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Background: The treatment landscape for HR(+)HER2(−) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA). We sought to inform clinical utility for comprehensive genomic profiling (CGP) using tissue (TBx) and liquid biopsies (LBx) in HR(+)HER2(−) MBC. Methods: Records from a de-identified breast cancer clinicogenomic database for patients who underwent TBx/LBx testing at Foundation Medicine during routine clinical care at ~ 280 US cancer clinics between 01/2011 and 09/2023 were assessed. GA prevalence [ESR1mut, PIK3CAmut, AKT1mut, PTENmut, and PTEN homozygous copy loss (PTENloss)] were calculated in TBx and LBx [stratified by ctDNA tumor fraction (TF)] during the first three lines of therapy. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between groups by Cox models adjusted for prognostic factors. Results: ~ 60% of cases harbored 1 + GA in 1st-line TBx (1266/2154) or LBx TF ≥ 1% (80/126) and 26.5% (43/162) in LBx TF < 1%. ESR1mut was found in 8.1% TBx, 17.5% LBx TF ≥ 1%, and 4.9% LBx TF < 1% in 1st line, increasing to 59% in 3rd line (LBx TF ≥ 1%). PTENloss was detected at higher rates in TBx (4.3%) than LBx (1% in TF ≥ 1%). Patients receiving 1st-line aromatase inhibitor + CDK4/6 inhibitor (n = 573) with ESR1mut had less favorable rwPFS and rwOS versus ESR1 wild-type; no differences were observed for fulvestrant + CDK4/6 inhibitor (n = 348). Conclusion: Our study suggests obtaining TBx for CGP at time of de novo/recurrent diagnosis, followed by LBx for detecting acquired GA in 2nd + lines. Reflex TBx should be considered when ctDNA TF < 1%. [ABSTRACT FROM AUTHOR]

We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR's potential for use in molecular tumour boards, clinician-patient communication, and education. XR serves as a universal language, fostering collaborative decision-making in oncology. [ABSTRACT FROM AUTHOR]

Studies of the association between dyslexia and mental health have typically tried to minimise the influence of dyslexia comorbidities on the outcomes. However, in the "real world", many children with dyslexia have these comorbidities. In this study, we tested (1) if children with dyslexia with three common comorbidities — inattention, hyperactivity, language difficulties — experience more anxiety than children with dyslexia without these comorbidities; and (2) if any type of comorbidity is related to a certain type of anxiety (reading, social, generalised, or separation). The data of 82 children with dyslexia (mean age = 9 years and 4 months; 25 girls) were analysed using Fisher exact tests, which revealed that those with inattention (40.54%) or hyperactivity (42.30%) were statistically significantly more likely to experience elevated anxiety than children with dyslexia without these comorbidities (8.11 and 14.28%, respectively). This was not the case for language difficulties (24.5% versus 30%). Spearman ρ correlations (α =.05) indicated significant moderate relationships between inattention and reading anxiety (.27), social anxiety (.37), and generalised anxiety (.24); and between hyperactivity and social anxiety (.24) and generalised anxiety (.28). There were no significant correlations between language and anxiety. Examination of highly inter-correlated variables suggested a specific relationship between one type of comorbidity (inattention) and one type of anxiety (reading anxiety). [ABSTRACT FROM AUTHOR]

Background: Non-valvular atrial fibrillation (AF) is a common heart arrhythmia in the elderly population. AF patients are at high-risk of ischemic strokes, but oral anticoagulant (OAC) therapy reduces such risks. Warfarin had been the standard OAC for AF patients, however its effectiveness is highly variable and dependent on close monitoring of the anticoagulant response. Newer OACs such as rivaroxaban and apixaban address these drawbacks but are more costly. It is uncertain which OAC therapy for AF is cost-saving from the healthcare system perspective. Methods: We followed a cohort of patients in Ontario, Canada, aged ≥ 66 who were newly diagnosed with AF and prescribed OACs between 2012 and 2017. We used a two-stage estimation procedure. First, we account for the patient selection into OACs using a multinomial logit regression model and estimated propensity scores. Second, we used an inverse probability weighted regression adjustment approach to determine cost-saving OAC options. We also examined component-specific costs (i.e., drug, hospitalization, emergency department and physician) to understand the drivers of cost-saving OACs. Results: We found that compared to warfarin, rivaroxaban and apixaban treatments were cost-saving options, with per-patient 1-year healthcare cost savings at $2436 and $1764, respectively. These savings were driven by cost-savings in hospitalization, emergency department visits, and physician visits, outweighing higher drug costs. These results were robust to alternative model specifications and estimation procedures. Conclusions: Treating AF patients with rivaroxaban and apixaban than warfarin reduces healthcare costs. OAC reimbursement policies for AF patients should consider rivaroxaban or apixaban over warfarin as the first-line treatment. [ABSTRACT FROM AUTHOR]

Public transport accessibility to urban and regional services has been found to relate to various social and economic processes, such as unemployment, transport mode choice, property prices, and public health. A frequent type of measures representing accessibility are location-based. While these offer advantages, like flexibility and ease of interpretation, their estimation usually requires specialized skills and substantial computational resources. To lower these barriers, we have prepared a suite of accessibility indicators for key services across Great Britain at a spatially disaggregated level. The dataset includes ready-to-use public transport accessibility indicators for employment, general practitioners (GP, or family physician), hospitals, grocery stores, supermarkets, primary and secondary schools, and urban centres. It also includes the raw travel time matrix from each origin to every potential destination, a primary input for such indicator estimation. Altogether, this resource offers various levels of application, from direct input into a range of research topics to the foundation for creating comprehensive custom indicators. [ABSTRACT FROM AUTHOR]

