risk for SFx. Prompt recognition of the intrinsic and extrinsic risk factors for SFx in female athletes is imperative to early diagnosis and to develop targeted strategies to prevent SFx occurrence or recurrence.

Objective: The objective of this study was to evaluate whether there are disparities in academic rank and promotion between men and women neurosurgeons., Methods: The profiles of faculty members from 50 academic neurosurgery programs were reviewed to identify years in practice, number of PubMed-indexed publications, Doctor of Philosophy (PhD) attainment, and academic rank. The number of publications at each academic rank was compared between men and women after controlling for years in practice by using a negative binomial regression model. The relationship between gender and each academic rank was also determined after controlling for clustering at the institutional level, years in practice, and number of publications., Results: Of 841 faculty members identified, 761 (90%) were men (p = 0.0001). Women represented 12% of the assistant and associate professors but only 4% of the full professors. Men and women did not differ in terms of the percentage holding a PhD, years in practice, or number of publications at any academic rank. After controlling for years in practice and clustering at the facility level, the authors found that men were twice as likely as women to be named full professor (OR 2.2, 95% CI 1.09-4.44, p = 0.03). However, when institution, years in practice, PhD attainment, h-index, and number of publications were considered, men and women were equally likely to attain full professorship (OR 0.9, 95% CI 0.42-1.93)., Conclusions: Data analysis of the top neurosurgery programs suggests that although there are fewer women than men holding positions in academic neurosurgery, faculty rank attainment does not seem to be influenced by gender.

Background: An unruptured brain arteriovenous malformation (bAVM) is a complex pathological entity with the potential to lead to disabling or fatal intracranial hemorrhage. The treatment approaches for these lesions have included microsurgical resection, endovascular embolization, stereotactic radiosurgery (SRS), and medical management or any combination of these modalities. However, the optimal treatment approach for unruptured bAVMs has not yet been determined. In the present case, we used SRS strategically to downgrade an AVM to allow for improved resectability., Case Description: A 28-year-old woman had presented with 10 years of headaches and was found to have a Spetzler-Martin grade IV AVM not amenable to resection. She underwent targeted SRS only of the deep portions of the AVM, resulting in a decrease of the AVM to grade III. Subsequent microsurgical resection was successful in complete removal of the AVM. At the 1-year follow-up examination she had no deficits., Conclusions: We have proposed a protocol of using focused SRS to eliminate the portions of the AVM that confer an increased surgical risk. SRS, followed by microsurgical resection, could represent an optimal treatment strategy for high-grade AVMs with difficult surgical anatomy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Botulinum neurotoxins (BoNTs) inhibit the release of the neurotransmitter acetylcholine from motor neurons, resulting in highly effective muscle relaxation. In clinical and aesthetic medicine, serotype BoNT/A, which is most potent for humans, is widely used to treat a continuously increasing spectrum of disorders associated with muscle overactivity. Because of the high toxicity associated with BoNTs, it is mandatory to precisely determine the potency of every batch produced for pharmaceutical purposes. Here we report a new quantitative functional in vitro assay for BoNT/A. In this binding and cleavage (BINACLE) assay, the toxin is first bound to specific receptor molecules. Then a chemical reduction is performed, thereby releasing the light chain of BoNT/A and activating its proteolytic domain. The activated light chain is finally exposed to its substrate protein SNAP-25, and the fragment resulting from the proteolytic cleavage of this protein is quantified in an antibody-mediated reaction. The BoNT/A BINACLE assay offers high specificity and sensitivity with a detection limit below 0.5 mouse lethal dose (LD 50 )/ml. In conclusion, this new in vitro assay for determining BoNT/A toxicity represents an alternative to the LD 50 test in mice, which is the "gold standard" method for the potency testing of BoNT/A products., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We investigate and generalize an existing model of competitive helping within a biological market, first introduced for a population of competing individuals in which one individual provides help to all others; the rest compete for the help available from this individual by providing help themselves. Our generalized model comprises two strategies in which each individual of a specific type provides the same amount of help as all other individuals of that type. Each individual's fitness function is dependent on this level of help, the cost of providing the help, and the fact that help is proportionally reciprocated by other individuals. Competitive helping occurs when individuals actively try to help more than other individuals. To assess the emergence of equilibrium help strategies as adopted by proportions of the population, we examine the competition over available help within two settings: replicator dynamics and agent-based numerical simulations. To move one step further in our generalization, we use the agent-based model to study the N-person competitive helping game, where all individuals in the population are heterogeneous with respect to help provided. Our results show that helping does not increase indefinitely with the population size, as concluded previously, and while there are some instances of an increase in help provided as a result of competition, this competition can be detrimental to all individuals and in most cases, one type simply gives up (thus evolving to a "no help" strategy). The degree to which an individual's help is reciprocated by the others in the population has strong implications in the long-term behaviour of equilibrium help levels of types of individuals (and of individuals themselves); these equilibrium help levels diverge from existing conjectures in current literature. Lastly, small amounts of passively provided (costless) help results in runaway competition among all individuals., Competing Interests: The authors have declared that no competing interests exist.

