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Abstract Openness and transparency in the research process are a prerequisite to the production of high quality research outputs. Efforts to maximise these features have substantially accelerated in recent years, placing open and transparent research practices at the forefront of funding and related priorities, and encouraging investment in resources and infrastructure to enable such practices. Despite these efforts, there has been no systematic documentation of current practices, infrastructure, or training and resources that support open and transparent research in the UK. To address this gap, we developed and conducted the Open and Transparent Research Practices survey, a large-scale audit study completed by research-active staff in UK research institutions to better understand existing practices, needs, support, and barriers faced when implementing open and transparent research. The data presented here capture responses from over 2,500 research-active staff based at 15 institutions affiliated with the UK Reproducibility Network. The data provide a snapshot of open research practices that can be used to identify barriers, training needs, and areas that require greater investments.

The few examples of structures containing the 2-chloro-N,N-dimethylethan-1-aminium or 3-chloro-N,N-dimethylpropan-1-aminium cations show a competition between gauche and anti conformations for the chloroalkyl chain. To explore further the conformational landscape of these cations, and their possible use as molecular switches, the title salts, (C4H11ClN)2[CoCl4] and (C4H11ClN)2[ZnCl4], were prepared and structurally characterized. Details of both structures are in close agreement. The inorganic complex exhibits a slightly flattened tetrahedral geometry that likely arises from bifurcated N—H hydrogen bonds from the organic cations. The alkyl chain of the cation is disordered between gauche and anti conformations with the gauche conformation occupancy refined to 0.707 (2) for the cobaltate. The gauche conformation places the terminal Cl atom at a tetrahedral face of the inorganic complex with a contact distance of 3.7576 (9) Å to the Co2+ center. The anti conformation places the terminal Cl atom at a contact distance to a neighboring anti conformation terminal Cl atom that is ∼1 Å less than the sum of the van der Waals radii. Thus, if the anti conformation is present at a site, then the nearest neighbor must be gauche. DFT geometry optimizations indicate the gauche conformation is more stable in vacuo by 0.226 eV, which reduces to 0.0584 eV when calculated in a uniform dielectric. DFT geometry optimizations for the unprotonated molecule indicate the anti conformation is stabilized by 0.0428 eV in vacuo, with no strongly preferred conformation in uniform dielectric, to provide support to the notion that this cation could function as a molecular switch via deprotonation.

Abstract Background Although electronic cigarettes (e-cigarettes) appear to be effective in helping people who smoke to stop smoking, concerns about use of e-cigarettes among young people have led to restrictions on non-tobacco flavoured e-liquids in some countries and some US states. These restrictions could reduce the appeal of these products to non-smoking youth but could have negative consequences for people who smoke or use e-cigarettes. Methods In this mixed methods study, we recruited UK adults who smoked or used to smoke and subsequently vaped to explore their opinions of unflavoured e-liquids and their beliefs about how they would be impacted by hypothetical e-liquid flavour restrictions. Participants trialled an unflavoured e-liquid instead of their usual nicotine product for four hours and completed a survey and an online interview. Results Using Interpretive Phenomenological Analysis and graphically presented data, we found differences in participants’ opinions of unflavoured e-liquid. If only unflavoured, tobacco flavoured, and menthol flavoured e-liquids remained on the UK market, some people who smoke or vape may be unaffected, but some may relapse to smoking or continue smoking. Despite most wanting to prevent young people from initiating vaping, participants had varying opinions on whether flavour restrictions would be an effective method. Conclusions The findings highlight that people who smoke and vape could be impacted by flavour restrictions in a range of ways, some of which could have a potential adverse impact on harm reduction efforts in the UK (e.g., by making smoking more appealing than vaping).

Abstract Background Nowadays, there is no method to quantitatively characterize the material composition of acute ischemic stroke thrombi prior to intervention, but dual-energy CT (DE-CT) offers imaging-based multimaterial decomposition. We retrospectively investigated the material composition of thrombi ex vivo using DE-CT with histological analysis as a reference. Methods Clots of 70 patients with acute ischemic stroke were extracted by mechanical thrombectomy and scanned ex vivo in formalin-filled tubes with DE-CT. Multimaterial decomposition in the three components, i.e., red blood cells (RBC), white blood cells (WBC), and fibrin/platelets (F/P), was performed and compared to histology (hematoxylin/eosin staining) as reference. Attenuation and effective Z values were assessed, and histological composition was compared to stroke etiology according to the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. Results Histological and imaging analysis showed the following correlation coefficients for RBC (r = 0.527, p

BackgroundThe extent to which interventions are perceived as acceptable to users impacts engagement and efficacy. ObjectiveIn this study, we evaluated the acceptability of (1) the smartphone app Drink Less (intervention) and (2) the National Health Service (NHS) alcohol advice web page (usual digital care and comparator) among adult drinkers in the United Kingdom participating in a randomized controlled trial evaluating the effectiveness of the Drink Less app. MethodsA subsample of 26 increasing- and higher-risk drinkers (Alcohol Use Disorders Identification Test score≥8) assigned to the intervention group (Drink Less; n=14, 54%; female: n=10, 71%; age: 22-72 years; White: n=9, 64%) or usual digital care group (NHS alcohol advice web page; n=12, 46%; female: n=5, 42%; age: 23-68 years: White: n=9, 75%) took part in semistructured interviews. The interview questions were mapped on to the 7 facets of acceptability according to the Theoretical Framework of Acceptability: affective attitude, burden, perceived effectiveness, ethicality, intervention coherence, opportunity costs, and self-efficacy. Alongside these constructs, we also included a question on perceived personal relevance, which previous research has linked to acceptability and engagement. Framework and thematic analysis of data was undertaken. ResultsThe Drink Less app was perceived as being ethical, easy, user-friendly, and effective for the period the app was used. Participants reported particularly liking the tracking and feedback sections of the app, which they reported increased personal relevance and which resulted in positive affect when achieving their goals. They reported no opportunity cost. Factors such as negative affect when not meeting goals and boredom led to disengagement in the longer term for some participants. The NHS alcohol advice web page was rated as being easy and user-friendly with no opportunity costs. However, the information presented was not perceived as being personally relevant or effective in changing drinking behavior. Most participants reported neutral or negative affect, most participants thought the alcohol advice web page was accessible, and some participants reported ethical concerns around the availability of suggested resources. Some participants reported that it had acted as a starting point or a signpost to other resources. Participants in both groups discussed motivation to change and contextual factors such as COVID-19 lockdowns, which influenced their perceived self-efficacy regardless of their assigned intervention. ConclusionsDrink Less appears to be an acceptable digital intervention among the recruited sample. The NHS alcohol advice web page was generally considered unacceptable as a stand-alone intervention among the recruited sample, although it may signpost and help people access other resources and interventions.