Theories about autism spectrum disorder (ASD) have addressed cognitive deficits however few have examined how comorbid diagnoses, including sleep disturbance, anxiety and depression contribute to the underlying deficits. We investigated potential mediations of common ASD comorbidities in the relationship between sub-clinical autism traits and cognitive performance using an international community sample. Cognitive tasks assessed working memory [executive functioning (EF) theory], mental state attribution [theory of mind (ToM)], and global/local visual processing [weak central coherence (WCC) theory]. Structural equation modelling (SEM) demonstrated sleep disturbance and anxiety mediated the relationship of autism traits on measures of EF, but not WCC and ToM. This suggests that treating the symptoms of sleep disturbance and anxiety may lead to improvements in working memory. [ABSTRACT FROM AUTHOR]

Elevated inflammatory activity is one possible pathway through which exposure to childhood adversity engenders risk for physical and psychiatric illnesses. Limited research has investigated the compounding effects of childhood and adolescent stress exposure on changes in circulating levels of inflammatory biomarkers. This study assessed whether childhood adversity interacted with chronic or acute stress during adolescence to affect the temporal trajectories of five inflammatory biomarkers across at least three blood draws in a diverse sample of adolescents (N = 134; observations = 462). Using multilevel modeling, the interaction of childhood adversity, time, and within-person variance of acute stressors significantly predicted trajectories of higher interleukin-10 levels, controlling for demographics, medication use, and body mass index. Adolescents with high levels of childhood adversity who were exposed to a higher frequency of acute stressors compared to their own average rate of stress exposure consistently had higher levels of IL-10 as they got older, but those with average and below frequency of acute stressors had decreasing trajectories of log IL-10 as they matured. The results demonstrate how events early in life shape biological responses to the adolescent environment. This study also highlights the importance of developmental timing on the body's enhanced reactivity to acute and sustained stressors following childhood adversity. [ABSTRACT FROM AUTHOR]

Purpose: Recombinant erythropoietin (EPO) administered for traumatic brain injury (TBI) may increase short-term survival, but the long-term effect is unknown. Methods: We conducted a pre-planned long-term follow-up of patients in the multicentre erythropoietin in TBI trial (2010–2015). We invited survivors to follow-up and evaluated survival and functional outcome with the Glasgow Outcome Scale-Extended (GOSE) (categories 5–8 = good outcome), and secondly, with good outcome determined relative to baseline function (sliding scale). We used survival analysis to assess time to death and absolute risk differences (ARD) to assess favorable outcomes. We categorized TBI severity with the International Mission for Prognosis and Analysis of Clinical Trials in TBI model. Heterogeneity of treatment effects were assessed with interaction p-values based on the following a priori defined subgroups, the severity of TBI, and the presence of an intracranial mass lesion and multi-trauma in addition to TBI. Results: Of 603 patients in the original trial, 487 patients had survival data; 356 were included in the follow-up at a median of 6 years from injury. There was no difference between treatment groups for patient survival [EPO vs placebo hazard ratio (HR) (95% confidence interval (CI) 0.73 (0.47–1.14) p = 0.17]. Good outcome rates were 110/175 (63%) in the EPO group vs 100/181 (55%) in the placebo group (ARD 8%, 95% CI - 3 to 18%, p = 0.14). When good outcome was determined relative to baseline risk, the EPO groups had better GOSE (sliding scale ARD 12%, 95% CI 2–22%, p = 0.02). When considering long-term patient survival, there was no evidence for heterogeneity of treatment effect (HTE) according to severity of TBI (p = 0.85), presence of an intracranial mass lesion (p = 0.48), or whether the patient had multi-trauma in addition to TBI (p = 0.08). Similarly, no evidence of treatment heterogeneity was seen for the effect of EPO on functional outcome. Conclusion: EPO neither decreased overall long-term mortality nor improved functional outcome in moderate or severe TBI patients treated in the intensive care unit (ICU). The limited sample size makes it difficult to make final conclusions about the use of EPO in TBI. [ABSTRACT FROM AUTHOR]

This article discusses the relationship between dyslexia and mental health problems. While some studies have shown that individuals with dyslexia experience higher rates of anxiety, depression, somatic complaints, and social withdrawal, others have reported no significant effects. The special issue includes seven articles from different countries, examining the association between dyslexia and anxiety and depression. The studies suggest a significant connection between dyslexia and social anxiety, and the impact of reading difficulties on depression may vary depending on cultural factors. The article emphasizes the need for more intervention studies and highlights the importance of fostering resilience and coping mechanisms for children with learning difficulties. [Extracted from the article]

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF. Biologic epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted mice and swine hearts shows an immune cell response that results in an infiltration of M2 macrophages [ABSTRACT FROM AUTHOR]

Chlamydiosis is a significant disease affecting Eastern Australian koala (Phascolarctos cinereus) populations, impacting individual animal welfare and fecundity and therefore influencing population dynamics. The aim of this study was to investigate the effect of a synthetic peptide vaccine based on 4 components of the Chlamydia pecorum major outer membrane protein (MOMP), over an 18-month period in a koala population severely impacted by chlamydiosis. Wild koalas were recruited into a vaccination or a placebo treatment group on a random allocation, then followed through a period of 18 months, with recapture at 6 monthly intervals. Vaccination did not alter clinical disease expression or chlamydial shedding from the ocular or urogenital sites. Vaccination did not stimulate a significant plasma anti-MOMP IgG response, when compared to the placebo group. There was no significant effect of vaccination on IFN-γ and IL-17A mRNA expression of peripheral blood lymphocytes when stimulated with rMOMP. We have demonstrated that a synthetic peptide vaccination against chlamydiosis is not an effective management tool in a koala population with a high prevalence of C. pecorum infection and related disease. The lack of antigenic response found in this study suggests that further research utilising a larger, full-length antigen is an avenue worth investigation if we are to consider vaccination as a part of a management strategy in diseased koala populations. [ABSTRACT FROM AUTHOR]

