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Background Upper extremity (UE) transplantation is a complex undertaking that may require emergent or elective secondary surgery (SS) days to years following transplant. Various patient and transplantation may help determine what SS is needed. In this study, we characterize the SS needed by our UE transplant patients. Methods We retrospectively reviewed 6 patients who underwent hand and UE transplantation by one of the authors. Transplantation and SS details were obtained from medical records. Hand and arm function was quantified both subjectively (patient-reports) and objectively (Disabilities of the Arm, Shoulder, and Hand Score; Carroll test; Action Research Arm Tests; Box and Block test). Results Six patients underwent transplantation for a total of 10 transplanted limbs. Five transplants were performed below and 5 above the elbow. Mean time post-transplantation at last follow-up was 5 years (range: 1-9 years). In all, 66.7% of the patients required SS: total 7 surgeries comprising 13 procedures. The most common procedures were to improve hand function—nerve decompressions and tendon transfer, both in above-elbow transplant. Both patients showed a mean improvement of 15 points on Carroll scores. One above-elbow transplant had a brachioplasty for excess skin and another had a hematoma evacuation immediately after transplantation. Procedures in the below-elbow transplants included multiple incision and drainages for a septic wrist and an open reduction and internal fixation for a forearm fracture. Conclusion Patients receiving UE transplantation often require one or more secondary procedures which may vary with level of transplantation. Secondary surgery should be an important aspect of pretransplant planning and cost-effectiveness determinations. Level of Evidence Level IV

IntroductionIndividuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4–12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysisA cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and disseminationEthical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Trial registration number1567490.

We investigate the sources of detected unrecoverable errors (DUEs) in graphics processing units (GPUs) exposed to a neutron beam. Illegal memory accesses and interface errors are among the more likely sources of DUEs. Error-correcting code (ECC) increases the launch failure events. Our test procedure has shown that ECC can reduce the DUEs caused by Illegal Address access up to 92% for Kepler and up to 98% for Volta. In addition, we analyze whether the compiler optimizations can impact the DUE sources distribution for the matrix multiplication. We found that the machine codes generated by the different optimization levels can change the DUE source by no more than 24% on average.

In this article, we investigate the reliability of Google’s coral tensor processing units (TPUs) to both high-energy atmospheric neutrons (at ChipIR) and thermal neutrons from a pulsed source [at equipment materials and mechanics analyzer (EMMA)] and from a reactor [at Thermal and Epithermal Neutron Irradiation Station (TENIS)]. We report data obtained with an overall fluence of3.41×1012n/cm2for atmospheric neutrons (equivalent to more than 30 million years of natural irradiation) and of7.55×1012n/cm2for thermal neutrons. We evaluate the behavior of TPUs executing elementary operations with increasing input sizes (standard convolutions or depthwise convolutions) as well as eight convolutional neural networks (CNNs) configurations (single-shot multibox detection (SSD) MobileNet v2 and SSD MobileDet, trained with COCO dataset, and Inception v4 and ResNet-50, with ILSVRC2012 dataset). We found that, despite the high error rate, most neutron-induced errors only slightly modify the convolution output and do not change the detection or classification of CNNs. By reporting details about the error model, we provide valuable information on how to design the CNNs to avoid neutron-induced events to lead to misdetections or classifications.

IntroductionIndividuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysisA cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink (CPRD) and invited by their general practitioners to participate on a digital platform (Atom5™). Individuals will report symptoms, quality of life, work capability, and patient reported outcome measures. Data will be collected monthly for one year.Statistical clustering methods will be used to identify distinct Long COVID symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear sub-study which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for post-viral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and disseminationEthical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). The study is registered on the ISRCTN Registry (1567490). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Article SummaryStrengths and limitations of the studyThe study will generate a nationally representative cohort of individuals with Long COVID recruited from primary care.We will recruit controls matched on a wide range of demographic and clinical factors to assess differences in symptoms between people with Long COVID and similar individuals without a history of COVID-19.We will use a newly developed electronic patient reported outcome measure (Symptom Burden Questionnaire™) for Long COVID to comprehensively assess a wide range of symptoms highlighted by existing literature, patients, and clinicians.Immunological, proteomic, genetic, and wearable data captured in the study will allow deep phenotyping of Long COVID syndromes to help better target therapies.A limitation is that a significant proportion of non-hospitalised individuals affected by COVID-19 in the first wave of the pandemic will lack confirmatory testing and will be excluded from recruitment to the study.

