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Compared to controlled donation after cardiac death (cDCD), uncontrolled DCD (uDCD) kidney transplantation remains an underutilized resource in the United States. However, it is unclear whether long-term allograft outcomes following uDCD are inferior to that of cDCD kidney transplantation.From January 1995 to January 2018, the OPTN/UNOS database was queried to discover all reported cases of uDCD and cDCD kidney transplantation. Primary non-function, delayed graft function, ten-year graft and patient survival were compared among uDCD and cDCD patients.Rates of primary non-function (4.0% [uDCD] vs. 1.8% [cDCD], P 0.001) and delayed graft function (51.1% [uDCD] vs. 41.7% [cDCD], P 0.001) were higher following uDCD transplant. However, ten-year graft survival (47.5% [uDCD] vs. 48.4% [cDCD], P = 0.21) and patient survival were similar to cDCD transplantation (59.4% [uDCD] vs. 59.2% [cDCD], P = 0.32).Although initial allograft outcomes are inferior following uDCD, long-term durability of uDCD kidney allografts is on par to cDCD transplantation. Kidney allografts derived by uDCD may be a viable and durable option to increase the donor pool.

Background: A number of corticosteroids are commonly used to treat COVID-19 infection. The aim of this retrospective study was to compare various hospital outcomes among mechanically ventilated COVID-19 patients in an ICU, who were administered either dexamethasone or methylprednisolone. Methods: A total of 121 mechanically ventilated COVID-19 patients from the ICU were included in the analysis, of which 43.8% (n = 53) received methylprednisolone, while 56.2% (n = 68) received dexamethasone. Results: In-hospital mortality (p = 0.381) and hospital length of stay (p = 0.307) were lower among the methylprednisolone group, compared to the dexamethasone group, though not significantly. Survival analysis showed that there were no significant differences between the methylprednisolone and dexamethasone groups (p = 0.978). A Cox proportional regression analysis showed that in-hospital mortality was lower among COVID-19 patients receiving methylprednisolone, compared to the dexamethasone group, though not significantly (hazard ratio (HR), 0.64; 95% CI: 0.35–3.17). Conclusion: Our study showed that in-hospital mortality was lower and hospital length of stay was higher among COVID-19 patients receiving methylprednisolone, compared to dexamethasone. These findings could have been due to the small sample size and limited scope of the study. Therefore, future large-scale studies should evaluate and confirm the findings in this study.

Disparities in SLE rates and outcomes have been attributed to genetic and hormonal factors, cigarette smoking and environmental pollutants. However, a growing body of research indicates that social determinants of health (SDH) also have substantial impact on the disparities that characterize SLE. According to the World Health Organization, SDH are defined as ‘the conditions in which people are born, grow, work, live, and age’, account for 30–55% of health outcomes, and adversely impact health outcomes among those of low socioeconomic status and stigmatized racial/ethnic groups. We reviewed the impact of key SDH on SLE presentation, management and outcomes, including income, education, neighbourhood factors, healthcare access, discrimination and social support. We found that adverse SDH conditions may lead to more severe SLE with increased morbidity and mortality, and that SDH affect SLE management by dictating the most feasible monitoring and treatment plan for each individual patient based on his or her specific life circumstances (for example, based on health insurance status, distance to nearest provider and/or drug affordability). SDH also have a significant impact on SLE outcomes, with worse disease and psychosocial outcomes associated with lower income level, lower educational attainment, disadvantaged neighbourhoods, lack of health insurance or public health insurance in the USA, travel burden to nearest provider, anti-Black racism and lower social support. Future efforts to improve the management and outcomes of patients with SLE must combat the societal, economic and political forces that perpetuate these inequities.

SUMMARY Historical and instrumental earthquake catalogs in low strain rate regions are not necessarily indicative of the long-term spatio-temporal distribution of seismicity. This implies that probabilistic seismic hazard analysis (PSHA) should also consider geologic and geodetic data through fault-based seismogenic sources. However, it is not always clear how on-fault magnitude-frequency distributions (MFDs) should be described and, if the seismogenic layer is especially thick, how fault sources should be extrapolated down-dip. We explore these issues in the context of a new PSHA for Malawi, where regional extensional rates are 0.5–2 mm yr−1, the seismogenic layer is 30–40-km thick, the instrumental catalog is ∼60 yr long and fault-based sources were recently collated in the Malawi Seismogenic Source Model. Furthermore, Malawi is one of several countries along the East African Rift where exposure to seismic hazard is growing, but PSHA does not typically consider fault sources. We use stochastic event catalogs to explore different fault source down-dip extents and MFDs. Our PSHA indicates that hazard levels are highest for a Gutenberg–Richter on-fault MFD, even at low probabilities of exceedance (2 per cent in 50 yr), whilst seismic hazard levels are also sensitive to how relatively short (