In summer 2021, during the coronavirus pandemic, 8 parent-child dyads were recruited to participate in a pilot project to investigate the potential benefit of an at-home adaptation of an Animal-Assisted Intervention (AAI) for literacy. After completing a demographic survey and the Perceived Stress Scale-10 (Cohen et al., 1983), children's reading level was established using the Fry method and past report card information. Parents were given access to an online levelled-reader e-book provider along with written instructions and video training. Parent-child dyads engaged in the at-home AAI literacy support for 6-weeks during which time children's reading level was tracked online. Parental stress was assessed again upon completion. Findings indicate that reading level increased in 6 out of 8 cases, although not significantly. Parental stress, however, increased significantly from the start to end of the project. This descriptive pilot project discusses the potential and pitfalls of an at-home AAI literacy intervention. [ABSTRACT FROM AUTHOR]

Animal-assisted interventions (AAI) have been found to benefit human emotional state and cognitive performance. Recent applications of AAI have extended to classrooms with a range of intentions including to improve literacy. This Canadian study sought to examine differences in reading performance and behaviour in early readers identified as requiring extra supports following exposure to a canine-assisted and adult-assisted reading support. Twenty-four 7- to 8-year-olds experienced both supports in random order. At the start of the study and after completion of either support learners' oral reading, reading comprehension, social functioning, and reading affect were assessed. Parents, teachers, and children were also asked a range of closed- and open-ended questions. Findings showed evidence of improvement in reading performance, particularly after reading to a dog. There was also evidence of improved social competence overall and decreased problematic behaviour, although this was dependent on order of exposure. Teacher and parent reports showed they believed both supports to improve learner skills and affect for reading, and that teachers made more distinctions here. Implications for the practical application and relevance of methodological detail for future work are discussed. [ABSTRACT FROM AUTHOR]

Longitudinal changes in maternal depressive and anxiety symptoms and predictors of symptom variation among a group of middle-to-upper income Canadian women (n = 2152) were examined prior to the pandemic (2017–2019) and at three pandemic timepoints (May–July 2020, March–April 2021, November–December 2021). Mean maternal depression and anxiety scores were elevated throughout the pandemic. Pre-pandemic depressive symptoms were associated with greater increases in depressive symptoms. Coping and relationship quality were protective factors. Supporting the development of coping strategies may mitigate mental health concerns among mothers. [ABSTRACT FROM AUTHOR]

The fast development of mid-wave infrared photonics has increased the demand for high-performance photodetectors that operate in this spectral range. However, the signal-to-noise ratio, regarded as a primary figure of merit for mid-wave infrared detection, is strongly limited by the high dark current in narrow-bandgap materials. Therefore, conventional mid-wave infrared photodetectors such as HgCdTe require cryogenic temperatures to avoid excessively high dark current. To address this challenge, we report an avalanche photodiode design using photon-trapping structures to enhance the quantum efficiency and minimize the absorber thickness to suppress the dark current. The device exhibits high quantum efficiency and dark current density that is nearly three orders of magnitude lower than that of the state-of-the-art HgCdTe avalanche photodiodes and nearly two orders lower than that of previously reported AlInAsSb avalanche photodiodes that operate at 2 µm. Additionally, the bandwidth of these avalanche photodiodes reaches ~7 GHz, and the gain–bandwidth product is over 200 GHz; both are more than four times those of previously reported 2 µm avalanche photodiodes. We demonstrate an avalanche photodiode design using photon-trapping structures to enhance the quantum efficiency and minimizing the absorber thickness, yielding high quantum efficiency, suppressed dark current density and bandwidth of ~7 GHz. [ABSTRACT FROM AUTHOR]

NDP52 is an autophagy receptor involved in the recognition and degradation of invading pathogens and damaged organelles. Although NDP52 was first identified in the nucleus and is expressed throughout the cell, to date, there is no clear nuclear functions for NDP52. Here, we use a multidisciplinary approach to characterise the biochemical properties and nuclear roles of NDP52. We find that NDP52 clusters with RNA Polymerase II (RNAPII) at transcription initiation sites and that its overexpression promotes the formation of additional transcriptional clusters. We also show that depletion of NDP52 impacts overall gene expression levels in two model mammalian cells, and that transcription inhibition affects the spatial organisation and molecular dynamics of NDP52 in the nucleus. This directly links NDP52 to a role in RNAPII-dependent transcription. Furthermore, we also show that NDP52 binds specifically and with high affinity to double-stranded DNA (dsDNA) and that this interaction leads to changes in DNA structure in vitro. This, together with our proteomics data indicating enrichment for interactions with nucleosome remodelling proteins and DNA structure regulators, suggests a possible function for NDP52 in chromatin regulation. Overall, here we uncover nuclear roles for NDP52 in gene expression and DNA structure regulation. An autophagy receptor, NDP52, is recruited to the nucleus where it can bind DNA. The authors show this promotes changes in chromatin accessibility which supports transcription initiation, providing a direct link between autophagy and transcription regulation. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic negatively impacted the mental health of children, youth, and their families which must be addressed and prevented in future public health crises. Our objective was to measure how self-reported mental health symptoms of children/youth and their parents evolved during COVID-19 and to identify associated factors for children/youth and their parents including sources accessed for information on mental health. We conducted a nationally representative, multi-informant cross-sectional survey administered online to collect data from April to May 2022 across 10 Canadian provinces among dyads of children (11–14 years) or youth (15–18 years) and a parent (> 18 years). Self-report questions on mental health were based on The Partnership for Maternal, Newborn & Child Health and the World Health Organization of the United Nations H6+ Technical Working Group on Adolescent Health and Well-Being consensus framework and the Coronavirus Health and Impact Survey. McNemar's test and the test of homogeneity of stratum effects were used to assess differences between children-parent and youth-parent dyads, and interaction by stratification factors, respectively. Among 933 dyads (N = 1866), 349 (37.4%) parents were aged 35–44 years and 485 (52.0%) parents were women; 227 (47.0%) children and 204 (45.3%) youth were girls; 174 (18.6%) dyads had resided in Canada < 10 years. Anxiety and irritability were reported most frequently among child (44, 9.1%; 37, 7.7%) and parent (82, 17.0%; 67, 13.9%) dyads, as well as among youth (44, 9.8%; 35, 7.8%) and parent (68, 15.1%; 49, 10.9%) dyads; children and youth were significantly less likely to report worsened anxiety (p < 0.001, p = 0.006, respectively) or inattention (p < 0.001, p = 0.028, respectively) compared to parents. Dyads who reported financial or housing instability or identified as living with a disability more frequently reported worsened mental health. Children (96, 57.1%), youth (113, 62.5%), and their parents (253, 62.5%; 239, 62.6%, respectively) most frequently accessed the internet for mental health information. This cross-national survey contextualizes pandemic-related changes to self-reported mental health symptoms of children, youth, and families. [ABSTRACT FROM AUTHOR]

