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ABSTRACT: Adolescence is a stage of development characterized by neurodevelopmental specialization of cognitive processes. In particular, working memory continues to improve through adolescence, with increases in response accuracy and decreases in response latency continuing well into the twenties. Human electroencephalogram (EEG) studies indicate that gamma oscillations (35–65 Hz) during the working memory delay period support the maintenance of mnemonic information guiding subsequent goal-driven behavior, which decrease in power with development. Importantly, recent electrophysiological studies have shown that gamma events, more so than sustained activity, may underlie working memory maintenance during the delay period. However, developmental differences in gamma events during working memory have not been studied. Here, we used EEG in conjunction with a novel spectral event processing approach to investigate age-related differences in transient gamma band activity during a memory guided saccade (MGS) task in 164 10- to 30-year-olds. Total gamma power was found to significantly decrease through adolescence, replicating prior findings. Results from the spectral event pipeline showed age-related decreases in the mean power of gamma events and trial-by-trial power variability across both the delay period and fixation epochs of the MGS task. In addition, we found that while event number decreased with age during the fixation period, the developmental decrease during the delay period was more dramatic, resulting in an increase in event spiking from fixation to delay in adolescence but not adulthood. While average power of the transient gamma events was found to mediate age-related differences in total gamma power in the fixation and delay periods, the number of gamma events was related to total power in only the delay period, suggesting that the power of gamma events may underlie the sustained gamma activity seen in EEG literature while the number of events may directly support age-related improvements in working memory maintenance. Our findings provide compelling new evidence for mechanistic changes in neural processing characterized by refinements in neural function as behavior becomes optimized in adulthood.

The 21-site Adolescent Brain Cognitive Development (ABCD) study provides an unparalleled opportunity to characterize functional brain development via resting-state functional connectivity (RSFC) and to quantify relationships between RSFC and behavior. This multi-site data set includes potentially confounding sources of variance, such as differences between data collection sites and/or scanner manufacturers, in addition to those inherent to RSFC (e.g., head motion). The ABCD project provides a framework for characterizing and reproducing RSFC and RSFC-behavior associations, while quantifying the extent to which sources of variability bias RSFC estimates. We quantified RSFC and functional network architecture in 2,188 9-10-year old children from the ABCD study, segregated into demographically-matched discovery (N = 1,166) and replication datasets (N = 1,022). We found RSFC and network architecture to be highly reproducible across children. We did not observe strong effects of site; however, scanner manufacturer effects were large, reproducible, and followed a "short-to-long" association with distance between regions. Accounting for potential confounding variables, we replicated that RSFC between several higher-order networks was related to general cognition. In sum, we provide a framework for how to characterize RSFC-behavior relationships in a rigorous and reproducible manner using the ABCD dataset and other large multi-site projects.

Fatigue is often one of the most commonly reported symptoms in prostate cancer survivors, but it is also one of the least understood cancer-related symptoms. Fatigue is associated with psychological distress, disruptions in sleep quality, and impairments in health-related quality of life. Moreover, inflammatory processes and changes related to the hypothalamic-pituitary-adrenal (HPA) axis and/or autonomic nervous system may also play a role in cancer-related fatigue. Thus, effective treatments for fatigue in prostate cancer survivors represent a current unmet need. Prior research has shown that Tai Chi Qigong, a mind-body exercise intervention, can improve physical and emotional health. Herein, we describe the protocol of the ongoing 3-arm randomized controlled Health Empowerment & Recovery Outcomes (HERO) clincal trial. One hundred sixty-six prostate cancer survivors with fatigue are randomized to a modified Tai Chi Qigong intervention (TCQ), intensity-matched body training intervention (BT), or usual care (UC) condition. Guided by biopsychosocial and psychoneuroimmunology models, we propose that TCQ, as compared to BT or UC will: i) reduce fatigue (primary outcome) in prostate cancer survivors; ii) reduce inflammation; and iii) regulate the expression of genes from two major functional clusters: a) inflammation, vasodilation and metabolite sensing and b) energy and adrenergic activation. Assessments are conducted at baseline, the 6-week midpoint of the intervention, and 1 week, 3 months, and 12 months post-intervention. If our findings show that TCQ promotes recovery from prostate cancer and its treatment, this type of intervention can be integrated into survivorship care plans as the standard of care. The study's findings will also provide novel information about underlying biobehavioral mechanisms of cancer-related fatigue. Trial registration number:NCT03326713; clinicaltrials.gov.

