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This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Wiley., 1. Supervised learning of behavioral modes from body-acceleration data has become a widely used research tool in Behavioral Ecology over the past decade. One of the primary usages of this tool is to estimate behavioral time budgets from the distribution of behaviors as predicted by the model. These serve as the key parameters to test predictions about the variation in animal behavior. In this paper we show that the widespread computation of behavioral time budgets is biased, due to ignoring the classification model confusion probabilities. 2. Next, we introduce the confusion matrix correction for time budgets - a simple correction method for adjusting the computed time budgets based on the model's confusion matrix. 3. Finally, we show that the proposed correction is able to eliminate the bias, both theoretically and empirically in a series of data simulations on body acceleration data of a fossorial rodent species (Damaraland mole-rat, Fukomys damarensis). 4. Our paper provides a simple implementation of the confusion matrix correction for time budgets, and we encourage researchers to use it to improve accuracy of behavioral time budget calculations.

Metabarcoding of DNA extracted from environmental or bulk specimen samples is increasingly used to profile biota in basic and applied biodiversity research because of its targeted nature that allows sequencing of genetic markers from many samples in parallel. To achieve this, PCR amplification is carried out with primers designed to target a taxonomically informative marker within a taxonomic group, and sample-specific nucleotide identifiers are added to the amplicons prior to sequencing. The latter enables assignment of the sequences back to the samples they originated from. Nucleotide identifiers can be added during the metabarcoding PCR and during "library preparation", that is, when amplicons are prepared for sequencing. Different strategies to achieve this labelling exist. All have advantages, challenges and limitations, some of which can lead to misleading results, and in the worst case compromise the fidelity of the metabarcoding data. Given the range of questions addressed using metabarcoding, ensuring that data generation is robust and fit for the chosen purpose is critically important for practitioners seeking to employ metabarcoding for biodiversity assessments. Here, we present an overview of the three main workflows for sample-specific labelling and library preparation in metabarcoding studies on Illumina sequencing platforms; one-step PCR, two-step PCR, and tagged PCR. Further, we distill the key considerations for researchers seeking to select an appropriate metabarcoding strategy for their specific study. Ultimately, by gaining insights into the consequences of different metabarcoding workflows, we hope to further consolidate the power of metabarcoding as a tool to assess biodiversity across a range of applications., Molecular Ecology Resources, 22 (4), ISSN:1755-098X, ISSN:1471-8278, ISSN:1755-0998, ISSN:1471-8286

Organic solar cells (OSCs) have recently shown a rapid improvement in their performance, bringing power conversion efficiencies to above 18%. However, the open‐circuit voltage of OSCs remains low relative to their optical gap and this currently limits efficiency. Recombination to spin‐triplet excitons is a key contributing factor, and is widely, but not universally, observed in donor–acceptor blends using both fullerene and nonfullerenes as electron acceptors. Here, an experimental framework that combines time‐resolved optical and magnetic resonance spectroscopies to detect triplet excitons and identify their formation mechanisms, is reported. The methodology is applied to two well‐studied polymer:fullerene systems, PM6:PC60BM and PTB7‐Th:PC60BM. In contrast to the more efficient nonfullerene acceptor systems that show only triplet states formed via nongeminate recombination, the fullerene systems also show significant triplet formation via geminate processes. This requires that geminate electron–hole pairs be trapped long enough to allow intersystem crossing. It is proposed that this is a general feature of fullerene acceptor systems, where isolated fullerenes are known to intercalate within the alkyl sidechains of the donor polymers. Thus, the study demonstrates that engineering good donor and acceptor domain purity is key for suppressing losses via triplet excitons in OSCs.

For better or worse, digital technologies are reshaping everything we know, from customer behaviour and expectations to organizational and manufacturing systems, business models, markets, and ultimately society as a whole. To understand this overarching transformation, this paper extends the previous literature, which has focused mostly on the organizational level, by developing a multi-level research agenda for digital transformation (DT). In this regard, we propose an extended definition of DT as a socioeconomic change across individuals, organizations, ecosystems, and societies that is shaped by the adoption and utilization of digital technologies. We propose four lenses to interpret the DT phenomenon: individuals (utilizing and adopting digital technologies), organizations (strategizing and coordinating both internal and external transformation), ecosystems (harnessing digital technologies in governance and co-producing value propositions), and geopolitical frameworks (regulating the environments in which individuals and organizations are embedded). Based on these lenses, we build a multi-level research agenda at the intersection between the bright and dark sides of DT and propose the PIAI framework, which captures a process of perception, interpretation, and action that ultimately leads to the possible impact of intended and unintended consequences for the socioeconomic infrastructure. The PIAI framework identifies a research agenda consisting of a non-exhaustive list of topics that can assist researchers to deepen their understanding of the DT phenomenon and provide guidance to managers and policymakers when making strategic decisions that seek to shape and guide the DT.

This study combines the microstructural and petrological analysis of garnet and its inclusions in quartzite‐hosted garnetite from the ultrahigh‐pressure Lago di Cignana metaophiolite (Western Alps). We present a comprehensive record of metamorphism, compaction, and the state of stress during interaction between oceanic metasediments and infiltrating fluids along a major open‐system fluid pathway. The arrangement of garnet into garnetite layers is attributed to concomitant compaction and dissolution that resulted in the formation of a garnet stylolite. The fluid pulses that were accommodated by this pathway subsequently resulted in several stages of garnet deformation, dissolution, local reprecipitation, and recrystallization. Abundant evidence for pressure solution in garnet, alongside near‐hydrostatic to hydrostatic conditions indicated by elastic strains of quartz inclusions in garnet obtained through Raman spectroscopy, support low differential stresses during fluid–rock interaction. The high degree of dissolution recorded by the garnetite showcases the strong potential for compaction by fluid‐assisted volume loss and mass transfer. Dehydration of subducting rocks with subsequent migration of resulting fluids through the slab provides a mechanism of mass transfer and has the potential to drive compaction and exert control on differential stress along fluid pathways.

The popularity of polyhedral oligomeric silsesquioxanes (POSS) for use in hybrid organic–inorganic materials and devices has grown in the past two decades due to desirable properties such as good thermal stability and biocompatibility, as well as their potential to be functionalized for a wide range of applications, from polymer composites to optoelectronics. Herein, the role of POSS for photonic applications, including sensing, bioimaging, and optoelectronic devices, is summarized. Functionalized POSS building blocks commonly incorporated with luminescent materials are identified, and areas of potential growth within the field are discussed. The addition of POSS to light‐emitting materials is widely shown to prevent aggregation in organic lumophores and inorganic nanocrystals, leading to reduced photoluminescence quenching. The POSS unit is also capable of acting as a passivating agent for nanocrystals and thin films, improving the emission quantum yields of photoluminescent materials and devices. POSS therefore offers the potential to enhance both the functional and photonic properties of cutting‐edge hybrid technologies.