Background: In adults with Clostridioides difficile infection (CDI), higher stool concentrations of toxins A and B are associated with severe baseline disease, CDI-attributable severe outcomes, and recurrence. We evaluated whether toxin concentration predicts these presentations in children with CDI. Methods: We conducted a prospective cohort study of inpatients aged 2–17 years with CDI who received treatment. Patients were followed for 40 days after diagnosis for severe outcomes (intensive care unit admission, colectomy, or death, categorized as CDI primarily attributable, CDI contributed, or CDI not contributing) and recurrence. Baseline stool toxin A and B concentrations were measured using ultrasensitive single-molecule array assay, and 12 plasma cytokines were measured when blood was available. Results: We enrolled 187 pediatric patients (median age, 9.6 years). Patients with severe baseline disease by IDSA-SHEA criteria (n = 34) had nonsignificantly higher median stool toxin A+B concentration than those without severe disease (n = 122; 3,217.2 vs 473.3 pg/mL; P = .08). Median toxin A+B concentration was nonsignificantly higher in children with a primarily attributed severe outcome (n = 4) versus no severe outcome (n = 148; 19,472.6 vs 429.1 pg/mL; P = .301). Recurrence occurred in 17 (9.4%) of 180 patients. Baseline toxin A+B concentration was significantly higher in patients with versus without recurrence: 4,398.8 versus 280.8 pg/mL (P = .024). Plasma granulocyte colony-stimulating factor concentration was significantly higher in CDI patients versus non-CDI diarrhea controls: 165.5 versus 28.5 pg/mL (P < .001). Conclusions: Higher baseline stool toxin concentrations are present in children with CDI recurrence. Toxin quantification should be included in CDI treatment trials to evaluate its use in severity assessment and outcome prediction.

Muscadine grape (Vitis rotundifolia var. rotundifolia) is a rare crop in that it has transitioned from a wild fruiting plant to a domesticated fruit within the past 150 years. Furthermore, this domestication process was carried out by just a few institutions that published copious records of the origin and traits of the first wild selections, goals and methods of the breeding programs, and the pedigrees of releases. We thus have a near complete record of the domestication of this interesting fruit crop. Early breeding efforts made use of fewer than a dozen wild selections, most of which were collected from the coastal plain of North Carolina and South Carolina. This narrow germplasm base has led to increasing levels of inbreeding in the most recent muscadine cultivar releases. To better understand the germplasm base of muscadine, the pedigrees of 54 muscadine cultivars released since 1970 were examined. Only 15 founders (founding clones) were identified that appeared in more than two cultivars, and five of these represent open pollination events that may not indicate the addition of new genetic material. By far the most used founder was ‘Scuppernong’, which appeared in 53 of 54 pedigrees and had an average genetic contribution of 22.8%. The remaining founders varied from 0.9% to 14.8% in their average genetic contribution. Coancestry coefficients between cultivars averaged 0.18, but were often much higher among recent fresh-market releases. Analysis of vine vigor as measured by trunk caliper in seedling progenies suggests that coancestry coefficients greater than 0.23 result in below average seedling vigor. The University of Georgia muscadine breeding program is evaluating multiple wild muscadine accessions to reduce inbreeding and increase the genetic diversity of its germplasm.