The diagnosis of germline predisposition to myeloid neoplasms (MN) secondary to DDX41 variants is currently hindered by the long latency period, variable family histories and the frequent occurrence of DDX41 variants of uncertain significance (VUS). We reviewed 4,524 consecutive patients who underwent targeted sequencing for suspected or known MN and analyzed the clinical impact and relevance of DDX41VUS in comparison to DDX41path variants. Among 107 patients (44 [0.9%] DDX41path and 63 DDX41VUS [1.4%; 11 patients with both DDX41path and DDX41VUS]), we identified 17 unique DDX41path and 45 DDX41VUS variants: 24 (23%) and 77 (72%) patients had proven and presumed germline DDX41 variants, respectively. The median age was similar between DDX41path and DDX41VUS (66 vs. 62 years; P=0.41). The median variant allele frequency (VAF) (47% vs. 48%; P=0.62), frequency of somatic myeloid co-mutations (34% vs 25%; P= 0.28), cytogenetic abnormalities (16% vs. 12%; P=>0.99) and family history of hematological malignancies (20% vs. 33%; P=0.59) were comparable between the two groups. Time to treatment in months (1.53 vs. 0.3; P=0.16) and proportion of patients progressing to acute myeloid leukemia (14% vs. 11%; P=0.68), were similar. The median overall survival in patients with high-risk myelodysplastic syndrome/acute myloid leukemia was 63.4 and 55.7 months in the context of DDX41path and DDX41VUS, respectively (P=0.93). Comparable molecular profiles and clinical outcomes among DDX41path and DDX41VUS patients highlights the need for a comprehensive DDX41 variant interrogation/classification system, to improve surveillance and management strategies in patients and families with germline DDX41 predisposition syndromes.

Identification of language disorders in children younger than 3 years remains challenging despite agreement that early intervention improves outcomes. This study of twin language and gesture development substantiated the twinning effect, an unexplained lag in expressive and receptive language seen in twins, for a group of 88, 16- to 18-month-old twins who did not present with extreme perinatal risk. A valid, parent-report measure revealed word production of 10th percentile and less for 15 twins. Pregnancy complications, but not a positive family history of speech, language, or learning disorders or other case history factors, significantly increased the odds of this early expressive delay. The twinning effect was more pronounced for gesture than for spoken vocabulary: 29 twins fell below gesture norms. This was unexpected. Because gesture signals early communicative intentionality, twins with early expressive delay who present with limited gestures, with or without additional risk factors, warrant priority consideration for early intervention.

Abstract Patients with asthma frequently over rely on short-acting beta-agonists (SABA) to treat acute symptoms. This can adversely impact quality of life and increase the risk of exacerbations. SABA overuse is also associated with an increased risk of mortality. In their 2021 update on the diagnosis and management of mild asthma, the Canadian Thoracic Society (CTS) newly recommended that a combination inhaled corticosteroid (ICS) and long-acting beta-agonist, specifically budesonide/formoterol, may be used as-needed (PRN) as an alternative reliever to SABA. The CTS developed an algorithm as a guide for deciding for whom PRN budesonide/formoterol versus PRN SABA is appropriate as a reliever. While the CTS algorithm provides necessary and precise guidance, the somewhat complicated requirements for determining control and exacerbation risk may still end up leaving some patients at-risk of SABA overreliance. This communication simplifies the reliever decision algorithm developed by the CTS for application in daily practice. A 30-s evaluation of 2 simple questions related to reliever use can usually accurately assess if a patient’s asthma is controlled: How many SABA canisters do you use a year AND how many times do you use SABA a week? If the patient indicates use of > 2 SABA canisters per year or > 2 administrations of SABA per week for any reason, the patient does not have controlled asthma and PRN SABA is not an appropriate treatment regimen. Similarly, for patients using PRN ICS/formoterol, more than 2 administrations per week indicates a clinical review and reevaluation of their management, including augmentation. An education process is essential to inform patients, caregivers, and healthcare providers that overuse of any reliever is not acceptable and is potentially harmful.

A two-year targeted intervention designed to improve students' oral communication skills in an organic chemistry laboratory course is described. The study compares the oral communication skills of groups who received interventions versus those who did not. The collaborative effort involving chemistry and English faculty and an instruction librarian assessed student performance on several measures of oral communication competency. Participants blindly placed themselves in either treatment or control groups. Both groups received identical basic instruction on poster layout and design. The treatment group received additional instruction on multiple aspects of oral communication and presentation skills. A comparison of the outcomes of the two groups found that those receiving the additional targeted interventions performed better on measures such as the ability to describe clearly the research project and fluency with scientific terminology.