Abstract Two-sample MR is an increasingly popular method for strengthening causal inference in epidemiological studies. For the effect estimates to be meaningful, variant-exposure and variant-outcome associations must come from comparable populations. A recent systematic review of two-sample MR studies found that, if assessed at all, MR studies evaluated this assumption by checking that the genetic association studies had similar demographics. However, it is unclear if this is sufficient because less easily accessible factors may also be important. Here we propose an easy-to-implement falsification test. Since recent theoretical developments in causal inference suggest that a causal effect estimate can generalise from one study to another if there is exchangeability of effect modifiers, we suggest testing the homogeneity of variant-phenotype associations for a phenotype which has been measured in both genetic association studies as a method of exploring the ‘same-population’ test. This test could be used to facilitate designing MR studies with diverse populations. We developed a simple R package to facilitate the implementation of our proposed test. We hope that this research note will result in increased attention to the same-population assumption, and the development of better sensitivity analyses.

This study demonstrates that GPT-4V outperforms GPT-4 across radiology subspecialties in analyzing 207 cases with 1312 images from the Radiological Society of North America Case Collection.

Abstract Comparative anatomy is an important tool for investigating evolutionary relationships among species, but the lack of scalable imaging tools and stains for rapidly mapping the microscale anatomies of related species poses a major impediment to using comparative anatomy approaches for identifying evolutionary adaptations. We describe a method using synchrotron source micro‐x‐ray computed tomography (syn‐μXCT) combined with machine learning algorithms for high‐throughput imaging of Lepidoptera (i.e., butterfly and moth) eyes. Our pipeline allows for imaging at rates of ~15 min/mm3 at 600 nm3 resolution. Image contrast is generated using standard electron microscopy labeling approaches (e.g., osmium tetroxide) that unbiasedly labels all cellular membranes in a species‐independent manner thus removing any barrier to imaging any species of interest. To demonstrate the power of the method, we analyzed the 3D morphologies of butterfly crystalline cones, a part of the visual system associated with acuity and sensitivity and found significant variation within six butterfly individuals. Despite this variation, a classic measure of optimization, the ratio of interommatidial angle to resolving power of ommatidia, largely agrees with early work on eye geometry across species. We show that this method can successfully be used to determine compound eye organization and crystalline cone morphology. Our novel pipeline provides for fast, scalable visualization and analysis of eye anatomies that can be applied to any arthropod species, enabling new questions about evolutionary adaptations of compound eyes and beyond.

Abstract When dealing with a newly emerging disease such as COVID-19, the impact of patient- and disease-specific factors (e.g., body weight or known co-morbidities) on the immediate course of the disease is largely unknown. An accurate prediction of the most likely individual disease progression can improve the planning of limited resources and finding the optimal treatment for patients. In the case of COVID-19, the need for intensive care unit (ICU) admission of pneumonia patients can often only be determined on short notice by acute indicators such as vital signs (e.g., breathing rate, blood oxygen levels), whereas statistical analysis and decision support systems that integrate all of the available data could enable an earlier prognosis. To this end, we propose a holistic, multimodal graph-based approach combining imaging and non-imaging information. Specifically, we introduce a multimodal similarity metric to build a population graph that shows a clustering of patients. For each patient in the graph, we extract radiomic features from a segmentation network that also serves as a latent image feature encoder. Together with clinical patient data like vital signs, demographics, and lab results, these modalities are combined into a multimodal representation of each patient. This feature extraction is trained end-to-end with an image-based Graph Attention Network to process the population graph and predict the COVID-19 patient outcomes: admission to ICU, need for ventilation, and mortality. To combine multiple modalities, radiomic features are extracted from chest CTs using a segmentation neural network. Results on a dataset collected in Klinikum rechts der Isar in Munich, Germany and the publicly available iCTCF dataset show that our approach outperforms single modality and non-graph baselines. Moreover, our clustering and graph attention increases understanding of the patient relationships within the population graph and provides insight into the network’s decision-making process.

Cardiac motion causes unpredictable signal loss in respiratory-triggered diffusion-weighted magnetic resonance imaging (DWI) of the liver, especially inside the left lobe. The left liver lobe may thus be frequently neglected in the clinical evaluation of liver DWI. In this work, a data-driven algorithm that relies on the statistics of the signal in the left liver lobe to mitigate the motion-induced signal loss is presented. The proposed data-driven algorithm utilizes the exclusion of severely corrupted images with subsequent spatially dependent image scaling based on a signal-loss model to correctly combine the multi-average diffusion-weighted images. The signal in the left liver lobe is restored and the liver signal is more homogeneous after applying the proposed algorithm. Furthermore, overestimation of the apparent diffusion coefficient (ADC) in the left liver lobe is reduced. The proposed algorithm can therefore contribute to reduce the motion-induced bias in DWI of the liver and help to increase the diagnostic value of DWI in the left liver lobe.

The detrimental health effects of smoking are well-known, but the impact of regular nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing daily use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]). We used Genome-Wide Association Study (GWAS) summary statistics from Buchwald and colleagues, the GWAS and Sequencing Consortium of Alcohol and Nicotine, the International Lung Cancer Consortium, and UK Biobank. Increased nicotine metabolism increased the risk of COPD, lung cancer, and lung function in the univariable analysis. However, when accounting for smoking heaviness in the multivariable analysis, we found that increased nicotine metabolite ratio (indicative of decreased nicotine exposure per cigarette smoked) decreases heart rate (b = -0.30, 95% CI -0.50 to -0.10) and lung function (b = -33.33, 95% CI -41.76 to -24.90). There was no clear evidence of an effect on the remaining outcomes. The results suggest that these smoking-related outcomes are not due to nicotine exposure but are caused by the other components of tobacco smoke; however, there are multiple potential sources of bias, and the results should be triangulated using evidence from a range of methodologies.

The responsible conduct of research is foundational to the production of valid and trustworthy research. Despite this, our grasp of what dimensions responsible conduct of research (RCR) might contain—and how it differs across disciplines (i.e. how it is conceptualized and operationalized)—is tenuous. Moreover, many initiatives related to developing and maintaining RCR are developed within disciplinary and institutional silos which naturally limits the benefits that RCR practice can have. To this end, we are working to develop a better understanding of how RCR is conceived and realized, both across disciplines and across institutions in Europe. The first step in doing this is to scope existing knowledge on the topic, of which this scoping review is a part. We searched several electronic databases for relevant published and grey literature. An initial sample of 715 articles was identified, with 75 articles included in the final sample for qualitative analysis. We find several dimensions of RCR that are underemphasized or are excluded from the well-established World Conferences on Research Integrity (WCRI) Singapore Statement on Research Integrity and explore facets of these dimensions that find special relevance in a range of research disciplines.