Data Availability Statement: All data are included in the Supporting Information for publication online. Supporting Information is available online at https://setac.onlinelibrary.wiley.com/doi/10.1002/etc.5620#support-information-section . Copyright © 2023 Crown copyright and The Authors. While chemicals are vital to modern society through materials, agriculture, textiles, new technology, medicines, and consumer goods, their use is not without risks. Unfortunately, our resources seem inadequate to address the breadth of chemical challenges to the environment and human health. Therefore, it is important we use our intelligence and knowledge wisely to prepare for what lies ahead. The present study used a Delphi-style approach to horizon-scan future chemical threats that need to be considered in the setting of chemicals and environmental policy, which involved a multidisciplinary, multisectoral, and multinational panel of 25 scientists and practitioners (mainly from the United Kingdom, Europe, and other industrialized nations) in a three-stage process. Fifteen issues were shortlisted (from a nominated list of 48), considered by the panel to hold global relevance. The issues span from the need for new chemical manufacturing (including transitioning to non-fossil-fuel feedstocks); challenges from novel materials, food imports, landfills, and tire wear; and opportunities from artificial intelligence, greater data transparency, and the weight-of-evidence approach. The 15 issues can be divided into three classes: new perspectives on historic but insufficiently appreciated chemicals/issues, new or relatively new products and their associated industries, and thinking through approaches we can use to meet these challenges. Chemicals are one threat among many that influence the environment and human health, and interlinkages with wider issues such as climate change and how we mitigate these were clear in this exercise. The horizon scan highlights the value of thinking broadly and consulting widely, considering systems approaches to ensure that interventions appreciate synergies and avoid harmful trade-offs in other areas. We recommend further collaboration between researchers, industry, regulators, and policymakers to perform horizon scanning to inform policymaking, to develop our ability to meet these challenges, and especially to extend the approach to consider also concerns from countries with developing economies. Environ Toxicol Chem 2023;00:1–17. © 2023 Crown copyright and The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article is published with the permission of the Controller of HMSO and the King's Printer for Scotland. Department for Environment, Food and Rural Affairs

Scientists traditionally use passive stimulation to examine the organisation of primary somatosensory cortex (SI). However, given the close, bidirectional relationship between the somatosensory and motor systems, active paradigms involving free movement may uncover alternative SI representational motifs. Here, we used 7 Tesla functional magnetic resonance imaging to compare hallmark features of SI digit representation between active and passive tasks which were unmatched on task or stimulus properties. The spatial location of digit maps, somatotopic organisation, and inter-digit representational structure were largely consistent between tasks, indicating representational consistency. We also observed some task differences. The active task produced higher univariate activity and multivariate representational information content (inter-digit distances). The passive task showed a trend towards greater selectivity for digits versus their neighbours. Our findings highlight that, while the gross features of SI functional organisation are task invariant, it is important to also consider motor contributions to digit representation.

Protecting important sites is a key strategy for halting the loss of biodiversity. However, our understanding of the relationship between management inputs and biodiversity outcomes in protected areas (PAs) remains weak. Here, we examine biodiversity outcomes using species population trends in PAs derived from the Living Planet Database in relation to management data derived from the Management Effectiveness Tracking Tool (METT) database for 217 population time-series from 73 PAs. We found a positive relationship between our METT-based scores for Capacity and Resources and changes in vertebrate abundance, consistent with the hypothesis that PAs require adequate resourcing to halt biodiversity loss. Additionally, PA age was negatively correlated with trends for the mammal subsets and PA size negatively correlated with population trends in the global subset. Our study highlights the paucity of appropriate data for rigorous testing of the role of management in maintaining species populations across multiple sites, and describes ways to improve our understanding of PA performance.

Longitudinal observational data on patients can be used to investigate causal effects of time-varying treatments on time-to-event outcomes. Several methods have been developed for estimating such effects by controlling for the time-dependent confounding that typically occurs. The most commonly used is marginal structural models (MSM) estimated using inverse probability of treatment weights (IPTW) (MSM-IPTW). An alternative, the sequential trials approach, is increasingly popular, and involves creating a sequence of "trials" from new time origins and comparing treatment initiators and non-initiators. Individuals are censored when they deviate from their treatment assignment at the start of each "trial" (initiator or noninitiator), which is accounted for using inverse probability of censoring weights. The analysis uses data combined across trials. We show that the sequential trials approach can estimate the parameters of a particular MSM. The causal estimand that we focus on is the marginal risk difference between the sustained treatment strategies of "always treat" vs "never treat." We compare how the sequential trials approach and MSM-IPTW estimate this estimand, and discuss their assumptions and how data are used differently. The performance of the two approaches is compared in a simulation study. The sequential trials approach, which tends to involve less extreme weights than MSM-IPTW, results in greater efficiency for estimating the marginal risk difference at most follow-up times, but this can, in certain scenarios, be reversed at later time points and relies on modelling assumptions. We apply the methods to longitudinal observational data from the UK Cystic Fibrosis Registry to estimate the effect of dornase alfa on survival.

Funder: Georges and Antoine Claraz Foundation grant, Funder: University Research Priority Program “Evolution in Action” of the University of Zurich, Land plants comprise two large monophyletic lineages, the vascular plants and the bryophytes, which diverged from their most recent common ancestor approximately 480 million years ago. Of the three lineages of bryophytes, only the mosses and the liverworts are systematically investigated, while the hornworts are understudied. Despite their importance for understanding fundamental questions of land plant evolution, they only recently became amenable to experimental investigation, with Anthoceros agrestis being developed as a hornwort model system. Availability of a high-quality genome assembly and a recently developed genetic transformation technique makes A. agrestis an attractive model species for hornworts. Here we describe an updated and optimized transformation protocol for A. agrestis, which can be successfully used to genetically modify one more strain of A. agrestis and three more hornwort species, Anthoceros punctatus, Leiosporoceros dussii, and Phaeoceros carolinianus. The new transformation method is less laborious, faster, and results in the generation of greatly increased numbers of transformants compared with the previous method. We have also developed a new selection marker for transformation. Finally, we report the development of a set of different cellular localization signal peptides for hornworts providing new tools to better understand the hornwort cell biology.