Abstract Background The ideal treatment of early-stage arthrofibrosis after total knee arthroplasty is unclear. The purpose of this study was to determine the treatment effect, including variability, and feasibility of a multimodal physical therapy program as compared to manipulation under anesthesia. Methods This was a prospective feasibility study with a retrospective cohort comparison. Ten consecutive patients (aged 64 ± 9 years, 7 females) with early-stage arthrofibrosis were enrolled 6 weeks after primary total knee arthroplasty and participated in the multimodal physical therapy program. The multimodal physical therapy program consisted of manual therapy, therapeutic exercise, and static progressive splinting delivered over 4 weeks. The outcomes included knee range of motion (ROM), adherence, patient satisfaction, and safety. Data were compared to a retrospective cohort of 31 patients with arthrofibrosis (aged 65 ± 9 years, 20 females) who underwent manipulation under anesthesia followed by physical therapy. Results Overall, knee ROM outcomes were similar between multimodal physical therapy (110° ± 14) and manipulation under anesthesia (109° ± 11). Seven out of ten patients achieved functional ROM (≥ 110°) and avoided manipulation under anesthesia with the multimodal physical therapy program. Three out of 10 multimodal physical therapy patients required manipulation under anesthesia secondary to failure to demonstrate progress within 4 weeks of the multimodal physical therapy program. Adherence to the multimodal physical therapy program was 87 ± 9%. The median patient satisfaction with the multimodal physical therapy program was “very satisfied.” Safety concerns were minimal. Conclusion The use of the multimodal physical therapy program is feasible for treating early-stage arthrofibrosis after total knee arthroplasty, with 70% of patients avoiding manipulation under anesthesia. Randomized controlled trials are needed to determine the efficacy of the multimodal physical therapy program and to determine the optimal patient selection for the multimodal physical therapy program versus manipulation under anesthesia. Trial registration ClinicalTrials.gov, NCT04837872 .

Hundreds of genetic variants implicated in Mendelian disease have been characterized in dogs and commercial screening is being offered for most of them worldwide. There is typically limited information available regarding the broader population frequency of variants and uncertainty regarding their functional and clinical impact in ancestry backgrounds beyond the discovery breed. Genetic panel screening of disease-associated variants, commercially offered directly to the consumer or via a veterinary clinician, provides an opportunity to establish large-scale cohorts with phenotype data available to address open questions related to variant prevalence and relevance. We screened the largest canine cohort examined in a single study to date (1,054,293 representative dogs from our existing cohort of 3.5 million; a total of 811,628 mixed breed dogs and 242,665 purebreds from more than 150 countries) to examine the prevalence and distribution of a total of 250 genetic disease-associated variants in the general population. Electronic medical records from veterinary clinics were available for 43.5% of the genotyped dogs, enabling the clinical impact of variants to be investigated. We provide detailed frequencies for all tested variants across breeds and find that 57% of dogs carry at least one copy of a studied Mendelian disease-associated variant. Focusing on a subset of variants, we provide evidence of full penetrance for 10 variants, and plausible evidence for clinical significance of 22 variants, on diverse breed backgrounds. Specifically, we report that inherited hypocatalasia is a notable oral health condition, confirm that factor VII deficiency presents as subclinical bleeding propensity and verify two genetic causes of reduced leg length. We further assess genome-wide heterozygosity levels in over 100 breeds, and show that a reduction in genome-wide heterozygosity is associated with an increased Mendelian disease variant load. The accumulated knowledge represents a resource to guide discussions on genetic test relevance by breed.

Abstract Smith‐Lemli‐Opitz syndrome (SLOS) is a relatively common genetic cause of developmental delay and may only present in conjunction with 2,3 toe syndactyly. This case series illustrates a milder phenotype of SLOS, where the predominant findings are neurocognitive in the presence of 2,3 toe syndactyly.