A decade ago, it was shown that associated with any model for U(1) duality-invariant nonlinear electrodynamics there is a unique U(1) duality-invariant supersymmetric nonlinear sigma model formulated in terms of chiral and complex linear superfields. Here we study the N = 1 superconformal σ-model analogue of the conformal duality-invariant electrodynamics known as the ModMax theory. We derive its dual formulation in terms of chiral superfields and show that the target space is a Kähler cone with U(1) × U(1) being the connected component of the isometry group. [ABSTRACT FROM AUTHOR]

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon... In 2008, Coles and colleagues published a phase II RCT that challenged conventional RRMS first line treatment. Inclusion criteria required at least 6 months of prior natalizumab therapy, a treatment gap not exceeding 3 months (to prevent rebound activity) and subsequent treatment with dimethyl fumarate, fingolimod, or ocrelizumab. [Extracted from the article]

Understanding the implications of the COVID-19 pandemic on the current generation of youth is critical for post-pandemic recovery planning. This study aimed to identify the most salient child (i.e., connectedness to caregivers, screen time, sleep, physical activity, peer relationships, and recreational activities) and family (i.e., COVID-19 financial impact, maternal depression and anxiety) factors associated with children's mental health and well-being during the COVID-19 pandemic, after controlling for pre-pandemic mental health. This study included 846 mother–child dyads (child age 9–11) from the All Our Families cohort. Mothers reported on the child's pre-pandemic mental health at age 8 (2017–2019) and during COVID-19 (May–July 2020), the family's financial impact due to COVID-19, and maternal depression and anxiety. During COVID-19 (July–August 2020), children reported on their screen time, sleep, physical activity, peer and family relationships, and recreational activities, as well as their happiness, anxiety and depression. After controlling for pre-pandemic anxiety, connectedness to caregivers (B − 0.16; 95% CI − 0.22 to − 0.09), child sleep (B − 0.11; 95% CI − 0.19 to − 0.04), and child screen time (B 0.11; 95% CI 0.04–0.17) predicted child COVID-19 anxiety symptoms. After controlling for pre-pandemic depression, connectedness to caregivers (B − 0.26; 95% CI − 0.32 to − 0.21) and screen time (B 0.09; 95% CI 0.02–0.16) predicted child COVID-19 depressive symptoms. After controlling for covariates, connectedness to caregivers (B 0.36; 95% CI 0.28–0.39) predicted child COVID-19 happiness. Fostering parent–child connections and promoting healthy device and sleep habits are critical modifiable factors that warrant attention in post-pandemic mental health recovery planning. [ABSTRACT FROM AUTHOR]

This article seeks a deeper understanding of the concept of authentic assessment which ensures it does not become another educational buzzword, slowly diminishing in real meaning. I consider the origins of the term in the US schooling sector, and how it has developed over time, and in different countries, to today focus in higher education largely on real world tasks. There is, however, I argue, a common conflation of real world with the world of work. Little of this literature actually engages with the rich philosophical debates on authenticity, and in this article, I suggest that this deeper understanding of authenticity can enable us to build on existing work on authentic assessment to develop a more holistic and richer concept that will be more beneficial to individual students and to the larger society of which they are part. I argue that we should move from thinking in terms of either the so-called real world, or the world of work, to focus our justification for authentic assessment on its social value (which encompasses but is not limited to its economic value). To achieve this aim, I suggest we move from simply focusing on the authentic task to considering why that task matters? This then enables a shift from the student in isolation to the student as a member of society. Senses of achievement can become richer, thus enhancing the students' sense of self, self-worth, and well-being. [ABSTRACT FROM AUTHOR]

Dissolved organic matter (DOM) impacts the structure and function of aquatic ecosystems. DOM absorbs light in the UV and visible (UV–Vis) wavelengths, thus impacting light attenuation. Because absorption by DOM depends on its composition, UV–Vis absorbance is used to constrain DOM composition, source, and amount. Ferric iron, Fe(III), also absorbs in the UV–Vis; when Fe(III) is present, DOM-attributed absorbance is overestimated. Here, we explore how differing behavior of DOM and Fe(III) at the catchment scale impacts UV–Vis absorbance and evaluate how system-specific variability impacts the effectiveness of existing Fe(III) correction factors in a temperate watershed. We sampled five sites in the Connecticut River mainstem bi-weekly for ~ 1.5 years, and seven sites in the Connecticut River watershed once during the summer 2019. We utilized size fractionation to isolate the impact of DOM and Fe(III) on absorbance and show that variable contributions of Fe(III) to absorbance at 254 nm (a254) and 412 nm (a412) by size fraction complicates correction for Fe(III). We demonstrate that the overestimation of DOM-attributed absorbance by Fe(III) is correlated to the Fe(III):dissolved organic carbon concentration ratio; thus, overestimation can be high even when Fe(III) is low. a254 overestimation is highly variable even within a single system, but can be as high as 53%. Finally, we illustrate that UV-Vis overestimation might impart bias to seasonal, discharge, and land-use trends in DOM quality. Together, these findings argue that Fe(III) should be measured in tandem with UV–Vis absorbance for estimates of CDOM composition or amount. [ABSTRACT FROM AUTHOR]