INTRODUCTION: A range of nonpharmaceutical public health interventions has been introduced in many countries following the rapid spread of Covid-19 since 2020, including recommendations or mandates for the use of face masks or coverings in the community. While the effectiveness of face masks in reducing Covid-19 transmission has been extensively discussed, scant attention has been paid to the lived experience of those wearing face masks. METHOD: Drawing on 40 narrative interviews with a purposive sample of people in the United Kingdom, with a particular focus on marginalised and minoritized groups, our paper explores experiences of face mask use during the pandemic. RESULTS: We find that face masks have a range of societal, health and safety impacts, and prompted positive and negative emotional responses for users. We map our findings onto Lorenc and Oliver's framework for intervention risks. We suggest that qualitative data offer particular insights into the experiences of public health interventions, allowing the potential downsides and risks of interventions to be more fully considered and informing public health policies that might avoid inadvertent harm, particularly towards marginalised groups. PATIENT OR PUBLIC CONTRIBUTION: The study primarily involved members of the public in the conduct of the research, namely through participation in interviews (email and telephone). The conception for the study involved extensive discussions on social media with a range of people, and we received input and ideas from presentations we delivered on the preliminary analysis.

Funder: Aarhus Universitets Forskningsfond; Id: http://dx.doi.org/10.13039/501100002739, Funder: Health Data Research UK; Id: http://dx.doi.org/10.13039/501100023699, Funder: Jabbs Foundation; Id: http://dx.doi.org/10.13039/501100016132, Funder: National Institute of Health Research Biomedical Research Centre, Interoception is the sensation, perception, and integration of signals from within the body. It has been associated with a broad range of physiological and psychological processes. Further, interoceptive variables are related to specific regions and networks in the human brain. However, it is not clear whether or how these networks relate empirically to different domains of physiological and psychological health at the population level. We analysed a data set of 19,020 individuals (10,055 females, 8965 males; mean age: 63 years, age range: 45-81 years), who have participated in the UK Biobank Study, a very large-scale prospective epidemiological health study. Using canonical correlation analysis (CCA), allowing for the examination of associations between two sets of variables, we related the functional connectome of brain regions implicated in interoception to a selection of nonimaging health and lifestyle related phenotypes, exploring their relationship within modes of population co-variation. In one integrated and data driven analysis, we obtained four statistically significant modes. Modes could be categorised into domains of arousal and affect and cardiovascular health, respiratory health, body mass, and subjective health (all p < .0001) and were meaningfully associated with distinct neural circuits. Circuits represent specific neural "fingerprints" of functional domains and set the scope for future studies on the neurobiology of interoceptive involvement in different lifestyle and health-related phenotypes. Therefore, our research contributes to the conceptualisation of interoception and may lead to a better understanding of co-morbid conditions in the light of shared interoceptive structures.

Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Fonds de Recherche du Québec ‐ Santé, Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024, Funder: NIHR Rare Diseases Translational Research Collaboration, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

We study the Turán number of long cycles in random and pseudo‐random graphs. Denote by ex ( G ( n , p ) , H ) $\operatorname{ex}(G(n,p),H)$ the random variable counting the number of edges in a largest subgraph of G ( n , p ) $G(n,p)$ without a copy of H $H$ . We determine the asymptotic value of ex ( G ( n , p ) , C t ) $\operatorname{ex}(G(n,p), C_t)$ , where C t $C_t$ is a cycle of length t $t$ , for p ⩾ C n $p\geqslant \frac{C}{n}$ and A log n ⩽ t ⩽ ( 1 − ε ) n $A \log n \leqslant t \leqslant (1 - \varepsilon )n$ . The typical behaviour of ex ( G ( n , p ) , C t ) $\operatorname{ex}(G(n,p), C_t)$ depends substantially on the parity of t $t$ . In particular, our results match the classical result of Woodall on the Turán number of long cycles, and can be seen as its random version, showing that the transference principle holds here as well. In fact, our techniques apply in a more general sparse pseudo‐random setting. We also prove a robustness‐type result, showing the likely existence of cycles of prescribed lengths in a random subgraph of a graph with a nearly optimal density. Finally, we also present further applications of our main tool (the Key Lemma) for proving results on Ramsey‐type problems about cycles in sparse random graphs.

This essay focuses on the work of New York‐based artist and poet Candace Hill‐Montgomery. In 1979, Hill‐Montgomery described her work as changing ‘the containment we all live within’, pointing both to the social and political investments of her practice, and to her formal transition from making art in her studio to making installations in public, often from found materials and detritus. Her desire for recognition and understanding across difference at a moment of rising neo‐conservatism was an investment in social and subjective repair. I trace this impulse across ‘environmental sculptures’, collages and artist's books made between 1979 and 1983, articulating a general impetus to be against containment that, I argue, is also instructive as an art‐historical method.

We explore models for the natural history of breast cancer, where the main events of interest are the start of asymptomatic detectability of the disease (through screening) and the time of symptomatic detection (through symptoms). We develop several parametric specifications based on a cure rate structure, and present the results of the analysis of data collected as part of a motivating study from Milan. Participants in the study were part of a regional breast cancer screening program, and their ten-year trajectories were obtained from administrative data available from the Italian national health care system. We first present a tractable model for which we develop the likelihood contributions of the observed trajectories and perform maximum likelihood inference on the latent process. Likelihood based inference is not feasible for more flexible models, and we implement approximate Bayesian computation (ABC) for inference. Issues that arise from the use of ABC for model choice and parameter estimation are discussed, including the problem of choosing appropriate summary statistics. The estimated parameters of the underlying disease process allow for the study of the effect of different examination schedules (age range and frequency of screening examinations) on a population of asymptomatic subjects.

BACKGROUND: Children with neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often experience sleep disturbances, but little is known about when these sleep differences emerge and how they relate to later development. METHODS: We used a prospective longitudinal design in infants with a family history of ASD and/or ADHD to examine infant sleep and its relation to trajectories of attention and later neurodevelopmental disorders. We formed factors of Day and Night Sleep from parent-reported measures (including day/night sleep duration, number of naps in the day, frequency of night awakenings and sleep onset problems). We examined sleep in 164 infants at 5-, 10- and 14-months with/without a first-degree relative with ASD and/or ADHD who underwent a consensus clinical assessment for ASD at age 3. RESULTS: By 14-months, infants with a first-degree relative with ASD (but not ADHD) showed lower Night Sleep scores than infants with no family history of ASD; lower Night Sleep scores in infancy were also associated with a later ASD diagnosis, decreased cognitive ability, increased ASD symptomatology at 3-years, and developing social attention (e.g., looking to faces). We found no such effects with Day Sleep. CONCLUSIONS: Sleep disturbances may be apparent at night from 14-months in infants with a family history of ASD and also those with later ASD, but were not associated with a family history of ADHD. Infant sleep disturbances were also linked to later dimensional variation in cognitive and social skills across the cohort. Night Sleep and Social Attention were interrelated over the first 2 years of life, suggesting that this may be one mechanism through which sleep quality influences neurodevelopment. Interventions targeted towards supporting families with their infant's sleep problems may be useful in this population.