Introduction: Conduction system pacing (CSP), consisting of His bundle pacing (HBP) or left bundle branch area pacing (LBBAP) is a rapidly developing field. These pacing techniques result in single lead left ventricular resynchronisation. Understanding of the associated learning curve of the two techniques is an important consideration for new implanters/implanting centres. Methods: We conducted a review of the first 30 cases of both HBP and LBBAP at The Royal Brompton Hospital. The procedural duration and fluoroscopy time were used as surrogates for the learning curve of each technique. Results: Patient characteristics were similar in HBP and LBBAP groups; LV ejection fraction (46% vs 54%, p = 0.08), pre-procedural QRS duration (119 ms vs 128 ms, p = 0.32).Mean procedural duration was shorter for LBBAP than for HBP (87 vs 107mins, p = 0.04) and the drop in procedural duration was more marked in LBBAP, plateauing and remaining low at 80mins after the initial 10 cases. Fluoroscopic screening time mirrored procedural duration (8 min vs 16 min, p

Converging evidence from both human neuroimaging and animal studies has supported a model of mesolimbic processing underlying reward learning behaviors, based on the computation of reward prediction errors. However, competing evidence supports human dopamine signaling in the basal ganglia as also contributing to the generation of higher order learning heuristics. Here, we present data from a large (N = 81, 18–30yo), multi-modal neuroimaging study using simultaneously acquired task fMRI, affording temporal resolution of reward system function, and PET imaging with [11C]Raclopride (RAC), assessing striatal dopamine (DA) D2/3 receptor binding, during performance of a probabilistic reward learning task. Both fMRI activation and PET DA measures showed ventral striatum involvement for signaling rewards. However, greater DA release was uniquely associated with learning strategies (i.e., learning rates) that were more task-optimal within the best fitting reinforcement learning model. This DA response was associated with BOLD activation of a network of regions including anterior cingulate cortex, medial prefrontal cortex, thalamus and posterior parietal cortex, primarily during expectation, rather than prediction error, task epochs. Together, these data provide novel, human in vivo evidence that striatal dopaminergic signaling interacts with a network of cortical regions to generate task-optimal learning strategies, rather than representing reward outcomes in isolation.

Paraneurial adhesions have been implicated in the pathological progression of entrapment neuropathies. Surgical decompression of adhesions is often performed, with the intent of restoring nerve kinematics. The normal counterpart of adhesions, native paraneurium, is also thought to influence nerve deformation and mobility. However, influences of native or abnormal paraneurial structures on nerve kinematics have not been investigated. We measured regional strains in rat sciatic nerves before and immediately after decompression of native paraneurial tissue, and before and after decompression of abnormal paraneurial adhesions, which formed within 6 weeks of the initial decompression. Strain was significantly higher in the distal-femoral than in the mid-femoral region of the nerve before either decompression. Decompression of native and abnormal paraneurial tissue removed this regional strain difference. Paraneurial tissues appear to play a major role in distributing peripheral nerve strain. Normal nerve strain distributions may be reconstituted following decompression, even in the presence of paraneurial adhesions.

Abstract Background Childhood adversities, such as poor parental practices, exposure to violence, and risk behaviours strongly impact children’s future mental and behavioural problems. Adversities affect families living in disadvantaged environments and low- and middle-income countries (LMICs) to a greater extent than in high-income countries. Parenting programmes are an effective way to alleviate them, although their outreach and scalability is still limited in LMICs. Methods/design A multi-site randomised controlled trial will be conducted in North Macedonia, Republic of Moldova and Romania to test the efficacy and cost-effectiveness of an optimised version of the promising Parenting for Lifelong Health Programme for Young Children (PLH-YC, 5 sessions), against a standard lecture on parenting issues (control group, 1 session). At least 864 participants who report having children between 2 and 9 years old who display elevated levels of behavioural difficulties will be randomised on a 1:1 basis to the intervention and control groups. The primary outcome will consist of parent report of child oppositional aggressive behaviour. Post-test (four months) and follow-up (12 months) assessments will provide information on short- and longer-term effects of PLH-YC compared to the parenting lecture in the control group. Discussion This randomised trial will test the efficacy of PLH-YC in alleviating child behavioural problems and assess the cost-effectiveness, transportability across three different cultural contexts, and potential for scalability of the programme. Trial registration ClinicalTrials.gov ., Registration number: NCT04721730 ( https://clinicaltrials.gov/ct2/show/NCT04721730 ). Registered 13.01.2021