We report K–Pg-age deposits in Baja California, Mexico, consisting of terrestrial and shallow-marine materials re-sedimented onto the continental slope, including corals, gastropods, bivalves, shocked quartz grains, an andesitic tuff with a SHRIMP U–Pb age (66.12 ± 0.65 Ma) indistinguishable from that of the K–Pg boundary, and charred tree trunks. The overlying mudstones show an iridium anomaly and fungal and fern spores spikes. We interpret these heterogeneous deposits as a direct result of the Chicxulub impact and a mega-tsunami in response to seismically-induced landsliding. The tsunami backwash carried the megaflora offshore in high-density flows, remobilizing shallow-marine fauna and sediment en route. Charring of the trees at temperatures up to > 1000 °C took place in the interval between impact and arrival of the tsunami, which on the basis of seismic velocities and historic analogues amounted to only tens of minutes at most. This constrains the timing and causes of fires and the minimum distance from the impact site over which fires may be ignited. [ABSTRACT FROM AUTHOR]

Whole genome sequencing (WGS) is a key tool in identifying and characterising disease-associated bacteria across clinical, agricultural, and environmental contexts. One increasingly common use of genomic and metagenomic sequencing is in identifying the type and range of antimicrobial resistance (AMR) genes present in bacterial isolates in order to make predictions regarding their AMR phenotype. However, there are a large number of alternative bioinformatics software and pipelines available, which can lead to dissimilar results. It is, therefore, vital that researchers carefully evaluate their genomic and metagenomic AMR analysis methods using a common dataset. To this end, as part of the Microbial Bioinformatics Hackathon and Workshop 2021, a 'gold standard' reference genomic and simulated metagenomic dataset was generated containing raw sequence reads mapped against their corresponding reference genome from a range of 174 potentially pathogenic bacteria. These datasets and their accompanying metadata are freely available for use in benchmarking studies of bacteria and their antimicrobial resistance genes and will help improve tool development for the identification of AMR genes in complex samples. Measurement(s) bacterial genomes Technology Type(s) next generation DNA sequencing Factor Type(s) None Sample Characteristic - Organism Bacterium Sample Characteristic - Environment Varying Sample Characteristic - Location World [ABSTRACT FROM AUTHOR]

Purpose: Does re-biopsy of blastocysts classified as abnormal (ABN) due to segmental aneuploidy (SA) have clinical utility? Methods: The live birth (LB) outcomes of mosaic SAs, compared to other categories, were determined after transfer of 3084 PGT-A tested blastocysts. An initial 12-month trial thawed 111 blastocysts classified as ABN due to a SA for clinical re-biopsy, with an additional 58 from a subsequent 16-month revised protocol. Where re-biopsy failed to corroborate the original classification, blastocysts were reported as mosaic and suitable for clinical use. Results: Segmental mosaics had a LB rate (54.1%) which was indistinguishable from that of euploid (53.7%). Numeric mosaics had statistically significant (P < 0.05) reduced LB rates compared to euploid, with high-level numerics (19.2%) also exhibiting a significant reduction compared to low level (42.3%). Of the initial 111 blastocysts with SAs, 85 could be re-biopsied. Segmental gains became suitable for re-biopsy at a high rate (90.9%), with 84.2% (16/19) of these reclassified as mosaic. Only 73.0% of deletions and complex changes were suitable for re-biopsy, of which 73.0% (46/63) were confirmed ABN. The subsequent 16-month period primarily focused on gains, confirming the high rate at which they can be reclassified as clinically useable. Conclusions: Blastocysts harboring mosaic segmental duplications, rather than SAs in general, are the primary source of false-positive PGT-A results and represent a category with a LB rate similar to that of euploid. A high degree of confidence in the reliability of PGT-A results can be maintained by performing confirmatory clinical TE biopsies. [ABSTRACT FROM AUTHOR]

