Understanding the Risk Factors and Pathogenesis of Disseminated Nocardiosis in Immunocompromised Patients.

Nocardia is a genus of aerobic, Gram-positive, partially acid-fast, filamentous bacilli notoriously known for causing multisystemic infections in immunocompromised individuals. Notably, this genus of bacteria commonly infects the pleural and central nervous system, leading to pneumonia and brain abscesses, respectively. Our patient is a 71-year-old female who initially presented to the emergency department complaining of shortness of breath and altered mental status. Imaging revealed multiple enhancing brain lesions, a pleural effusion, and a paraspinal abscess, which upon aspiration and culture demonstrated Nocardia farcinica/kroppenstedtii. The patient underwent antibiotic treatment, including intravenous (IV) imipenem and trimethoprim/sulfamethoxazole (TMP-SMX), before being transitioned to oral TMP-SMX and amoxicillin/clavulanate. This case demonstrates the importance of diagnosing nocardiosis acutely and treating it appropriately.

Gender differences in PTSD severity and pain outcomes: Baseline results from the LAMP trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms. AIM: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. METHODS: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. RESULTS: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). CONCLUSION: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

Post-resolution macrophages shape long-term tissue immunity and integrity in a mouse model of pneumococcal pneumonia.

Resolving inflammation is thought to return the affected tissue back to homoeostasis but recent evidence supports a non-linear model of resolution involving a phase of prolonged immune activity. Here we show that within days following resolution of Streptococcus pneumoniae-triggered lung inflammation, there is an influx of antigen specific lymphocytes with a memory and tissue-resident phenotype as well as macrophages bearing alveolar or interstitial phenotype. The transcriptome of these macrophages shows enrichment of genes associated with prostaglandin biosynthesis and genes that drive T cell chemotaxis and differentiation. Therapeutic depletion of post-resolution macrophages, inhibition of prostaglandin E2 (PGE2) synthesis or treatment with an EP4 antagonist, MF498, reduce numbers of lung CD4+/CD44+/CD62L+ and CD4+/CD44+/CD62L-/CD27+ T cells as well as their expression of the α-integrin, CD103. The T cells fail to reappear and reactivate upon secondary challenge for up to six weeks following primary infection. Concomitantly, EP4 antagonism through MF498 causes accumulation of lung macrophages and marked tissue fibrosis. Our study thus shows that PGE2 signalling, predominantly via EP4, plays an important role during the second wave of immune activity following resolution of inflammation. This secondary immune activation drives local tissue-resident T cell development while limiting tissue injury.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case-control study.

Background: Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. Methods: The INTERSTROKE study is a case-control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). Findings: Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46-1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61-2.11) than ICH (OR 1.19 95% CI 1.00-1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24-4.10) and PAR (18.6%, 15.1-22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63-2.87) and undetermined cause (OR 1.97, 95% CI 1.55-2.50). Both filtered (OR 1.73, 95% CI 1.50-1.99) and non-filtered (OR 2.59, 95% CI 1.79-3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69-2.27), ischemic stroke (OR 1.89, 95% CI 1.59-2.24) and ICH (OR 2.00, 95% CI 1.60-2.50). Interpretation: There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. Funding: The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Sutton-Kadir Syndrome can be treated safely with endovascular embolisation alone.

