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Refuge preferences can be crucial behavioural traits for survival. Here, we explore the refuge preferences of the threatened katipō spider (Latrodectus katipo) and invasive false katipō (Steatoda capensis) (Araneae, Theridiidae). We conducted experimental assays using artificial refuges in the laboratory to test individual preferences for refuge shape, surface, and height. We also tested how refuge type affects the number of web trap lines built for prey capture. Both species preferred V-shaped refuges over rectangular refuges, with no evidence of a preference for other refuge types. For reasons that remain unclear, individuals varied in their preferences for surface and height in both their daily and final choices, but only in shape during their daily choices. Katipō spiders showed refuge fidelity in all three assays, however, there was also evidence of individual variation in refuge fidelity in the shape assay. False katipō spiders only displayed refuge fidelity in the shape and surface assays. Spiders built more web trap lines under V-shaped refuges than rectangular refuges, suggesting higher activity and greater refuge investment, which may further reflect a preference for V-shaped refuges. While V-shaped refugia are not exclusively preferred by katipō, introducing V-shaped artificial refuges into their habitats could help support the persistence and expansion of katipō populations. Although false katipō are also likely to use these refugia, the decline of sand dunes has limited the availability of natural refugia. Therefore, providing artificial refuges could increase the available habitat and reduce competition between katipō and false katipō. [ABSTRACT FROM AUTHOR]

Primary care clinicians play a key role in asthma and asthma exacerbation management worldwide because most patients with asthma are treated in primary care settings. The high burden of asthma exacerbations persists and important practice gaps remain, despite continual advances in asthma care. Lack of primary care-specific guidance, uncontrolled asthma, incomplete assessment of exacerbation and asthma control history, and reliance on systemic corticosteroids or short-acting beta2-agonist-only therapy are challenges clinicians face today with asthma care. Evidence supports the use of inhaled corticosteroids (ICS) + fast-acting bronchodilator treatments when used as needed in response to symptoms to improve asthma control and reduce rates of exacerbations, and the symptoms that occur leading up to an asthma exacerbation provide a window of opportunity to intervene with ICS. Incorporating patient perspectives and preferences when designing asthma regimens will help patients be more engaged in their therapy and may contribute to improved adherence and outcomes. This expert consensus contains 10 Best Practice Advice Points from a panel of primary care clinicians and a patient representative, formed in collaboration with the International Primary Care Respiratory Group (IPCRG), a clinically led charitable organization that works locally and globally in primary care to improve respiratory health. The panel met virtually and developed a series of best practice statements, which were drafted and subsequently voted on to obtain consensus. Primary care clinicians globally are encouraged to review and adapt these best practice advice points on preventing and managing asthma exacerbations to their local practice patterns to enhance asthma care within their practice. [ABSTRACT FROM AUTHOR]

Modern life is essentially homochiral, containing D-sugars in nucleic acid backbones and L-amino acids in proteins. Since coded proteins are theorized to have developed from a prebiotic RNA World, the homochirality of L-amino acids observed in all known life presumably resulted from chiral transfer from a homochiral D-RNA World. This transfer would have been mediated by aminoacyl-RNAs defining the genetic code. Previous work on aminoacyl transfer using tRNA mimics has suggested that aminoacylation using D-RNA may be inherently biased toward reactivity with L-amino acids, implying a deterministic path from a D-RNA World to L-proteins. Using a model system of self-aminoacylating D-ribozymes and epimerizable activated amino acid analogs, we test the chiral selectivity of 15 ribozymes derived from an exhaustive search of sequence space. All of the ribozymes exhibit detectable selectivity, and a substantial fraction react preferentially to produce the D-enantiomer of the product. Furthermore, chiral preference is conserved within sequence families. These results are consistent with the transfer of chiral information from RNA to proteins but do not support an intrinsic bias of D-RNA for L-amino acids. Different aminoacylation structures result in different directions of chiral selectivity, such that L-proteins need not emerge from a D-RNA World. Life is homochiral, and prior work posited that D-RNA may interact preferentially with L-amino acids. Here, the authors show that self-aminoacylating D-RNAs do not have an intrinsic preference for L-amino acids, suggesting that either handedness could emerge from early living systems. [ABSTRACT FROM AUTHOR]

Propagule dispersal is a crucial aspect of the survival and reproduction of sessile organisms, such as plants and fungi. As such, the colours of fleshy fruits serve as a visual cue for animal dispersers. However, little is known about how, or whether, specific traits of fungal fruiting bodies, such as colour or shape, attract animal dispersers, and additionally the identities of fungal dispersers are poorly understood. Globally, most truffle-like fungi are dull-coloured, subterranean, and likely have scents that are attractive to mammalian dispersers. In Aotearoa-New Zealand, however, brightly coloured truffle-like fungi that emerge from the forest floor have seemingly proliferated. This proliferation has prompted the hypothesis that they are adapted to dispersal by a bird-dominated fauna. In our study, we used the literature and citizen science data (GBIF) to explore whether colourful species occur at a higher proportion of the total truffle-like fungi flora in Aotearoa-New Zealand than elsewhere in the world. In addition, we tested for a relationship between biotic factors (avian frugivory and forest cover) and abiotic factors (precipitation, radiation, and temperature) and the prevalence of brightly coloured truffle-like fungi across the world. The most colourful truffle-like fungi are in three defined regions: Australia, South and Central America and the Caribbean, and Aotearoa-NZ. Potential dispersers and the environment both relate to the distribution of truffle-like fungi: we found that increasing levels of frugivory were associated with higher proportions of colourful truffle-like fungi. This finding provides new insights into drivers of certain fungal traits, and their interactions between birds and fungi. Unique ecosystems, such as Aotearoa-NZ's bird-dominated biota, provide fascinating opportunities to explore how plants and fungi interact with the sensory systems of animals. [ABSTRACT FROM AUTHOR]