As surgical research expands in both breadth and scope, translational models become increasingly important. The accessibility, reproducibility, and clinical applicability of translational models is of vital importance to ensure adequate and accurate research. Though different flap models have been described, the literature lacks an in-depth, technical description of an easy large-animal preclinical model. We here describe the procedure for elevation of a latissimus dorsi flap in a swine. This flap contains muscle and skin that can be isolated on a vascular pedicle, transferred as a free flap, perfused, or innervated/denervated as dictated by the needs of the experiment.Five different latissimus dorsi flaps were elevated in miniature swine. Careful attention was paid to anatomical landmarks and optimal placement of incision, dissection, and retraction. Temporary ischemia with vascular clamping was performed along with serial digital and infrared imaging both intra- and postoperatively. In three of the flaps with induced ischemia, the animal was observed for a 30-day follow up with daily photodocumentation and intermittent biopsy.A reproducible latissimus flap model was designed with optimized conditions. In the animals in which flaps were followed postoperatively, complete healing was seen within 30 days without evidence of procedure-related ischemia or loss of motor function.We have identified and described a pre-clinical large animal flap model that can be easily reproduced for translational studies of multiple scientific areas including flap-based repair, ischemia, ischemia reperfusion, and operative technique. This provides an important model for ready replication in preclinical studies of many varieties.

Background The recent rise in medical tourism, especially for cosmetic procedures, has been mirrored by an increase in the incidence of infections with Mycobacterium abscessus, which is an atypical mycobacterium that is ubiquitous in aquatic environments. M. abscessus soft tissue infections arise from the use of improperly sterilized water and surgical equipment during surgical procedures, and these infections have devastating consequences if not promptly treated. M. abscessus infections are notoriously difficult to diagnose and properly treat, and therefore, we illustrate a typical case presentation and provide a comprehensive diagnostic and treatment algorithm. Methods Of the patients who have presented to our hospital for treatment of cutaneous M. abscessus infections, a representative patient's story was included to illustrate the typical presentation and treatment timeline. The current literature on M. abscessus infections was reviewed, and this literature and the clinical experience of our plastic surgery and infectious disease teams were used in the creation of a diagnostic and treatment algorithm for M. abscessus infections. Results M. abscessus infections can have an incubation period of months, and the classic presenting signs include purulent drainage, violaceous nodules, and subcutaneous abscesses at the site of a recent surgery. A key finding is persistence of the infection despite debridement and empiric antibiotic treatment. Cultures grown on mycobacterial-specific growth media are considered the diagnostic criterion standard, but high clinical suspicion is enough to warrant the initiation of treatment. Treatment itself consists of surgical drainage and debridement in combination with multidrug antibiotic regimens that typically include amikacin, a macrolide, and a carbapenem or cephalosporin antibiotic, with the option for macrolide and fluoroquinolone maintenance therapy. Conclusions M. abscessus cutaneous infections present with unique history and physical examination findings and often require complex diagnostic workups and treatment plans. Increased provider awareness of the management and potential complications of M. abscessus is crucial to the improvement patient outcomes, as is a multidisciplinary approach that incorporates primary care providers, pathologists, plastic surgeons, and infectious disease specialists.

Background Breast reconstruction is becoming an increasingly important and accessible component of breast cancer care. Among the many reconstructive options available, the latissimus dorsi flap has experienced a renewal in popularity because of its favorable properties and outcomes when used for breast reconstruction. However, a limitation unique to latissimus-based reconstruction is inappropriate breast animation postoperatively, due to persistent thoracodorsal innervation of the latissimus dorsi muscle after transfer to the mastectomy site. Methods A comprehensive literature search of PubMed and MEDLINE was conducted for studies investigating the role of thoracodorsal denervation in latissimus-based breast reconstruction. Data on surgical techniques, type of intervention, objective outcome measurements, and patient satisfaction-based outcomes were reported. Additional data included patient sample size, follow-up length, and treatment of thoracodorsal nerve (e.g., resection versus transection and length of transection) when applicable. Results Sixty-six search results were reviewed for inclusion and nine qualified after exclusion criteria for a total of 361 patients undergoing either unilateral or bilateral latissimus flap reconstruction. Successful thoracodorsal denervation rates were included in most studies and outcomes measurements were heterogeneous. Eight out of nine studies included patient-reported symptoms of breast animation postoperatively. Based on these findings, a systematic approach is presented. Conclusion We present this review to elucidate successful practices, identify current gaps in knowledge, and offer a systematic approach to this clinical challenge.