Adolescence is defined by puberty and represents a period characterized by neural circuitry maturation (e.g., fronto-striatal systems) facilitating cognitive improvements. Though studies have characterized age-related changes, the extent to which puberty influences maturation of fronto-striatal networks is less known. Here, we combine two longitudinal datasets to characterize the role of puberty in the development of fronto-striatal resting-state functional connectivity (rsFC) and its relationship to inhibitory control in 106 10–18-year-olds. Beyond age effects, we found that puberty was related to decreases in rsFC between the caudate and the anterior vmPFC, rostral and ventral ACC, and v/dlPFC, as well as with rsFC increases between the dlPFC and nucleus accumbens (NAcc) across males and females. Stronger caudate rsFC with the dlPFC and vlPFC during early puberty was associated with worse inhibitory control and slower correct responses, respectively, whereas by late puberty, stronger vlPFC rsFC with the dorsal striatum was associated with faster correct responses. Taken together, our findings suggest that certain fronto-striatal connections are associated with pubertal maturation beyond age effects, which, in turn are related to inhibitory control. We discuss implications of puberty-related fronto-striatal maturation to further our understanding of pubertal effects related to adolescent cognitive and affective neurodevelopment.

Inhibitory control improves into young adulthood after specialization of relevant brain systems during adolescence. However, the biological mechanisms supporting this unique transition are not well understood. Given that adolescence is defined by puberty, we examined relative contributions of chronological age and pubertal maturation to inhibitory control development. 105 8–19-year-olds completed 1–5 longitudinal visits (227 visits total) in which pubertal development was assessed via self-reported Tanner stage and inhibitory control was assessed with an in-scanner antisaccade task. As expected, percentage and latency of correct antisaccade responses improved with age and pubertal stage. When controlling for pubertal stage, chronological age was distinctly associated with correct response rate. In contrast, pubertal stage was uniquely associated with antisaccade latency even when controlling for age. Chronological age was associated with fMRI task activation in several regions including the right dorsolateral prefrontal cortex, while puberty was associated with right ventrolateral prefrontal cortex (VLPFC) activation. Furthermore, task-related connectivity between VLPFC and cingulate was associated with both pubertal stage and response latency. These results suggest that while age-related developmental processes may support maturation of brain systems underlying the ability to inhibit a response, puberty may play a larger role in the effectiveness of generating cognitive control responses.

Category: Diabetes; Midfoot/Forefoot; Trauma; Other Introduction/Purpose: The level of amputation in patients with severe lower extremity pathology often presents a challenge. Surgeons are often confronted with deciding between a transmetatarsal amputation (TMA) or below-knee amputation (BKA). Certainly, in cases where patients are candidates for a TMA, the decision might seem rather straightforward. However, the literature has demonstrated that minor foot amputations, like TMAs, often have high rates of revision and often necessitate a higher level of amputation. This study compared revision rates, need for higher level of amputation, post-operative ambulatory rates, and the demographics between patients undergoing either TMA or BKA. Methods: This was a retrospective analysis of patients who underwent BKA or TMA and received follow-up care at a single academic medical center from January of 2013 to May of 2021. Demographic and medical historical data was collected and compared between patients undergoing BKA or TMA. A binary logistic regression model was used to evaluate independent predictors for necessitation of revision surgery and/or higher levels of amputation between the two groups. Secondary outcomes included hospital length of stay, as well as ambulatory and wound status at last patient follow-up. Statistical significance was defined as p

Background: The onset of the COVID-19 pandemic necessitated rapid changes to the practice of head and neck oncology in UK. There was a delay between the onset of the pandemic and the release of guidelines from cancer societies and networks, leading to a variable response of individual centres. This survey was conducted to assess the pre-Covid-19 pandemic standard of practice for head and neck oncology patients and the treatment modifications introduced during the first wave of the pandemic in UK. Methodology: The UK National Cancer Research Institute (NCRI) Head and Neck Clinical Studies Group initiated a multi-centre survey using questionnaire to investigate the effect on feeding tube practice, radiotherapy (RT) fractionation and volumes, use of chemotherapy in the neo-adjuvant, concurrent and palliative setting, the use of immunotherapy in the palliative setting, access to radiology and histopathology services, and availability of surgical procedures. Results: 30 centres were approached across UK; 23 (76.7%) centres responded and were included in the survey. There were differences in the standard practices in feeding tube policy, RT dose and fractionation as well as concurrent chemotherapy use. 21 (91%) participating centres had at least one treatment modification. 15 (65%) centres initiated a change in radical RT; changing to either a hypofractionation or acceleration schedule. For post-operative RT 10 centres (43.5%) changed to a hypofractionation schedule. 12 (52.2%) centres stopped neo-adjuvant chemotherapy for all patients; 13 (56.5%) centres followed selective omission of chemotherapy in concurrent chemo-radiotherapy patients, 17 (73.9%) centres changed first-line chemotherapy treatment to pembrolizumab (following NHS England’s interim guidance) and 8 (34.8%) centres stopped the treatment early or offered delays for patients that have been already on systemic treatment. The majority of centres did not have significant changes associated with surgery, radiology, histopathology and dental screening. Conclusion: There are variations in the standard of practice and treatment modifications for head and neck cancer patients during Covid-19 pandemic. A timely initiative is required to form a consensus on head and neck cancer management in the UK and other countries.