Funder: Cambridge Trust (University of Cambridge); Id: http://dx.doi.org/10.13039/501100000735, Funder: National Institute for Health Research (NIHR) Biomedical Research Centre at South London, Funder: Maudsley NHS Foundation Trust and King's College London, Funder: Medical Research Foundation; Id: http://dx.doi.org/10.13039/501100009187, Funder: Mission Interministérielle de Lutte‐contre‐les‐Drogues‐et‐les‐Conduites‐Addictives (MILDECA), Funder: Assistance‐Publique‐Hôpitaux‐de‐Paris and INSERM, Funder: Paris Sud University IDEX 2012, Funder: Fédération pour la Recherche sur le Cerveau; Id: http://dx.doi.org/10.13039/501100006424, BACKGROUND: Stress exposure in childhood and adolescence has been linked to reductions in cortical structures and cognitive functioning. However, to date, most of these studies have been cross-sectional, limiting the ability to make long-term inferences, given that most cortical structures continue to develop through adolescence. METHODS: Here, we used a subset of the IMAGEN population cohort sample (N = 502; assessment ages: 14, 19, and 22 years; mean age: 21.945 years; SD = 0.610) to understand longitudinally the long-term interrelations between stress, cortical development, and cognitive functioning. To these ends, we first used a latent change score model to examine four bivariate relations - assessing individual differences in change in the relations between adolescent stress exposure and volume, surface area, and cortical thickness of cortical structures, as well as cognitive outcomes. Second, we probed for indirect neurocognitive effects linking stress to cortical brain structures and cognitive functions using rich longitudinal mediation modeling. RESULTS: Latent change score modeling showed that greater baseline adolescence stress at age 14 predicted a small reduction in the right anterior cingulate volume (Std. β = -.327, p = .042, 95% CI [-0.643, -0.012]) and right anterior cingulate surface area (Std. β = -.274, p = .038, 95% CI [-0.533, -0.015]) across ages 14-22. These effects were very modest in nature and became nonsignificant after correcting for multiple comparisons. Our longitudinal analyses found no evidence of indirect effects in the two neurocognitive pathways linking adolescent stress to brain and cognitive outcomes. CONCLUSION: Findings shed light on the impact of stress on brain reductions, particularly in the prefrontal cortex that have consistently been implicated in the previous cross-sectional studies. However, the magnitude of effects observed in our study is smaller than that has been reported in past cross-sectional work. This suggests that the potential impact of stress during adolescence on brain structures may likely be more modest than previously noted.

What caused the recovery from the British Great Depression? A leading explanation – the ‘expectations channel’ – suggests that a shift in expected inflation lowered real interest rates and stimulated consumption and investment. However, few studies have measured, or tested the economic consequences of, inflation expectations. In this paper, we collect high‐frequency information from primary and secondary sources to measure expected inflation in the United Kingdom between the wars. A high‐frequency vector autoregression suggests that inflation expectations were an important source of the early stages of economic recovery in interwar Britain.

We investigate the cross‐section asset‐pricing patterns of major cryptocurrencies from 2017 to 2021. We show that the basis, momentum, and basis–momentum factors earn statistically significant excess returns, a result consistent with the findings reported in the commodity futures literature. The basis is the strongest signal predicting cross‐sectional differences in cryptocurrency futures returns; the momentum‐induced risk premium is not statistically powerful, whereas the basis momentum‐induced risk premium disappears when accounting for the basis‐induced risk premium. Daily factor returns are statistically much stronger than weekly factor returns. Monthly factor returns are nonsignificant.

Persistent symptoms in patients treated for hypothyroidism are common. Despite more than 20 years of debate, the use of liothyronine for this indication remains controversial, as numerous randomised trials have failed to show a benefit of treatment regimens that combine liothyronine (T3) with levothyroxine over levothyroxine monotherapy. This consensus statement attempts to provide practical guidance to clinicians faced with patients who have persistent symptoms during thyroid hormone replacement therapy. It applies to non-pregnant adults and is focussed on care delivered within the UK National Health Service, although it may be relevant in other healthcare environments. The statement emphasises several key clinical practice points for patients dissatisfied with treatment for hypothyroidism. Firstly, it is important to establish a diagnosis of overt hypothyroidism; patients with persistent symptoms during thyroid hormone replacement but with no clear biochemical evidence of overt hypothyroidism should first have a trial without thyroid hormone replacement. In those with established overt hypothyroidism, levothyroxine doses should be optimised aiming for a TSH in the 0.3-2.0 mU/L range for 3 to 6 months before a therapeutic response can be assessed. In some patients, it may be acceptable to have serum TSH below reference range (e.g. 0.1-0.3 mU/L), but not fully suppressed in the long term. We suggest that for some patients with confirmed overt hypothyroidism and persistent symptoms who have had adequate treatment with levothyroxine and in whom other comorbidities have been excluded, a trial of liothyronine/levothyroxine combined therapy may be warranted. The decision to start treatment with liothyronine should be a shared decision between patient and clinician. However, individual clinicians should not feel obliged to start liothyronine or to continue liothyronine medication provided by other health care practitioners or accessed without medical advice, if they judge this not to be in the patient's best interest.

in press; CA extern There is a pressing need to understand the factors that predict prognosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), with high heterogeneity over the poor average survival. We test the hypothesis that the magnitude and distribution of connectivity changes in PSP and CBS predict the rate of progression and survival time, using datasets from the Cambridge Centre for Parkinson-plus and the UK National PSP Research Network (PROSPECT-MR). Resting-state functional MRI images were available from 146 participants with PSP, 82 participants with CBS, and 90 healthy controls. Large-scale networks were identified through independent component analyses, with correlations taken between component time series. Independent component analysis was also used to select between-network connectivity components to compare with baseline clinical severity, longitudinal rate of change in severity, and survival. Transdiagnostic survival predictors were identified using partial least squares regression for Cox models, with connectivity compared to patients' demographics, structural imaging, and clinical scores using five-fold cross-validation. In PSP and CBS, between-network connectivity components were identified that differed from controls, were associated with disease severity, and were related to survival and rate of change in clinical severity. A transdiagnostic component predicted survival beyond demographic and motion metrics but with lower accuracy than an optimal model that included the clinical and structural imaging measures. Cortical atrophy enhanced the connectivity changes that were most predictive of survival. Between-network connectivity is associated with variability in prognosis in PSP and CBS but does not improve predictive accuracy beyond clinical and structural imaging metrics.