Botulinum neurotoxins (BoNTs) are the most potent toxins known. However, the paralytic effect caused by BoNT serotypes A and B is taken advantage of to treat different forms of dystonia and in cosmetic procedures. Due to the increasing areas of application, the demand for BoNTs A and B is rising steadily. Because of the high toxicity, it is mandatory to precisely determine the potency of every produced BoNT batch, which is usually accomplished by performing toxicity testing (LD50 test) in mice. Here we describe an alternative in vitro assay for the potency determination of the BoNT serotype B. In this assay, the toxin is first bound to its specific receptor molecules. After the proteolytic subunit of the toxin has been released and activated by chemical reduction, it is exposed to synaptobrevin, its substrate protein. Finally the proteolytic cleavage is quantified by an antibody-mediated detection of the neoepitope, reaching a detection limit below 0.1mouseLD50/ml. Thus, the assay, named BoNT/B binding and cleavage assay (BoNT/B BINACLE), takes into account the binding as well as the protease function of the toxin, thereby measuring its biological activity., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose: Laparoscopic interventions require the precise navigation of medical instruments through the patient's body, while taking critical structures into account. Although numerous concepts have been proposed for displaying subsurface anatomical detail using augmented reality, clinical translation of these methods has suffered from a lack of robustness as well as from cumbersome integration into the clinical workflow. The purpose of this study was to investigate the feasibility of a new approach to intra-operative registration based on fluorescent markers., Methods: The proposed approach to augmented reality visualization relies on metabolizable fluorescent markers that are attached to the target organ to guide a 2D/3D intra-operative registration algorithm. In an ex vivo porcine study, marker tracking performance is evaluated in the presence of smoke, blood, and tissue in the field of view of the endoscope., Results: In contrast to state-of-the-art needle-shaped fiducial markers, the fluorescent markers can be reliably tracked when occluded by smoke, blood or tissue. This makes the new 2D/3D intra-operative registration approach considerably more robust than state-of-the-art marker-based methods., Conclusion: As the concept can be smoothly integrated into the clinical workflow, its potential for application in clinical laparoscopy is high.

