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Detailed heat transfer coefficient and film effectiveness distributions over a gas turbine blade with film cooling are obtained using a transient liquid crystal image technique. The test blade has three rows of film holes on the leading edge and two rows each on the pressure and suction surfaces. A transient liquid crystal technique maps the entire blade midspan region, and helps provide detailed measurements, particularly near the film hole. Tests were performed on a five-blade linear cascade in a low-speed wind tunnel. The mainstream Reynolds number based on cascade exit velocity is 5.3×105. Two different coolants (air and Co2) were used to simulate coolant density effect. Coolant blowing ratio was varied between 0.8 and 1.2 for air injection and 0.4–1.2 for Co2 injection. Results show that film injection promotes earlier laminar-turbulent boundary layer transition on the suction surface and also enhances local heat transfer coefficients (up to 80%) downstream of injection. An increase in coolant blowing ratio produces higher heat transfer coefficients for both coolants. This effect is stronger immediately downstream of injection holes. Film effectiveness is highest at a blowing ratio of 0.8 for air injection and at a blowing ratio of 1.2 for Co2 injection. Such detailed results will help provide insight into the film cooling phenomena on a gas turbine blade.

Transvaginal ultrasound-guided ovum pick-up (OPU) was performed on 40 Nili-Ravi and Murrah buffaloes for consecutive 3 times each, at an interval of 3 days. A total of 936 follicles were aspirated, 643 oocytes were retrieved and 456 oocytes of them were usable. The recovery rate was 68.77% (643/935) and the percentage of usable oocytes was 70.92% (456/643), with an average of 3.80±0.23 oocytes usable per buffalo. The number of usable oocytes for the first, second and third OPU was 3.82±0.50;3.82±0.35; 4.05±0.43, respectively, and the difference among them was not significant (P

BackgroundRoe was overturned in 2022. No peer-reviewed evidence exists for the indirect spillover effects of overturning Roe on non-abortion reproductive care access for diverse patient populations.MethodsNational data were from 2013–2023 HHS Title X Directory, 2013–2020 CDC Artificial Reproductive Technologies (ART) Surveillance and 2021–2023 manual collection, and Guttmacher Institute. Outcome measures included numbers of ART clinics and Title X entities. Title X entities are those that receive federal funds to establish and operate voluntary family planning projects, especially for low-income patients. We reported pre-and post-Roe changes, associations between changes in measures and abortions, and characteristics of changed measures by region and political geography.ResultsPost-Roe America witnessed national declines of 1.03% in ART clinics and 18.34% in Title X entities, and average state decreases of 0.08 ART clinics (p

Introduction Trans young people are at a higher risk of mental health difficulties such as depression, anxiety and suicidality than their cisgender peers, due in part to their experiences of minority stress. This protocol describes a feasibility trial and subsequent pilot randomised controlled trial (RCT) of a codesigned group cognitive–behavioural therapy intervention for trans young people, named Trans Adolescent Group ThErapy for Alleviating Minority stress (TAG TEAM).Methods and analysis To evaluate TAG TEAM, we will conduct a feasibility trial followed by a pilot RCT with trans young people aged 14–16 years who have been referred to the Royal Children’s Hospital Gender Service in Melbourne, Australia. In the feasibility trial, we aim to enrol 32 participants who will be randomised at a 1:1 ratio to either in-person or online intervention arms. Participants will be assessed at baseline and post-treatment, with a nested qualitative evaluation post-treatment. Primary outcomes are the feasibility and acceptability of the intervention and the study design and associated procedures, including comparison of the in-person and online delivery modes. In the subsequent pilot RCT, we aim to enrol 64 participants who will be randomised at a 1:1 ratio to an intervention or waitlist control arm, with delivery mode determined by the feasibility trial. Participants will complete assessments at baseline, post-treatment and 3-month follow-up. Primary outcomes are the feasibility and acceptability of the RCT study design. In both the feasibility trial and pilot RCT, participants will complete assessments related to mood, anxiety, suicidality, quality of life, minority stress, family support and social transition. Quantitative data will be analysed using descriptive statistics. Qualitative data will be analysed using thematic and interpretive analysis.Ethics and dissemination The Royal Children’s Hospital Human Research Ethics Committee has approved this study (#91162). Informed consent will be obtained in writing from all participants and a legal guardian. Findings will inform the development of a full-scale RCT to evaluate the efficacy of TAG TEAM and will be disseminated through conferences and peer-reviewed journals.Trial registration number ACTRN12623000302651, ACTRN12623000318684.