INTRODUCTION: Sutton-Kadir Syndrome (SKS) describes true inferior pancreaticoduodenal artery (IPDA) aneurysms in the setting of coeliac artery (CA) stenosis or occlusion. Although rare, SKS aneurysms can rupture and cause morbidity. Due to its rarity and lack of controlled treatment data, correct treatment for the CA lesion is currently unknown. Our aim was to assess if endovascular embolisation alone was safe and effective in treatment of SKS aneurysms, in emergent and elective settings. Secondary objectives were to describe presentation and imaging findings. METHODS: A retrospective cohort study of patients treated at Sir Charles Gairdner Hospital between January 2014 and December 2021 was done. Data on presentation, diagnostics, aneurysm characteristics, CA lesion aetiology, treatment and outcomes were extracted from chart review. RESULTS: Twenty-four aneurysms in 14 patients were identified. Rupture was seen in 7/15 patients. Most aneurysms (22/24) were in the IPDA or one of its anterior or posterior branches. Median arcuate ligament (MAL) compression was identified in all. There was no difference in median (IQR) maximal transverse diameter between ruptured and non-ruptured aneurysms (6 mm (9), 12 mm (6), P = 0.18). Of ruptures, 6/7 had successful endovascular embolisation and 1/7 open surgical ligation. Of non-ruptures, 6/7 had successful endovascular embolisation, 1/7 open MAL division then endovascular CA stenting and aneurysm embolisation. No recurrences or new aneurysms were detected with computed tomography or magnetic resonance angiography over a median (IQR) follow-up period of 30 (10) months in 12 patients. CONCLUSION: Endovascular embolisation of SKS aneurysms without treatment of MAL compression is safe and effective in both the emergent and elective settings.

Pre-morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study.

BACKGROUND AND PURPOSE: Whilst sleep disturbances are associated with stroke, their association with stroke severity is less certain. In the INTERSTROKE study, the association of pre-morbid sleep disturbance with stroke severity and functional outcome following stroke was evaluated. METHODS: INTERSTROKE is an international case-control study of first acute stroke. This analysis included cases who completed a standardized questionnaire concerning nine symptoms of sleep disturbance (sleep onset latency, duration, quality, nocturnal awakening, napping duration, whether a nap was planned, snoring, snorting and breathing cessation) in the month prior to stroke (n = 2361). Two indices were derived representing sleep disturbance (range 0-9) and obstructive sleep apnoea (range 0-3) symptoms. Logistic regression was used to estimate the magnitude of association between symptoms and stroke severity defined by the modified Rankin Score. RESULTS: The mean age of participants was 62.9 years, and 42% were female. On multivariable analysis, there was a graded association between increasing number of sleep disturbance symptoms and initially severe stroke (2-3, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.94; 4-5, OR 1.66, 95% CI 1.23-2.25; >5, OR 2.58, 95% CI 1.83-3.66). Having >5 sleep disturbance symptoms was associated with significantly increased odds of functional deterioration at 1 month (OR 1.54, 95% CI 1.01-2.34). A higher obstructive sleep apnoea score was also associated with significantly increased odds of initially severe stroke (2-3, OR 1.48; 95% CI 1.20-1.83) but not functional deterioration at 1 month (OR 1.19, 95% CI 0.93-1.52). CONCLUSIONS: Sleep disturbance symptoms were common and associated with an increased odds of severe stroke and functional deterioration. Interventions to modify sleep disturbance may help prevent disabling stroke/improve functional outcomes and should be the subject of future research.

Tobacco use and risk of acute stroke in 32 countries in the INTERSTROKE study: a case­control study

BACKGROUND Smoking is a major risk factor for the global burden of stroke. We have previously reported a global population attributable risk (PAR) of stroke of 12.4% associated with current smoking. In this study we aimed to explore the association of current tobacco use with different types of tobacco exposure and environmental tobacco smoke (ETS) exposure on the risk of stroke and stroke subtypes, and by regions and country income levels. METHODS The INTERSTROKE study is a case­control study of acute first stroke and was undertaken with 13,462 stroke cases and 13,488 controls recruited between January 11, 2007 and August 8, 2015 in 32 countries worldwide. Association of risk of tobacco use and ETS exposure were analysed with overall stroke, ischemic and intracerebral hemorrhage (ICH), and with TOAST etiological stroke subtypes (large vessel, small vessel, cardioembolism, and undetermined). FINDINGS Current smoking was associated with an increased risk of all stroke (odds ratio [OR] 1.64, 95% CI 1.46­1.84), and had a stronger association with ischemic stroke (OR 1.85, 95% CI 1.61­2.11) than ICH (OR 1.19 95% CI 1.00­1.41). The OR and PAR of stroke among current smokers varied significantly between regions and income levels with high income countries (HIC) having the highest odds (OR 3.02 95% CI 2.24­4.10) and PAR (18.6%, 15.1­22.8%). Among etiological subtypes of ischemic stroke, the strongest association of current smoking was seen for large vessel stroke (OR 2.16, 95% CI 1.63­2.87) and undetermined cause (OR 1.97, 95% CI 1.55­2.50). Both filtered (OR 1.73, 95% CI 1.50­1.99) and non-filtered (OR 2.59, 95% CI 1.79­3.77) cigarettes were associated with stroke risk. ETS exposure increased the risk of stroke in a dose-dependent manner, exposure for more than 10 h per week increased risk for all stroke (OR 1.95, 95% CI 1.69­2.27), ischemic stroke (OR 1.89, 95% CI 1.59­2.24) and ICH (OR 2.00, 95% CI 1.60­2.50). INTERPRETATION There are significant variations in the magnitude of risk and PAR of stroke according to the types of tobacco used, active and ETS exposure, and countries with different income levels. Specific strategies to discourage tobacco use by any form and to build a smoke free environment should be implemented to ease the global burden of stroke. FUNDING The Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from Astra Zeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MERCK, Sharp and Dohme, Swedish Heart and Lung Foundation, UK Chest, and UK Heart and Stroke.