In the age of globalization, commercial aviation plays a central role in maintaining our international connectivity by providing fast air transport services for passengers and freight. However, the upper limit of the aircraft flight envelope, i.e., its operational limit in the high-speed (transonic) regime, is usually fixed by the occurrence of transonic aeroelastic effects. These harmful structural vibrations are associated with an aerodynamic instability called transonic buffet. It refers to shock wave oscillations occurring on the aircraft wings, which induce unsteady aerodynamic loads acting on the wing structure. Since the structural response can cause severe structural damage endangering flight safety, the aviation industry is highly interested in suppressing transonic buffet to extend the flight envelope to higher aircraft speeds. In this contribution, we demonstrate experimentally that the application of porous trailing edges substantially attenuates the buffet phenomenon. Since porous trailing edges have the additional benefit of reducing acoustic aircraft emissions, they could prospectively provide faster air transport with reduced noise emissions. Transonic buffet is a ubiquitous challenge in commercial aviation since it can result in catastrophic structural failure of the aircraft wings. Here, authors experimentally show that this critical aerodynamic phenomenon can be mitigated using a carefully designed porous trailing edge on the wing. [ABSTRACT FROM AUTHOR]

Objectives: To quantify brain microstructural changes in recently diagnosed relapsing-remitting multiple sclerosis (RRMS) using longitudinal T1 measures, and determine their associations with clinical disability. Methods: Seventy-nine people with recently diagnosed (< 6 months) RRMS were recruited from a single-centre cohort sub-study, and underwent baseline and 1-year brain MRI, including variable flip angle T1 mapping. Median T1 was measured in white matter lesions (WML), normal-appearing white matter (NAWM), cortical/deep grey matter (GM), thalami, basal ganglia and medial temporal regions. Prolonged T1 (≥ 2.00 s) and supramedian T1 (relative to cohort WML values) WML voxel counts were also measured. Longitudinal change was assessed with paired t-tests and compared with Bland-Altman limits of agreement from healthy control test-retest data. Regression analyses determined relationships with Expanded Disability Status Scale (EDSS) score and dichotomised EDSS outcomes (worsening or stable/improving). Results: Sixty-two people with RRMS (mean age 37.2 ± 10.9 [standard deviation], 48 female) and 11 healthy controls (age 44 ± 11, 7 female) contributed data. Prolonged and supramedian T1 WML components increased longitudinally (176 and 463 voxels, respectively; p <.001), and were associated with EDSS score at baseline (p <.05) and follow-up (supramedian: p <.01; prolonged: p <.05). No cohort-wide median T1 changes were found; however, increasing T1 in WML, NAWM, cortical/deep GM, basal ganglia and thalami was positively associated with EDSS worsening (p <.05). Conclusion: T1 is sensitive to brain microstructure changes in early RRMS. Prolonged WML T1 components and subtle changes in NAWM and GM structures are associated with disability. Clinical relevance statement: MRI T1 brain mapping quantifies disability-associated white matter lesion heterogeneity and subtle microstructural damage in normal-appearing brain parenchyma in recently diagnosed RRMS, and shows promise for early objective disease characterisation and stratification. Key Points: • Quantitative T1 mapping detects brain microstructural damage and lesion heterogeneity in recently diagnosed relapsing-remitting multiple sclerosis. • T1 increases in lesions and normal-appearing parenchyma, indicating microstructural damage, are associated with worsening disability. • Brain T1 measures are objective markers of disability-relevant pathology in early multiple sclerosis. [ABSTRACT FROM AUTHOR]

Purpose of Review: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndrome (ACS), particularly among women < 50 years of age. Here, we aim to review the pathogenesis of SCAD, discuss SCAD as an initial manifestation of systemic arterial disease, and highlight invasive strategies as well as unique challenges in the care of women with SCAD. Recent Findings: A paradigm shift has occurred in the care of SCAD patients in the past decade as recommendations for conservative management have become widespread. Invasive interventions are reserved for patients with hemodynamic compromise or active ischemia due to increased periprocedural complications and failure rates. Certain patient populations have been identified for larger territory infarcts and proximal disease including patients with known connective tissue disease, premenopausal women, and patients with pregnancy-associated SCAD (P-SCAD). Summary: Current recommended management of SCAD is conservative. Despite a growing awareness of SCAD and its known association with systemic arteriopathies in women, evidence-based data remains scarce. Future studies focused on identifying genetic factors, optimal medical therapy after SCAD, and techniques to minimize interventional complications are needed. [ABSTRACT FROM AUTHOR]

Context: Processes that shape genomic and ecological divergence can reveal important evolutionary dynamics to inform the conservation of threatened species. Fontainea is a genus of rainforest shrubs and small trees including critically endangered and threatened species restricted to narrow, but complex geographic and ecological regions. Several species of Fontainea are subject to spatially explicit conditions and experience limited intra-specific gene flow, likely generating genetic differentiation and local adaptation. Objectives: Here, we explored the genetic and ecological mechanisms underlying patterns of diversification in two, closely related threatened Fontainea species. Our aim was to compare spatial patterns of genetic variation between the vulnerable Fontainea australis (Southern Fontainea) and critically endangered F. oraria (Coastal Fontainea), endemic to the heterogeneous subtropical region of central, eastern Australia, where large-scale clearing has severely reduced rainforest habitat to a fraction (< 1%) of its pre-European settlement extent. Methods: We used a set of 10,000 reduced-representation markers to infer genetic relationships and the drivers of spatial genetic variation across the two species. In addition, we employed a combination of univariate and multivariate genome-environment association analysis using a set of topo-climatic variables to explore potential patterns of local adaptation as a factor impacting genomic divergence. Results: Our study revealed that Coastal Fontainea have a close genetic relationship with Southern Fontainea. We showed that isolation by distance has played a key role in their genetic variation, indicating that vicariance can explain the spatial genetic distribution of the two species. Genotype-environment analyses showed a strong association with temperature and topographic features, suggesting adaptation to localised thermal environments. We used a multivariate redundancy analysis to identify a range of putatively adapted loci associated with local environmental conditions. Conclusions: Divergent selection at the local-habitat scale as a result of dispersal limitations and environmental heterogeneity (including physical barriers) are likely contributors to adaptive divergence between the two Fontainea species. Our findings have presented evidence to indicate that Southern and Coastal Fontainea were comprised of distinct genetic groups and ecotypes, that together may form a single species continuum, with further phenotype research suggested to confirm the current species boundaries. Proactive conservation actions, including assisted migration to enhance the resilience of populations lacking stress-tolerant single nucleotide polymorphisms (SNPs) may be required to secure the long-term future of both taxa. This is especially vital for the critically endangered Coastal Fontainea given projections of habitat decline for the species under future climate scenarios. [ABSTRACT FROM AUTHOR]