Aims: This prospective longitudinal study over 6 years compared schoolteachers and emergency physicians as resuscitation trainers for schoolchildren. It also investigated whether pupils who were trained annually for 3 years retain their resuscitation skills after the end of this study., Methods: A total of 261 pupils (fifth grade) at two German grammar schools received resuscitation training by trained teachers or by emergency physicians. The annual training events stopped after 3 years in one group and continued for 6 years in a second group. We measured knowledge about resuscitation (questionnaire), chest compression rate (min(-1)), chest compression depth (mm), ventilation rate (min(-1)), ventilation volume (mL), self-efficacy (questionnaire). Their performance was evaluated after 1, 3 and 6 years., Results: The training events increased the pupils' knowledge and practical skills. When trained by teachers, the pupils achieved better results for knowledge (92.86% ± 8.38 vs. 90.10% ± 8.63, P=0.04) and ventilation rate (4.84/min ± 4.05 vs. 3.76/min ± 2.37, P=0.04) than when they were trained by emergency physicians. There were no differences with regard to chest compression rate, depth, ventilation volume, or self-efficacy at the end of the study. Knowledge and skills after 6 years were equivalent in the group with 6 years training compared with 3 years training., Conclusions: Trained teachers can provide adequate resuscitation training in schools. Health-care professionals are not mandatory for CPR training (easier for schools to implement resuscitation training). The final evaluation after 6 years showed that resuscitation skills are retained even when training is interrupted for 3 years., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Purpose: The authors investigated the potential of optimized noncoplanar irradiation trajectories for volumetric modulated arc therapy (VMAT) treatments of nasopharyngeal patients and studied the trade-off between treatment plan quality and delivery time in radiation therapy., Methods: For three nasopharyngeal patients, the authors generated treatment plans for nine different delivery scenarios using dedicated optimization methods. They compared these scenarios according to dose characteristics, number of beam directions, and estimated delivery times. In particular, the authors generated the following treatment plans: (1) a 4π plan, which is a not sequenced, fluence optimized plan that uses beam directions from approximately 1400 noncoplanar directions and marks a theoretical upper limit of the treatment plan quality, (2) a coplanar 2π plan with 72 coplanar beam directions as pendant to the noncoplanar 4π plan, (3) a coplanar VMAT plan, (4) a coplanar step and shoot (SnS) plan, (5) a beam angle optimized (BAO) coplanar SnS IMRT plan, (6) a noncoplanar BAO SnS plan, (7) a VMAT plan with rotated treatment couch, (8) a noncoplanar VMAT plan with an optimized great circle around the patient, and (9) a noncoplanar BAO VMAT plan with an arbitrary trajectory around the patient., Results: VMAT using optimized noncoplanar irradiation trajectories reduced the mean and maximum doses in organs at risk compared to coplanar VMAT plans by 19% on average while the target coverage remains constant. A coplanar BAO SnS plan was superior to coplanar SnS or VMAT; however, noncoplanar plans like a noncoplanar BAO SnS plan or noncoplanar VMAT yielded a better plan quality than the best coplanar 2π plan. The treatment plan quality of VMAT plans depended on the length of the trajectory. The delivery times of noncoplanar VMAT plans were estimated to be 6.5 min in average; 1.6 min longer than a coplanar plan but on average 2.8 min faster than a noncoplanar SnS plan with comparable treatment plan quality., Conclusions: The authors' study reconfirms the dosimetric benefits of noncoplanar irradiation of nasopharyngeal tumors. Both SnS using optimized noncoplanar beam ensembles and VMAT using an optimized, arbitrary, noncoplanar trajectory enabled dose reductions in organs at risk compared to coplanar SnS and VMAT. Using great circles or simple couch rotations to implement noncoplanar VMAT, however, was not sufficient to yield meaningful improvements in treatment plan quality. The authors estimate that noncoplanar VMAT using arbitrary optimized irradiation trajectories comes at an increased delivery time compared to coplanar VMAT yet at a decreased delivery time compared to noncoplanar SnS IMRT.

Surgical navigation describes the concept of real-time processing and presentation of preoperative and intraoperative data from different sources to intraoperatively provide surgeons with additional cognitive support. Imaging methods such as 3D ultrasound, magnetic resonance imaging (MRI) and computed tomography (CT) and data from optical, electromagnetic or mechanical tracking methods are used. The resulting information of the navigation system will be presented by the means of visual methods. Mostly virtual reality or augmented reality visualization is used. There are different guidance systems for various disciplines introduced. Mostly it operates on rigid structures (bone, brain). For soft tissue navigation motion compensation and deformation detection are necessary. Therefore, marker-based tracking methods are used in several urological application examples; however, the systems are often still under development and have not yet arrived in the clinical routine.