Effectiveness of HealthTracker for post-caesarean section surgical site infection surveillance: An intervention study.

This intervention study aimed to implement and evaluate the effectiveness of HealthTracker, a post-discharge surgical site infection surveillance system. Participants were 730 women birthing by caesarean section at a large hospital over a 6-month period. Data were downloaded from clinical data systems and HealthTracker. Receiver operating characteristics were used to assess HealthTracker. Over a 6-month period, 382 women completed HealthTracker, with 83 scoring ≥6, indicating signs and symptoms of surgical site infection. Of this 83, 58 sought advice from health professionals, 29 returned to hospital, and 45 received antibiotics. A total of 20 infections from a total population of 730 were confirmed, with 14 out of 382 respondents confirmed via HealthTracker. Receiver operating characteristics identified HealthTracker as an excellent indicator of surgical site infection. HealthTracker is a feasible mHealth option for monitoring post-discharge surgical site infection post-caesarean section. In addition, by providing alerts, advising women to monitor their symptoms and seek treatment if necessary, HealthTracker has the potential to enhance self-efficacy for surgical wound monitoring at home.

Exploring Gender Differences in Veterans in a Secondary Analysis of a Randomized Controlled Trial of Mindfulness for Chronic Pain.

Background: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. Materials and Methods: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. Results: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. Conclusion: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans.Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

A guide to photosynthetic gas exchange measurements: Fundamental principles, best practice and potential pitfalls.

Gas exchange measurements enable mechanistic insights into the processes that underpin carbon and water fluxes in plant leaves which in turn inform understanding of related processes at a range of scales from individual cells to entire ecosytems. Given the importance of photosynthesis for the global climate discussion it is important to (a) foster a basic understanding of the fundamental principles underpinning the experimental methods used by the broad community, and (b) ensure best practice and correct data interpretation within the research community. In this review, we outline the biochemical and biophysical parameters of photosynthesis that can be investigated with gas exchange measurements and we provide step-by-step guidance on how to reliably measure them. We advise on best practices for using gas exchange equipment and highlight potential pitfalls in experimental design and data interpretation. The Supporting Information contains exemplary data sets, experimental protocols and data-modelling routines. This review is a community effort to equip both the experimental researcher and the data modeller with a solid understanding of the theoretical basis of gas-exchange measurements, the rationale behind different experimental protocols and the approaches to data interpretation.

Bias assessment and correction for Levin's population attributable fraction in the presence of confounding.

