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Pearson’s correlation is widely used to test for an association between two variables and also forms the basis of several multivariate statistical procedures including many latent variable models. Spearman’s ρ\rho is a popular alternative. These procedures are compared with ranking the data and then applying the inverse normal transformation, or for short the normrank transformation. Using the normrank transformation was more powerful than Pearson’s and Spearman’s procedures when the distributions have less than normal kurtosis (platykurtic), when the distributions have greater than normal kurtosis (leptokurtic), and when the distribution is skewed. This is examined for testing if there is an association between two variables, identifying the number of factors in an exploratory factor analysis, identifying appropriate loadings in these analyses, and identifying relations among latent variables in structural equation models. R functions and their use are shown.

Plant-parasitic and free-living nematodes – bacterivores, fungivores, omnivores, predators – comprise the nematode community. Nematicide application and crop rotation are important tools to manage plant-parasitic nematodes, but effects on free-living nematodes and nematode ecological indices need further study. The nematicide fluopyram was recently introduced in cotton (Gossypium hirsutum) production and its effects on the nematode community need assessment. This research was conducted in 2017 and 2018 at a long-term field site in Quincy, FL where perennial grass/sod-based (bahiagrass, Paspalum notatum) and conventional cotton rotations were established in 2000. The objective of this research was to evaluate the effects of fluopyram nematicide, crop rotation phase, and irrigation on free-living nematodes and nematode ecological indices based on three soil sampling dates each season. We did not observe consistent effects of crop rotation phase on free-living nematodes or nematode ecological indices. Only omnivores were consistently negatively impacted by fluopyram. Nematode ecological indices reflected this negative effect by exhibiting a degraded/ stressed environmental condition relative to untreated plots. Free-living nematodes were not negatively impacted by nematicide when sod-based rotation was used.

The Ca Mau Peninsula (CMP) in Vietnam’s Lower Mekong Delta faces pressing challenges, including sea-level rise (SLR), land subsidence, flooding, and saltwater intrusion. Recent years have witnessed an earlier and more severe dry season, leading to heightened saltwater intrusion. As many CMP provinces rely on the Mekong River for their water supply, they are highly susceptible to prolonged drought and salinization. This study employs the MIKE 11 hydraulic model to project saltwater intrusion scenarios in the CMP up to 2050, based on Vietnam’s 2016 Ministry of Natural Resources and Environment (MONRE) SLR projections, considering water regulation from the Cai Lon-Cai Be sluice system. The modelled discharge, water level and salinity were calibrated and validated successfully based on di_erent statistical measures. The projections indicate that saltwater intrusion during the dry season could start 1 to 1.5 months earlier by 2050, with salinity levels exceeding 30 g/l in February. The findings underscore the importance of developing adaptation strategies to address the challenges of climate change and saltwater intrusion, notably in the region’s significant agricultural sector.

As the threat of African swine fever (ASF) introduction into new areas continues, animal health officials and epidemiologists need novel tools for early detection and surveillance. Passive surveillance from swine producers and veterinarians is critical to identify cases, especially the first introduction. Enhanced passive surveillance (EPS) protocols are needed that maximize temporal sensitivity for early ASF detection yet are easily implemented. Regularly collected production and disease data on swine farms may pose an opportunity for developing EPS protocols. To better understand the types of data regularly collected on swine farms and on-farm disease surveillance, a questionnaire was distributed in summer 2022 across multiple channels to MN swine producers. Thirty responses were received that indicated the majority of farms collect various types of disease information and conduct routine diagnostic testing for endemic swine diseases. Following this, a focus group discussion was held at the 2022 Leman Swine Conference where private and public stakeholders discussed the potential value of EPS, opportunities for collaboration, and challenges. The reported value of EPS varied by stakeholder group, but generally participants felt that for swine producers and packers, EPS would help identify abnormal disease occurrences. Many opportunities were identified for collaboration with ongoing industry initiatives and swine management software. Challenges included maintaining motivation for participation in ASF-free areas, labor, data sharing issues, and the cost of diagnostic testing. These highlight important issues to address, and future collaborations can help in the development of practical, fit-for-purpose, and valuable EPS protocols for ASF detection in the swine industry.

Researchers have several options available to analyze data from interventions when participants have not been randomly allocated into conditions. Among these are the gain score, ANCOVA, and propensity matching procedures. Each of these attempts to account for pre-treatment differences among the conditions, but they do so differently. These procedures are reviewed and methods for estimating them in R are shown. The choice of which of these procedures to use can be difficult. Different situations are shown where they perform differently. The primary conclusion of this paper is that models should be hypothesized for how the data may arise, data simulated for these models, and the properties of statistical procedures evaluated. A goal of this paper is to show these procedures without extensive mathematics in order to allow a broad read-ership to use these methods in their situations.

Trust in science is important, and Open Education Studies aims to publish trusted research. Two issues are addressed here: access to the data on which the research is based and how these data are analyzed. Some guidelines from other entities are discussed. As a new journal our guidelines should be influenced by the opinions of readers and authors, and as such we welcome discussion of how to ensure trust in the research OES publishes.