Colorectal cancer (CRC) is a leading cause of cancer-related death. There is an urgent need for new methods of early CRC detection and monitoring to improve patient outcomes. Extracellular vesicles (EVs) are secreted, lipid-bilayer bound, nanoparticles that carry biological cargo throughout the body and in turn exhibit cancer-related biomarker potential. RNA binding proteins (RBPs) are posttranscriptional regulators of gene expression that may provide a link between host cell gene expression and EV phenotypes. Insulin-like growth factor 2 RNA binding protein 1 (IGF2BP1/IMP1) is an RBP that is highly expressed in CRC with higher levels of expression correlating with poor prognosis. IMP1 binds and potently regulates tumor-associated transcripts that may impact CRC EV phenotypes. Our objective was to test whether IMP1 expression levels impact EV secretion and/or cargo. We used RNA sequencing, in vitro CRC cell lines, ex vivo colonoid models, and xenograft mice to test the hypothesis that IMP1 influences EV secretion and/or cargo in human CRC. Our data demonstrate that IMP1 modulates the RNA expression of transcripts associated with extracellular vesicle pathway regulation, but it has no effect on EV secretion levels in vitro or in vivo. Rather, IMP1 appears to affect EV regulation by directly entering EVs in a transformation-dependent manner. These findings suggest that IMP1 has the ability to shape EV cargo in human CRC, which could serve as a diagnostic/prognostic circulating tumor biomarker.

North American Indigenous youth experience disproportionate harm associated with alcohol and cigarette use compared to other racial/ethnic groups. The Acquired Preparedness Model (APM), developed and tested in primarily White samples, hypothesizes that urgency contributes to risk for substance use by influencing the degree to which adolescents attend to positive aspects of substance use, leading to the development of more positive expectations about the consequences of substance use, and increasing subsequent substance use. The purpose of the present study was to provide an initial test of whether the APM generalizes to understanding alcohol and cigarette use among high-risk First Nation adolescents.First Nation adolescents (The hypothesized model demonstrated excellent fit for alcohol use, χ²(1) = 1.07,Findings of the present study provide initial support for the generalizability of the APM in understanding risk for alcohol and cigarette use among reserve-dwelling First Nation youth. The next important step is to replicate this finding in a prospective sample. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The conflict between prioritizing education for surgical trainees, promoting trainee wellness, and maintaining optimal patient care has remained challenging since the introduction of the Accreditation Council for Graduate Medical Education (ACGME) work hour restrictions in 2003. There is still a dearth of research examining which interventions successfully enable duty hour adherence. This study assessed the impact of a combination of strategic interventions on improving clinical work hour adherence.Monthly clinical work hour submission rates were assessed for all general surgery residents at a single university-based residency program over a 3-year period (2018-2021). Interventions targeted 3 domains and were implemented between academic years 2018 to 2019 (control) and 2020 to 2021 (intervention): 1) improving the accuracy and transparency of work hour reporting, 2) facilitating more timely interventions, and 3) structural scheduling changes. All 80-hour work week and continuous work hour violations were assessed. Findings were also compared to the corresponding ACGME Resident Survey results.There was no significant difference in the rate of monthly work hour submissions pre- and postintervention (78% vs 75%, p = 0.057). However, the number of total reported monthly violations decreased significantly (mean 13.8 vs 2.4, p0.01), including decreases in both 80-hour work week and continuous work hour violations (mean 4.7 vs 1.6, p0.001 and 9.1 vs 0.8, p0.001, respectively). Reported compliance also increased on the annual ACGME resident surveys, where 61% vs 95% of residents felt they were compliant with the 80-hour work week and 71% vs 95% felt they were compliant with the continuous work hours (2018-19 vs 2020-21).Innovative strategies addressing schedule changes, the culture of work hour reporting, and early intervention significantly decreased the number of duty hour violations at our institution. Reported resident compliance also improved based on ACGME Resident Survey data. These data may inform similar multifaceted approaches at other institutions to improve overall work hour adherence.

The presence of any comorbid condition may lead to worse outcomes after burn injury. Chronic obstructive pulmonary disease (COPD) is a condition with significant morbidity and mortality. In 2018, about 16 million adults in the United States reported a diagnosis of COPD based on data from the American Lung Association. The objective of this study was to explore the outcomes of patients with COPD admitted to our Burn Center with flame burns and/or inhalation injury. Patients were identified using our Institutional Burn Center registry and linked to the clinical and administrative data. All adult flame-injured and/or inhalation injury-only patients admitted to our burn center between July 1, 2011 and June 30, 2020 were included. Demographics, length of stay, burn, and patient characteristics and outcomes, including mortality, were evaluated. Four thousand three hundred ninety-seven patients were included in the study. Patients were divided into two populations, those with COPD (n = 515) and those without a diagnosis of COPD (n = 3882). Patients with COPD were older, more likely to be white and male, and had smaller sized burns, p < .001. Patients with COPD were more likely to be smokers and have comorbid conditions. There was no statistically significant difference between the incidence of inhalation injury, lengths of stay, or number of ventilator days. Burn size and inhalation injury increased mortality risk regardless of COPD severity, as did age among those not on home oxygen. More studies are needed to determine the genomic or proteomic changes in patients with COPD that lead to worse outcomes after flame injury, and/or inhalation injury alone.