Socio-demographic risks are associated with higher child screen time and higher screen time is associated with poor socioemotional and developmental health. Existing studies have not examined children's screen time as a mechanism through which distal risks may be associated with child outcomes. In the current study, we examined whether two proximal factors, screen time and parenting quality, mediate the relation between distal cumulative risk and child outcomes. Participants (N = 1992) were drawn from a birth cohort of mothers and their children (81% white; 46% female). Mothers reported on cumulative risk factors (maternal income, education, depression, stress, marital status, housing instability, unemployment, and maternal history of childhood adversity) during the prenatal period. Parenting quality (ineffective/hostile, positive interactions) and children's screen time (hours/week) were assessed when children were three years of age. Child socioemotional (internalizing and externalizing problems) and developmental (achievement of developmental milestones) outcomes were measured at five years of age. Path analysis revealed indirect effects from cumulative risk to internalizing symptoms and achievement of developmental milestones via screen time. Indirect effects were observed from cumulative risk to internalizing and externalizing behavior via hostile parenting behavior. Over and above the effects of parenting, screen time may be a factor that links structural forms of social disadvantage during the prenatal period to child socioemotional and developmental outcomes. Due to modest effect sizes of screen time, it remains the case that child socioemotional and developmental health should be conceptualized within the context of distal cumulative risk factors such as caregiver psychological and material resources. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate factors associated with ICU delirium in patients who underwent damage control laparotomy (DCL), with the hypothesis that benzodiazepines and paralytic infusions would be associated with increased delirium risk. We also sought to evaluate the differences in sedation practices between trauma (T) and non-trauma (NT) patients. Methods: We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry admitted from January 1, 2017 to December 31, 2018. We included all adults undergoing DCL, regardless of diagnosis, who had completed daily Richmond Agitation Sedation Score (RASS) and Confusion Assessment Method-ICU (CAM-ICU). We excluded patients younger than 18 years, pregnant women, prisoners and patients who died before the first re-laparotomy. Data collected included age, number of re-laparotomies after DCL, duration of paralytic infusion, duration and type of sedative and opioid infusions as well as daily CAM-ICU and RASS scores to analyze risk factors associated with the proportion of delirium-free/coma-free ICU days during the first 30 days (DF/CF-ICU-30) using multivariate linear regression. Results: A 353 patient subset (73.2% trauma) from the overall 567-patient cohort had complete daily RASS and CAM-ICU data. NT patients were older (58.9 ± 16.0 years vs 40.5 ± 17.0 years [p < 0.001]). Mean DF/CF-ICU-30 days was 73.7 ± 96.4% for the NT and 51.3 ± 38.7% in the T patients (p = 0.030). More T patients were exposed to Midazolam, 41.3% vs 20.3% (p = 0.002). More T patients were exposed to Propofol, 91.0% vs 71.9% (p < 0.001) with longer infusion times in T compared to NT (71.2 ± 85.9 vs 48.9 ± 69.8 h [p = 0.017]). Paralytic infusions were also used more in T compared to NT, 34.8% vs 18.2% (p < 0.001). Using linear regression, dexmedetomidine infusion and paralytic infusions were associated with decreases in DF/CF-ICU-30, (− 2.78 (95%CI [− 5.54, − 0.024], p = 0.040) and (− 7.08 ([− 13.0, − 1.10], p = 0.020) respectively. Conclusions: Although the relationship between paralytic use and delirium is well-established, the observation that dexmedetomidine exposure is independently associated with increased delirium and coma is novel and bears further study. [ABSTRACT FROM AUTHOR]

Purpose: Damage control laparotomy (DCL) is used for both traumatic and non-traumatic indications. Failure to achieve primary fascial closure (PFC) in a timely fashion has been associated with complications including sepsis, fistula, and mortality. We sought to identify factors associated with time to PFC in a multicenter retrospective cohort. Methods: We reviewed retrospective data from 15 centers in the EAST SLEEP-TIME registry, including age, comorbidities (Charlson Comorbidity Index [CCI]), small and large bowel resection, bowel discontinuity, vascular procedures, retained packs, number of re-laparotomies, net fluid balance after 24 h, trauma, and time to first takeback in 12-h increments to identify key factors associated with time to PFC. Results: In total, 368 patients (71.2% trauma, of which 50.6% were penetrating, median ISS 25 [16, 34], with median Apache II score 15 [11, 22] in non-trauma) were in the cohort. Of these, 92.9% of patients achieved PFC at 60.8 ± 72.0 h after 1.6 ± 1.2 re-laparotomies. Each additional re-laparotomy reduced the odds of PFC by 91.5% (95%CI 88.2–93.9%, p < 0.001). Time to first re-laparotomy was highly significant (p < 0.001) in terms of odds of achieving PFC, with no difference between 12 and 24 h to first re-laparotomy (ref), and decreases in odds of PFC of 78.4% (65.8–86.4%, p < 0.001) for first re-laparotomy after 24.1–36 h, 90.8% (84.7–94.4%, p < 0.001) for 36.1–48 h, and 98.1% (96.4–99.0%, p < 0.001) for > 48 h. Trauma patients had increased likelihood of PFC in two separate analyses (p = 0.022 and 0.002). Conclusion: Time to re-laparotomy ≤ 24 h and minimizing number of re-laparotomies are highly predictive of rapid achievement of PFC in patients after trauma- and non-trauma DCL. Level of evidence: 2B. [ABSTRACT FROM AUTHOR]

Purpose: Sedation management of trauma patients after damage control laparotomy (DCL) has not been optimized. We evaluated if shorter sedation exposure was associated with increased proportion of delirium-free/coma-free (DF/CF-ICU) days and change in time to definitive fascial closure (DFC). Methods: We reviewed trauma DCL patients at an ACS-verified level I center over 5 years as shorter (SE) or longer than median (LE) sedation exposure. We compared demographics, injury patterns, hemodynamic parameters, and injury severity between groups. We calculated the propensity for each patient to achieve DFC using age, gender, ISS, red blood cell transfusion, bowel discontinuity, abdominal vascular injury, and time to first takeback; we then determined the effect of sedation exposure on rate of DFC by multivariate Cox regression, adjusted for propensity to achieve DFC. We used linear regression adjusted for age, ISS, head-AIS, bowel discontinuity, and vascular injury to determine the effect of sedation exposure on the proportion of DF/CF-ICU days. Results: 65 patients (33.8% penetrating) had mean age 41.8 ± 16.0, ISS 27.1 ± 14.2, Head-AIS 1.2 ± 1.6 and median sedation exposure of 2.2 [IQR 0.78, 7.3] days (35 SE and 30 LE). Pattern and severity of solid organ injuries and proportion of small and large bowel and vascular injuries were similar between groups. LE had more abdominal sepsis (23.3% vs 0%, p = 0.003) and enterocutaneous fistula (16.7% vs 0%, p = 0.016), and more ventilator (17.3 ± 12.7 vs 6.1 ± 6.8, p < 0.001), ICU (20.8 ± 14.2 vs 7.2 ± 7.6, p < 0.001), and hospital days (29.6 ± 19.6 vs 13.9 ± 9.0, p < 0.001). DFC was achieved more rapidly in the SE group (2.0 ± 1.5 days vs 3.9 ± 3.7 days [unadjusted], p = 0.023) and SE had a higher proportion of unadjusted DF/CF-ICU days (33.0 ± 32.0% vs 18.1 ± 16.4%, p = 0.020). SE was associated with an increased proportion of adjusted DF/CF-ICU days by multivariate linear regression (13.1% [95% CI 1.4–24.8%], p = 0.029) and with faster adjusted rate of DFC by multivariate Cox regression (RR 2.28 [95% CI 1.25–4.15, p = 0.007]). Conclusions: Shorter sedation exposure is associated with increased proportion of DF/CF-ICU days and more rapid DFC after DCL for trauma. [ABSTRACT FROM AUTHOR]