BackgroundIn patients with cerebellar ataxia (CA), dual-tasking deteriorates the performance of one or both tasks.ObjectiveEvaluate the effects of 4 weeks of cognitive-coupled intensive balance training (CIBT) on dual-task cost, dynamic balance, disease severity, number of falls, quality of life, cognition and cost among patients with CA.MethodsThis RCT compared CIBT (Group 1) to single-task training (Group 2) among 32 patients with CA. The intervention included either dual-task (CIBT) or single-task training for 4 weeks followed by 6 months of unsupervised home exercises. Dual-task timed up-and-go test (D-TUG) assessed dual-task cost of the physical and cognitive tasks. Assessment time points included baseline 1 (Week 0:T1), baseline 2 (Week 6:T2), post-intervention (Week 10:T3), and follow-up (Week 34:T4).ResultsCompared to single-task training CIBT improved the dual-task cost of physical task [MD −8.36 95% CI (−14.47 to −2.36, p < 0.01), dual-tasking ability [−6.93 (−13.16 to −0.70); p = 0.03] assessed using D-TUG, balance assessed using the scale for the assessment and rating of ataxia (SARAbal) [−2.03 (−4.04 to −0.19); p = 0.04], visual scores of the SOT (SOT-VIS) [−18.53 (−25.81 to −11.24, p ≤ 0.01] and maximal excursion [13.84 (4.65 to 23.03; p ≤ 0.01] of the Limits of Stability (LOS) in the forward direction and reaction time in both forward [−1.11 (−1.42 to −0.78); p < 0.01] and right [−0.18 (0.05 to 0.31); p < 0.01] directions following 4 weeks of training. CIBT did not have any additional benefits in reducing the number of falls, or improving disease severity, quality of life and cognition. The mean cost of intervention and healthcare costs for 7 months was HKD 33,380 for CIBT group and HKD 38,571 for single-task training group.ConclusionWe found some evidence to support the use of CIBT for improving the dual-tasking ability, dual-task cost of physical task and dynamic balance in CA. Future large fully-powered studies are needed to confirm this claim.Clinical trial registrationhttps://clinicaltrials.gov/study/NCT04648501, identifier [Ref: NCT04648501].

BackgroundGender euphoria (i.e., a positive feeling associated with one’s gender identity, expression, or affirmation) is widely discussed among transgender and gender diverse (hereafter referred to as trans) individuals. However, as a construct, gender euphoria has never been formally measured and has rarely been empirically studied. Hence, this protocol paper illustrates our process for developing and validating a new tool to measure gender euphoria, known as the Gender Euphoria Scale (GES), for use with trans populations.MethodsDeductive methods including findings from previous research and a review of existing measures, together with inductive methods such as expert feedback and focus groups with trans individuals, were used to generate a preliminary item pool for the GES. Pilot testing with trans community members and mental health clinicians was then used to refine items and develop a preliminary scale. Trans participants involved in an ongoing longitudinal study (TRANSform) were invited to complete the scale alongside measures of personality and gender factors to assess validity. Participants were then invited to complete the scale two weeks after initial completion to assess the test–retest reliability of the scale. The next stage in the scale development process will be to examine the dimensionality of the GES using exploratory factor analytic techniques. The scale will then be assessed for internal consistency, temporal stability, discriminant validity, and convergent validity.ConclusionThis paper outlines the development and characterization of a novel tool to measure gender euphoria for the first time. The GES will facilitate research opportunities to better understand the nature of gender euphoria and its influences, and may be used clinically to examine relationships between gender euphoria and gender affirming interventions. Hence, we expect the GES to make a significant contribution to both research and clinical practice with trans communities.

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Abstract Point of care Ultrasound (POCUS) has been adopted into clinical practice across many fields of medicine. Undergraduate medical education programs have recognized the need to incorporate POCUS training into their curricula, traditionally done in small groups with in-person sessions. This method is resource intensive and requires sufficient equipment and expertise. These requirements are often cited as barriers for implementation. During the Coronavirus Disease 2019 (COVID-19) pandemic, POCUS education was required to adapt to physical distancing regulations, giving rise to novel teaching methods for POCUS. This article outlines the implementation of a POCUS teaching session before and during the pandemic. It describes how these innovations can scale POCUS teaching and overcome barriers moving forward. A flipped classroom model was implemented for all learners. Learners were given an introductory POCUS module before the scheduled in-person or virtual teaching session. Sixty-nine learners participated in conventional in-person teaching, while twenty-two learners participated in virtual teaching following the pandemic-related restrictions. Learners completed a written test before and following the teaching. In-person learners were assessed using an objective structured assessment of ultrasound skills (OSAUS) pre- and post-learning sessions. A follow-up survey was conducted three years after the teaching sessions were completed. Both in-person and virtual groups demonstrated statistically significant improvement in knowledge scores (p