Skilful hydrological forecasts can benefit decision-making in water resources management and other water-related sectors that require long-term planning. In Ireland, no such service exists to deliver forecasts at the catchment scale. In order to understand the potential for hydrological forecasting in Ireland, we benchmark the skill of ensemble streamflow prediction (ESP) for a diverse sample of 46 catchments using the GR4J (Génie Rural à 4 paramètres Journalier) hydrological model. Skill is evaluated within a 52-year hindcast study design over lead times of 1 d to 12 months for each of the 12 initialisation months, January to December. Our results show that ESP is skilful against a probabilistic climatology benchmark in the majority of catchments up to several months ahead. However, the level of skill was strongly dependent on lead time, initialisation month, and individual catchment location and storage properties. Mean ESP skill was found to decay rapidly as a function of lead time, with a continuous ranked probability skill score (CRPSS) of 0.8 (1 d), 0.32 (2-week), 0.18 (1-month), 0.05 (3-month), and 0.01 (12-month). Forecasts were generally more skilful when initialised in summer than other seasons. A strong correlation (ρ=0.94) was observed between forecast skill and catchment storage capacity (baseflow index), with the most skilful regions, the Midlands and the East, being those where slowly responding, high-storage catchments are located. Forecast reliability and discrimination were also assessed with respect to low- and high-flow events. In addition to our benchmarking experiment, we conditioned ESP with the winter North Atlantic Oscillation (NAO) using adjusted hindcasts from the Met Office's Global Seasonal Forecasting System version 5. We found gains in winter forecast skill (CRPSS) of 7 %–18 % were possible over lead times of 1 to 3 months and that improved reliability and discrimination make NAO-conditioned ESP particularly effective at forecasting dry winters, a critical season for water resources management. We conclude that ESP is skilful in a number of different contexts and thus should be operationalised in Ireland given its potential benefits for water managers and other stakeholders.

Background: Selecting the level of amputation for patients with severe foot pathology can be challenging. The surgeon is sometimes confronted with an option between transmetatarsal amputation (TMA) and below-knee amputation (BKA). Recent studies have suggested that minor foot amputations have high revision rates and need for higher level of amputation. This study sought to compare the revision rates, need for higher level of amputation, postoperative ambulatory rate, and the demographic factors between these 2 operations. Methods: We retrospectively reviewed the records of patients undergoing either BKA or TMA at a single academic institution during an 8-year period. Demographic characteristics and medical history were collected and included in a binary logistic regression model to evaluate for independent predictors of needing revision surgery or needing higher-level amputation. Secondary outcomes included ambulatory status and wound status at last follow-up. Results: There was a total of 367 patients who underwent either BKA (n=293) or TMA (n=74). On binary logistic regression, the only significant independent predictor of needing revision surgery was undergoing TMA (odds ratio [OR] 2.30, CI 1.199-4.146, P = .011). The presence of PAD trended toward significance (OR 2.12, CI 0.99-4.493, P = .051). Similarly, significant independent predictors of needing higher level amputation were undergoing TMA (OR 4.117, CI 1.9-8.9, P < .001) and presence of PAD (OR 4.85, CI 1.59-14.85, P = .006). More TMA patients were ambulatory (56.8%) on last follow-up compared with BKA patients (30.9%). Conclusion: Transmetatarsal amputation has a higher risk of reoperation and need for revision amputation compared with below-knee amputation. Transmetatarsal amputation has a higher chance of returning patients to independent ambulation. Patients with peripheral arterial disease are at a higher risk of revision surgery and higher-level amputation with both operations. Level of Evidence: Level III, retrospective case review.