In 1953, Morton Levin introduced a simple approach to estimating population attributable fractions (PAF) depending only on risk factor prevalence and relative risk. This formula and its extensions are still in widespread use today, particularly to estimate PAF in populations where individual data is unavailable. Unfortunately, Levin's approach is known to be asymptotically biased for the PAF when the risk factor-disease relationship is confounded even if relative risks that are correctly adjusted for confounding are used in the estimator. Here we describe a simple re-expression of Miettinen's estimand that depends on the causal relative risk, the unadjusted relative risk and the population risk factor prevalence. While this re-expression is not new, it has been underappreciated in the literature, and the associated estimator may be useful in estimating PAF in populations when individual data is unavailable provided estimated adjusted and unadjusted relative risks can be transported to the population of interest. Using the re-expressed estimand, we develop novel analytic formulae for the relative and absolute asymptotic bias in Levin's formula, solidifying earlier work by Darrow and Steenland that used simulations to investigate this bias. We extend all results to settings with non-binary valued risk factors and continuous exposures and discuss the utility of these results in estimating PAF in practice.

Remission of chronic actinic dermatitis on baricitinib: A case report.

Chronic actinic dermatitis (CAD) is an immune-mediated photodermatosis characterised by eczematous, pruritic changes to sun-exposed skin. The pathophysiology of CAD is poorly understood, with current explanations including a hypersensitivity reaction and cross-reactivity to contact allergens. The disease is often refractory to immunosuppressive treatment and has a marked impact on patient quality of life. Janus kinase inhibitors (JAKi) are a novel class of small molecules licenced for the management of certain inflammatory conditions, including atopic dermatitis We present the case of a 69-year-old gentleman with a history of severe CAD, unresponsive to standard therapies, who was prescribed baricitinib, a janus kinase (JAK) inhibitor as a single agent treatment for his disease. The patient experienced a dramatic clinical improvement with this therapy. In addition, normalisation of photo test and improvement of patch test results following treatment were observed. There is one previous case report in the literature describing the clinical response of patients with CAD to JAK inhibitor therapy, but no comment on pre or post treatment photo testing, patch testing or photo-patch testing results was made. In this case report, we discuss our understanding of the role of JAK inhibitors in CAD and highlight a potential new therapeutic avenue for this disabling disease.

Antiplatelet therapy and incident cognitive impairment or dementia-a systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: The benefit of antiplatelet therapy in preventing cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy and incident cognitive impairment or dementia in randomised clinical trials. METHODS: We searched PubMed, EMBASE and CENTRAL for randomised clinical trials published from database inception through 1 February 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single-agent antiplatelet, the control group was placebo. For dual agent antiplatelet therapy, the control group was single-agent monotherapy. A random-effects meta-analysis model was used to report pooled treatment effects and 95% confidence intervals (CIs). The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. RESULTS: A total of 11 randomised clinical trials were included (109,860 participants). All reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years. Antiplatelet therapy was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% versus 4.18% of patients over a mean trial follow-up of 5.8 years; odds ratio [OR], 0.94 [95% CI, 0.88-1.00]; absolute risk reduction, 0.2% [95% CI, -0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. CONCLUSION: In this meta-analysis, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia, but the CIs around this outcome do not exclude a modest preventative effect.

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

Effects of Real-Time Pressure Map Feedback on Confidence in Pressure Management in Wheelchair Users With Spinal Cord Injury: Pilot Intervention Study.

BACKGROUND: Wheelchair users with a spinal cord injury (SCI) are at a high risk for developing pressure injuries (PIs). Performing weight shifts is a primary method of pressure management for PI prevention; however, individuals with SCI may lack confidence in their abilities to perform adequate pressure relief due to their lack of sensation. Real-time seat interface pressure mapping feedback may provide partial substitution for sensory feedback such that an individual's confidence is improved. OBJECTIVE: We aim to examine how confidence for pressure management by wheelchair users with SCI was impacted by providing access to real-time, on-demand seat interface pressure mapping feedback. METHODS: Adults with SCI (N=23) completed self-efficacy questions addressing confidence around 4 factors related to performing weight shifts in this longitudinal, repeated-measures study. We evaluated the impact of providing standard PI prevention education and access to live pressure map feedback on confidence levels for performing weight shifts. RESULTS: Access to live pressure map feedback while learning how to perform weight shifts resulted in significantly higher confidence about moving far enough to relieve pressure at high-risk areas. Confidence for adhering to the recommended weight shift frequency and duration was not significantly impacted by in-clinic education or use of pressure map feedback. Confidence that performing weight shifts reduces PI risk increased most following education, with slight additional increase when pressure map feedback was added. CONCLUSIONS: Access to live pressure mapping feedback improves confidence about performing weight shifts that relieve pressure when provided in the clinical setting and demonstrates potential for the same in the home. This preliminary exploration of a smartphone-based pressure mapping intervention highlights the value of access to continuous pressure mapping feedback to improve awareness and confidence for managing pressure. TRIAL REGISTRATION: ClinicalTrials.gov NCT03987243; https://clinicaltrials.gov/study/NCT03987243.