Summary: Pathogenic fungi use secreted effector proteins to suppress immunity and support their infection, but effectors have also been reported from fungi that engage in nutritional symbioses with plants. Sequence‐based effector comparisons between pathogens and symbiotic arbuscular mycorrhizal (AM) fungi are hampered by the huge diversity of effector sequences even within closely related microbes. To find sequence‐divergent but structurally similar effectors shared between symbiotic and pathogenic fungi, we compared secreted protein structure models of the AM fungus Rhizophagus irregularis to known pathogen effectors. We identified proteins with structural similarity to known Fusarium oxysporum f. sp. lycopersici dual domain (FOLD) effectors, which occur in low numbers in several fungal pathogens. Contrastingly, FOLD genes from AM fungi (MycFOLDs) are found in enlarged and diversified gene families with higher levels of positive selection in their C‐terminal domains. Our structure model comparison suggests that MycFOLDs are similar to carbohydrate‐binding motifs. Different MycFOLD genes are expressed during colonisation of different hosts and MycFOLD‐17 transcripts accumulate in plant intracellular arbuscules. The exclusive presence of MycFOLDs across unrelated plant‐colonising fungi, their inducible expression, lineage‐specific sequence diversification and transcripts in arbuscules suggest that FOLD proteins act as effectors during plant colonisation of symbiotic and pathogenic fungi.

Antimalarial drug discovery has until recently been driven by high-throughput phenotypic cellular screening, allowing millions of compounds to be assayed and delivering clinical drug candidates. In this review, we will focus on target-based approaches, describing recent advances in our understanding of druggable targets in the malaria parasite. Targeting multiple stages of the Plasmodium lifecycle, rather than just the clinically symptomatic asexual blood stage, has become a requirement for new antimalarial medicines, and we link pharmacological data clearly to the parasite stages to which it applies. Finally, we highlight the IUPHAR/MMV Guide to MALARIA PHARMACOLOGY, a web resource developed for the malaria research community that provides open and optimized access to published data on malaria pharmacology.

AIMS: Lifestyle and dietary modification are effective in the prevention and management of Type 2 diabetes Mellitus (T2DM). However, South Asian (SA) populations living in Western countries have low adherence rates to healthcare advice and experience poor diabetes control and clinical outcomes compared with the general population. This systematic review aimed to summarise the barriers and facilitators of dietary modification within people from South Asian (SA) ethnicity with T2DM or pre-diabetes. METHODS: A systematic search of PubMed, Web of Science and Scopus generated 3739 articles, of which seven were included. Qualitative and quantitative data were inputted utilising COVIDENCE. Qualitative data were analysed by thematic analysis. RESULTS: Thematic analysis identified three facilitators: (1) cultural sensitivity, (2) health education and (3) support networks. Barriers include (1) healthcare inequity, (2) cultural insensitivity, (3) social pressures, (4) misconceptions and (5) time constraints. Good access to health care and motivation were the most common facilitators discussed. Misconceptions on T2DM management and cultural insensitivity contributed to the majority of barriers discussed. CONCLUSIONS: Culturally tailored interventions could improve adherence to diet modification in people with T2DM from SA ethnicity. Interventions involving the application of social media to challenge intergenerational stigmas and misinformation, distributing culturally appropriate resources and providing diets tailored to the SA palate could help.

Viral infections form a substantial part of the intensive care workload, even before the recent and ongoing COVID-19 pandemic. The growing availability of molecular diagnostics for viral infections has led to increased recognition of these pathogens. This additional information, however, provides new challenges for interpretation and management. As the SARS-CoV-2 pandemic has amply demonstrated, the emergence and global spread of novel viruses are likely to provide continued challenges for critical care physicians into the future. This article will provide an overview of viral infections relevant to the critical care physician, discussing the diagnosis and management of respiratory viral infections, blood borne and enteric viruses. We will also discuss herpesviridae complications, commonly seen due to reactivation of latent infections. Further, we explore some rarer and emerging viruses, including recognition of viral haemorrhagic fevers, and briefly discuss post-viral syndromes which may present to the intensive care unit. Finally, we will discuss infection control and its importance in preventing nosocomial viral transmission.

Funder: UCLH Biomedical Research Centre, There is a paucity of population-based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age-standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age-specific overall survival was assessed using Kaplan-Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five-year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population-based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality.

Genome editing - a plant-breeding technology that facilitates the manipulation of genetic traits within living organisms - has captured the imagination of scholars and professionals working on agricultural development in Africa. Echoing the arrival of genetically modified (GM) crops decades ago, genome editing is being heralded as a technology with the potential to revolutionize breeding based on enhanced precision, reduced cost and increased speed. This article makes two interventions. First, it identifies the discursive continuity linking genome editing and the earlier technology of genetic modification. Second, it offers a suite of recommendations regarding how lessons learned from GM crops might be integrated into future breeding programmes focused on genome editing. Ultimately, the authors argue that donors, policy makers and scientists should move beyond the genome towards systems-level thinking by prioritizing the co-development of technologies with farmers; using plant material that is unencumbered by intellectual property restrictions and therefore accessible to resource-poor farmers; and acknowledging that seeds are components of complex and dynamic agroecological production systems. If these lessons are not heeded, genome-editing projects are in danger of repeating mistakes of the past.

Aims: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. Design, Setting and Participants: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. Measurements: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. Findings: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. Conclusions: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options., Medical Research Future Fund (MRFF) MRF1141214, National Health and Medical Research Council (NHMRC) of Australia GNT2009464

This article examines the meaning and function of the Old English noun reaflac in two tenth‐century lawsuit documents, Sawyer 877 and Sawyer 1211. It suggests that reaflac was the vernacular counterpart to the Latin terms violentia and rapina. Such connected terminology suggests that a collection of now lost tenth‐century Old English charters, like S 877 and S 1211 in form, was the original source for the twelfth‐century Ely house chronicle, the Libellus Æthelwoldi. Charter draftsmen purposefully selected a language of violence in order to delegitimize a rival party’s claim to an estate, regardless of whether any acts of violence had taken place. Reaflac formed part of this narrative strategy in early English lawsuit documents because of its association with contemporary discourses on moralized wrongdoing.