Abstract Approaches to prolong responses to BRAF targeting drugs in melanoma patients are challenged by phenotype heterogeneity. Melanomas of a “MITF‐high” phenotype usually respond well to BRAF inhibitor therapy, but these melanomas also contain subpopulations of the de novo resistance “AXL‐high” phenotype. > 50% of melanomas progress with enriched “AXL‐high” populations, and because AXL is linked to de‐differentiation and invasiveness avoiding an “AXL‐high relapse” is desirable. We discovered that phenotype heterogeneity is supported during the response phase of BRAF inhibitor therapy due to MITF‐induced expression of endothelin 1 (EDN1). EDN1 expression is enhanced in tumours of patients on treatment and confers drug resistance through ERK re‐activation in a paracrine manner. Most importantly, EDN1 not only supports MITF‐high populations through the endothelin receptor B (EDNRB), but also AXL‐high populations through EDNRA, making it a master regulator of phenotype heterogeneity. Endothelin receptor antagonists suppress AXL‐high‐expressing cells and sensitize to BRAF inhibition, suggesting that targeting EDN1 signalling could improve BRAF inhibitor responses without selecting for AXL‐high cells.

This study examined whether pregnant women alter their alcohol consumption upon pregnancy awareness and any additive effect of a maternal history of child abuse and pregnancy-related anxiety in predicting antenatal alcohol consumption. Pregnant women (N = 548, M = 31.44, SD = 4.58) completed an online survey consisting of the Pregnancy-related Anxiety Scale, Adverse Childhood Experience Questionnaire, questions on alcohol consumption and demographics. The Wilcoxon test examined difference scores between pre-pregnancy awareness and post-awareness drinking. More women reduced or ceased drinking after pregnancy awareness (M = 0.15, SD = 1.03) than before pregnancy recognition (M = 3.12, SD = 3.91). Only two women increased their alcohol consumption, with 140 reporting no change. In the hierarchical regression analysis, child abuse was not significant in the model, whereas pregnancy-related anxiety predicted alcohol consumption, with pre-pregnancy drinking the strongest predictor. There was no significant interaction effect between pregnancy-related anxiety and child abuse. While limited by a cross-sectional design and single questions to assess alcohol intake, our findings are consistent with extant literature. Findings related to child abuse were not significant, and likely due to low prevalence in the sample, Despite this, we further established that pregnancy-related anxiety remains a significant predictor of antenatal drinking regardless of how much alcohol a woman may consume pre-pregnancy. This relationship may be explained by drinking used to cope with pregnancy-related anxieties. While current guidelines recommend alcohol screening, many women may not accurately report their alcohol intake screening for pregnancy-related anxiety may provide an avenue to identify women more at risk of drinking during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: Assess the extent to which measurement error in police recorded crime rates impact the estimates of regression models exploring the causes and consequences of crime. Methods: We focus on linear models where crime rates are included either as the response or as an explanatory variable, in their original scale or log-transformed. Two measurement error mechanisms are considered, systematic errors in the form of under-recorded crime, and random errors in the form of recording inconsistencies across areas. The extent to which such measurement error mechanisms impact model parameters is demonstrated algebraically using formal notation, and graphically using simulations. Results: The impact of measurement error is highly variable across different settings. Depending on the crime type, the spatial resolution, but also where and how police recorded crime rates are introduced in the model, the measurement error induced biases could range from negligible to severe, affecting even estimates from explanatory variables free of measurement error. We also demonstrate how in models where crime rates are introduced as the response variable, the impact of measurement error could be eliminated using log-transformations. Conclusions: The validity of a large share of the evidence base exploring the effects and consequences of crime is put into question. In interpreting findings from the literature relying on regression models and police recorded crime rates, we urge researchers to consider the biasing effects shown here. Future studies should also anticipate the impact in their findings and employ sensitivity analysis if the expected measurement error induced bias is non-negligible. [ABSTRACT FROM AUTHOR]

As commissioned by the WHO, we updated and expanded the scope of four systematic reviews to inform its (in development) clinical practice guideline for the management of CPLBP in adults, including older adults. Methodological details and results of each review are described in the respective articles in this series. In the last article of this series, we discuss methodological considerations, clinical implications and recommendations for future research. [ABSTRACT FROM AUTHOR]