Abstract We used an agent-based model Covasim to assess the risk of sustained community transmission of SARSCoV-2/COVID-19 in Queensland (Australia) in the presence of high-transmission variants of the virus. The model was calibrated using the demographics, policies, and interventions implemented in the state. Then, using the calibrated model, we simulated possible epidemic trajectories that could eventuate due to leakage of infected cases with high-transmission variants, during a period without recorded cases of locally acquired infections, known in Australian settings as “zero community transmission”. We also examined how the threat of new variants reduces given a range of vaccination levels. Specifically, the model calibration covered the first-wave period from early March 2020 to May 2020. Predicted epidemic trajectories were simulated from early February 2021 to late March 2021. Our simulations showed that one infected agent with the ancestral (A.2.2) variant has a 14% chance of crossing a threshold of sustained community transmission (SCT) (i.e., > 5 infections per day, more than 3 days in a row), assuming no change in the prevailing preventative and counteracting policies. However, one agent carrying the alpha (B.1.1.7) variant has a 43% chance of crossing the same threshold; a threefold increase with respect to the ancestral strain; while, one agent carrying the delta (B.1.617.2) variant has a 60% chance of the same threshold, a fourfold increase with respect to the ancestral strain. The delta variant is 50% more likely to trigger SCT than the alpha variant. Doubling the average number of daily tests from ∼ 6,000 to 12,000 results in a decrease of this SCT probability from 43 to 33% for the alpha variant. However, if the delta variant is circulating we would need an average of 100,000 daily tests to achieve a similar decrease in SCT risk. Further, achieving a full-vaccination coverage of 70% of the adult population, with a vaccine with 70% effectiveness against infection, would decrease the probability of SCT from a single seed of alpha from 43 to 20%, on par with the ancestral strain in a naive population. In contrast, for the same vaccine coverage and same effectiveness, the probability of SCT from a single seed of delta would decrease from 62 to 48%, a risk slightly above the alpha variant in a naive population. Our results demonstrate that the introduction of even a small number of people infected with high-transmission variants dramatically increases the probability of sustained community transmission in Queensland. Until very high vaccine coverage is achieved, a swift implementation of policies and interventions, together with high quarantine adherence rates, will be required to minimise the probability of sustained community transmission.

Structural variations (SVs) play a key role in the pathogenicity of hematological malignancies. Standard-of-care (SOC) methods such as karyotyping and fluorescence in situ hybridization (FISH), which have been employed globally for the past three decades, have significant limitations in terms of resolution and the number of recurrent aberrations that can be simultaneously assessed, respectively. Next-generation sequencing (NGS)-based technologies are now widely used to detect clinically significant sequence variants but are limited in their ability to accurately detect SVs. Optical genome mapping (OGM) is an emerging technology enabling the genome-wide detection of all classes of SVs at a significantly higher resolution than karyotyping and FISH. OGM requires neither cultured cells nor amplification of DNA, addressing the limitations of culture and amplification biases. This study reports the clinical validation of OGM as a laboratory-developed test (LDT) according to stringent regulatory (CAP/CLIA) guidelines for genome-wide SV detection in different hematological malignancies. In total, 60 cases with hematological malignancies (of various subtypes), 18 controls, and 2 cancer cell lines were used for this study. Ultra-high-molecular-weight DNA was extracted from the samples, fluorescently labeled, and run on the Bionano Saphyr system. A total of 215 datasets, Inc.luding replicates, were generated, and analyzed successfully. Sample data were then analyzed using either disease-specific or pan-cancer-specific BED files to prioritize calls that are known to be diagnostically or prognostically relevant. Sensitivity, specificity, and reproducibility were 100%, 100%, and 96%, respectively. Following the validation, 14 cases and 10 controls were run and analyzed using OGM at three outside laboratories showing reproducibility of 96.4%. OGM found more clinically relevant SVs compared to SOC testing due to its ability to detect all classes of SVs at higher resolution. The results of this validation study demonstrate the superiority of OGM over traditional SOC methods for the detection of SVs for the accurate diagnosis of various hematological malignancies.