Numerous studies have reported substantive correlations between indicators of parenting, children's emotion regulation (ER), and children's psychosocial adjustment. However, studies on underlying mechanisms are scarce. Particularly in early adolescence, it is still unclear whether relations between parenting and ER are caused by adolescent behavior, by parent behavior, or by reciprocal processes. Moreover, it is unclear whether ER can be seen as an antecedent or a consequence of psychosocial adjustment. The aim of this study was to examine predictive relations among parenting and adolescents' ER, and adolescents' ER and psychosocial adjustment, respectively. We collected longitudinal, multiple informant data at two measurement occasions (Grade 6, Grade 7). All told, 1,100 adolescents (10-14 years) and their parents filled out questionnaires assessing responsiveness and psychological control, adolescents' anger regulation, and adolescents' problem and prosocial behavior. Cross-lagged analyses revealed reciprocal effects between parenting, ER, and adjustment for the parent and boys', but not for the girls', report. Moreover, relations were different for adolescents with versus without clinically elevated symptoms of psychopathology. Our findings support the assumption that reciprocal relations between parenting, ER, and psychosocial adjustment are likely to persist until early adolescence. Nevertheless, the moderating role of gender and psychopathology should be taken into account. Possible reasons for the different findings, and practical implications, are discussed.

Schizophrenia and bipolar disorder broadly overlap in multiple areas involving clinical phenomenology, genetics, and neurobiology. Still, the investigation into specific elementary (sub-)processes of executive functioning may help to define clear points of distinction between these categorical diagnoses to validate the nosological dichotomy and, indirectly, to further elucidate their pathophysiological underpinnings. In the present behavioral study, we sought to separate common from diagnosis-specific deficits in a series of specific elementary sub-functions of executive processing in patients with schizophrenia and bipolar disorder. For our purpose, we administered a modern and multi-purpose neuropsychological task paradigm to equal-sized and matched groups of schizophrenia patients, patients with bipolar disorder, and healthy control subjects. First, schizophrenia patients compared to the bipolar group exhibited a more pronounced deficit in general measures of task performance comprising both response speed and accuracy. Additionally, bipolar patients showed increased advance task preparation, i.e., were better able to compensate for response speed deficits when longer preparation intervals were provided. Set-shifting, on the other hand, was impaired to a similar degree in both patient groups. Finally, schizophrenia patients exhibited a specific deficit in conflict processing (inhibitory control) and the shielding of task-relevant processing from distraction (i.e., attentional maintenance). The present investigation suggests that specific neuropsychological measures of elementary executive functions may represent important points of dissociation between schizophrenia and bipolar disorder, which may help to differentiate the pathophysiological underpinnings of these major psychiatric disorders. In this context, the present findings highlight the measures of inhibitory control and attentional maintenance as promising candidates.

Myoepitheliomas are rare tumours that originate from glandular tissues such as the parotid or salivary glands, and less commonly from soft tissues of the head, neck, and other parts of the body. Intraorbital myoepitheliomas generally arise from the lacrimal gland. Intracranial myoepitheliomas are rare. We report a myoepithelioma of the orbital apex that did not originate from the lacrimal gland. It extended to the middle cranial fossa from the orbital apex and involved the dura and adjacent bone. A diagnostic biopsy via a lateral orbitotomy preceded resection. We review the natural course and histopathology of myoepithelial neoplasms, the surgical nuances of approaching an orbital apex tumour with maximal functional preservation, and the optimal management practices of these rare lesions.

Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin (HTT) gene. Both central and peripheral innate immune activation have been described as features of the disease. Isolated human HD monocytes have been shown to produce more cytokines upon LPS stimulation compared to control monocytes. Understanding alterations in the signalling cascades responsible and activated by this increase in pro-inflammatory cytokine production is crucial in understanding the molecular basis of this phenomenon. Here we investigated the signalling cascade most commonly activated by pro-inflammatory cytokines such as IL-6 - the JAK/STAT signalling cascade. Using flow cytometry, we show that one out of three key transcription factors activated by JAK/STAT signalling is altered in primary human HD innate immune cells, suggesting that this pathway may only play a minor, additive role in the immune cell dysfunction in HD.

To cope with heterogeneous subsurface environments mycelial microorganisms have developed a unique ramified growth form. By extending hyphae, they can obtain nutrients from remote places and transport them even through air gaps and in small pore spaces, repectively. To date, studies have been focusing on the role that networks play in the distribution of nutrients. Here, we investigated the role of mycelia for the translocation of nonessential substances, using polycyclic aromatic hydrocarbons (PAHs) as model compounds. We show that the hyphae of the mycelial soil oomycete Pythium ultimum function as active translocation vectors for a wide range of PAHs. Visualization by two-photon excitation microscopy (TPEM) demonstrated the uptake and accumulation of phenanthrene (PHE) in lipid vesicles and its active transport by cytoplasmic streaming of the hyphae ('hyphal pipelines'). In mycelial networks, contaminants were translocated over larger distances than by diffusion. Given their transport capacity and ubiquity, hyphae may substantially distribute remote hydrophobic contaminants in soil, thereby improving their bioavailability to bacterial degradation. Hyphal contaminant dispersal may provide an untapped potential for future bioremediation approaches.

Aims: Evaluation of school pupils' resuscitation performance after different types of training relative to the effects of training frequency (annually vs. biannually), starting age (10 vs. 13 years) and facilitator (emergency physician vs. teacher)., Methods: Prospective longitudinal study investigating 433 pupils in training and control groups. Outcome criteria were chest compression depth, compression frequency, ventilation volume, ventilation frequency, self-image and theoretical knowledge. In the training groups, 251 pupils received training annually or biannually either from emergency physicians or CPR-trained teachers. The control group without any training consisted of 182 pupils., Results: Improvements in training vs. control groups were observed in chest compression depth (38 vs. 24 mm), compression frequency (74 vs. 42 min(-1)), ventilation volume (734 ml vs. 21 ml) and ventilation frequency (9/min vs. 0/min). Numbers of correct answers in a written test improved by 20%, vs. 5% in the control group. Pupils starting at age 10 showed practical skills equivalent to those starting at age 13. Theoretical knowledge was better in older pupils. Self-confidence grew in the training groups. Neither more frequent training nor training by emergency physicians led to better performance among the pupils., Conclusions: Pupils starting at age 10 are able to learn cardiopulmonary resuscitation with one annual training course only. After a 60-min CPR-training update, teachers are able to provide courses successfully. Early training reduces anxieties about making mistakes and markedly increases participants' willingness to help. Courses almost doubled the confidence of pupils that what they had learned would enable them to save lives., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Three-dimensional micro-objects are fabricated by the controlled release of inherently strained SrRuO3/Pr0.7Ca0.3MnO3/SrRuO3 nanometer-sized trilayers from SrTiO3(001) substrates. Freestanding cantilevers and rolled-up microtubes with a diameter of 6 to 8 μm are demonstrated. The etching behavior of the SrRuO3 film is investigated, and a selectivity of 1:9,100 with respect to the SrTiO3 substrate is found. The initial and final strain states of the rolled-up oxide layers are studied by X-ray diffraction on an ensemble of tubes. Relaxation of the sandwiched Pr0.7Ca0.3MnO3 layer towards its bulk lattice parameter is observed as the major driving force for the roll-up of the trilayers. Finally, μ-diffraction experiments reveal that a single object can represent the ensemble proving a good homogeneity of the rolled-up tubes.PACS: 81.07.-b; 68.60.-p; 68.37.Lp; 81.16.Dn.