Sleep disturbances impact over half of older children and teens with acquired brain injury (ABI) following critical care hospitalization but are underevaluated in infants and young children. Given the importance of sleep in brain development and healing after injury, we hypothesized sleep disturbances would be associated with worse neurodevelopmental outcomes in infants with ABI.We performed a retrospective cohort study of 68 children aged 2-32 months following critical care hospitalization for ABI. The Brief Infant Sleep Questionnaire assessed sleep disturbances. Bayley Scales of Infant and Toddler Development, third edition and Adaptive Behavior Assessment System, third edition assessed developmental and adaptive functioning outcomes, respectively.Compared to healthy controls, children with ABI had shorter nighttime sleep duration (Sleep disturbances are associated with poorer outcomes in infants and toddlers after ABI. Sleep is vital to recovery and a potentially modifiable target to improve outcomes.Klapp JM, Hall TA, Riley AR, Williams CN. Sleep disturbances in infants and young children following an acquired brain injury.

Understanding family dyadic communication in dementia is essential to promote the well-being of family caregivers and persons living with dementia. The Dyadic Communication Observational coding scheme in DEmentia care (DCODE) was developed and tested to assess family dyadic communication in dementia.The DCODE was developed from a review of literature, expert review, and pretesting. A secondary analysis of the 75 in-home care video observations from 19 family caregiver-care recipient dyads was conducted to test psychometric properties.The DCODE consists of 43 caregiver items and 41 care recipient items. We observed internal consistency, intra-rater reliability, and inter-rater reliability as adequate. Content validity and convergent validity were moderate. Predictive validity was moderate in predicting caregiver burden. The overall psychometric properties demonstrated a moderate quality of the DCODE.Findings provided the preliminary psychometric evidence of the DCODE as a promising instrument to assess family dyadic communication in dementia. Future testing for concurrent, divergent, and structural validity of the DCODE is needed.

Learning management systems (LMS) are prevalent in modern day education, but their implementation is often highly diverse based on individual faculty and course needs. This can result in students falling behind in their schoolwork if they do not understand how faculty use the e-learning platform in specific courses, which may be further exacerbated when students are exposed to many different faculty using learning management systems in different ways at a single institution. The current research sought to create a practical tool to reduce the impact of diverse LMS implementation through the generation of a homepage template that could be customized across courses. We utilized focus groups and literature review to identify requirements and create the template. This template was implemented across a diverse set of classes and its impact is being assessed through surveys administered to faculty and students. From the faculty perspective, the template has been well received and the majority of faculty who have completed our feedback survey intend to continue to reuse the template in many of their courses.

Reducing the age of first autism diagnosis facilitates access to critical early intervention services. A current "waitlist crisis" for autism diagnostic evaluation thus demands that we consider novel use of available clinical resources. Previous work has found that expert autism clinicians can identify autism in young children with high specificity after only a brief observation; rapid identification by non-experts remains untested. In the current study, 252 children ages 12-53 months presented for a comprehensive autism diagnostic evaluation. We found that junior clinicians in training to become autism specialists (n = 29) accurately determined whether or not a young child would be diagnosed with autism in the first five minutes of the clinic visit in 75% of cases. Specificity of brief observations was high (0.92), suggesting that brief observations may be an effective tool for triaging young children toward autism-specific interventions. In contrast, the lower negative predictive value (0.71) of brief observations, suggest that they should not be used to rule out autism. When trainees expressed more confidence in their initial impression, their impression was more likely to match the final diagnosis. These findings add to a body of literature showing that clinical observations of suspected autism should be taken seriously, but lack of clinician concern should not be used to rule out autism or overrule other indicators of likely autism, such as parent concern or a positive screening result.