Asymmetries of the cerebral cortex are found across diverse phyla and are particularly pronounced in humans, with important implications for brain function and disease. However, many prior studies have confounded asymmetries due to size with those due to shape. Here, we introduce a novel approach to characterize asymmetries of the whole cortical shape, independent of size, across different spatial frequencies using magnetic resonance imaging data in three independent datasets. We find that cortical shape asymmetry is highly individualized and robust, akin to a cortical fingerprint, and identifies individuals more accurately than size-based descriptors, such as cortical thickness and surface area, or measures of inter-regional functional coupling of brain activity. Individual identifiability is optimal at coarse spatial scales (~37 mm wavelength), and shape asymmetries show scale-specific associations with sex and cognition, but not handedness. While unihemispheric cortical shape shows significant heritability at coarse scales (~65 mm wavelength), shape asymmetries are determined primarily by subject-specific environmental effects. Thus, coarse-scale shape asymmetries are highly personalized, sexually dimorphic, linked to individual differences in cognition, and are primarily driven by stochastic environmental influences.

The human brain is distinct from those of other species in terms of size, organization, and connectivity. How do structural evolutionary differences drive patterns of neural activity enabling brain function? Here, we combine brain imaging and biophysical modeling to show that the anatomical wiring of the human brain distinctly shapes neural dynamics. This shaping is characterized by a narrower distribution of dynamic ranges across brain regions compared with that of chimpanzees, our closest living primate relatives. We find that such a narrow dynamic range distribution supports faster integration between regions, particularly in transmodal systems. Conversely, a broad dynamic range distribution as seen in chimpanzees facilitates brain processes relying more on neural interactions within specialized local brain systems. These findings suggest that human brain dynamics have evolved to foster rapid associative processes in service of complex cognitive functions and behavior.

Routine assessments of gait and balance have been recognized as an effective approach for preventing falls by issuing early warnings and implementing appropriate interventions. However, current limited public healthcare resources cannot meet the demand for continuous monitoring of deteriorations in gait and balance. The objective of this study was to develop and evaluate the feasibility of a prototype surrogate system driven by sensor technology and multi-sourced heterogeneous data analytics, for gait and balance assessment and monitoring. The system was designed to analyze users’ multi-mode data streams collected via inertial sensors and a depth camera while performing a 3-m timed up and go test, a five-times-sit-to-stand test, and a Romberg test, for predicting scores on clinical measurements by physiotherapists. Generalized regression of sensor data was conducted to build prediction models for gait and balance estimations. Demographic correlations with user acceptance behaviors were analyzed using ordinal logistic regression. Forty-four older adults (38 females) were recruited in this pilot study (mean age = 78.5 years, standard deviation [SD] = 6.2 years). The participants perceived that using the system for their gait and balance monitoring was a good idea (mean = 5.45, SD = 0.76) and easy (mean = 4.95, SD = 1.09), and that the system is useful in improving their health (mean = 5.32, SD = 0.83), is trustworthy (mean = 5.04, SD = 0.88), and has a good fit between task and technology (mean = 4.97, SD = 0.84). In general, the participants showed a positive intention to use the proposed system in their gait and balance management (mean = 5.22, SD = 1.10). Demographic correlations with user acceptance are discussed. This study provides preliminary evidence supporting the feasibility of using a sensor-technology-augmented system to manage the gait and balance of community-dwelling older adults. The intervention is validated as being acceptable, viable, and valuable.

Introduction:: Updating the mode of data collection may affect response rates or survey results. The ongoing, national Monitoring the Future (MTF) panel study has traditionally used mailed paper surveys. In 2018, MTF experimented with a web-push data collection design for young adults ages 19–30, concluding that the web-push design improved response rates and did not change substance use estimates after controlling for sociodemographic characteristics (Patrick et al., 2021). The current study sought to replicate the web-push experiment with MTF adults ages 35 to 60 in 2020. Methods:: In 2020, the MTF panel study included an experiment to test a web-push protocol for respondents ages 35 to 60 (N=14,379). Participants were randomized to the web-push (i.e., a web survey invitation, with paper surveys available for non-respondents) or traditional MTF (i.e., mailed paper surveys) data collection condition. Results:: Results indicated no significant difference in overall response rate for the web-push vs. standard MTF conditions in this age group. Differences in reported estimates of past 30-day substance use prevalence by condition were not significant after adjusting for sociodemographic characteristics. In multivariable models, participants in the web-push condition were less likely to respond via web (than paper) if they were Black, smoked cigarettes in the past 30 days, were unmarried, or did not have a college degree. Conclusions:: Overall, the move to the web-push design had minimal impact on response rates and substance use prevalence estimates for this age group. However, in the web-push condition, sociodemographic differences were associated with mode of response.