Chronic primary low back pain (CPLBP) is a prevalent and disabling condition that often requires rehabilitation interventions to improve function and alleviate pain. This paper aims to advance future research, including systematic reviews and randomized controlled trials (RCTs), on CPLBP management. We provide methodological and reporting recommendations derived from our conducted systematic reviews, offering practical guidance for conducting robust research on the effectiveness of rehabilitation interventions for CPLBP. Our systematic reviews contributed to the development of a WHO clinical guideline for CPLBP. Based on our experience, we have identified methodological issues and recommendations, which are compiled in a comprehensive table and discussed systematically within established frameworks for reporting and critically appraising RCTs. In conclusion, embracing the complexity of CPLBP involves recognizing its multifactorial nature and diverse contexts and planning for varying treatment responses. By embracing this complexity and emphasizing methodological rigor, research in the field can be improved, potentially leading to better care and outcomes for individuals with CPLBP. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate benefits and harms of needling therapies (NT) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. Methods: Electronic databases were searched for randomized controlled trials (RCTs) assessing NT compared with placebo/sham, usual care, or no intervention (comparing interventions where the attributable effect could be isolated). We conducted meta-analyses where indicated and graded the certainty of evidence. Results: We screened 1831 citations and 109 full text RCTs, yeilding 37 RCTs. The certainty of evidence was low or very low across all included outcomes. There was little or no difference between NT and comparisons across most outcomes; there may be some benefits for certain outcomes. Compared with sham, NT improved health-related quality of life (HRQoL) (physical) (2 RCTs; SMD = 0.20, 95%CI 0.07; 0.32) at 6 months. Compared with no intervention, NT reduced pain at 2 weeks (21 RCTs; MD = − 1.21, 95%CI − 1.50; − 0.92) and 3 months (9 RCTs; MD = − 1.56, 95%CI − 2.80; − 0.95); and reduced functional limitations at 2 weeks (19 RCTs; SMD = − 1.39, 95%CI − 2.00; − 0.77) and 3 months (8 RCTs; SMD = − 0.57, 95%CI − 0.92; − 0.22). In older adults, NT reduced functional limitations at 2 weeks (SMD = − 1.10, 95%CI − 1.71; − 0.48) and 3 months (SMD = − 1.04, 95%CI − 1.66; − 0.43). Compared with usual care, NT reduced pain (MD = − 1.35, 95%CI − 1.86; − 0.84) and functional limitations (MD = − 2.55, 95%CI − 3.70; − 1.40) at 3 months. Conclusion: Based on low to very low certainty evidence, adults with CPLBP experienced some benefits in pain, functioning, or HRQoL with NT; however, evidence showed little to no differences for other outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate benefits and harms of structured exercise programs for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. Methods: We searched for randomized controlled trials (RCTs) in electronic databases (inception to 17 May 2022). Eligible RCTs targeted structured exercise programs compared to placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of exercise could be isolated). We extracted outcomes, appraised risk of bias, conducted meta-analyses where appropriate, and assessed certainty of evidence using GRADE. Results: We screened 2503 records (after initial screening through Cochrane RCT Classifier and Cochrane Crowd) and 398 full text RCTs. Thirteen RCTs rated with overall low or unclear risk of bias were synthesized. Assessing individual exercise types (predominantly very low certainty evidence), pain reduction was associated with aerobic exercise and Pilates vs. no intervention, and motor control exercise vs. sham. Improved function was associated with mixed exercise vs. usual care, and Pilates vs. no intervention. Temporary increased minor pain was associated with mixed exercise vs. no intervention, and yoga vs. usual care. Little to no difference was found for other comparisons and outcomes. When pooling exercise types, exercise vs. no intervention probably reduces pain in adults (8 RCTs, SMD = − 0.33, 95% CI − 0.58 to − 0.08) and functional limitations in adults and older adults (8 RCTs, SMD = − 0.31, 95% CI − 0.57 to − 0.05) (moderate certainty evidence). Conclusions: With moderate certainty, structured exercise programs probably reduce pain and functional limitations in adults and older people with CPLBP. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate benefits and harms of transcutaneous electrical nerve stimulation (TENS) for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. Methods: We searched for randomized controlled trials (RCTs) from various electronic databases from July 1, 2007 to March 9, 2022. Eligible RCTs targeted TENS compared to placebo/sham, usual care, no intervention, or interventions with isolated TENS effects (i.e., combined TENS with treatment B versus treatment B alone) in adults with CPLBP. We extracted outcomes requested by the WHO Guideline Development Group, appraised the risk of bias, conducted meta-analyses where appropriate, and graded the certainty of evidence using GRADE. Results: Seventeen RCTs (adults, n = 1027; adults ≥ 60 years, n = 28) out of 2010 records and 89 full text RCTs screened were included. The evidence suggested that TENS resulted in a marginal reduction in pain compared to sham (9 RCTs) in the immediate term (2 weeks) (mean difference (MD) = -0.90, 95% confidence interval -1.54 to -0.26), and a reduction in pain catastrophizing in the short term (3 months) with TENS versus no intervention or interventions with TENS specific effects (1 RCT) (MD = -11.20, 95% CI -17.88 to -3.52). For other outcomes, little or no difference was found between TENS and the comparison interventions. The certainty of the evidence for all outcomes was very low. Conclusions: Based on very low certainty evidence, TENS resulted in brief and marginal reductions in pain (not deemed clinically important) and a short-term reduction in pain catastrophizing in adults with CPLBP, while little to no differences were found for other outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate benefits and harms of education/advice for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. Methods: Electronic databases were searched for randomized controlled trials (RCTs) assessing education/advice compared with placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of education/advice could be isolated). We conducted meta-analyses and graded the certainty of evidence. Results: We screened 2514 citations and 86 full text RCTs and included 15 RCTs. Most outcomes were assessed 3 to 6 months post-intervention. Compared with no intervention, education/advice improved pain (10 RCTs, MD = -1.1, 95% CI -1.63 to -0.56), function (10 RCTs, SMD = -0.51, 95% CI -0.89 to -0.12), physical health-related quality of life (HRQoL) (2 RCTs, MD = 24.27, 95% CI 12.93 to 35.61), fear avoidance (5 RCTs, SMD = -1.4, 95% CI -2.51 to -0.29), depression (1 RCT; MD = 2.10, 95% CI 1.05 to 3.15), and self-efficacy (1 RCT; MD = 4.4, 95% CI 2.77 to 6.03). Education/advice conferred less benefit than sham Kinesio taping for improving fear avoidance regarding physical activity (1 RCT, MD = 5.41, 95% CI 0.28 to 10.54). Compared with usual care, education/advice improved pain (1 RCT, MD = -2.10, 95% CI -3.13 to -1.07) and function (1 RCT, MD = -7.80, 95% CI -14.28 to -1.32). There was little or no difference between education/advice and comparisons for other outcomes. For all outcomes, the certainty of evidence was very low. Conclusion: Education/advice in adults with CPLBP was associated with improvements in pain, function, HRQoL, and psychological outcomes, but with very low certainty. [ABSTRACT FROM AUTHOR]

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation. [ABSTRACT FROM AUTHOR]

It is well known that police recorded crime data is susceptible to substantial measurement error. However, despite its limitations, police data is widely used in regression models exploring the causes and effects of crime, which can lead to different types of bias. Here, we introduce a new R package ('rcme': Recounting Crime with Measurement Error) that can be used to facilitate sensitivity assessments of the impact of measurement error in analyses using police recorded crime rates across a wide range of settings. To demonstrate the potential of such sensitivity analysis, we explore the robustness of the effect of collective efficacy on criminal damage across Greater London's neighbourhoods. We show how the crime reduction effect attributed to collective efficacy appears robust, even when most criminal damage incidents are not recorded by the police, and if we accept that under-recording rates are moderately affected by collective efficacy. [ABSTRACT FROM AUTHOR]

Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19) and is influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the genetically diverse Collaborative Cross (CC) founder strains crossed to human ACE2 transgenic mice (K18-hACE2) that confers susceptibility to SARS-CoV-2. Infection of CC x K18-hACE2 resulted in a spectrum of survival, viral replication kinetics, and immune profiles. Importantly, in contrast to the K18-hACE2 model, early type I interferon (IFN-I) and regulated proinflammatory responses were required for control of SARS-CoV-2 replication in PWK x K18-hACE2 mice that were highly resistant to disease. Thus, virus dynamics and inflammation observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding anti-coronavirus immunity. Dynamics of type I interferon (IFN) following infection with SARS-CoV-2 are critical in determining disease severity in humans but have been difficult to model in mice. Here, infection of genetically diverse mice reveals how delayed or immediate IFN signaling coordinates antiviral immunity. [ABSTRACT FROM AUTHOR]

Sparse system identification is the data-driven process of obtaining parsimonious differential equations that describe the evolution of a dynamical system, balancing model complexity and accuracy. There has been rapid innovation in system identification across scientific domains, but there remains a gap in the literature for large-scale methodological comparisons that are evaluated on a variety of dynamical systems. In this work, we systematically benchmark sparse regression variants by utilizing the dysts standardized database of chaotic systems introduced by Gilpin (in: Advances in neural information processing systems (NeurIPS), 2021. arXiv:2110.05266). In particular, we demonstrate how this open-source tool can be used to quantitatively compare different methods of system identification. To illustrate how this benchmark can be utilized, we perform a large comparison of four algorithms for solving the sparse identification of nonlinear dynamics (SINDy) optimization problem, finding strong performance of the original algorithm and a recent mixed-integer discrete algorithm. In all cases, we used ensembling to improve the noise robustness of SINDy and provide statistical comparisons. In addition, we show very compelling evidence that the weak SINDy formulation provides significant improvements over the traditional method, even on clean data. Lastly, we investigate how Pareto-optimal models generated from SINDy algorithms depend on the properties of the equations, finding that the performance shows no significant dependence on a set of dynamical properties that quantify the amount of chaos, scale separation, degree of nonlinearity, and the syntactic complexity. [ABSTRACT FROM AUTHOR]

Pendulums are simple mechanical systems that have been studied for centuries and exhibit many aspects of modern dynamical systems theory. In particular, the double pendulum is a prototypical chaotic system that is frequently used to illustrate a variety of phenomena in nonlinear dynamics. In this work, we explore the existence and implications of codimension-1 invariant manifolds in the double pendulum, which originate from unstable periodic orbits around saddle equilibria and act as separatrices that mediate the global phase space transport. Motivated in part by similar studies on the three-body problem, we are able to draw a direct comparison between the dynamics of the double pendulum and transport in the solar system, which exist on vastly different scales. Thus, the double pendulum may be viewed as a table-top benchmark for chaotic, saddle-mediated transport, with direct relevance to energy-efficient space mission design. The analytical results of this work provide an existence result, concerning arbitrarily long itineraries in phase space, that is applicable to a wide class of two degree of freedom Hamiltonian systems, including the three-body problem and the double pendulum. This manuscript details a variety of periodic orbits corresponding to acrobatic motions of the double pendulum that can be identified and controlled in a laboratory setting. [ABSTRACT FROM AUTHOR]

Asthma is a heterogenous respiratory disease, usually associated with chronic airway inflammation and hyper-responsiveness, which affects an estimated 339 million people worldwide. Severe asthma affects approximately 5–10% of patients with asthma, approximately 17–34 million people globally, more than half of whom have uncontrolled disease. Severe asthma carries a substantial burden of disease, including unpredictable symptoms and potentially life-threatening flare-ups. Furthermore, severe asthma has a substantial burden on health care systems and economies worldwide. In 2018, a group of experts from the clinical community, patient support groups, and professional organisations joined together to develop the Severe Asthma Patient Charter, which set out six principles to define what patients should expect for the management of their severe asthma and what should constitute a basic standard of care. Since the publication of that original Charter in 2018, several important changes have occurred, including an improved understanding of asthma and effective asthma management; several new therapies have become available; and finally, the COVID-19 pandemic has placed a spotlight on respiratory conditions, the workforces that treat them, and the fundamental importance of health care system resilience. With those developments in mind, we, representatives of the academic, clinical, and patient advocacy group communities, have updated the Charter to Improve Patient Care in Severe Asthma with a focus on six principles: (1) I deserve a timely, comprehensive assessment of my asthma and its severity; (2) I deserve a timely, straightforward referral to an appropriate specialist for my asthma when it is not well controlled; (3) I deserve to understand what makes my asthma worse; (4) I deserve access to treatment and care that reduces the impact of asthma on my daily life; (5) I deserve not to be reliant on systemic corticosteroids; (6) I deserve to be involved in decisions about my treatment and care. [ABSTRACT FROM AUTHOR]

Biological invasions are a multi-stage process (i.e., transport, introduction, establishment, spread), with each stage potentially acting as a selective filter on traits associated with invasion success. Behavior (e.g., exploration, activity, boldness) plays a key role in facilitating species introductions, but whether invasion acts as a selective filter on such traits is not well known. Here we capitalize on the well-characterized introduction of an invasive lizard (Lampropholis delicata) across three independent lineages throughout the Pacific, and show that invasion shifted behavioral trait means and reduced among-individual variation—two key predictions of the selective filter hypothesis. Moreover, lizards from all three invasive ranges were also more behaviorally plastic (i.e., greater within-individual variation) than their native range counterparts. We provide support for the importance of selective filtering of behavioral traits in a widespread invasion. Given that invasive species are a leading driver of global biodiversity loss, understanding how invasion selects for specific behaviors is critical for improving predictions of the effects of alien species on invaded communities. Invasive species are a leading driver of global biodiversity loss. Here, the authors show that the process of invasion itself can promote behavioral changes important to the success of widespread invaders, with implications for understanding the effects of alien species on invaded communities. [ABSTRACT FROM AUTHOR]