Abstract Concussion is a global health concern. Despite its high prevalence, a sound understanding of the mechanisms underlying this type of diffuse brain injury remains elusive. It is, however, well established that concussions cause significant functional deficits; that children and youths are disproportionately affected and have longer recovery time than adults; and that individuals suffering from a concussion are more prone to experience additional concussions, with each successive injury increasing the risk of long term neurological and mental health complications. Currently, the most significant challenge in concussion management is the lack of objective, clinically- accepted, brain-based approaches for determining whether an athlete has suffered a concussion. Here, we report on our efforts to address this challenge. Specifically, we introduce a deep learning long short-term memory (LSTM)-based recurrent neural network that is able to distinguish between non-concussed and acute post-concussed adolescent athletes using only short (i.e. 90 s long) samples of resting state EEG data as input. The athletes were neither required to perform a specific task nor expected to respond to a stimulus during data collection. The acquired EEG data were neither filtered, cleaned of artefacts, nor subjected to explicit feature extraction. The LSTM network was trained and validated using data from 27 male, adolescent athletes with sports related concussion, benchmarked against 35 non-concussed adolescent athletes. During rigorous testing, the classifier consistently identified concussions with an accuracy of > 90% and achieved an ensemble median Area Under the Receiver Operating Characteristic Curve (ROC/AUC) equal to 0.971. This is the first instance of a high-performing classifier that relies only on easy-to-acquire resting state, raw EEG data. Our concussion classifier represents a promising first step towards the development of an easy-to-use, objective, brain-based, automatic classification of concussion at an individual level.

Abstract Background Young people with eating disorders (EDs) and ED symptoms are at risk during university adjustment, suggesting a need to protect their health. The social identity approach proposes that people’s social connections – and the identity-related behaviour they derive from them – are important for promoting positive health outcomes. However, there is a limited understanding as to how meaningful everyday connections, supported by affiliative identities, may act to reduce ED symptoms during a life transition. Methods Two hundred eighty-one first year university students with an ED or ED symptoms completed an online survey during the first month of university. Participants completed self-reported measures of affiliative identity, social support, injunctive norms and ED symptoms. Path analysis was used to test a hypothesised mediated model, whereby affiliative identity has a significant indirect relation with ED symptoms via social support and injunctive norms. Results Results support the hypothesised model. We show that affiliative identity predicts lower self-reported ED symptoms, because of its relation with social support and injunctive norms. Conclusions The findings imply that affiliative identities have a positive impact on ED symptoms during university adjustment, because the social support derived from affiliative identity is associated with how people perceive norms around disordered eating. Our discussion emphasises the possibility of identity processes being a social cure for those at risk of ED symptoms.

Abstract A 4‐year‐old girl was referred for reassessment of dyskinetic cerebral palsy. Initial investigations in her country of birth, India, had not yielded a diagnosis. MRI brain in infancy revealed bilateral putamen hyperintensity. She had generalized dyskinesia predominantly bulbar and limbs. Motor and speech development were most affected with preservation of cognitive development. There was no history of acute encephalopathic crisis or status dystonicus. Initial urine organic acids and amino acids and acylcarnitine profile (ACP) were normal. A dystonia genetic panel showed compound heterozygosity with a pathogenic variant and a variant of uncertain significance in the GCDH gene. The latter is hitherto undescribed and is indicative of a potential diagnosis of glutaric aciduria type 1 (alternatively glutaric acidemia type 1) (GA‐1), an autosomal recessive disorder of mitochondrial lysine/hydroxylysine and tryptophan metabolism. Repeat urine organic acids showed isolated slightly increased 3‐hydroxy glutarate excretion consistent with GA‐1 and characterizing the patient as a “low excretor,” a diagnostic sub‐group where diagnosis is more challenging but prognosis is similar. Repeat MRI Brain at age 4 showed volume loss and symmetric T2 hyperintensity in the posterior putamina bilaterally. This case highlights the diagnostic dilemma of GA‐1 where differing clinical courses, genetic variants, neuroradiological findings, and biochemical excretion patterns may lead to a later diagnosis. The presence of newborn screening for GA‐1 should not dull the clinician's suspicion of the possibility that GA‐1 may present with a complex movement disorder. Timely diagnosis and treatment is essential, as neurological sequelae are largely irreversible.