Angiostrongyliasis (Rat Lungworm disease) is an emerging parasitic disease caused by the ingestion of gastropods infected with the neurotropic nematode Angiostrongylus cantonensis. The reduction of crop infestation with infected slug carriers may vary widely by protection method. We explored the application of barriers with valve mechanisms, whereby selective directional forces caused a greater number of slugs to exit than enter the protected plot, leading to decreased slug population densities at a steady state. Using field data, we constructed predictive models to estimate slug population densities at a steady state in protected plots with (1) no valve effect, (2) a valve effect, (3) no valve effect with a single breach of the barrier, (4) a valve effect with a single breach of the barrier, (5) a valve effect with a constant breach of the barrier, and (6) a repelling effect. For all scenarios, plots protected using a barrier with a valve effect had consistently lower slug densities at a steady state. Our findings support the use of barriers with valve mechanisms under different conditions, and potentially in combination with other interventions to reduce the contamination of crops by slug carriers of A. cantonensis. Improving barriers extends beyond disease mitigation to economic and cultural impacts on the local farmer and consumer communities.

Abstract This randomized controlled trial aimed to evaluate the effects of different whole body vibration (WBV) frequencies on concentric and eccentric leg muscle strength, bone turnover and walking endurance after stroke. The study involved eighty-four individuals with chronic stroke (mean age = 59.7 years, SD = 6.5) with mild to moderate motor impairment (Fugl-Meyer Assessment lower limb motor score: mean = 24.0, SD = 3.5) randomly assigned to either a 20 Hz or 30 Hz WBV intervention program. Both programs involved 3 training sessions per week for 8 weeks. Isokinetic knee concentric and eccentric extension strength, serum level of cross-linked N-telopeptides of type I collagen (NTx), and walking endurance (6-min walk test; 6MWT) were assessed at baseline and post-intervention. An intention-to-treat analysis revealed a significant time effect for all muscle strength outcomes and NTx, but not for 6MWT. The time-by-group interaction was only significant for the paretic eccentric knee extensor work, with a medium effect size (0.44; 95% CI: 0.01, 0.87). Both WBV protocols were effective in improving leg muscle strength and reducing bone resorption. Comparatively greater improvement in paretic eccentric leg strength was observed for the 30 Hz protocol.

IntroductionLumbar multifidus muscle (LMM) dysfunction is thought to be related to pain and/or disability in people with chronic low back pain (CLBP). Although psychosocial factors play a major role in pain/disability, they are seldom considered as confounders in analyzing the association between LMM and CLBP.ObjectivesThis study aimed to determine: (1) differences in psychological factors, insomnia, and LMM characteristics between people with and without CLBP; (2) associations between psychological factors, insomnia, or LMM characteristics and low back pain (LBP) intensity or LBP-related disability in people with CLBP; and (3) whether LMM characteristics are related to LBP symptoms in people with CLBP after considering confounders.MethodsSeventy-eight volunteers with CLBP and 73 without CLBP provided sociodemographic information, filled the 11-point numeric pain rating scale and Roland-Morris disability questionnaire (RMDQ). They completed the Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), Fear Avoidance Belief Questionnaire (FAB), and Insomnia Severity Index Scale (ISI). Resting and contracted thickness of LMM at L4-S1 levels were measured from brightness-mode ultrasound images. Percent thickness changes of LMM at L4-S1 levels during contraction were calculated. Resting LMM stiffness at L4-S1 was measured by shear wave elastography. Associations among LMM, psychosocial or insomnia parameters and clinical outcomes were analyzed by univariate and multivariate analyses.ResultsPeople with CLBP demonstrated significantly higher LBP-intensity, RMDQ, HADS, FAB, PCS, and ISI scores than asymptomatic controls (p < 0.05). The former also had significantly smaller percent thickness changes of LMM at L4/L5 during contraction. LBP-intensity was positively related to scores of PCS-total, PCS-helplessness, FAB-total, FAB-work, and ISI in people with CLBP (p < 0.05). RMDQ scores were positively associated with the scores of HADS-total, HADS-depression, PCS-total, FAB-total, FAB-physical activity, PCS-helplessness, and ISI in people with CLBP (p < 0.05). FAB-work and ISI scores together explained 24% of LBP-intensity. FAB-total scores alone explained 34% of variance of LBP-related disability in people with CLBP.ConclusionMore fear-avoidance belief or insomnia is related to greater LBP-intensity and/or LBP-related disability in people with CLBP. Although people with CLBP were thought to have aberrant LMM morphometry/function, no LMM characteristics were related to LBP-intensity or LBP-related disability after considering other confounders.

Taurine and indicine cattle have different desirable traits making them better adapted to different climates across the world. Here, Low et al. describe a pipeline to produce haplotype-resolved, chromosome-level genomes of Angus and Brahman cattle breeds from a crossbred individual and report on comparisons of the two genomes.