COVID-19 vaccinations are widely available across the United States (U.S.), yet little is known about the spatial clustering of COVID-19 vaccinations. This study aimed to test for geospatial clustering of COVID-19 vaccine rates among adolescents aged 12–17 across the U.S. counties and to compare these clustering patterns by sociodemographic characteristics.County-level data on COVID-19 vaccinations and sociodemographic characteristics were obtained from the COVID-19 Community Profile Report up to April 14, 2022. A total of 3,108 counties were included in the analysis. Global Moran’s I statistic and Anselin Local Moran’s analysis were used, and clustering patterns were compared to sociodemographic variables using t-tests. Counties with low COVID-19 vaccinated clusters were more likely, when compared to unclustered counties, to have higher numbers of individuals in poverty and uninsured individuals, and higher values of Social Vulnerability Index (SVI) and COVID-19 Community Vulnerability Index (CCVI). While high COVID-19 vaccinated clusters, compared to neighboring counties, had lower numbers of Black population, individuals in poverty, and uninsured individuals, and lower values of SVI and CCVI, but a higher number of Hispanic population. This study emphasizes the importance of addressing systemic barriers, such as poverty and lack of health insurance, which were found to be associated with low COVID-19 vaccination coverage.

Abstract Background To determine whether denoised areal bone mineral density (BMD) measurements from scout scans in spectral detector computed tomography (CT) correlate with volumetric trabecular BMD for opportunistic osteoporosis screening. Methods A 64-slice single-source dual-layer spectral CT scanner was used to acquire scout scan data of 228 lumbar vertebral bodies within 57 patients. Scout scans in anterior–posterior (AP) view were performed with a dose of

Abstract Objective To explore the use of multivariable instrumental variables to resolve the “damned if you do, damned if you don’t” adjustment problem created for Mendelian randomisation (MR) analysis using the smoking or lung function related phenotypes in the UK Biobank (UKB). Result “damned if you do, damned if you don’t” adjustment problems occur when both adjusting and not-adjusting for a variable will induce bias in an analysis. One instance of this occurs because the genotyping chip of UKB participants differed based on lung function/smoking status. In simulations, we show that multivariable instrumental variables analyses can attenuate potential collider bias introduced by adjusting for a proposed covariate, such as the UKB genotyping chip. We then explore the effect of adjusting for genotyping chip in a multivariable MR model exploring the effect of smoking on seven medical outcomes (lung cancer, emphysema, hypertension, stroke, heart diseases, depression, and disabilities). We additionally compare our results to a traditional univariate MR analysis using genome-wide analyses summary statistics which had and had not adjusted for genotyping chip. This analysis implies that the difference in genotyping chip has introduced only a small amount of bias.

Abstract Objective To use genome-wide association study (GWAS) by subtraction, a method for deriving novel GWASs from existing summary statistics, to derive genome-wide summary statistics for paternal smoking. Result A GWAS by subtraction was implemented using a weighted linear model that defined the child-genotype paternal-phenotype association as the child-genotype child-phenotype association minus the child-genotype maternal-phenotype association. We first use the laws of inherence to derive the weighted linear model. We then implemented the linear model to create a GWAS of paternal smoking by subtracting the summary statistics from a GWAS of maternal smoking from the summary statistics of a GWAS of the index individual’s smoking. We used a Monte-Carlo simulation to validate the model and showed that this approach performed similarly in terms of bias to performing a traditional GWAS of paternal smoking. Finally, we validated the summary statistics in a Mendelian randomisation analysis by demonstrating an association of genetically predicted paternal smoking with paternal lung cancer and emphysema.

Abstract KRAS is a frequent driver in lung cancer. To identify KRAS-specific vulnerabilities in lung cancer, we performed RNAi screens in primary spheroids derived from a Kras mutant mouse lung cancer model and discovered an epigenetic regulator Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1). In human lung cancer models UHRF1 knock-out selectively impaired growth and induced apoptosis only in KRAS mutant cells. Genome-wide methylation and gene expression analysis of UHRF1-depleted KRAS mutant cells revealed global DNA hypomethylation leading to upregulation of tumor suppressor genes (TSGs). A focused CRISPR/Cas9 screen validated several of these TSGs as mediators of UHRF1-driven tumorigenesis. In vivo, UHRF1 knock-out inhibited tumor growth of KRAS-driven mouse lung cancer models. Finally, in lung cancer patients high UHRF1 expression is anti-correlated with TSG expression and predicts worse outcomes for patients with KRAS mutant tumors. These results nominate UHRF1 as a KRAS-specific vulnerability and potential target for therapeutic intervention.

Abstract Background Gene duplication events are critical for the evolution of new gene functions. Aristaless is a major regulator of distinct developmental processes. It is most known for its role during appendage development across animals. However, more recently other distinct biological functions have been described for this gene and its duplicates. Butterflies and moths have two copies of aristaless, aristaless1 (al1) and aristaless2 (al2), as a result of a gene duplication event. Previous work in Heliconius has shown that both copies appear to have novel functions related to wing color patterning. Here we expand our knowledge of the expression profiles associated with both ancestral and novel functions of Al1 across embryogenesis and wing pigmentation. Furthermore, we characterize Al2 expression, providing a comparative framework between gene copies within the same species, allowing us to understand the origin of new functions following gene duplication. Results Our work shows that the expression of both Al1 and Al2 is associated with the ancestral function of sensory appendage (leg, mouth, spines, and eyes) development in embryos. Interestingly, Al1 exhibits higher expression earlier in embryogenesis while the highest levels of Al2 expression are shifted to later stages of embryonic development. Furthermore, Al1 localization appears extranuclear while Al2 co-localizes tightly with nuclei earlier, and then also expands outside the nucleus later in development. Cellular expression of Al1 and Al2 in pupal wings is broadly consistent with patterns observed during embryogenesis. We also describe, for the first time, how Al1 localization appears to correlate with zones of anterior/posterior elongation of the body during embryonic growth, showcasing a possible new function related to Aristaless’ previously described role in appendage extension. Conclusions Overall, our data suggest that while both gene copies play a role in embryogenesis and wing pigmentation, the duplicates have diverged temporally and mechanistically across those functions. Our study helps clarify principles behind sub-functionalization and gene expression evolution associated with developmental functions following gene duplication events.

Abstract Background Highly diverse butterfly wing patterns have emerged as a powerful system for understanding the genetic basis of phenotypic variation. While the genetic basis of this pattern variation is being clarified, the precise developmental pathways linking genotype to phenotype are not well understood. The gene aristaless, which plays a role in appendage patterning and extension, has been duplicated in Lepidoptera. One copy, aristaless1, has been shown to control a white/yellow color switch in the butterfly Heliconius cydno, suggesting a novel function associated with color patterning and pigmentation. Here we investigate the developmental basis of al1 in embryos, larvae, and pupae using new antibodies, CRISPR/Cas9, RNAi, qPCR assays of downstream targets, and pharmacological manipulation of an upstream activator. Results We find that Al1 is expressed at the distal tips of developing embryonic appendages consistent with its ancestral role. In developing wings, we observe Al1 accumulation within developing scale cells of white H. cydno during early pupation while yellow scale cells exhibit little Al1 at this time point. Reduced Al1 expression is also associated with yellow scale development in al1 knockouts and knockdowns. We propose that Al1 expression in future white scales might be related to an observed downregulation of the enzyme Cinnabar and other genes that synthesize and transport the yellow pigment, 3–hydroxykynurenine (3-OHK). Finally, we provide evidence that Al1 activation is under the control of Wnt signaling. Conclusions We propose a model in which high levels of Al1 during early pupation, which are mediated by Wnt, are important for melanic pigmentation and specifying white portions of the wing while reduced levels of Al1 during early pupation promote upregulation of proteins needed to move and synthesize 3-OHK, promoting yellow pigmentation. In addition, we discuss how the ancestral role of aristaless in appendage extension may be relevant in understanding the cellular mechanism behind color patterning in the context of the heterochrony hypothesis.