The yeast vacuole is functionally and structurally equivalent to the mammalian lysosome. Delivery of resident and cargo proteins to the lysosome is vital for proper cellular operations, and failure to correctly target proteins to the organelle is correlated with the development of neurodegenerative and lysosomal storage diseases. We previously reported a novel mutant screen for vacuolar trafficking defects in yeast Saccharomyces cerevisiae that resulted in the isolation of env1, an allelic mutant of VPS35. As a member of the retromer complex, Vps35p binds directly to cargos and facilitates their retrograde transport to trans Golgi from endosomes. Our previous studies established that env1 exhibits unique pleiotropic phenotype in comparison to other tested VPS35 alleles including severe growth sensitivity to hygromycin B and internal accumulation of the precursor form of the vacuolar enzyme carboxypeptidase Y. Here, through a combination of sub-cellular fractionation and indirect immunofluorescence microscopy, we confirm and extend the unique phenotype of env1 to processing and localization of additional proteins within the vacuolar trafficking pathway. In comparative studies with a null and an allelic mutant of VPS35, env1 exhibited unique processing defects of retromer-independent vacuolar membrane enzyme alkaline phosphatase at the vacuole and significant Golgi localization of retromer cargos Vps10p and Kex2p despite compromised trafficking at the Golgi and late endosome interface.

This paper explores issues connected with the UK Government's plans to reform the land-use planning system, and highlights some concerns that currently exist. It outlines some of the changes proposed, and focuses on the proposed reforms to the Use Classes Order (UCO) as they affect retail and food and drink outlets. In particular it takes as a case study the City of Westminster in London, where changes to local planning policies, aimed at resolving conflict between restaurant and pub operators and local residents, have led instead to market distortion and conflict between operators, developers and the local authority. The paper concludes that reforms are to be welcomed but that a considered approach is required to ensure that land-use planning is seen as only part of the measures required to ensure that conflict between city-centre users is minimised.

Since the earliest reports in 1982 (1,2), there have been more than 24 reported cases of survival after failed resuscitation (3,4). This phenomenon has been variously referred to as “spontaneous return of circulation” (SROC) or “Lazarus syndrome”(5). Of these cases, at least eight patients have surv

The late endosome and vacuole of yeast Saccharomyces cerevisiae are functionally equivalent to the mammalian late endosome and lysosome. The late endosome is the convergence point of the biosynthetic and endocytic trafficking to the vacuole. Here, we describe a novel immunodetection screen to isolate mutants defective in trafficking the soluble hydrolase carboxypeptidase Y (CPY) at the late endosome to vacuole interface (env mutants). Mutants exhibit vacuolar morphology and endocytosis defects as assayed by electron, fluorescent, and nomarski microscopy. In biochemical assays, they internally accumulate p2CPY in a dense membrane compartment lacking vacuolar properties yet display normal secretion phenotypes. The results suggest vacuolar morphology and function defects that are exclusively at the late endosome/vacuole interface. env mutants define five complementation groups. The first gene of the collection to be cloned, ENV1 is allelic to VPS35 whose established function is in retrograde trafficking from late endosome to trans-Golgi network (TGN). Microscopic, biochemical, and growth analyses establish that env1 is distinct from other alleles of VPS35 in vacuolar morphology, growth characteristics, and internal accumulation of p2CPY. Our results indicate that ENV genes may define new gene functions at the late endosome to vacuole interface.

International audience; SRAMs have been used for many years as leading radiation test detector. Standard testing procedures for accelerated neutron radiation suggest testing the memory under static or dynamic operation mode, in nominal conditions and introducing variation to these conditions. The most commonly used method is testing the memory in static mode and varying the supply voltage. In this work, we study the response of a commercial 90nm 32Mbit SRAM under the ISIS atmospheric neutron beam, applying temperature variations in static and dynamic operational modes. Experimental results show that Single Event Upsets (SEUs) and the device Soft Error Rate (SER) are strongly related to both temperature and operation mode.