Increasing numbers of trans and gender diverse young people are presenting to health services seeking gender-affirming medical care. While testosterone therapy in transgender males is generally effective in inducing masculinization, some adolescents encounter barriers to accessing such treatment or may not wish to experience all the changes that usually accompany testosterone. Here, we describe the case of a 17 year old trans male who presented with gender dysphoria but was initially unable to start testosterone therapy. Due to a desire for facial hair, he was therefore treated with topical minoxidil, an easily accessible, over-the-counter medication that has been used to treat androgenic alopecia for several decades. In this case, minoxidil was applied regularly to the lower face and, after three months of treatment, he developed obvious pigmented facial hair that was sufficient to help him avoid being misgendered. The only reported side effect was excessive skin dryness. Unexpectedly, despite no direct application to other areas, there was also an increase in pigmented body hair, suggestive of systemic absorption and effect. Given its long-standing use and safety record in the management of alopecia, minoxidil might thus represent a useful treatment option for trans males who desire an increase in facial hair.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

Gender dysphoria describes the distress associated with having a gender identity that differs from one’s birth-assigned sex. To relieve this distress, transgender, and gender diverse (henceforth, trans) individuals commonly undergo medical transition involving hormonal treatments. Current hormonal treatment guidelines cater almost exclusively for those who wish to transition from male to female or vice versa. In contrast, there is a dearth of hormonal options for those trans individuals who identify as non-binary and seek an androgynous appearance that is neither overtly male nor female. Though prolonged puberty suppression with gonadotrophin releasing hormone agonists (GnRHa) could in theory be gender-affirming by preventing the development of unwanted secondary sex characteristics, this treatment option would be limited to pre- or peri-pubertal adolescents and likely have harmful effects. Here, we discuss the theoretical use of Selective Estrogen Receptor Modulators (SERMs) for non-binary people assigned male at birth (AMAB) who are seeking an androgynous appearance through partial feminization without breast growth. Given their unique range of pharmacodynamic effects, SERMs may represent a potential gender-affirming treatment for this population, but there is a lack of knowledge regarding their use and potentially adverse effects in this context.

Heterozygous missense mutations in the human COL7A1 gene – coding for collagen VII – lead to the rare, dominantly inherited skin disorder dominant dystrophic epidermolysis bullosa (DDEB), which is characterised by skin fragility, blistering, scarring and nail dystrophy. To better understand the pathophysiology of DDEB and develop more effective treatments, suitable mouse models for DDEB are required but to date none have existed. We identified the two most common COL7A1 mutations in DDEB patients (p.G2034R and p.G2043R) and used CRISPR-Cas9 to introduce the corresponding mutations into mouse Col7a1 (p.G2028R and p.G2037R). Dominant inheritance of either of these two alleles results in a phenotype that closely resembles that seen in DDEB patients. Specifically, mice carrying these alleles show recurrent blistering that is first observed transiently around the mouth and paws in the early neonatal period and then again around the digits from 5-10 weeks of age. Histologically, the mice show micro-blistering and reduced collagen VII immunostaining. Biochemically, collagen VII from these mice displays reduced thermal stability, which we also observed to be the case for DDEB patients carrying the analogous mutations. Unlike previous rodent models of epidermolysis bullosa, which frequently show early lethality and severe disease, these mouse models, which to our knowledge are the first for DDEB, show no reduction in growth and survival, and – together with a relatively mild phenotype – represent a practically and ethically tractable tool for better understanding and treating epidermolysis bullosa. This article has an associated First Person interview with the first author of the paper.

Objective Fertility counselling for trans and gender diverse (TGD) adolescents has many complexities, but there is currently little guidance for clinicians working in this area. This study aimed to identify effective strategies for—and qualities of—fertility counselling for TGD adolescents based on clinicians’ experiences.Design We conducted qualitative semi-structured individual interviews in 2019 which explored clinician experiences and fertility counselling practices, perspectives of the young person’s experience and barriers and facilitators to fertility preservation access. Data were analysed using thematic analysis.Setting This qualitative study examined experiences of clinicians at the Royal Children’s Hospital—a tertiary, hospital-based, referral centre and the main provider of paediatric TGD healthcare in Victoria, Australia.Participants We interviewed 12 clinicians from a range of disciplines (paediatrics, psychology, psychiatry and gynaecology), all of whom were involved with fertility counselling for TGD adolescents.Results Based on clinician experiences, we identified five elements that can contribute to an effective approach for fertility counselling for TGD adolescents: a multidisciplinary team approach; shared decision-making between adolescents, their parents and clinicians; specific efforts to facilitate patient engagement; flexible personalised care; and reflective practice.Conclusions Identification of these different elements can inform and hopefully improve future fertility counselling practices for TGD adolescents, but further studies examining TGD adolescents’ experiences of fertility counselling are also required.