Abstract Background Guidance to improve fertility includes reducing alcohol and caffeine consumption, achieving healthy weight-range and stopping smoking. Advice is informed by observational evidence, which is often biased by confounding. Methods This study primarily used data from a pregnancy cohort, the Norwegian Mother, Father and Child Cohort Study. First, we conducted multivariable regression of health behaviours (alcohol and caffeine consumption, body-mass index (BMI), and smoking) on fertility outcomes (e.g. time to conception) and reproductive outcomes (e.g. age at first birth) (n = 84,075 females, 68,002 males), adjusting for birth year, education and attention-deficit and hyperactive-impulsive (ADHD) traits. Second, we used individual-level Mendelian randomisation (MR) to explore possible causal effects of health behaviours on fertility/reproductive outcomes (n = 63,376 females, 45,460 males). Finally, we performed summary-level MR for available outcomes in UK Biobank (n = 91,462–1,232,091) and controlled for education and ADHD liability using multivariable MR. Results In multivariable regression analyses, higher BMI associated with fertility (longer time to conception, increased odds of infertility treatment and miscarriage), and smoking was associated with longer time to conception. In individual-level MR analyses, there was strong evidence for effects of smoking initiation and higher BMI on younger age at first birth, of higher BMI on increased time to conception, and weak evidence for effects of smoking initiation on increased time to conception. Age at first birth associations were replicated in summary-level MR analysis; however, effects attenuated using multivariable MR. Conclusions Smoking behaviour and BMI showed the most consistent associations for increased time to conception and a younger age at first birth. Given that age at first birth and time to conception are positively correlated, this suggests that the mechanisms for reproductive outcomes are distinct to the mechanisms acting on fertility outcomes. Multivariable MR suggested that effects on age at first birth might be explained by underlying liability to ADHD and education.

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of “common cold”. In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and β-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

Background. Although preregistration can reduce researcher bias and increase transparency in primary research settings, it is less applicable to secondary data analysis. An alternative method that affords additional protection from researcher bias, which cannot be gained from conventional forms of preregistration alone, is an Explore and Confirm Analysis Workflow (ECAW). In this workflow, a data management organization initially provides access to only a subset of their dataset to researchers who request it. The researchers then prepare an analysis script based on the subset of data, upload the analysis script to a registry, and then receive access to the full dataset. ECAWs aim to achieve similar goals to preregistration, but make access to the full dataset contingent on compliance. The present survey aimed to garner information from the research community where ECAWs could be applied—employing the Avon Longitudinal Study of Parents and Children (ALSPAC) as a case example. Methods. We emailed a Web-based survey to researchers who had previously applied for access to ALSPAC's transgenerational observational dataset. Results. We received 103 responses, for a 9% response rate. The results suggest that—at least among our sample of respondents—ECAWs hold the potential to serve their intended purpose and appear relatively acceptable. For example, only 10% of respondents disagreed that ALSPAC should run a study on ECAWs (versus 55% who agreed). However, as many as 26% of respondents agreed that they would be less willing to use ALSPAC data if they were required to use an ECAW (versus 45% who disagreed). Conclusion. Our data and findings provide information for organizations and individuals interested in implementing ECAWs and related interventions. Preregistration. https://osf.io/g2fw5 Deviations from the preregistration are outlined in electronic supplementary material A.

Objectives Prospectively registering study plans in a permanent time-stamped and publicly accessible document is becoming more common across disciplines and aims to reduce risk of bias and make risk of bias transparent. Selective reporting persists, however, when researchers deviate from their registered plans without disclosure. This systematic review aimed to estimate the prevalence of undisclosed discrepancies between prospectively registered study plans and their associated publication. We further aimed to identify the research disciplines where these discrepancies have been observed, whether interventions to reduce discrepancies have been conducted, and gaps in the literature.Design Systematic review and meta-analyses.Data sources Scopus and Web of Knowledge, published up to 15 December 2019.Eligibility criteria Articles that included quantitative data about discrepancies between registrations or study protocols and their associated publications.Data extraction and synthesis Each included article was independently coded by two reviewers using a coding form designed for this review (osf.io/728ys). We used random-effects meta-analyses to synthesise the results.Results We reviewed k=89 articles, which included k=70 that reported on primary outcome discrepancies from n=6314 studies and, k=22 that reported on secondary outcome discrepancies from n=1436 studies. Meta-analyses indicated that between 29% and 37% (95% CI) of studies contained at least one primary outcome discrepancy and between 50% and 75% (95% CI) contained at least one secondary outcome discrepancy. Almost all articles assessed clinical literature, and there was considerable heterogeneity. We identified only one article that attempted to correct discrepancies.Conclusions Many articles did not include information on whether discrepancies were disclosed, which version of a registration they compared publications to and whether the registration was prospective. Thus, our estimates represent discrepancies broadly, rather than our target of undisclosed discrepancies between prospectively registered study plans and their associated publications. Discrepancies are common and reduce the trustworthiness of medical research. Interventions to reduce discrepancies could prove valuable.Registration osf.io/ktmdg. Protocol amendments are listed in online supplemental material A.

Abstract Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain individual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this sample, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining individual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale samples of genotyped families with information on childhood psychiatric outcomes.