In swine models, there are well-established protocols for creating a closed-chest myocardial infarction (MI) as well as protocols for characterization of cardiac function with cardiac magnetic resonance (CMR). This methods manuscript outlines a novel technique in CMR data acquisition utilizing smart-signal gradient recalled echo (GRE)-based array sequences in a free-breathing swine heart failure model allowing for both high spatial and temporal resolution imaging. Nine male Yucatan mini swine weighing 48.7 ± 1.6 kg at 58.2 ± 3.1 weeks old underwent the outlined imaging protocol before and 1-month after undergoing closed chest left anterior descending coronary artery (LAD) occlusion/reperfusion. The left ventricular ejection fraction (LVEF) at baseline was 59.3 ± 2.4% and decreased to 48.1 ± 3.7% 1-month post MI (P = 0.029). The average end-diastolic volume (EDV) at baseline was 55.2 ± 1.7 ml and increased to 74.2 ± 4.2 ml at 1-month post MI (P = 0.001). The resulting images from this novel technique and post-imaging analysis are presented and discussed. In a Yucatan swine model of heart failure via closed chest left anterior descending coronary artery (LAD) occlusion/reperfusion, we found that CMR with GRE-based array sequences produced clinical-grade images with high spatial and temporal resolution in the free-breathing setting. [ABSTRACT FROM AUTHOR]

Global quantum communications will enable long-distance secure data transfer, networked distributed quantum information processing, and other entanglement-enabled technologies. Satellite quantum communication overcomes optical fibre range limitations, with the first realisations of satellite quantum key distribution (SatQKD) being rapidly developed. However, limited transmission times between satellite and ground station severely constrains the amount of secret key due to finite-block size effects. Here, we analyse these effects and the implications for system design and operation, utilising published results from the Micius satellite to construct an empirically-derived channel and system model for a trusted-node downlink employing efficient Bennett-Brassard 1984 (BB84) weak coherent pulse decoy states with optimised parameters. We quantify practical SatQKD performance limits and examine the effects of link efficiency, background light, source quality, and overpass geometries to estimate long-term key generation capacity. Our results may guide design and analysis of future missions, and establish performance benchmarks for both sources and detectors. [ABSTRACT FROM AUTHOR]

Summary: The prevalence of self-reported and DXA-confirmed osteoporosis was 7.8% (males 2.2%; females 12.7%), and 3.6% (males 1.2%; females 5.9%), respectively. We found that most community-dwelling older adults at high fracture risk are not taking osteoporosis medication, particularly males. There is a major opportunity for improved primary fracture prevention in the community. Purpose: To provide an up-to-date prevalence estimate of osteoporosis, fracture risk factors, fracture risk, and the proportion of older Canadians at high fracture risk who are not taking an osteoporosis medication. Methods: We included Canadian Longitudinal Study on Aging (CLSA) participants: a community-dwelling cohort aged 45 to 85 years who completed the baseline (2015) comprehensive interview and had dual-energy X-ray absorptiometry (DXA) scans (N = 30,097). We describe the age- and sex-stratified prevalence of (1) self-reported osteoporosis; (2) DXA-confirmed osteoporosis; (3) fracture risk factors and people who are at high risk (FRAX® major osteoporotic fracture probability ≥ 20%); and (4) people who are at high fracture risk not taking osteoporosis medications. Sampling weights, as defined by the CLSA, were applied. Results: The mean age of participants was 70.0 (SD 10.3). Overall, 7.8% had self-reported osteoporosis (males 2.2%; females 12.7%) while 3.6% had DXA-confirmed osteoporosis (males 1.2%; females 5.9%), and 2.8% were at high fracture risk (males 0.3%; females 5.1%). Of people who had osteoporosis and were at high risk, 77.3% were not taking an osteoporosis medication (males 92.3%; females 76.8%). Conclusions: Our study provides an up-to-date prevalence estimate of osteoporosis for community-dwelling older Canadians. We found that most community-dwelling older adults at high fracture risk are not taking an osteoporosis medication, particularly males. There is a major opportunity for improved primary fracture prevention in the community. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibition (ICI) has demonstrated clinically significant efficacy when combined with chemotherapy in triple negative breast cancer (TNBC). Although many patients derived benefit, others do not respond to immunotherapy, therefore relying upon innovative combinations to enhance response. Local therapies such as radiation therapy (RT) and cryotherapy are immunogenic and potentially optimize responses to immunotherapy. Strategies combining these therapies and ICI are actively under investigation. This review will describe the rationale for combining ICI with targeted local therapies in breast cancer. Methods: A literature search was performed to identify pre-clinical and clinical studies assessing ICI combined with RT or cryotherapy published as of August 2021 using PubMed and ClinicalTrials.gov. Results: Published studies of ICI with RT and IPI have demonstrated safety and signals of early efficacy. Conclusion: RT and cryotherapy are local therapies that can be integrated safely with ICI and has shown promise in early trials. Randomized phase II studies testing both of these approaches, such as P-RAD (NCT04443348) and ipilimumab/nivolumab/cryoablation for TNBC (NCT03546686) are current enrolling. The results of these studies are paramount as they will provide long term data on the safety and efficacy of these regimens. [ABSTRACT FROM AUTHOR]