Synchronization is a collective mechanism by which oscillatory networks achieve their functions. Factors driving synchronization include the network’s topological and dynamical properties. However, how these factors drive the emergence of synchronization in the presence of potentially disruptive external inputs like stochastic perturbations is not well understood, particularly for real-world systems such as the human brain. Here, we aim to systematically address this problem using a large-scale model of the human brain network (i.e., the human connectome). The results show that the model can produce complex synchronization patterns transitioning between incoherent and coherent states. When nodes in the network are coupled at some critical strength, a counterintuitive phenomenon emerges where the addition of noise increases the synchronization of global and local dynamics, with structural hub nodes benefiting the most. This stochastic synchronization effect is found to be driven by the intrinsic hierarchy of neural timescales of the brain and the heterogeneous complex topology of the connectome. Moreover, the effect coincides with clustering of node phases and node frequencies and strengthening of the functional connectivity of some of the connectome’s subnetworks. Overall, the work provides broad theoretical insights into the emergence and mechanisms of stochastic synchronization, highlighting its putative contribution in achieving network integration underpinning brain function.

Cigarette smoke (CS) is the major risk factor for chronic obstructive pulmonary disease (COPD) and can induce systemic manifestations, such as skeletal muscle derangement. However, inconsistent findings of muscle derangement were reported in previous studies. The aim of the present study was to consolidate the available evidence and assess the impact of CS on muscle derangement in rodents. A comprehensive literature search of five electronic databases identified ten articles for final analysis. Results showed that the diaphragm, rectus femoris, soleus, and gastrocnemius exhibited significant oxidative to glycolytic fiber conversions upon CS exposure. In contrast, the extensor digitorum longus (EDL), plantaris, and tibialis did not exhibit a similar fiber-type conversion after CS exposure. Hindlimb muscles, including the quadriceps, soleus, gastrocnemius, and EDL, showed significant reductions in the CSA of the muscle fibers in the CS group when compared to the control group. Changes in inflammatory cytokines, exercise capacity, and functional outcomes induced by CS have also been evaluated. CS could induce a shift from oxidative fibers to glycolytic fibers in high-oxidative muscles such as the diaphragm, rectus femoris, and soleus, and cause muscle atrophy, as reflected by a reduction in the CSA of hindlimb muscles such as the quadriceps, soleus, gastrocnemius, and EDL.

Introduction: While young adults with chronic low back pain (CLBP) exhibit impaired lumbar proprioception, it remains unclear if the same phenomenon is observed in middle-aged adults with CLBP.Objectives: This study aimed to investigate whether young or middle-aged adults with CLBP displayed different proprioception ability as compared to age-matched asymptomatic controls.Methods: Sixty-four young adults with [median age:34 [interquartile range (IQR): 29–37] years] and without [median age:29 (IQR; 23–34) years] CLBP, and 87 middle-aged adults with [median age:53 (IQR: 49–58) years] and without [median age: 54 (IQR: 45–64) years] CLBP underwent postural sway tests on a force-plate with (unstable surface) and without a foam (stable surface), while bilateral L5/S1 multifidi and triceps-surae were vibrated separately. An individual's proprioception reweighting ability was estimated by relative proprioceptive reweighting (RPW). Higher RPW values indicate less reliance on lumbar multifidus proprioceptive signals for balance. Participants also underwent lumbar repositioning tests in sitting to determine repositioning errors in reproducing target lumbar flexion/extension positions.Results: Young adults with CLBP demonstrated significantly higher median RPW values than age-matched asymptomatic controls for maintaining standing balance [stable surface: CLBP: 0.9 (IQR: 0.7–0.9), asymptomatic: 0.7 (IQR: 0.6–0.8), p < 0.05; unstable surface: CLBP: 0.6 (IQR: 0.4–0.8), asymptomatic: 0.5 (IQR: 0.3–0.7), p < 0.05]. No significant differences in repositioning error were noted between young or middle-aged adults with and without CLBP (p > 0.05). RPW values were unrelated to repositioning errors in all groups (p > 0.05).Conclusion: Young adults with CLBP, and middle-aged adults with and without CLBP had inferior proprioceptive reweighting capability. This finding may indicate potential age-related deterioration in central and peripheral processing of lumbar proprioceptive signals. Future studies should use advanced imaging and/or electroencephalogram to determine mechanisms underlying changes in proprioceptive reweighting in middle-aged adults.