Abstract Introduction Improving Access to Psychological Therapies (IAPTs) Services could offer smoking cessation treatment to improve physical and psychological outcomes for service users, but it currently does not. This study aimed to understand participants' views and experiences of receiving a novel smoking cessation intervention as part of the ESCAPE trial (intEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety). We used the Capability, Opportunity and Motivation Model of Behaviour (COM‐B) to understand the (i) acceptability of the integrated smoking cessation treatment, (ii) views of psychological well‐being practitioners' (PWPs) ability to deliver the smoking cessation treatment and (iii) positive and negative impacts of smoking cessation treatment. Methods This was a qualitative study embedded within a feasibility randomized‐controlled trial (ESCAPE) in primary care services in the United Kingdom (IAPT). Thirty‐six participants (53% female) from both usual care and intervention arms of the ESCAPE trial, including both quitters and nonquitters, were interviewed using semi‐structured interviews. Data were analysed using a framework approach to thematic analysis, using the COM‐B as a theoretical frame. Results Psychological Capability: Integrated smoking cessation treatment was acceptable and encouraged participants to reflect on their mental health. Some participants found it difficult to understand nicotine withdrawal symptoms. Motivation: Participants were open to change during the event of presenting to IAPT. Some described being motivated to take part in the intervention by curiosity, to see whether quitting smoking would help their mental health. Physical Opportunity: IAPT has a natural infrastructure for supporting integrated treatment, but there were some barriers such as session duration and interventions feeling segmented. Social Opportunity: Participants viewed PWPs as having good interpersonal skills to deliver a smoking cessation intervention. Conclusion People with common mental illness generally accepted integrated smoking cessation and mental health treatment. Smoking cessation treatment fits well within IAPT's structure; however, there are barriers to implementation. Patient or Public Contribution Before data collection, we consulted with people with lived experience of smoking and/or mental illness and lay public members regarding the aims, design and interview schedules. After analysis, two people with lived experience of smoking and mental illness individually gave feedback on the final themes and quotes.

Facial emotion recognition (ER) difficulties are associated with mental health and neurodevelopmental conditions, including autism and poorer social functioning. ER interventions may therefore have clinical potential. We investigated the efficacy of ER training (ERT). We conducted three online studies with healthy volunteers completing one ERT session. Studies 1 and 2 included active and control/sham training groups and tested the efficacy of (i) four-emotion ERT (angry, happy, sad and scared) (n = 101), and (ii) six-emotion ERT (adding disgusted and surprised) (n = 109). Study 3 tested generalizability of ERT to non-trained stimuli with groups trained and tested on the same stimuli, or different stimuli (n = 120). Training effects on total correct hits were estimated using linear mixed effects models. We did not observe clear evidence of improvement in study 1 but note the effect was in the direction of improvement (b = 0.02, 95% confidence interval (CI) = −0.02 to 0.07). Study 2 indicated greater total hits following training (b = 0.07, 95% CI = 0.03–0.12). Study 3 demonstrated similar improvement across groups (b = −0.01, 95% CI = −0.05 to 0.02). Our results indicate improved ER (as measured by our task), which generalizes to different facial stimulus sets. Future studies should further explore generalizability, longer-term effects and ERT in populations with known ER difficulties.

In the title compound (systematic name: 2,3-dihydro-1,4-dithiino[2,3-c]furan-5,7-dione), C6H4O3S2, the observed geometry agrees well with those of its phthalamide, thieno and hydroxy analogs, and with a calculated geometry obtained by density functional theory (DFT) calculations. Specific structural features are an S—C—C—S torsion angle of −70.39 (17)° and S—C bonds to sp2-hybridized C atoms approximately 0.1 Å shorter than those to sp3-hybridized C atoms. Unlike the extended structures of the analogs, there are no directed intermolecular interactions and the head-to-tail rows of molecules that are a prominent structural motif of the packing can be rationalized in terms of optimized dipole–dipole interactions.

Hanly et al.1 and Nishida et al.2 use distinct approaches to provide exceptional lessons regarding the genetic, molecular, morphological, and biochemical bases of butterfly wing pigmentation. These mechanistic insights collectively have important implications for our understanding of phenotype evolution.

Anxiety and depression are associated with a range of impairments in cognitive functioning. Understanding the nature of these deficits may identify targets for intervention and prevent functional decline. We used observational and genetic methods to investigate the relationship of anxiety and depression with three cognitive domains: emotion recognition, response inhibition, and working memory, in the Avon Longitudinal Study of Parents and Children (ALSPAC). We examined: (i) cross-sectional associations between anxiety, depression, and cognition at age 24 (n = 2187), (ii) prospective associations between anxiety and depression at age 18 and cognition at age 24 (n = 1855), and (iii) the casual effect of anxiety and depression on cognition using Mendelian randomization (MR). Both disorders were associated with altered emotion recognition; anxiety with decreased happiness recognition (b = −0.27 [−0.54,0.01], p = 0.045), and depression with increased sadness recognition (b = 0.35 [0.07,0.64], p = 0.016). Anxiety was also associated with poorer working memory (b = −0.14 [−0.24,0.04], p = 0.005). There was no evidence for an association with response inhibition. MR provided no clear evidence of causal relationships between mental health and cognition, but these analyses were underpowered. Overall, there was little evidence for impairments in executive functioning, but moderate alterations in emotion recognition. This may inform the development of psychosocial interventions.

Background: Dark-field imaging is a novel imaging modality that allows for the assessment of material interfaces by exploiting the wave character of x-ray. While it has been extensively studied in chest imaging, only little is known about the modality for imaging other tissues. Therefore, the purpose of this study was to evaluate whether a clinical X-ray dark-field scanner prototype allows for the assessment of osteoporosis.Materials and methods: In this prospective study we examined human cadaveric lumbar spine specimens (vertebral segments L2 to L4). We used a clinical prototype for dark-field radiography that yields both attenuation and dark-field images. All specimens were scanned in lateral orientation in vertical and horizontal position. All specimens were additionally imaged with CT as reference. Bone mineral density (BMD) values were derived from asynchronously calibrated quantitative CT measurements. Correlations between attenuation signal, dark-field signal and BMD were assessed using Spearman’s rank correlation coefficients. The capability of the dark-field signal for the detection of osteoporosis/osteopenia was evaluated with receiver operating characteristics (ROC) curve analysis.Results: A total of 58 vertebrae from 20 human cadaveric spine specimens (mean age, 73 years ±13 [standard deviation]; 11 women) were studied. The dark-field signal was positively correlated with the BMD, both in vertical (r = 0.56, p < .001) and horizontal position (r = 0.43, p < .001). Also, the dark-field signal ratio was positively correlated with BMD (r = 0.30, p = .02). No correlation was found between the signal ratio of attenuation signal and BMD (r = 0.14, p = .29). For the differentiation between specimens with and without osteoporosis/osteopenia, the area under the ROC curve (AUC) was 0.80 for the dark-field signal in vertical position.Conclusion: Dark-field imaging allows for the differentiation between spine specimens with and without osteoporosis/osteopenia and may therefore be a potential biomarker for bone stability.