Background The prevalence of childhood obesity in the U.S. has tripled over the last three decades. However, fewer than 1% of children with severe obesity undergo surgical weight loss interventions each year. Materials and methods All patients age 10 to 19 years old who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) from 2015 through 2018 in the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database were included in this retrospective cohort analysis. The primary outcomes were mortality and overall complications. Procedural trends, readmission and reoperation rates were also examined using a multivariate regression model. Results Patients had a mean BMI of 47.3 kg/m2 and 80.0% were either 18 or 19 years old (n = 4,051). There were two reported deaths. Reoperation within 30 days occurred in 1.1% of patients, readmission in 3.5%, and complications in 1.2%. Among all readmissions, primary reasons included nausea/vomiting or nutritional depletion (41.3%) and abdominal pain (16.3%). RYGB was associated with higher odds for readmission (p = 0.006) and complications (p = 0.005). Higher BMI and younger age were not associated with an increased likelihood to experience poorer outcomes. The proportion of patients undergoing SG increased yearly over RYGB from 73.9% in 2015 to 84.3% in 2018. Conclusions Bariatric surgery appears to be low risk for adolescents and SG has become the operation of choice. More research on early consideration of surgical therapy in adolescents with severe obesity is needed given the safety profile. Level of Evidence III

Effective mentorship is widely believed to be an important factor in career satisfaction and advancement. Adequate mentorship has been linked to perceived institutional support, research productivity, and protects against burnout. Despite these facts, less than half of junior faculty in academic medicine feel as if they have adequate mentorship. Given that the current landscape in academic medicine has a paucity of available mentors, both in rank and representation for true dyadic mentorship, junior faculty clinician educators may need mentorship and paths to sponsorship. The importance of peer networks has become increasingly recognized, and some institutions have begun to use peer mentoring as a means of addressing mentorship and sponsorship needs. This model can potentially circumvent some of the main barriers to mentorship by providing protected time, ameliorating power differentials, creating an environment where members have shared goals, and mitigating the need for senior faculty mentorship. The following are twelve tips to create and maintain a successful peer mentoring group for junior faculty clinician educators in academic medicine which can serve to complement the dyadic mentorship model.

Aims The aim of this study was to understand the experience of mature patients who undergo a periacetabular osteotomy (PAO), a major hip-preserving surgical procedure that treats symptomatic hip dysplasia by realigning the acetabulum. Our aim was to improve our understanding of how the operation affected the lives of patients and their families, with a long-term goal of improving their experience. Methods We used a phenomenological approach with in-depth, semi-structured interviews to investigate the experience of seven female patients, aged between 25 and 40 years, who underwent a PAO. A modified homogeneity sampling approach coupled with criterion sampling was used. Inclusion criteria involved having at least one child at home and being in a committed relationship with a spouse or partner. Results Analysis of interview transcripts revealed five major themes: feelings of frustration before having a treatment plan; fear of the operation; the importance of understanding the procedure in order to feel in control of their care; feelings of helplessness, dependence, and depression during recovery; and the need for support during recovery. Conclusion Our findings suggest that both the physical and psychosocial burdens of undergoing a PAO are great, with a major impact on the patient and their family. Many important issues lie outside the scope of what healthcare teams currently address. Cite this article: Bone Joint J 2022;104-B(7):781–785.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation (PG/05/036) Primary Care Research Network-Central England. Background People of South-Asian origin have high cardiovascular morbidity, contributed by health inequalities. Hypertension is the key modifiable cardiovascular risk factor but is underdiagnosed, but its scale in South Asian communities is unknown. Left ventricular hypertrophy (LVH) on echocardiography is a measure of target organ damage related to uncontrolled hypertension. The study aims to assess prevalence of LVH in South Asian community and its impact on mortality. This study is based on the large prospective UK community Ethnic-Echocardiographic Heart of England Screening Study (E-ECHOES, age ≥45 years). Methods Left ventricular mass index (LVMI) was calculated using echocardiography. LVH was established as increased LVMI. Predictive value of LVH all-cause and cardiovascular mortality was assessed using Cox regression. Results The study included 3200 South Asians (age 59±10, 52% women, 45% had a history of hypertension). There were 182 deaths, including 64 cardiovascular deaths during a 5.8±1.0-year follow-up. LVH was found in 1568 (49%). In those with LVH, 705 (45%) did not have a diagnosis of hypertension. On Cox regression LVH was independently associated with all-cause mortality (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.01-1.88), cardiovascular mortality (HR 2.64, 95% CI 1.21-3.73). The projected overall hypertension prevalence was 82%. Conclusion South Asians in the UK have a very high prevalence of hypertension which is often underdiagnosed and poorly controlled, leading to LVH and excess in overall and cardiovascular mortality. The findings call for more effective screening and management of hypertension with lower BP targets.