Background: Malnutrition or its risk affects up to 70% of cancer patients. Compared to adequately nourished oncology patients, those with malnutrition experience more complications and have poorer prognoses, thus higher needs for healthcare. We compared utilization of emergency department (ED) services and costs for Medicare-covered cancer patients with or without a malnutrition diagnosis. Methods: We used the Centers for Medicare & Medicaid Services (CMS) Standard Analytic File to identify fee-for-service beneficiaries who had a cancer diagnosis, and had one or more outpatient claims in 2018. We totaled individual claims and costs for ED visits per beneficiary, then calculated mean per-person claims and costs for malnourished vs non-malnourished patients. Results: Using data from over 2.8 million claims of patients with cancer diagnoses, the prevalence of diagnosed malnutrition was 2.5%. The most common cancer types were genitourinary, hematologic/blood, and breast. Cancer patients with a malnutrition diagnosis, compared to those without, had a significantly higher annual total number of outpatient claims (21.4 vs. 11.5, P<.0001), including a 2.5-fold higher rate of ED visits (1.43 vs. 0.56, p<.0001). As result, such patients incurred more than 2-fold higher mean ED claim costs than did their adequately nourished counterparts ($10,724 vs. $4,935, P<.0001). Conclusions: Our results suggest that malnutrition in cancer patients imposes a high outpatient burden on resource utilization and costs of care in terms of ED use. We propose that nutritional interventions can be used to improve health outcomes for people with cancer and to improve economic outcomes for patients and providers. [ABSTRACT FROM AUTHOR]

Throughout the history of science, physics-based modeling has relied on judiciously approximating observed dynamics as a balance between a few dominant processes. However, this traditional approach is mathematically cumbersome and only applies in asymptotic regimes where there is a strict separation of scales in the physics. Here, we automate and generalize this approach to non-asymptotic regimes by introducing the idea of an equation space, in which different local balances appear as distinct subspace clusters. Unsupervised learning can then automatically identify regions where groups of terms may be neglected. We show that our data-driven balance models successfully delineate dominant balance physics in a much richer class of systems. In particular, this approach uncovers key mechanistic models in turbulence, combustion, nonlinear optics, geophysical fluids, and neuroscience. The dynamics of complex physical systems can be determined by the balance of a few dominant processes. Callaham et al. propose a machine learning approach for the identification of dominant regimes from experimental or numerical data with examples from turbulence, optics, neuroscience, and combustion. [ABSTRACT FROM AUTHOR]

Background: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Objective: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Design: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Participants: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Interventions: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Main Measures: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Key Results: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores.Conclusions: Team-based learning (TBL) is an active learning strategy gaining traction in medical education. However, studies demonstrating successful incorporation into Graduate Medical Education (GME) curricula are limited.To assess the feasibility, acceptability and efficacy of Infectious Disease (ID) TBL sessions within an Internal Medicine (IM) residency curriculum as part of a traditional 60-minute conference.We conducted a prospective cohort study of TBL implementation assessing acceptability and feasibility (Phase 1), and efficacy (Phase 2).Phase 1 included 101 IM residents and eight TBL naïve faculty. Phase 2 included aggregate cohort IM In-Training Exam (ITE) data before (2008-2013) and after (2014-2019) TBL implementation.Eight TBL sessions were delivered once or twice weekly during 60-minute noon conferences.We assessed feasibility by measuring individual Readiness Assurance Test (iRAT) completion rates and inclusion of TBL elements in each session; acceptability through attendance, perceived effectiveness rating and attitudes about TBL; efficacy by comparing ITE data for the overall ID content and specific TBL associated learning objectives.Seventy-five of 93 (80%) residents attended at least one session. All TBL elements were successfully incorporated each session. Of those surveyed, 86% rated the TBL sessions as facilitating their learning “very (4)” or “extremely (5)” well on a 5-point Likert scale (p<0.001). ITE mean percent correct scores of total ID content as well as TBL associated learning objective performance were both significantly higher for the post-TBL cohort among PGY-2 (76.2 vs 62.3; 76.2 vs 62.6) and PGY-3 (73 vs 64.5; 76.2 vs 64.5) IM residents (p<0.05; p<0.001 respectively).Implementing a complete TBL pedagogy within the traditional noontime conference hour in GME is feasible, acceptable to residents and faculty, and associated with improved learning efficacy demonstrated through improved ITE scores. [ABSTRACT FROM AUTHOR]

Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, the mechanistic progression from germline MUTYH mutations to MUTYH-Associated Polyposis (MAP) is incompletely understood. Here, we sequence normal tissue DNAs from 10 individuals with MAP. Somatic base substitution mutation rates in intestinal epithelial cells were elevated 2 to 4-fold in all individuals, except for one showing a 31-fold increase, and were also increased in other tissues. The increased mutation burdens were of multiple mutational signatures characterised by C > A changes. Different mutation rates and signatures between individuals are likely due to different MUTYH mutations or additional inherited mutations in other BER pathway genes. The elevated base substitution rate in normal cells likely accounts for the predisposition to neoplasia in MAP. Despite ubiquitously elevated mutation rates, individuals with MAP do not display overt evidence of premature ageing. Thus, accumulation of somatic mutations may not be sufficient to cause the global organismal functional decline of ageing. Inherited mutations in MUTYH have been shown to predispose patients to colorectal cancers. Here, the authors show that MUTYH mutations lead to an increased somatic base substitution mutation rate in normal intestinal epithelial cells, which is the likely cause for the increased cancer risk. [ABSTRACT FROM AUTHOR]

Animals and plants trick others in an extraordinary diversity of ways to gain fitness benefits. Mimicry and deception can, for example, lure prey, reduce the costs of parental care or aid in pollination–in ways that impose fitness costs on the exploited party. The evolutionary maintenance of such asymmetric relationships often relies on these costs being mitigated through counter-adaptations, low encounter rates, or indirect fitness benefits. However, these mechanisms do not always explain the evolutionary persistence of some classic deceptive interactions. Sexually deceptive pollination (in which plants trick male pollinators into mating with their flowers) has evolved multiple times independently, mainly in the southern hemisphere and especially in Australasia and Central and South America. This trickery imposes considerable costs on the males: they miss out on mating opportunities, and in some cases, waste their limited sperm on the flower. These relationships appear stable, yet in some cases there is little evidence suggesting that their persistence relies on counter-adaptations, low encounter rates, or indirect fitness benefits. So, how might these relationships persist? Here, we introduce and explore an additional hypothesis from systems biology: that some species are robust to exploitation. Robustness arises from a species' innate traits and means they are robust against costs of exploitation. This allows species to persist where a population without those traits would not, making them ideal candidates for exploitation. We propose that this mechanism may help inform new research approaches and provide insight into how exploited species might persist. [ABSTRACT FROM AUTHOR]