Purpose: We aimed to determine the minimum 20-year survival rates of a cementless press-fit cup in young patients. Patients and methods: This is a retrospective, single-center, multi-surgeon cohort study investigating the minimum 20-year clinical and radiological outcome of the first 121 consecutive total hip replacements (THRs) using a cementless, press-fit cup (Allofit, Zimmer, Warsaw, IN, USA) performed between 1999 and 2001. 28-mm metal-on-metal (MoM) and ceramic-on-conventionally not highly crosslinked polyethylene (CoP) bearings were used in 71% and 28%, respectively. Median patient age at surgery was 52 (range 21–60) years. Kaplan–Meier survival analysis was conducted for different endpoints. Results: The 22-year survival rate for the endpoint aseptic cup or inlay revision was 94% (95% confidence interval [CI] 87–96) and 99% (CI 94–100) for aseptic cup loosening. 20 patients (21 THRs; 17%) had died and 5 (5 THRs; 4%) were lost to follow-up. No THR showed evidence of radiographic cup loosening. Osteolysis was observed in 40% of THRs with MoM and 77% with CoP bearings. 88% of THRs with CoP bearings showed significant polyethylene wear. Conclusion: The investigated cementless press-fit cup, which is still in clinical use today, showed excellent long-term survival rates in patients under the age of 60 years at surgery. However, osteolysis due to polyethylene and metal wear was frequently observed and is a matter of concern in the third decade after surgery.

Frank, Gassert et al. use dark-field chest X-ray imaging to assess COVID-19-pneumonia. Dark-field imaging has a higher sensitivity for COVID-19-pneumonia than attenuation-based imaging and provides an ultralow dose alternative to computed tomography imaging for that purpose.

Abstract Background To investigate the detection capabilities of myocardial perfusion defects of dual-energy computed tomography (CT) technology using time-resolved iodine-based maps for functional assessment of coronary stenosis in a dynamic heart phantom. Methods An anatomical heart model was designed using a three-dimensional (3D) printing technique. The lumen of the right coronary artery was reduced to 25% of the original areal cross-section. Scans were acquired with a 64-slice dual-layer CT equipment using a perfusion protocol with 36 time points. For distinguishing haemodynamically affected from unaffected myocardial regions, conventional and spectral mean transit time (MTT) parameter maps were compared. A dose reduction technique was simulated by using a subset of time points of the time attenuation curves (TACs). Results The tracer kinetic modeling showed decreased errors on fit parameters from conventional to spectral TACs (42% reduction for A and 40% for λ). Three characteristic regions (highly, moderately, and not affected by the simulated stenosis) can be distinguished in all spectral perfusion maps. The best distinction was observed on MTT maps. An area under the curve (AUC) value of 1.00 for the voxel-wise differentiation of haemodynamically affected tissue was achieved versus a 0.89 AUC for conventional MTT maps. By temporal under-sampling, a dose reduction of approximately 78% from 19 to 4.3 mSv was achieved with a 0.96 AUC. Conclusion Dual-energy CT can provide time-resolved iodine density data, which enables the calculation of absolute quantitative perfusion maps with decreased fitting errors, improving the accuracy for poststenotic myocardial ischaemic detection in a 3D-printed heart phantom.

Abstract The separation of mixtures of substances into their individual components plays an important role in many areas of science. In medical imaging, one method is the established analysis using dual-energy computed tomography. However, when analyzing mixtures consisting of more than three individual basis materials, a physical limit is reached that no longer allows this standard analysis. In addition, the X-ray attenuation coefficients of chemically complicated basis materials may not be known and also cannot be determined by other or previous analyses. To address these issues, we developed a novel theoretical approach and algorithm and tested it on samples prepared in the laboratory as well as on ex-vivo medical samples. This method allowed both five-material decomposition and determination or optimization of the X-ray attenuation coefficients of the sample base materials via optimizations of objective functions. After implementation, this new multimodal method was successfully tested on self-mixed samples consisting of the aqueous base solutions iomeprol, eosin Y disodiumsalt, sodium chloride, and pure water. As a first proof of concept of this technique for detailed material decomposition in medicine we analyzed exact percentage composition of ex vivo clots from patients with acute ischemic stroke, using histological analysis as a reference standard.

Electronic cigarette (e-cig) use during pregnancy has become a major health concern in recent years and many view them as less harmful and may help quit or reduce combustible cigarettes. Implementing a state-of-the-art engineered vaping system, comprising an atomizer similar to those sold in vape shops, we aimed to utilize a translational e-cig inhalation delivery method to provide crucial information on the impact of prenatal e-cig aerosols on the developing brain hippocampal mTOR system in a rat model system. Gestational e-cig vaping significantly increased P-mTOR levels (p

In the summer of 2020, multiple efforts were undertaken to establish safe and effective vaccines to combat the spread of the coronavirus disease (COVID-19). In the United States (U.S.), Operation Warp Speed (OWS) was the program designated to coordinate such efforts. OWS was a partnership between the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector, that aimed to help accelerate control of the COVID-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. The U.S. Department of Veterans Affairs’ (VA) was identified as a potential collaborator in several large-scale OWS Phase III clinical trial efforts designed to evaluate the safety and efficacy of various vaccines that were in development. Given the global importance of these trials, it was recognized that there would be a need for a coordinated, centralized effort within VA to ensure that its medical centers (sites) would be ready and able to efficiently initiate, recruit, and enroll into these trials.The manuscript outlines the partnership and start-up activities led by two key divisions of the VA's Office of Research and Development's clinical research enterprise. These efforts focused on site and enterprise-level requirements for multiple trials, with one trial serving as the most prominently featured of these studies within the VA. As a result, several best practices arose that included designating clinical trial facilitators to study sites to support study initiation activities and successful study enrollment at these locations in an efficient and timely fashion.

Summary: Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we show a B cell-intrinsic role for signal transducer and activator of transcription 3 (STAT3) in GC DZ and LZ organization. Altered zonal organization of STAT3-deficient GCs dampens development of long-lived plasma cells (LL-PCs) but increases memory B cells (MBCs). In an abundant antigenic environment, achieved here by prime-boost immunization, STAT3 is not required for GC initiation, maintenance, or proliferation but is important for sustaining GC zonal organization by regulating GC B cell recycling. Th cell-derived signals drive STAT3 tyrosine 705 and serine 727 phosphorylation in LZ B cells, regulating their recycling into the DZ. RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses identified STAT3 regulated genes that are critical for LZ cell recycling and transiting through DZ proliferation and differentiation phases. Thus, STAT3 signaling in B cells controls GC zone organization and recycling, and GC egress of PCs, but negatively regulates MBC output.

New biomarkers are required to improve the assessment of aortic wall integrity and risk of rupture. Here the authors report the development of an imaging probe for ADAMTS4, which they test in an abdominal aortic aneurysm mouse model and show in vivo prediction of aneurysm and rupture.