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. Immune activation is a well-established feature of the HD brain and we have previously demonstrated a widespread, progressive innate immune response detectable in plasma throughout the course of HD. In the present work we used multiplex ELISA to quantify levels of chemokines in plasma from controls and subjects at different stages of HD. We found an altered chemokine profile tracking with disease progression, with significant elevations of five chemokines (eotaxin-3, MIP-1β, eotaxin, MCP-1 and MCP-4) while three (eotaxin-3, MIP-1β and eotaxin) showed significant linear increases across advancing disease stages. We validated our results in a separate sample cohort including subjects at different stages of HD. Here we saw that chemokine levels (MCP-1 and eotaxin) correlated with clinical scores. We conclude that, like cytokines, chemokines may be linked to the pathogenesis of HD, and that immune molecules may be valuable in tracking and exploring the pathogenesis of HD.

Background: Huntington's disease (HD) is a rare triplet repeat (CAG) disorder. Advanced, multi-centre, multi-national research frameworks are needed to study simultaneously multiple complementary aspects of HD. This includes the natural history of HD, its management and the collection of clinical information and biosamples for research., Methods: We report on cross-sectional data of the first 1766 participants in REGISTRY, the European Huntington's Disease Network's (EHDN), multi-lingual, multi-national prospective observational study of HD in Europe. Data collection (demographics, phenotype, genotype, medication, co-morbidities, biosamples) followed a standard protocol., Results: Phenotype, and the HD genotype, of manifest HD participants across different European regions was similar. Motor onset was most common (48%) with a non-motor onset in more than a third of participants. Motor signs increased, and cognitive abilities and functional capacity declined as the disease burden (CAGn-35.5) X age) increased. A life-time history of behavioural symptoms was common, but the behavioural score was not related to disease burden. One fifth of participants had severe psychiatric problems, e.g. suicidal ideation and attempts, and/or irritability/aggression, with psychosis being less common. Participants on anti-dyskinetic medication had a higher motor and lower cognitive score, were older, and more prone to physical trauma. A higher motor and a lower cognitive score predicted more advanced disease., Conclusions: The unparalleled collection of clinical data and biomaterials within the EHDN's REGISTRY can expedite the search for disease modifiers (genetic and environmental) of age at onset and disease progression that could be harnessed for the development of novel treatments.

Background: Huntington's disease (HD) is a rare triplet repeat (CAG) disorder. Advanced, multi-centre, multi-national research frameworks are needed to study simultaneously multiple complementary aspects of HD. This includes the natural history of HD, its management and the collection of clinical information and biosamples for research., Methods: We report on cross-sectional data of the first 1766 participants in REGISTRY, the European Huntington's Disease Network's (EHDN), multi-lingual, multi-national prospective observational study of HD in Europe. Data collection (demographics, phenotype, genotype, medication, co-morbidities, biosamples) followed a standard protocol., Results: Phenotype, and the HD genotype, of manifest HD participants across different European regions was similar. Motor onset was most common (48%) with a non-motor onset in more than a third of participants. Motor signs increased, and cognitive abilities and functional capacity declined as the disease burden (CAGn-35.5) X age) increased. A life-time history of behavioural symptoms was common, but the behavioural score was not related to disease burden. One fifth of participants had severe psychiatric problems, e.g. suicidal ideation and attempts, and/or irritability/aggression, with psychosis being less common. Participants on anti-dyskinetic medication had a higher motor and lower cognitive score, were older, and more prone to physical trauma. A higher motor and a lower cognitive score predicted more advanced disease., Conclusions: The unparalleled collection of clinical data and biomaterials within the EHDN's REGISTRY can expedite the search for disease modifiers (genetic and environmental) of age at onset and disease progression that could be harnessed for the development of novel treatments.