To investigate the unique kinds of mentality involved in skilled performance, this paper explores the performance ecology of the Māori haka, a ritual form of song and dance of the indigenous people of Aotearoa New Zealand. We respond to a recent proposal to program robots to perform a haka as 'cultural preservationists' for 'intangible cultural heritage'. This 'Robot Māori Haka' proposal raises questions about the nature of skill and the transmission of embodied knowledge; about the cognitive and affective experiences cultivated in indigenous practices like haka; and about the role of robots in the archival aspirations of human societies. Reproducing haka, we suggest, requires more than copying physical actions; preserving the 'intangible' entails more than programming postures and movements. To make this case, we discuss the history of European responses to the haka, and analyse its diverse performance features in cultural context. Arguing that indigenous movement practices incorporate genuinely embodied knowledge, we claim that skilled performance of haka is deeply mindful, embodying and transmitting dynamic, culturally shared understandings of the natural and social world. The indigenous psychologies incorporated in haka performance are animated by a shared history integrated with its environment. Examining haka performance through the lens of 4E cognitive skill theory for mutual benefit, we discuss the effects of synchrony in collective action, the social and environmental scaffolding of affect and emotion, and the multilayered relations between past and present. Culturally-embedded systems of skilled movement like the Māori haka may, we suggest, constitute specific ways of thinking and feeling. [ABSTRACT FROM AUTHOR]

Background: Historically, pre-operative biliary stenting has been associated with higher infectious complication rates following pancreatoduodenectomy. However, alleviation of biliary obstruction is necessary for consideration of pre-operative chemotherapy, which may improve disease-free survival, or for mitigation of symptoms while awaiting surgery. Our aim is to compare contemporary post-operative complication risk among patients with pre-operative endoscopic retrograde cholangiopancreatography (ERCP) stenting compared to those without. Methods: Patients who underwent a pancreatoduodenectomy for pancreatic cancer with biliary obstruction within the ACS-NSQIP registry from 2014 to 2017 were identified. The primary outcome was to compare the risk of 30-day complication (composite outcome) between patients with and without pre-operative ERCP stenting. Propensity score matching was used to ensure balanced baseline characteristics and log-binomial regression models were used to estimate risk ratios for overall perioperative complication between groups. Results: From 6073 patients with obstructive jaundice undergoing pancreatoduodenectomy for pancreatic cancer, 92% (5564) were eligible for the study. After performing a propensity score matching on 20 baseline characteristics, 952 patients without stenting were matched to up to four patients who received pre-operative ERCP stenting (n = 3467) for a matched cohort of 4419. A total of 1901 (55%) patients with pre-operative ERCP stenting experienced a post-operative complication compared to 501 (53%) patients without stenting (risk ratio 1.04, 95% CI 0.97–1.11, p = 0.23). Conclusion: Pre-operative ERCP stenting was not associated with an increased risk of post-operative complication in patients undergoing pancreatoduodenectomy with obstructive jaundice. Biliary stenting may be safely considered for symptom relief and to potentially facilitate pre-operative chemotherapy for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) can produce heterogeneous injury patterns including a variety of hemorrhagic and non-hemorrhagic lesions. The impact of lesion size, location, and interaction between total number and location of contusions may influence the occurrence of seizures after TBI. We report our methodologic approach to this question in this preliminary report of the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx). We describe lesion identification and segmentation of hemorrhagic contusions by early posttraumatic magnetic resonance imaging (MRI). We describe the preliminary methods of manual lesion segmentation in an initial cohort of 32 TBI patients from the EpiBioS4Rx cohort and the preliminary association of hemorrhagic contusion and edema location and volume to seizure incidence. [ABSTRACT FROM AUTHOR]

Purpose: Literature supporting the efficacy of complementary and integrative medicine (CIM) alongside radiotherapy is fragmented with varying outcomes and levels of evidence. This review summarizes the available evidence on CIM used with radiotherapy in order to inform clinicians. Methods: A systematic literature review identified studies on the use of CIM during radiotherapy. Inclusion required the following criteria: the study was interventional, CIM therapy was for human patients with cancer, and CIM therapy was administered concurrently with radiotherapy. Data points of interest were collected from included studies. A subset was identified as high-quality using the Jadad scale. Fisher's exact test was used to assess the association between study results, outcome measured, and type of CIM. Results: Overall, 163 articles met inclusion. Of these, 68 (41.7%) were considered high-quality trials. Articles published per year increased over time (p < 0.01). Frequently identified therapies were biologically based therapies (47.9%), mind-body therapies (23.3%), and alternative medical systems (13.5%). Within the subset of high-quality trials, 60.0% of studies reported a favorable change with CIM while 40.0% reported no change. No studies reported an unfavorable change. Commonly assessed outcome types were patient-reported (41.1%) and provider-reported (21.5%). Rate of favorable change did not differ based on type of CIM (p = 0.90) or outcome measured (p = 0.24). Conclusions: Concurrent CIM may reduce radiotherapy-induced toxicities and improve quality of life, suggesting that physicians should discuss CIM with patients receiving radiotherapy. This review provides a broad overview of investigations on CIM use during radiotherapy and can inform how radiation oncologists advise their patients about CIM. [ABSTRACT FROM AUTHOR]