Review and further developments in statistical corrections for Winner's Curse in genetic association studies.

Genome-wide association studies (GWAS) are commonly used to identify genomic variants that are associated with complex traits, and estimate the magnitude of this association for each variant. However, it has been widely observed that the association estimates of variants tend to be lower in a replication study than in the study that discovered those associations. A phenomenon known as Winner's Curse is responsible for this upward bias present in association estimates of significant variants in the discovery study. We review existing Winner's Curse correction methods which require only GWAS summary statistics in order to make adjustments. In addition, we propose modifications to improve existing methods and propose a novel approach which uses the parametric bootstrap. We evaluate and compare methods, first using a wide variety of simulated data sets and then, using real data sets for three different traits. The metric, estimated mean squared error (MSE) over significant SNPs, was primarily used for method assessment. Our results indicate that widely used conditional likelihood based methods tend to perform poorly. The other considered methods behave much more similarly, with our proposed bootstrap method demonstrating very competitive performance. To complement this review, we have developed an R package, 'winnerscurse' which can be used to implement these various Winner's Curse adjustment methods to GWAS summary statistics.

Excised leaves show limited and species-specific effects on photosynthetic parameters across crop functional types.

Photosynthesis is increasingly becoming a recognized target for crop improvement. Phenotyping photosynthesis-related traits on field-grown material is a key bottleneck to progress here due to logistical barriers and short measurement days. Many studies attempt to overcome these challenges by phenotyping excised leaf material in the laboratory. To date there are no demonstrated examples of the representative nature of photosynthesis measurements performed on excised leaves relative to attached leaves in crops. Here, we tested whether standardized leaf excision on the day prior to phenotyping affected a range of common photosynthesis-related traits across crop functional types using tomato (C3 dicot), barley (C3 monocot), and maize (C4 monocot). Potentially constraining aspects of leaf physiology that could be predicted to impair photosynthesis in excised leaves, namely leaf water potential and abscisic acid accumulation, were not different between attached and excised leaves. We also observed non-significant differences in spectral reflectance and chlorophyll fluorescence traits between the treatments across the three species. However, we did observe some significant differences between traits associated with gas exchange and photosynthetic capacity across all three species. This study represents a useful reference for those who perform measurements of this nature and the differences reported should be considered in associated experimental design and statistical analyses.

Understanding the role of mask-wearing during COVID-19 on the island of Ireland.

Non-pharmaceutical interventions have played a key role in managing the COVID-19 pandemic, but it is challenging to estimate their impacts on disease spread and outcomes. On the island of Ireland, population mobility restrictions were imposed during the first wave, but mask-wearing was not mandated until about six months into the pandemic. We use data on mask-wearing, mobility, and season, over the first year of the pandemic to predict independently the weekly infectious contact estimated by an epidemiological model. Using our models, we make counterfactual predictions of infectious contact, and ensuing hospitalizations, under a hypothetical intervention where 90% of the population wore masks from the beginning of community spread until the dates of the mask mandates. Over periods including the first wave of the pandemic, there were 1601 hospitalizations with COVID-19 in Northern Ireland and 1521 in the Republic of Ireland. Under the counterfactual mask-wearing scenario, we estimate 512 (95% CI 400, 730) and 344 (95% CI 266, 526) hospitalizations in the respective jurisdictions during the same periods. This could be partly due to other factors that were also changing over time.