Abstract: This multisite quality improvement (QI) project reports on a psychotherapy group for family care partners of persons living with neurodegenerative conditions. Following the plan-do-study-act model, a team of geropsychologists iteratively developed, implemented, and refined the 8-week “Caring Through COVID” psychotherapy group across five cycles from January 2021 to April 2022. Participants were 21 spouses or adult children of persons living with neurodegenerative conditions. Across two clinics, participants evidenced moderate improvements in caregiver burden ( d = .59), self-efficacy for caregiving ( d = −.64), and self-efficacy for emotion regulation ( d = −.60). The group was perceived positively by participants. This QI project demonstrates the real-world implementation of a psychotherapy group developed during the COVID-19 pandemic and refined to remain ongoing.

Obesity prevalence continues to increase at an alarming rate worldwide and poses serious health risks to those affected including increased morbidity, mortality, and psychosocial consequences. Weight-loss surgery is currently the best evidence-based treatment for obesity, yet substantial postoperative weight regain is reported within 2-5 years. Successful weight management is complicated when longstanding psychological difficulties are present; these often require psychological input to address.In response, a private weight-loss surgery clinic developed an Acceptance and Commitment Therapy-based (ACT) Intervention entitled the Foundations of Healthy Living (FOHL) Retreat with the aim of improving weight-loss surgery outcomes by providing greater support to individuals in the post-operative period.A quasi-experimental pretest posttest non-equivalent control group design was utilised to investigate the impacts of the intervention on weight-related experiential avoidance, eating behaviour, and body mass index (BMI) among 87 individuals over time.ACT-based intervention demonstrated significant effects on disordered eating (β = - 0.11) and BMI (β = - 0.06). These effects were mediated by improvements in weight-related experiential avoidance, suggesting the importance of focussing on targeting experiential avoidance as a key mechanism of change in postoperative psychological outcomes and weight.Study findings highlight firstly, the importance of addressing the psychological needs of weight-loss surgery individuals, and secondly, the value of ACT in augmenting surgical outcomes. The study concludes by offering suggestions for further development and future dissemination of such interventions for this population.

Duplex sequencing (DuplexSeq) is an error-corrected next-generation sequencing (ecNGS) method in which molecular barcodes informatically link PCR-copies back to their source DNA strands, enabling computational removal of errors by comparing grouped strand sequencing reads. The resulting background of less than one artifactual mutation per 107nucleotides allows for direct detection of somatic mutations. TwinStrand Biosciences, Inc. has developed a DuplexSeq-based mutagenesis assay to sample the rat genome, which can be applied to genetic toxicity testing. To evaluate this assay for early detection of mutagenesis, a time-course study was conducted using male Hsd:Sprague Dawley SD rats (3 per group) administered a single dose of 40 mg/kg N-ethyl-N-nitrosourea (ENU) via gavage, with mutation frequency (MF) and spectrum analyzed in stomach, bone marrow, blood, and liver tissues at 3 h, 24 h, 7 d, and 28 d post-exposure. Significant increases in MF were observed in ENU-exposed rats as early as 24 h for stomach (site of contact) and bone marrow (a highly proliferative tissue) and at 7 d for liver and blood. The canonical, mutational signature of ENU was established by 7 d post-exposure in all four tissues. Interlaboratory analysis of a subset of samples from different tissues and time points demonstrated remarkable reproducibility for both MF and spectrum. These results demonstrate that MF and spectrum can be evaluated successfully by directly sequencing targeted regions of DNA obtained from various tissues, a considerable advancement compared to currently usedin vivogene mutation assays.HIGHLIGHTSDuplexSeq is an ultra-accurate NGS technology that directly quantifies mutationsENU-dependent mutagenesis was detected 24 h post-exposure in proliferative tissuesMultiple tissues exhibited the canonical ENU mutation spectrum 7 d after exposureResults obtained with DuplexSeq were highly concordant between laboratoriesThe Rat-50 Mutagenesis Assay is promising for applications in genetic toxicology