In the largest DNA-based study of domestic cats to date, 11,036 individuals (10,419 pedigreed cats and 617 non-pedigreed cats) were genotyped via commercial panel testing elucidating the distribution and frequency of known disease, blood type, and physical trait associated genetic variants across cat breeds. This study provides allele frequencies for many disease-associated variants for the first time and provides updates on previously reported information with evidence suggesting that DNA testing has been effectively used to reduce disease associated variants within certain pedigreed cat populations over time. We identified 13 disease-associated variants in 47 breeds or breed types in which the variant had not previously been documented, highlighting the relevance of comprehensive genetic screening across breeds. Three disease-associated variants were discovered in non-pedigreed cats only. To investigate the causality of nine disease-associated variants in cats of different breed backgrounds our veterinarians conducted owner interviews, reviewed clinical records, and invited cats to have follow-up clinical examinations. Additionally, genetic variants determining blood types A, B and AB, which are relevant clinically and in cat breeding, were genotyped. Appearance-associated genetic variation in all cats is also discussed. Lastly, genome-wide SNP heterozygosity levels were calculated to obtain a comparable measure of the genetic diversity in different cat breeds. This study represents the first comprehensive exploration of informative Mendelian variants in felines by screening over 10,000 pedigreed cats. The results qualitatively contribute to the understanding of feline variant heritage and genetic diversity and demonstrate the clinical utility and importance of such information in supporting breeding programs and the research community. The work also highlights the crucial commitment of pedigreed cat breeders and registries in supporting the establishment of large genomic databases, that when combined with phenotype information can advance scientific understanding and provide insights that can be applied to improve the health and welfare of cats.

BackgroundParents often search the web for health-related information for themselves or on behalf of their children, which may impact their health-related decision-making and behaviors. In particular, searching for somatic symptoms such as headaches, fever, or fatigue is common. However, little is known about how psychological and relational factors relate to the characteristics of successful symptom-related internet searches. To date, few studies have used experimental designs that connect participant subjective search evaluation with objective search behavior metrics. ObjectiveThis study aimed to examine the features of web-based health-related search behaviors based on video-coded observational data, to investigate which psychological and relational factors are related to successful symptom search appraisal, and to examine the differences in search-related outcomes among self-seekers and by-proxy seekers. MethodsIn a laboratory setting, parents living in Austria (N=46) with a child aged between 0 and 6 years were randomized to search their own (n=23, 50%) or their child’s (n=23, 50%) most recent somatic symptom on the web. Web-based activity was recorded and transcribed. Health anxiety, eHealth literacy, attitude toward web-based health information, relational variables, state of stress, participants’ search appraisals, and quantitative properties of the search session were assessed. Differences in search appraisals and search characteristics among parents who searched for themselves or their children were examined. ResultsAcross both groups, searches were carried out for 17 different symptom clusters. Almost all parents started with Google (44/46, 96%), and a majority used initial elaborated key phrases with >1 search keyword (38/45, 84%) and performed on average 2.95 (SD 1.83) search queries per session. Search success was negatively associated with health anxiety (rs=−0.39, P=.01), stress after the search (rs=−0.33, P=.02), and the number of search queries (rs=−0.29, P=.04) but was not significantly associated with eHealth literacy (rs=0.22, P=.13). Of note, eHealth literacy was strongly and positively correlated with satisfaction during the search (rs=0.50, P

Testicular germ cell regression is a rare, generally metastatic phenomenon which describes the spontaneous, complete, or partial regression of a testicular germ cell tumour. As a result, studies have focused on defining specific histopathological criteria to establish if the resected testis is the primary source of the germ cell tumour. There are few publications which describe its presentation in the absence of distant metastases with elevated tumour markers and suspicious findings on testicular ultrasound. We present the clinical presentation and radiological features of a non-metastatic regressed testicular germ cell tumour following scrotal trauma in a post pubertal male.

Inhibitory control can be less reliable in adolescence, however, in the presence of rewards, adolescents’ performance often improves to adult levels. Dopamine is known to play a role in signaling rewards and supporting cognition, but its role in the enhancing effects of reward on adolescent cognition and inhibitory control remains unknown. Here, we assessed the contribution of basal ganglia dopamine-related neurophysiology using longitudinal MR-based assessments of tissue iron in rewarded inhibitory control, using an antisaccade task. In line with prior work, we show that neutral performance improves with age, and incentives enhance performance in adolescents to that of adults. We find that basal ganglia tissue iron is associated with individual differences in the magnitude of this reward boost, which is strongest in those with high levels of tissue iron, predominantly in adolescence. Our results provide novel evidence that basal ganglia neurophysiology supports developmental effects of rewards on cognition, which can inform neurodevelopmental models of the role of dopamine in reward processing during adolescence.