3-Dimensional (3D) scanning systems are becoming more common in the industry nowadays, for inspection and reverse engineering (RE) purposes. Although technical specifications are provided with commercially available scanners, a question could be raised pertaining to the degree of sufficiency of the technical specifications typically provided, with regard to specific application needs such as the scanning of challenging objects. These challenging objects present a less than ideal working condition for some 3D scanners, and the specified accuracy cannot be achieved. This effect varies across different types of 3D scanning technology. A more intuitive specification with regard to the time taken and ease of use will be beneficial to the user, but often not available. Hence, this paper proposes a Morphological Box Classification Framework based on the functional decomposition of the non-contact 3D scanning technology, in order to help users better understand and compare 3D scanners efficiently, and choose a scanner for their application that is able to perform within their desired accuracy, time taken, and ease of use. A case study of 3D scanners evaluation using the proposed framework for a RE application is conducted, and results presented.

Small extracellular vesicles (SEVs) such as exosomes are released by multiple cell types. Originally believed to be a mechanism for selectively removing unwanted cellular components, SEVs have received increased attention in recent years for their ability to mediate intercellular communication. Apart from proteins and lipids, SEVs contain RNAs, but how RNAs are selectively loaded into SEVs remains poorly understood. To address this question, we profiled SEV RNAs from mouse dendritic cells using RNA-Seq and identified a long noncoding RNA of retroviral origin, VL30, which is highly enriched (>200-fold) in SEVs compared to parental cells. Bioinformatic analysis revealed that exosome-enriched isoforms of VL30 RNA contain a repetitive 26-nucleotide motif. This repeated motif is itself efficiently incorporated into SEVs, suggesting the likelihood that it directly promotes SEV loading. RNA folding analyses indicate that the motif is likely to form a long double-stranded RNA hairpin and, consistent with this, its overexpression was associated with induction of a potent type I interferon response. Taken together, we propose that preferential loading into SEVs of the VL30 RNA containing this immunostimulatory motif enables cells to remove a potentially toxic RNA and avoid autoinflammation. In this way, the original notion of SEVs as a cellular garbage bin should not be entirely discounted.

Introduction Being transgender is frequently accompanied by gender dysphoria, which often coexists with mental health concerns. Increased referrals of transgender and gender diverse (TGD) youth to gender clinics have been observed in many countries. Nevertheless, there are limited empirical data on the presentation and outcomes of these patients, and there is an urgent need for more evidence to ensure optimal medical and psychosocial interventions. Here, we describe Trans20, a longitudinal study of TGD patients attending a multidisciplinary paediatric gender service in Melbourne, Australia. Trans20 aims to understand the demographic and clinical characteristics of these patients, to document the natural history of gender diversity presenting in childhood and to investigate long-term outcomes for those receiving interventions.Methods and analysis Trans20 is a prospective cohort study based on children and adolescents first seen at the Royal Children’s Hospital Gender Service (RCHGS) between February 2017 and February 2020. Current estimates indicate the final sample size will be approximately 600. Patients and their parents complete online questionnaires prior to the first appointment with RCHGS and regularly thereafter as part of routine clinical care. On discharge from RCHGS, patients are invited to continue undertaking questionnaires biennially. In this way, a naturally forming cohort study has been created. The primary outcomes include gender dysphoria, physical and mental health, schooling, family functioning and quality of life. Subgroup analyses based on factors such as gender identity, birth-assigned sex and treatment received will be performed using bivariate and multivariate modelling as appropriate, and relevant statistical methods will be applied for the repeated measures over time.Ethics and dissemination The Royal Children's Hospital Human Research Ethics Committee approved this study (#36323). Findings from Trans20 will have translational impact by informing future treatment guidelines and gender affirming healthcare practices and will be disseminated through conferences and peer reviewed journals.

Purpose: Emergency nurses are engaged in the management of epidemic events that unfold along with the evolution of diseases. The goal of this study was to explore the contextual factors that inhibited the ability of emergency nurses to perform their duties in response to an outbreak. Methods: A qualitative descriptive design was used to explore the experiences and perceptions of emergency nurses. Participants were purposively recruited from 12 emergency departments in Hong Kong. Semi-structured face-to-face individual interviews were conducted with 26 emergency nurses. The audio-recorded interviews were transcribed verbatim and interpreted with a thematic analysis approach. Results: Four intertwined themes emerged from the analysis: resource constraints, threats of infection, ubiquitous changes and lingering uncertainties. These themes portrayed the constraints and challenges surrounding the work environment of emergency nurses. Conclusion: This study described the instabilities and vulnerabilities of the circumstances in which the emergency nurses were situated in during epidemic events. The findings shed light on the importance of hospitals and emergency departments in addressing both the technical problems and adaptive challenges that face emergency nurses during epidemic events.