Psychological inoculation has proven effective at reducing susceptibility to misinformation. We present a novel storytelling approach to inoculation against susceptibility to the conjunction fallacy (dmeta‐analysis = 0.82), a known cognitive predictor of conspiracy beliefs. In Study 1 (Pilot; N = 161), a narrative inoculation (vs. control) reduced susceptibility to conjunction errors, and in turn, conspiracy beliefs regarding government malfeasance. In Study 2 (main experiment; N = 141; pre‐registered), two separate narrative inoculations (vs. control) directly reduced susceptibility to conjunction errors, and indirectly reduced conspiracy beliefs regarding extra‐terrestrial cover‐ups. In addition, the inoculation messages improved detection of both real and fake news (‘truth discernment’). We discuss theoretical and practical implications, including the use of inoculation to induce critical thinking styles, and tailoring inoculations that may suit storytelling mediums.

Funder: Excellence Initiative—Research University (IDUB), This data‐driven study framed in the interactionist approach investigates the influence of social graph topology and peer interaction dynamics among foreign exchange students enrolled in an intensive German language course on second language acquisition (SLA) outcomes. Applying the algorithms and metrics of computational social network analysis (SNA), we find that (a) the best predictor of target language (TL) performance is reciprocal interactions in the language being acquired, (b) the proportion of output in the TL is a stronger predictor than input (Principle of Proportional Output), (c) there is a negative relationship between performance and interactions with same‐first‐language speakers, (d) a significantly underperforming English native‐speaker dominated cluster is present, and (e) there are more intense interactions taking place between students of different proficiency levels. Unlike previous study abroad social network research concentrating on the microlevel of individual learners’ egocentric networks and presenting an emic view only, this study constitutes the first application of computational SNA to a complete learner network (sociogram). It provides new insights into the link between social relations and SLA with an etic perspective, showing how social network configuration and peer learner interaction are stronger predictors of TL performance than individual factors such as attitude or motivation, and offering a rigorous methodology for investigating the phenomenon.

Complement, a critical defence against pathogens, has been implicated as a driver of pathology in COVID-19. Complement activation products are detected in plasma and tissues and complement blockade is considered for therapy. To delineate roles of complement in immunopathogenesis, we undertook the largest comprehensive study of complement in COVID-19 to date, comprehensive profiling of 16 complement biomarkers, including key components, regulators and activation products, in 966 plasma samples from 682 hospitalized COVID-19 patients collected across the hospitalization period as part of the UK ISARIC4C (International Acute Respiratory and Emerging Infection Consortium) study. Unsupervised clustering of complement biomarkers mapped to disease severity and supervised machine learning identified marker sets in early samples that predicted peak severity. Compared to healthy controls, complement proteins and activation products (Ba, iC3b, terminal complement complex) were significantly altered in COVID-19 admission samples in all severity groups. Elevated alternative pathway activation markers (Ba and iC3b) and decreased alternative pathway regulator (properdin) in admission samples were associated with more severe disease and risk of death. Levels of most complement biomarkers were reduced in severe disease, consistent with consumption and tissue deposition. Latent class mixed modelling and cumulative incidence analysis identified the trajectory of increase of Ba to be a strong predictor of peak COVID-19 disease severity and death. The data demonstrate that early-onset, uncontrolled activation of complement, driven by sustained and progressive amplification through the alternative pathway amplification loop is a ubiquitous feature of COVID-19, further exacerbated in severe disease. These findings provide novel insights into COVID-19 immunopathogenesis and inform strategies for therapeutic intervention.

Funder: AXA Research Fund; Id: http://dx.doi.org/10.13039/501100001961, Funder: Sime Darby Plantation Bhd; Id: http://dx.doi.org/10.13039/501100009548, Camera trap surveys are a popular ecological monitoring tool that produce vast numbers of images making their annotation extremely time‐consuming. Advances in machine learning, in the form of convolutional neural networks, have demonstrated potential for automated image classification, reducing processing time. These networks often have a poor ability to generalise, however, which could impact assessments of species in habitats undergoing change. Here, we (i) compare the performance of three network architectures in identifying species in camera trap images taken from tropical forest of varying disturbance intensities; (ii) explore the impacts of training dataset configuration; (iii) use habitat disturbance categories to investigate network generalisability and (iv) test whether classification performance and generalisability improve when using images cropped to bounding boxes. Overall accuracy (72.8%) was improved by excluding the rarest species and by adding extra training images (76.3% and 82.8%, respectively). Generalisability to new camera locations within a disturbance level was poor (mean F1‐score: 0.32). Performance across unseen habitat disturbance levels was worse (mean F1‐score: 0.27). Training the network on multiple disturbance levels improved generalisability (mean F1‐score on unseen disturbance levels: 0.41). Cropping images to bounding boxes improved overall performance (F1‐score: 0.77 vs. 0.47) and generalisability (mean F1‐score on unseen disturbance levels: 0.73), but at a cost of losing images that contained animals which the detector failed to detect. These results suggest researchers should consider using an object detector before passing images to a classifier, and an improvement in classification might be seen if labelled images from other studies are added to their training data. Composition of training data was shown to be influential, but including rarer classes did not compromise performance on common classes, providing support for the inclusion of rare species to inform conservation efforts. These findings have important implications for use of these methods for long‐term monitoring of habitats undergoing change, as they highlight the potential for misclassifications due to poor generalisability to impact subsequent ecological analyses. These methods therefore need to be considered as dynamic, in that changes to the study site would need to be reflected in the updated training of the network.

Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100007155, Funder: London School of Hygiene and Tropical Medicine; Id: http://dx.doi.org/10.13039/100009660, Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

There is a growing body of work suggesting that social class stereotypes are amplified when people perceive higher levels of economic inequality—that is, the wealthy are perceived as more competent and assertive and the poor as more incompetent and unassertive. The present study tested this prediction in 32 societies and also examines the role of wealth-based categorization in explaining this relationship. We found that people who perceived higher economic inequality were indeed more likely to consider wealth as a meaningful basis for categorization. Unexpectedly, however, higher levels of perceived inequality were associated with perceiving the wealthy as less competent and assertive and the poor as more competent and assertive. Unpacking this further, exploratory analyses showed that the observed tendency to stereotype the wealthy negatively only emerged in societies with lower social mobility and democracy and higher corruption. This points to the importance of understanding how socio-structural features that co-occur with economic inequality may shape perceptions of the wealthy and the poor. © 2022 The Authors. European Journal of Social Psychology published by John Wiley & Sons Ltd. WOS:000880016700001 2-s2.0-85141616689 Social Sciences Citation Index Q2 Article Uluslararası işbirliği ile yapılan - EVET 2022 YÖK - 2022-23 Kasım

Funder: Cranfield University; Id: http://dx.doi.org/10.13039/501100000859, Funder: European Association of Cooperative Banks, Funder: Centre for Social and Sustainable Innovation, University of Victoria, Funder: Santander Universities; Id: http://dx.doi.org/10.13039/501100019904, This paper examines how ownership structure interacts with monetary policy in shaping financial intermediaries' appetite for risk. By constructing a large panel of banks across Western Europe, we provide evidence that differences in bank ownership influence the transmission of monetary policy via the risk-taking channel. While shareholder banks actively adjust the riskiness of their portfolios to changes in interest rates, stakeholder banks appear to be less responsive to such changes. These findings call for greater attention to the nature of bank ownership when setting monetary policy.

Funder: NIHR Newcastle Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012295, Funder: Parkinson's UK; Id: http://dx.doi.org/10.13039/501100000304, Funder: UK National Health Service (NHS), Funder: NIHR East of England Applied Research Centre, BACKGROUND: Delirium is an acute onset and fluctuating impairment of cognition, attention and arousal, often precipitated by acute illness. Lewy body disease (LBD) is an umbrella term for a range of clinical conditions, including Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB). People living with LBD seem to be more susceptible to delirium than those with other subtypes of dementia. AIM: To describe the challenges in clinical diagnosis and management of LBD. METHODS: A systematic review of published literature on diagnosis and management of delirium in LBD. RESULTS: Delirium is particularly challenging to diagnose in LBD as many of the clinical characteristics which define delirium such as inattention, fluctuating arousal, complex visual hallucinations and delusions, are also common to LBD. Distinguishing delirium from LBD can be very difficult clinically especially in the prodromal stages. Both under and over diagnosis of delirium, and under and over treatment of the symptoms have the potential to compromise the care and safety of people with a diagnosed or undiagnosed LBD. Clinicians are currently working with an extremely limited set of evidence-based management options for those with delirium in the context of a LBD diagnosis. For patients with LBD and their families this is an area of clinical practice that needs focused research.

We offer a rivalry-based perspective of gender diversity as a form of competitive action. We theorize that a firm adjusts its senior-level female representation when they identify business opportunities that may be seized by demonstrating alignment to gender parity expectations. Examining US corporate law firms and potential buyers of their services, we theorize and find that when the buyers of rivals of the focal firm increase their gender diversity, the focal firm responds by increasing its female partner representation. Reinforcing the strategic approach to managing gender diversity, we also show that a focal firm reduces its gender-related response to rivals’ buyers as the opportunity to attract those buyers decreases, and when the focal firm can use racial diversity as a credible substitute for gender diversity.

INTRODUCTION AND OBJECTIVE: Conventional serum tumor markers (STMs) for testicular germ cell tumors (GCTs) offer limited performance with particularly poor sensitivity in cases of minimal residual disease and pure seminoma. While growing evidence has indicated miR-371a-3p to be a superior biomarker, its utility in detecting pure seminoma at recurrence has not been extensively explored. This study's objective was to explore miR-371a-3p's utility in detecting metastatic pure seminoma at retroperitoneal lymph node dissection (RPLND). METHODS: RNA was isolated from patient serum samples collected pre-RPLND. Fifteen patients were assigned to our 'benign' (n = 6) or 'seminoma' (n = 9) group based on pathological confirmation of viable seminoma. Five of the patients received chemotherapy before RPLND (PC-RPLND), and 10 were chemotherapy naïve. MiR-371a-3p expression was quantified via RT-quantitative polymerase chain reaction. The Cq values were statistically evaluated to obtain performance measurements. RESULTS: Median relative expression of miR-371a-3p was higher in the Seminoma group than the Benign, but this difference was not statistically significant (Rq = 3705 and 241, respectively, p = 0.2844). Of the 10 chemotherapy naïve patients, nine had viable seminoma at RPLND, and seven had elevated miR-371a-3p expression. Among the five postchemotherapy (PC) patients, zero had viable GCT at RPLND, and two had elevated miR-371a-3p expression. The primary RPLND group presented 78% sensitivity and 100% specificity. Specificity in the PC-RPLND group was 60%. An optimal Rq threshold of 28.62 was determined by Youden's J statistic, yielding 78% sensitivity and 67% specificity. Receiver operating characteristic analysis provided an AUC of 0.704 (95% CI: 0.43-0.98, p = 0.1949). Despite modest performance, miR-371a-3p exhibited improved sensitivity and specificity compared with conventional STMs. CONCLUSIONS: MiR-371a-3p outperformed STMs in the primary RPLND settings. However, miR-371a-3p was not a robust predictor of pathology in the PC setting. These results suggest that pure seminoma at RPLND is a clinical context, wherein the miRNA assay may require further refinement.

Introduction The last few decades have seen the rise of a discourse of crisis and a huge expansion in the use of the concept and meanings attached to it. A catch word, the term appears everywhere: financial crisis, housing crisis, humanitarian crisis, food crisis, leadership crisis, ecological crisis, development crisis and, of course, a crisis of modernity. Increasingly, a crisis is no longer declared in the singular. Instead, we are progressively faced with episodes of ‘twin crisis’ (Kaminsky and Reinhart 1999, SIRIP 2022) or ‘polycrisis’ (EU Commission 2021)1, which can be cascading, enduring, creeping or transboundary – or a combination. Crisis has become part of an ever-expanding lexical chain that weaves concepts such as disaster, emergency, risk, vulnerability and resilience which, in turn, interact to create an analytical lens through which we are expected to understand the world, survive it, and then reconstruct it (Calhoun 2004). By the end of the 20th century, crisis discourse had given rise to a global industry of crisis management complete with research centres, training courses, global reports, academic publications and a class of crisis management experts, all tasked with helping policy makers fix a world constantly ‘on the brink’ (Olds and Thrift, 2005). Interest in crisis, as a framework of analysis, cuts across different political and ideological camps and is embraced by ruling elites, global financial institutions and anti-systemic movements alike. The equivocal nature of the concept and its deployment in fields as wide ranging as politics, culture, environment, psychology, medicine and the economy, suggests potential for top-down reforms as well as revolutionary possibilities to radically reshape a hegemonic order.