In addition to central functions in cell adhesion signalling, integrin-associated proteins have wider roles at sites distal to adhesion receptors. In experimentally defined adhesomes, we noticed that there is clear enrichment of proteins that localise to the nucleus, and conversely, we now report that nuclear proteomes contain a class of adhesome components that localise to the nucleus. We here define a nucleo-adhesome, providing experimental evidence for a remarkable scale of nuclear localisation of adhesion proteins, establishing a framework for interrogating nuclear adhesion protein functions. Adding to nuclear FAK's known roles in regulating transcription, we now show that nuclear FAK regulates expression of many adhesion-related proteins that localise to the nucleus and that nuclear FAK binds to the adhesome component and nuclear protein Hic-5. FAK and Hic-5 work together in the nucleus, co-regulating a subset of genes transcriptionally. We demonstrate the principle that there are subcomplexes of nuclear adhesion proteins that cooperate to control transcription. Cell adhesion proteins have been described at sites away from the cell surface, including in the nucleus. Here, the authors report the scale of nuclear localisation of adhesion proteins, establishing a nucleo-adhesome and showing that nuclear adhesion proteins can cooperate to control transcription. [ABSTRACT FROM AUTHOR]

Understanding the neural basis of human movement in naturalistic scenarios is critical for expanding neuroscience research beyond constrained laboratory paradigms. Here, we describe our Annotated Joints in Long-term Electrocorticography for 12 human participants (AJILE12) dataset, the largest human neurobehavioral dataset that is publicly available; the dataset was recorded opportunistically during passive clinical epilepsy monitoring. AJILE12 includes synchronized intracranial neural recordings and upper body pose trajectories across 55 semi-continuous days of naturalistic movements, along with relevant metadata, including thousands of wrist movement events and annotated behavioral states. Neural recordings are available at 500 Hz from at least 64 electrodes per participant, for a total of 1280 hours. Pose trajectories at 9 upper-body keypoints were estimated from 118 million video frames. To facilitate data exploration and reuse, we have shared AJILE12 on The DANDI Archive in the Neurodata Without Borders (NWB) data standard and developed a browser-based dashboard. Measurement(s) Brain activity measurement • Body Position • Behavior labels • Brain electrode locations Technology Type(s) Electrocorticography • Video Recording Sample Characteristic - Organism Homo sapiens Sample Characteristic - Environment hospital Sample Characteristic - Location Harborview Medical Center [ABSTRACT FROM AUTHOR]

Data-driven modeling continues to be enabled by modern machine learning algorithms and deep learning architectures. The goals of such efforts revolve around the generation of models for prediction, characterization, and control of complex systems. In the context of physics and engineering, extrapolation and generalization are critical aspects of model discovery that are empowered by various aspects of parsimony. Parsimony can be encoded (i) in a low-dimensional coordinate system, (ii) in the representation of governing equations, or (iii) in the representation of parametric dependencies. In what follows, we illustrate techniques that leverage parsimony in deep learning to build physics-based models, culminating in a deep learning architecture that is parsimonious in coordinates and also in representing the dynamics and their parametric dependence through a simple normal form. Ultimately, we argue that promoting parsimony in machine learning results in more physical models, i.e., models that generalize and are parametrically represented by governing equations. [ABSTRACT FROM AUTHOR]

This paper provides a short overview of how to use machine learning to build data-driven models in fluid mechanics. The process of machine learning is broken down into five stages: (1) formulating a problem to model, (2) collecting and curating training data to inform the model, (3) choosing an architecture with which to represent the model, (4) designing a loss function to assess the performance of the model, and (5) selecting and implementing an optimization algorithm to train the model. At each stage, we discuss how prior physical knowledge may be embedding into the process, with specific examples from the field of fluid mechanics. [ABSTRACT FROM AUTHOR]

Boundary value problems (BVPs) play a central role in the mathematical analysis of constrained physical systems subjected to external forces. Consequently, BVPs frequently emerge in nearly every engineering discipline and span problem domains including fluid mechanics, electromagnetics, quantum mechanics, and elasticity. The fundamental solution, or Green's function, is a leading method for solving linear BVPs that enables facile computation of new solutions to systems under any external forcing. However, fundamental Green's function solutions for nonlinear BVPs are not feasible since linear superposition no longer holds. In this work, we propose a flexible deep learning approach to solve nonlinear BVPs using a dual-autoencoder architecture. The autoencoders discover an invertible coordinate transform that linearizes the nonlinear BVP and identifies both a linear operator L and Green's function G which can be used to solve new nonlinear BVPs. We find that the method succeeds on a variety of nonlinear systems including nonlinear Helmholtz and Sturm–Liouville problems, nonlinear elasticity, and a 2D nonlinear Poisson equation and can solve nonlinear BVPs at orders of magnitude faster than traditional methods without the need for an initial guess. The method merges the strengths of the universal approximation capabilities of deep learning with the physics knowledge of Green's functions to yield a flexible tool for identifying fundamental solutions to a variety of nonlinear systems. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 and its variants continue to infect hundreds of thousands every day despite the rollout of effective vaccines. Therefore, it is essential to understand the levels of protection that these vaccines provide in the face of emerging variants. Here, we report two demographically balanced cohorts of BNT162b2 vaccine recipients and COVID-19 patients, from which we evaluate neutralizing antibody titers against SARS-CoV-2 as well as the B.1.1.7 (alpha) and B.1.351 (beta) variants. We show that both B.1.1.7 and B.1.351 are less well neutralized by serum from vaccinated individuals, and that B.1.351, but not B.1.1.7, is less well neutralized by convalescent serum. We also find that the levels of variant-specific anti-spike antibodies are proportional to neutralizing activities. Together, our results demonstrate the escape of the emerging SARS-CoV-2 variants from neutralization by serum antibodies, which may lead to reduced protection from re-infection or increased risk of vaccine breakthrough. Here, the authors show that neutralization of human sera from both BNT162b2 vaccine recipients and from convalescent COVID-19 patients is less efficient against SARS- CoV-2 variants B.1.1.7 and B.1.351 and negatively associated with patient age. [ABSTRACT FROM AUTHOR]