Background: Postpartum psychiatric disorders in women have been discussed more often than postpartum psychiatric disorders in men. However, psychiatric disorders (especially depression) after birth are also experienced by men and may or may not be associated with a postpartum disorder of the mother. The aim of this study is to assess how distressed the partners of women with postpartum psychiatric disorders really are as well as associated factors and the degree of improvement of their emotional well-being after maternal treatment., Materials and Methods: For this study, we assessed the psychological distress (SCL-90) in a group of partners of severely ill postpartum depressive and psychotic mothers (N=40), who were inpatients in a Mother-Baby Unit and participated in a longitudinal therapy study., Results: Depression was the only dimension where the partners scored significantly higher than the norm. Between 7.5% and 35% of partners scored above the cut-off point for clinical relevance in the studied dimensions, with the highest figures for hostility (22.5%), interpersonal sensitivity (25%) and depression (35%). Miscarriage, a low severity level of maternal disease and a high level of maternal symptoms were significant predictors for paternal depression. After treatment of the mothers, the levels of symptoms of the partners were reduced., Conclusions: A postpartum psychiatric disorder of the mother is a risk not only for the baby but also for the father. High levels of awareness for the early detection and early treatment of this condition is essential., (Georg Thieme Verlag KG Stuttgart, New York.)

Background and Purpose: Longitudinal MR imaging measures provide an opportunity to track progression in HD before the emergence of clinical symptoms. This may prove useful in assessing disease-modifying treatments. We investigated how caudate and global volumes change as HD progresses from premanifest to early disease., Materials and Methods: Forty HD gene-positive individuals and 19 controls underwent serial volumetric MR imaging (baseline, 12 and 27 months; 2 or 3 scans per person). At baseline, 3 patients with HD were premanifest but developed overt motor features during the study, and 37 had early HD. All had dates of motor onset recorded. Caudates, lateral ventricles, and TIVs were measured using semiautomated procedures. Linear mixed models were used to investigate differences between HD and controls in relation to motor onset, controlling for TIV, sex, and age., Results: Extrapolating backwards in time, we found that differences in caudate and ventricular volumes between patients with HD and controls were evident 14 and 5 years, respectively, before motor onset (P < .05). At onset, caudate volume was 2.58 mL smaller than that in controls (P < .0001); ventricular volume was 9.27 mL larger (P < .0001). HD caudate atrophy rates were linear, showed low variability between subjects, and were approximately 10-fold higher than those in controls (P < .001). HD ventricular enlargement rates were variable between subjects, were approximately 4-fold higher than those in controls at onset (P < .001), and accelerated with disease duration (P = .02)., Conclusions: We provide evidence of acceleration of global atrophy in HD with disproportionate caudate involvement. Both caudate and global measures may be of use as early markers of HD pathology.

Background: Neandertals and the Middle Paleolithic persisted in the Iberian Peninsula south of the Ebro drainage system for several millennia beyond their assimilation/replacement elsewhere in Europe. As only modern humans are associated with the later stages of the Aurignacian, the duration of this persistence pattern can be assessed via the dating of diagnostic occurrences of such stages., Methodology/principal Findings: Using AMS radiocarbon and advanced pretreatment techniques, we dated a set of stratigraphically associated faunal samples from an Aurignacian III-IV context excavated at the Portuguese cave site of Pego do Diabo. Our results establish a secure terminus ante quem of ca. 34,500 calendar years ago for the assimilation/replacement process in westernmost Eurasia. Combined with the chronology of the regional Late Mousterian and with less precise dating evidence for the Aurignacian II, they place the denouement of that process in the 37th millennium before present., Conclusions/significance: These findings have implications for the understanding of the emergence of anatomical modernity in the Old World as a whole, support explanations of the archaic features of the Lagar Velho child's anatomy that invoke evolutionarily significant Neandertal/modern admixture at the time of contact, and counter suggestions that Neandertals could have survived in southwest Iberia until as late as the Last Glacial Maximum.