The effects of longwave radiation on tropical cyclone intensification, with an emphasis on the mature stage, are explored in an idealized modeling framework. Results show that although the cloud-radiative effect aids in early intensification of the vortex, it does not promote increase in the maximum tangential wind (Vmax) and could even reduce Vmax at the mature stage. At later stages, maximum radiative heating is located outside the eyewall and promotes convection there, and the secondary circulation encourages convergence of absolute angular momentum outside the eyewall instead of near the eyewall region, based on a budget analysis. Clear-sky radiative cooling helps invigorate domain-wide convection, also limiting the Vmax increase at later stages. The area-averaged frozen moist static energy (FMSE) variance increases even though Vmax decreases. In this sense, the FMSE variance is similar to the monotonically-growing integrated kinetic energy, and is more indicative of the system-scale strength than of Vmax. Sensitivity experiments are performed with random initial perturbations and varied initial soundings. An axisymmetric model with a 10-member ensemble not only confirms the results from three-dimensional simulations, but also demonstrates that the weak radiative heating outside the eyewall is indeed able to slow down Vmax within one day.

Introduction The NCIP tool uses HES data collected from Trusts to understand the spread and variation of a range of surgical procedures. This work uses the tool to understand the current practice of synchronous colorectal and liver resection in England and how Covid-19 affected practice. Methods Pseudonymised data was extracted from NCIP dashboards by NHS England Improvement data analysts. The various metrics looked at included surgical approach, number of cases, length of stay (LOS), incidence of stoma maturation and readmission, and mortality. Results 523 elective patients over 17+ years – 244 cases between April 2018-March 2020 and 279 cases between April 2020-March 2022. Most primary tumours were colonic (407), with fewer rectosigmoid (47) and rectal cancers (69). 81.26% of procedures were performed open. 57 centres undertook synchronous colorectal and liver resections, 68.42% of total providers did 20 cases (range 21%-58%). 14.90% of patients were readmitted within 30 days. The 90-day mortality was 1.53%. Conclusion There was no impact of the Covid pandemic on current practice, possibly due to reluctance to give chemotherapy in this patient group. There was a significant variation observed at provider level for each procedure sub-group. Data suggests stoma creation within episode is a contributor to higher average LOS, readmission rate and mortality rate. In addition, significant variation observed in stoma formation between units, and a significant number of units are performing a small number of procedures.

There has been widespread concern about the mental health impact of the global COVID-19 outbreak. Fears have been raised that depression and anxiety among older people may have increased in the pandemic, and that adverse health behaviours, such as increased alcohol use and decreased physical activity, may have contributed to the mental health decline. This longitudinal study aimed to estimate the effect of the crisis on depression, anxiety, alcohol use and physical activity scores of people aged 55 and older in New Zealand. The sample included 3,171 people who responded to wave 7 (August-November 2018) and wave 8 (June-September 2020) of the Health, Work and Retirement Study. Analyses were carried out using paired t tests and multilevel mediation modelling. There was no evidence of significant changes in depression or anxiety. Alcohol use and physical activity were shown to decrease significantly, albeit to a small degree, and there was evidence of an indirect effect of the pandemic on depression via physical activity. These findings suggest a general resilience among older people 3 to 6 months into the pandemic. However, increased attention should be paid to promoting physical exercise among older people during this crisis, as a means of decreasing depression risk. The ongoing collection of robust longitudinal data on mental health is necessary to monitor psychological change and ensure older people are adequately supported in this continuing pandemic.

Damage to the dura mater may occur during intracranial or spinal surgeries, which can result in cerebrospinal fluid leakage as well as other potentially fatal physiological changes. As a result, biological scaffolds derived from xenogeneic materials are typically used to repair and regenerate dura mater post intracranial or spinal surgeries. The extracellular matrix of xenogeneic dura scaffolds has been shown to exhibit better cell infiltration and regeneration than synthetic material. In this study, we investigated the biocompatibility of native and decellularized porcine dura. Cell proliferation, cell viability, and mechanical properties of dural grafts were evaluated post re-seeding on days 3,7, and 14. Live-dead staining and resazurin salts were used to quantify cell viability and cell proliferation, respectively. Micro indentation was conducted to quantify the mechanical integrity of the native and acellular dura graft. The results show that the acellular porcine dural graft provides a favorable environment for rat fibroblast cell infiltration. Cell viability, proliferation, and micro indentation results on the acellular grafts are comparable with the native control porcine dura tissue. In conclusion, the porcine scaffold material showed increasing viable cells at each time point. The mechanics and biocompatibility results provide promising insight into the potential use of porcine dura in future cranial dura mater graft applications.