Deception has evolved in a range of taxa. When deception imposes costs, yet persists over generations, exploited species typically have traits to help them bear or minimise costs. The sexually deceptive orchids, Cryptostylis spp., are pollinated by tricking male haplodiploid wasps (Lissopimpla excelsa) into mating with flowers, which offer no reward and often elicit sperm wastage. We hypothesise that by attracting haplodiploid species, orchids have a pollinator ideally suited to withstand the costs of sexual deception—and a selective advantage compared to other orchids. Haplodiploid females can reproduce with or without sperm—albeit when spermless, females can only have sons. Through orchid deception and sperm wastage, deceived haplodiploid populations could become male biased, providing enough males to share between orchids and females. In this way, pollinator populations can persist despite high densities of sexually deceptive orchids. Here, we aim to broadly test this prediction using museum and digital records of the pollinator, L. excelsa, from sites with or without orchids. For robustness, we also analyse the sex ratio of a sister ichneumonid species that occurs in the same areas but is not deceived by orchids. We found that at sites with orchids, L. excelsa was significantly more male biased than at sites without orchids and significantly more male biased than the sister ichneumonid. This survey is the first to test the population-level effects of sexually deceptive orchids on their pollinator. It supports our prediction that orchid deception can drive male-biased sex ratios in exploited pollinators. [ABSTRACT FROM AUTHOR]

Objectives: Test whether cooperation with the police can be modelled as a place-based norm that varies in strength from one neighborhood to the next. Estimate whether perceived police legitimacy predicts an individual's willingness to cooperate in weak-norm neighborhoods, but not in strong-norm neighborhoods where most people are either willing or unwilling to cooperate, irrespective of their perceptions of police legitimacy. Methods: A survey of 1057 individuals in 98 relatively high-crime English neighborhoods defined at a small spatial scale measured (a) willingness to cooperate using a hypothetical crime vignette and (b) legitimacy using indicators of normative alignment between police and citizen values. A mixed-effects, location-scale model estimated the cluster-level mean and cluster-level variance of willingness to cooperate as a neighborhood-level latent variable. A cross-level interaction tested whether legitimacy predicts individual-level willingness to cooperate only in neighborhoods where the norm is weak. Results: Willingness to cooperate clustered strongly by neighborhood. There were neighborhoods with (1) high mean and low variance, (2) high mean and high variance, (3) (relatively) low mean and low variance, and (4) (relatively) low mean and high variance. Legitimacy was only a positive predictor of cooperation in neighborhoods that had a (relatively) low mean and high variance. There was little variance left to explain in neighborhoods where the norm was strong. Conclusions: Findings support a boundary condition of procedural justice theory: namely, that cooperation can be modelled as a place-based norm that varies in strength from neighborhood to neighborhood and that legitimacy only predicts an individual's willingness to cooperate in neighborhoods where the norm is relatively weak. [ABSTRACT FROM AUTHOR]

Background: Managing patient radiation dose in pediatric computed tomography (CT) examinations is essential. Some organizations, most notably Image Gently, have suggested techniques to lower dose to pediatric patients and mitigate risk while maintaining image quality. Objective: We sought to validate whether institutions are observing Image Gently guidelines in practice. Materials and methods: Dose-relevant data from 663,417 abdomen-pelvis and chest CT scans were obtained from 53 facilities. Patients were assigned arbitrary age cohorts with a minimum size of n=12 patients in each age group, for statistical purposes. All pediatric (<19 years old) cohorts at a given facility were compared to the adult cohort by a Kruskal-Wallis test for each of the four scan parameters — (1) x-ray tube kilovoltage (kV), (2) tube-current-by-exposure-time product (tube mAs), (3) scan pitch and (4) tube rotation time — to assess whether the distribution of values in the pediatric cohorts differed from the adult cohort. The same was repeated with volume CT dose index (CTDIvol) and size-specific dose estimate (SSDE) to assess whether pediatric cohorts received less dose than adult cohorts. A P-value of <0.05 was deemed significant. Results: Across the 150 pediatric cohorts, 134 had scan parameters that were more child-sized than their adult counterparts. In 128 of these 134 pediatric cohorts, the CTDIvol was less than the adult counterpart. In 111 of these 128 pediatric cohorts, the SSDE was less than the adult counterpart. Conclusion: The study reaffirms that in practice, Image Gently's suggestions of lowering tube mAs and peak kilovoltage are commonly employed and effective at reducing pediatric CT dose. [ABSTRACT FROM AUTHOR]

Many animals have sensory biases towards signals or cues that typically provide some fitness benefit. Sensory traps occur when other species or anthropogenic sources produce similar signals or cues but responding is no longer adaptive and can impose significant costs or even death. Bycatch of seabirds by fishing boats has devastating impacts, causing hundreds of thousands of seabird deaths per annum. Here, we explore whether fishing vessels are acting as a sensory trap, inadvertently targeting seabirds with certain life-history traits or larger skeletal or sensory structures. We surveyed the literature to compare seabird order, diet, wingspan, body size, and nesting preference (surface or burrow) of 70 seabirds with varying numbers of reported bycatch in one of the world's most important regions for seabird breeding, in northern Aotearoa New Zealand. We also examined the skeletal and sensory measurements of six seabirds that co-occur spatially in this region, but have different numbers of reported bycatch and indices of bycatch risk. The literature survey revealed that the Charadriiformes and the Sphenisciformes were the most vulnerable groups (p = 0.01), especially to surface longline fisheries. There were no correlations with diet and foraging behaviour, but surface nesting seabirds and those with larger bodies and wingspans were at a greater risk of becoming bycatch. Skeletal measurements show that species with higher bycatch also have relatively larger skulls, bills and wings, eye sockets and nostrils (relative to body size) (p < 0.05). This suggests that having a larger overall body size and longer protruding body parts is a primary risk factor, but that species with relatively more sensitive sensory systems likely have even more acute bycatch risk. Considering fishing vessels as sensory traps provides a context to explore the multiple interconnecting factors of sensory sensitivity, sensory bias, behaviour and morphology. [ABSTRACT FROM AUTHOR]