Funder: UCLH Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012621, BACKGROUND: Antenatal corticosteroids (ACS) are recommended in threatened preterm labour to improve short-term neonatal outcome. Preclinical animal studies suggest detrimental effects of ACS exposure on offspring cardiac development; their effects in humans are unknown. OBJECTIVES: To systematically review the human clinical literature to determine the effects of ACS on offspring cardiovascular function. SEARCH STRATEGY: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines in MEDLINE, EMBASE and Cochrane databases. SELECTION CRITERIA: Offspring who had been exposed to ACS during fetal life, in comparison with those not receiving steroids, those receiving a placebo or population data, were included. Studies not performed in humans or that did not assess cardiovascular function were excluded. DATA COLLECTION AND ANALYSIS: Two authors independently screened the studies, extracted the data and assessed the quality of the studies. Results were combined descriptively and analysed using a standardised Excel form. MAIN RESULTS: Twenty-six studies including 1921 patients were included, most of which were cohort studies of mixed quality. The type of ACS exposure, gestational age at exposure, dose and number of administrations varied widely. Offspring cardiovascular outcomes were assessed from 1 day to 36 years postnatally. The most commonly assessed parameter was arterial blood pressure (18 studies), followed by echocardiography (eight studies), heart rate (five studies), electrocardiogram (ECG, three studies) and cardiac magnetic resonance imaging (MRI, one study). There were no clinically significant effects of ACS exposure on offspring blood pressure. However, there were insufficient studies assessing cardiac structure and function using echocardiography or cardiac MRI to be able to determine an effect. CONCLUSIONS: The administration of ACS is not associated with long-term effects on blood pressure in exposed human offspring. The effects on cardiac structure and other measures of cardiac function were unclear because of the small number, heterogeneity and mixed quality of the studies. Given the preclinical and human evidence of potential harm following ACS exposure, there is a need for further research to assess central cardiac function in human offspring exposed to ACS.

The compartmentation and distribution of metabolites between mitochondria and the rest of the cell is a key parameter of cell signalling and pathology. Here, we have developed a rapid fractionation procedure that enables us to take mouse heart and liver from in vivo and within ~ 30 s stabilise the distribution of metabolites between mitochondria and the cytosol by rapid cooling, homogenisation and dilution. This is followed by centrifugation of mitochondria through an oil layer to separate mitochondrial and cytosolic fractions for subsequent metabolic analysis. Using this procedure revealed the in vivo compartmentation of mitochondrial metabolites and will enable the assessment of the distribution of metabolites between the cytosol and mitochondria during a range of situations in vivo.

Objective: To develop a standardised tool to evaluate flexible ureterorenoscopes (fURS). Materials and Methods: A three-stage consensus building approach based on the modified Delphi technique was performed under guidance of a steering group. First, scope- and user-related parameters used to evaluate fURS were identified through a systematic scoping review. Then, the main categories and subcategories were defined, and the expert panel was selected. Finally, a two-step modified Delphi consensus project was conducted to firstly obtain consensus on the relevance and exact definition of each (sub)category necessary to evaluate fURS, and secondly on the evaluation method (setting, used tools and unit of outcome) of those (sub)categories. Consensus was reached at a predefined threshold of 80% high agreement. Results: The panel consisted of 30 experts in the field of endourology. The first step of the modified Delphi consensus project consisted of two questionnaires with a response rate of 97% (n = 29) for both. Consensus was reached for the relevance and definition of six main categories and 12 subcategories. The second step consisted of three questionnaires (response rate of 90%, 97% and 100%, respectively). Consensus was reached on the method of measurement for all (sub)categories. Conclusion: This modified Delphi consensus project reached consensus on a standardised grading tool for the evaluation of fURS – The Uniform grading tooL for flexIble ureterorenoscoPes (TULIP) tool. This is a first step in creating uniformity in this field of research to facilitate future comparison of outcomes of the functionality and handling of fURS.

Funder: Cambridge NIHR Biomedical Research Centre, Interleukin-1 alpha (IL-1α) is a powerful cytokine that drives inflammation and modulates adaptive immunity. Due to these powerful effects, IL-1α is controlled at multiple levels from transcription to cleavage and release from the cell. Genome-wide association studies can identify loci that drive important diseases, although often the functional effect of the variant on phenotype remains unknown or small, with most risk variants in non-coding regions. We find that the common variant rs17561 changes a conserved amino acid in the central region of IL-1α linking the pro piece to the cytokine domain. Using a recall-by-genotype study and whole blood stimulation, we find that minor allele homozygotes release ~50% less IL-1α than the major allele, with IL-1β release equivalent. IL-1α transcript level was identical between groups, implying a post-transcriptional effect, whilst cleavage of recombinant pro-IL-1α by multiple proteases was also equivalent for both forms. Importantly, transfected macrophages also release less minor allele IL-1α upon inflammasome activation, revealing that reduced secretion is directly caused by the missense amino acid substitution and more minor allele IL-1α was retained within the cell. Thus, rs17561 represents a very common hypomorphic mutation in IL-1α. We believe this novel data will be important for determining the potential contribution of IL-1α to disease and/or physiological processes, for example, by Mendelian randomisation, and may aid patient stratification when considering anti-IL-1 therapies.

This article examines the intersections between sweetness, femininity and the confectionery trade in eighteenth-century Barcelona, at a time of growing consumption of sugar and slavery. Drawing on a range of underexplored archival material, this study traces the stories of women of different social groups, namely, elite housewives, nuns and tradeswomen, who engaged with the production and trade of sweets in ingenious ways. This article argues that in the period when women were culturally diminished through their portrayals as ‘sweet’ and barred by guild structures, many women exercised social and economic agency in the confectionery trade in Barcelona.

When teaching statistics, educators sometimes overestimate their students' knowledge and abilities. This is due to the curse of knowledge, a cognitive bias that causes people—especially experts—to overestimate how likely others are to know and understand the same things as them. This can lead to various issues, including struggling to communicate with students, and making students feel less comfortable in the classroom. To address this, educators should first identify situations where this bias can affect their teaching. In doing so, they should consider relevant risk factors, and potentially also solicit feedback from relevant individuals. Then, educators can reduce this bias and its impact on their teaching by using techniques such as keeping the curse of knowledge and their audience in mind, assessing students' knowledge, assuming lack of knowledge unless there is strong evidence to the contrary, and avoiding saying that things are obvious.