Abstract Background Glassware can be an effective vehicle to recruit customers, revive brands, build profits and increase alcohol consumption by capitalising on the immediacy of glassware to the point of consumption. The design of glassware can also contribute to harm reduction by slowing and reducing consumption. Nucleated bases have been added to lager glasses in recent years which allow carbon dioxide (CO2) to be more rapidly released and ascend through the solution. The aim of these studies was to investigate the effect of nucleated glasses on the likeability and drinking rate of lager in alcohol drinkers. Methods In Study 1, participants (n = 116) were asked to taste two glasses of lager (280 millilitres (ml) each) in separate 5-min taste tests and fill out a likeability questionnaire after each glass in a within-subjects design with one factor of glass (nucleated, non-nucleated). The primary outcome was the likeability of lager and the secondary outcome was volume consumption during taste tests. In Study 2, participants (n = 160) were asked to consume a pint of lager (568 ml) and fill out a likeability questionnaire in a between-subjects design with one factor of glass (nucleated, non-nucleated). The primary outcome was time taken to consume a pint of lager and secondary outcomes were the likeability of lager, mood and alcohol craving. Results There was no clear evidence that likeability of lager differed between nucleated and non-nucleated glasses in either study. In Study 1, a paired-samples t test found strong evidence that lager in nucleated glasses was more visually appealing (single item from likeability measure) than lager in non-nucleated glasses (mean difference (MD) = 10.2, 95% confidence interval (CI) 6.1, 14.2, p

Generative models, such as DALL-E 2 (OpenAI), could represent promising future tools for image generation, augmentation, and manipulation for artificial intelligence research in radiology, provided that these models have sufficient medical domain knowledge. Herein, we show that DALL-E 2 has learned relevant representations of x-ray images, with promising capabilities in terms of zero-shot text-to-image generation of new images, the continuation of an image beyond its original boundaries, and the removal of elements; however, its capabilities for the generation of images with pathological abnormalities (eg, tumors, fractures, and inflammation) or computed tomography, magnetic resonance imaging, or ultrasound images are still limited. The use of generative models for augmenting and generating radiological data thus seems feasible, even if the further fine-tuning and adaptation of these models to their respective domains are required first.

BackgroundIncreasing the availability of non-alcoholic options is a promising population-level intervention to reduce alcohol consumption, currently unassessed in naturalistic settings. This study in an online retail context aimed to estimate the impact of increasing the proportion of non-alcoholic (relative to alcoholic) drinks, on selection and purchasing of alcohol.Methods and resultsAdults (n = 737) residing in England and Wales who regularly purchased alcohol online were recruited between March and July 2021. Participants were randomly assigned to one of 3 groups: "25% non-alcoholic/75% alcoholic"; "50% non-alcoholic/50% alcoholic"; and "75% non-alcoholic/25% alcoholic," then selected drinks in a simulated online supermarket, before purchasing them in an actual online supermarket. The primary outcome was the number of alcohol units selected (with intention to purchase); secondary outcomes included actual purchasing. A total of 607 participants (60% female, mean age = 38 years [range: 18 to 76]) completed the study and were included in the primary analysis. In the first part of a hurdle model, a greater proportion of participants in the "75% non-alcoholic" group did not select any alcohol (13.1%) compared to the "25% non-alcoholic" group (3.4%; 95% confidence interval [CI] -2.09, -0.63; p < 0.001). There was no evidence of a difference between the "75% non-alcoholic" and the "50% non-alcoholic" (7.2%) groups (95% CI 0.10, 1.34; p = 0.022) or between the "50% non-alcoholic" and the "25% non-alcoholic" groups (95% CI -1.44, 0.17; p = 0.121). In the second part of a hurdle model in participants (559/607) selecting any drinks containing alcohol, the "75% non-alcoholic" group selected fewer alcohol units compared to the "50% non-alcoholic" (95% CI -0.44, -0.14; p < 0.001) and "25% non-alcoholic" (95% CI -0.54, -0.24; p < 0.001) groups, with no evidence of a difference between the "50% non-alcoholic" and "25% non-alcoholic" groups (95% CI -0.24, 0.05; p = 0.178). Overall, across all participants, 17.46 units (95% CI 15.24, 19.68) were selected in the "75% non-alcoholic" group; 25.51 units (95% CI 22.60, 28.43) in the "50% non-alcoholic" group; and 29.40 units (95% CI 26.39, 32.42) in the "25% non-alcoholic" group. This corresponds to 8.1 fewer units (a 32% reduction) in the "75% non-alcoholic" compared to the "50% non-alcoholic" group, and 11.9 fewer alcohol units (41% reduction) compared to the "25% non-alcoholic" group; 3.9 fewer units (13% reduction) were selected in the "50% non-alcoholic" group than in the "25% non-alcoholic" group. For all other outcomes, alcohol selection and purchasing were consistently lowest in the "75% non-alcoholic" group. Study limitations include the setting not being entirely naturalistic due to using a simulated online supermarket as well as an actual online supermarket, and that there was substantial dropout between selection and purchasing.ConclusionsThis study provides evidence that substantially increasing the proportion of non-alcoholic drinks-from 25% to 50% or 75%-meaningfully reduces alcohol selection and purchasing. Further studies are warranted to assess whether these effects are realised in a range of real-world settings.Trial registrationISRCTN: 11004483; OSF: https://osf.io/qfupw.

Abstract Environmental heterogeneity in temperate latitudes is expected to maintain seasonally plastic life‐history strategies that include the tuning of morphologies and metabolism that support overwintering. For species that have expanded their ranges into tropical latitudes, it is unclear the extent to which the capacity for plasticity will be maintained or will erode with disuse. The migratory generations of the North American (NA) monarch butterfly Danaus plexippus lead distinctly different lives from their summer generation NA parents and their tropical descendants living in Costa Rica (CR). NA migratory monarchs postpone reproduction, travel thousands of kilometers south to overwinter in Mexico, and subsist on little food for months. Whether recently dispersed populations of monarchs such as those in Costa Rica, which are no longer subject to selection imposed by migration, retain ancestral seasonal plasticity is unclear. To investigate the differences in seasonal plasticity, we reared the NA and CR monarchs in summer and autumn in Illinois, USA, and measured the seasonal reaction norms for aspects of morphology and metabolism related to flight. NA monarchs were seasonally plastic in forewing and thorax size, increasing wing area and thorax to body mass ratio in autumn. While CR monarchs increased thorax mass in autumn, they did not increase the area of the forewing. NA monarchs maintained similar resting and maximal flight metabolic rates across seasons. However, CR monarchs had elevated metabolic rates in autumn. Our findings suggest that the recent expansion of monarchs into habitats that support year‐round breeding may be accompanied by (1) the loss of some aspects of morphological plasticity as well as (2) the underlying physiological mechanisms that maintain metabolic homeostasis in the face of temperature heterogeneity.

Background: Routine type and screens (T&S) prior to total hip (THA) and total knee arthroplasty (TKA) are common despite low transfusion rates. Our institution implemented a practice change after previously demonstrating a transfusion rate of 1.06%. The purpose of this study is to present the follow-up data 1 year after the practice change of discontinuing routine T&S orders in primary total joint arthroplasty. Methods: A practice change was implemented discontinuing routine T&S orders prior to elective primary total joint arthroplasties. We retrospectively reviewed prospectively collected data on preoperative T&S, hemoglobin values, transfusion rates, bleeding disorders, and anticoagulation status. Results: A total of 663 patients were included in the study (273 THAs and 390 TKAs). The cumulative transfusion rate was 0.75. No patients received an intraoperative transfusion. Three patients (1.1%) received a postoperative transfusion after THA, and 3 patients (0.5%) received a transfusion after TKA. The mean preoperative hemoglobin in the transfused patients was 12.1 g/dL. Thirteen patients underwent a preoperative T&S (2.0%), and only 2 required transfusion (15.4%). Only 1 patient who required transfusion was on preoperative anticoagulation, and no patients with bleeding disorders required transfusions. Discontinuing routine T&S resulted in an estimated cost savings of $124,325.50. Conclusions: Discontinuation of routine T&S did not result in any adverse consequences. If required, T&S can safely be performed intraoperatively or postoperatively. Surgeons may consider obtaining a T&S if their preoperative hemoglobin is less than 11-12 g/dL or if significant blood loss is expected in a complex primary total joint arthroplasty.

The organic cation in the title molecular salt, C5H13NCl+·Cl−, exhibits the gauche effect with a C—H bond of the C atom β to the chloro group donating electrons to the antibonding orbital of the C—Cl bond to stabilize the gauche conformation [Cl—C—C—C = −68.6 (6)°], as confirmed by DFT geometry optimizations that show a lengthening of the C—Cl bond relative to that of the anti conformation. Of further interest is the higher point group symmetry of the crystal (\overline{4}), compared that of the that of the molecular cation, which arises from a supramolecular head-to-tail square arrangement of four molecular cations that circulate in a counterclockwise direction when viewed down the tetragonal c axis.

The liver is the central metabolic organ. It constantly adapts its metabolic capacity to current physiological requirements. However, the relationship between tissue structure and hepatic function is incompletely understood; this results in a lack of diagnostic markers in medical imaging that can provide information about the liver’s metabolic capacity. Therefore, using normal rabbit livers, we combined magnetic resonance elastography (MRE) with proteomics-based kinetic modeling of central liver metabolism to investigate the potential role of MRE for predicting the liver’s metabolic function in vivo. Nineteen New Zealand white rabbits were investigated by multifrequency MRE and positron emission tomography (PET). This yielded maps of shear wave speed (SWS), penetration rate (PR) and standardized uptake value (SUV). Proteomic analysis was performed after the scans. Hepatic metabolic functions were assessed on the basis of the HEPATOKIN1 model in combination with a model of hepatic lipid-droplet metabolism using liquid chromatography–mass spectrometry. Our results showed marked differences between individual livers in both metabolic functions and stiffness properties, though not in SUV. When livers were divided into ‘stiff’ and ‘soft’ subgroups (cutoff SWS = 1.6 m/s), stiff livers showed a lower capacity for triacylglycerol storage, while at the same time showing an increased capacity for gluconeogenesis and cholesterol synthesis. Furthermore, SWS was correlated with gluconeogenesis and PR with urea production and glutamine exchange. In conclusion, our study indicates a close relationship between the viscoelastic properties of the liver and metabolic function. This could be used in future studies to predict non-invasively the functional reserve capacity of the liver in patients.

Abstract Background Spirometry and conventional chest x-ray have limitations in investigating early emphysema, while computed tomography, the reference imaging method in this context, is not part of routine patient care due to its higher radiation dose. In this work, we investigated a novel low-dose imaging modality, dark-field chest x-ray, for the evaluation of emphysema in patients with alpha1-antitrypsin deficiency. Methods By exploiting wave properties of x-rays for contrast formation, dark-field chest x-ray visualises the structural integrity of the alveoli, represented by a high signal over the lungs in the dark-field image. We investigated four patients with alpha1-antitrypsin deficiency with a novel dark-field x-ray prototype and simultaneous conventional chest x-ray. The extent of pulmonary function impairment was assessed by pulmonary function measurement and regional emphysema distribution was compared with CT in one patient. Results We show that dark-field chest x-ray visualises the extent of pulmonary emphysema displaying severity and regional differences. Areas with low dark-field signal correlate with emphysematous changes detected by computed tomography using a threshold of -950 Hounsfield units. The airway parameters obtained by whole-body plethysmography and single breath diffusing capacity of the lungs for carbon monoxide demonstrated typical changes of advanced emphysema. Conclusions Dark-field chest x-ray directly visualised the severity and regional distribution of pulmonary emphysema compared to conventional chest x-ray in patients with alpha1-antitrypsin deficiency. Due to the ultra-low radiation dose in comparison to computed tomography, dark-field chest x-ray could be beneficial for long-term follow-up in these patients.

Abstract Background To evaluate the diagnostic value of MR-derived CT-like images and simulated radiographs compared with conventional radiographs in patients with suspected shoulder pathology. Methods 3 T MRI of the shoulder including a 3D T1-weighted gradient echo sequence was performed in 25 patients (mean age 52.4 ± 18 years, 13 women) with suspected shoulder pathology. Subsequently a cone-beam forward projection algorithm was used to obtain intensity-inverted CT-like images and simulated radiographs. Two radiologists evaluated the simulated images separately and independently using the conventional radiographs as the standard of reference, including measurements of the image quality, acromiohumeral distance, critical shoulder angle, degenerative joint changes and the acromial type. Additionally, the CT-like MR images were evaluated for glenoid defects, subcortical cysts and calcifications. Agreement between the MR-derived simulated radiographs and conventional radiographs was calculated using Cohen’s Kappa. Results Measurements on simulated radiographs and conventional radiographs overall showed a substantial to almost perfect inter- and intra-rater agreement (κ = 0.69–1.00 and κ = 0.65–0.85, respectively). Image quality of the simulated radiographs was rated good to excellent (1.6 ± 0.7 and 1.8 ± 0.6, respectively) by the radiologists. A substantial agreement was found regarding diagnostically relevant features, assessed on Y- and anteroposterior projections (κ = 0.84 and κ = 0.69 for the measurement of the CSA; κ = 0.95 and κ = 0.60 for the measurement of the AHD; κ = 0.77 and κ = 0.77 for grading of the Samilson-Prieto classification; κ = 0.83 and κ = 0.67 for the grading of the Bigliani classification, respectively). Conclusion In this proof-of-concept study, clinically relevant features of the shoulder joint were assessed reliably using MR-derived CT-like images and simulated radiographs with an image quality equivalent to conventional radiographs. MR-derived CT-like images and simulated radiographs may provide useful diagnostic information while reducing the amount of radiation exposure.

Shortcomings in the rigour and reproducibility of research have become well-known issues and persist despite repeated calls for improvement. A coordinated effort among researchers, institutions, funders, publishers, learned societies, and regulators may be the most effective way of tackling these issues. The UK Reproducibility Network (UKRN) has fostered collaboration across various stakeholders in research and are creating the infrastructure necessary to advance rigorous and reproducible research practices across the United Kingdom. Other Reproducibility Networks, modelled on UKRN, are now emerging in other countries. Canada could benefit from a comparable network to unify the voices around research quality and maximize the value of Canadian research.