When students respond rapidly to an item during an assessment, it suggests that they may have guessed. Guessing adds error to ability estimates. Treating rapid responses as incorrect answers increases the accuracy of ability estimates for timed high-stakes summative tests like the ACT. There are fewer reasons to guess rapidly in non-timed formative tests, like those used as part of many personalized learning systems. Data from approximately 75 thousand formative assessments, from 777 students at two northern California charter high schools, were analyzed. The accuracy of ability estimates is only slightly improved by treating responses made in less than five seconds as incorrect responses. Simulations show that the advantage is related to: whether guesses are made rapidly, the amount of time required for thoughtful responses, the number of response alternatives, and the preponderance of guessing. An R function is presented to implement this procedure. Consequences of using this procedure are discussed.

Chinese translation BACKGROUND: Currently, there is no proven alternative therapy for patients with familial Mediterranean fever (FMF) that is resistant to or intolerant of colchicine. Interleukin-1 is a key proinflammatory cytokine in FMF. OBJECTIVE: To assess the efficacy and safety of rilonacept, an interleukin-1 decoy receptor, in treating patients with colchicine-resistant or -intolerant FMF. DESIGN: Randomized, double-blind, single-participant alternating treatment study. (ClinicalTrials.gov number: NCT00582907). SETTING: 6 U.S. sites. PATIENTS: Patients with FMF aged 4 years or older with 1 or more attacks per month. INTERVENTION: One of 4 treatment sequences that each included two 3-month courses of rilonacept, 2.2 mg/kg (maximum, 160 mg) by weekly subcutaneous injection, and two 3-month courses of placebo. MEASUREMENTS: Differences in the frequency of FMF attacks and adverse events between rilonacept and placebo. RESULTS: 8 males and 6 females with a mean age of 24.4 years (SD, 11.8) were randomly assigned. Among 12 participants who completed 2 or more treatment courses, the rilonacept-placebo attack risk ratio was 0.59 (SD, 0.12) (equal-tail 95% credible interval, 0.39 to 0.85). The median number of attacks per month was 0.77 (0.18 and 1.20 attacks in the first and third quartiles, respectively) with rilonacept versus 2.00 (0.90 and 2.40, respectively) with placebo (median difference, -1.74 [95% CI, -3.4 to -0.1]; P = 0.027). There were more treatment courses of rilonacept without attacks (29% vs. 0%; P = 0.004) and with a decrease in attacks of greater than 50% compared with the baseline rate during screening (75% vs. 35%; P = 0.006) than with placebo. However, the duration of attacks did not differ between placebo and rilonacept (median difference, 1.2 days [-0.5 and 2.4 days in the first and third quartiles, respectively]; P = 0.32). Injection site reactions were more frequent with rilonacept (median difference, 0 events per patient treatment month [medians of -4 and 0 in the first and third quartiles, respectively]; P = 0.047), but no differences were seen in other adverse events. LIMITATION: Small sample size, heterogeneity of FMF mutations, age, and participant indication (colchicine resistance or intolerance) were study limitations. CONCLUSION: Rilonacept reduces the frequency of FMF attacks and seems to be a treatment option for patients with colchicine-resistant or -intolerant FMF. PRIMARY FUNDING SOURCE: U.S. Food and Drug Administration, Office of Orphan Products Development. [ABSTRACT FROM AUTHOR]

The physiological cost of walking is greater in bilateral amputees (BA) than in both unilateral amputee and non-pathological gait. The aim of this study was to describe the physiological costs and other standard gait characteristics in a sample population of BA, walking at self-selected (comfortable) speeds. Amputees had bilateral trans-tibial, bilateral trans-femoral or trans-tibial/trans-femoral amputations as a result of trauma or congenital defects. All amputees wore their own prosthetic limbs which were either full-length prostheses or short non-articulating pylon prostheses (SNAPPs). The results were compared with a base line data set collected from a non-pathological control group. It was anticipated that amputees with high-level amputations would walk at the slowest speeds, have the highest physiological costs and lowest perception of walking ability. However, varying walking speeds resulted in varying exercise intensities, exercise heart rates and perceptions of walking that could not be directly related to amputation levels. It is therefore concluded that bilateral amputee gait is complex, varied and not easily categorized. [ABSTRACT FROM AUTHOR]

Abstract Background Evidence demonstrates that measures are needed to optimise therapy and improve administration of medicines in care homes for older people. The aim of this study is to determine the clinical and cost effectiveness of a novel model of multi-professional medication review. Methods A cluster randomised controlled trial design, involving thirty care homes. In line with current practice in medication reviews, recruitment and consent will be sought from general practitioners and care homes, rather than individual residents. Care homes will be segmented according to size and resident mix and allocated to the intervention arm (15 homes) or control arm (15 homes) sequentially using minimisation. Intervention homes will receive a multi-professional medication review at baseline and at 6 months, with follow-up at 12 months. Control homes will receive usual care (support they currently receive from the National Health Service), with data collection at baseline and 12 months. The novelty of the intervention is a review of medications by a multi-disciplinary team. Primary outcome measures are number of falls and potentially inappropriate prescribing. Secondary outcome measures include medication costs, health care resource use, hospitalisations and mortality. The null hypothesis proposes no difference in primary outcomes between intervention and control patients. The primary outcome variable (number of falls) will be analysed using a linear mixed model, with the intervention specified as a fixed effect and care homes included as a random effect. Analyses will be at the level of the care home. The economic evaluation will estimate the cost-effectiveness of the intervention compared to usual care from a National Health Service and personal social services perspective. The study is not measuring the impact of the intervention on professional working relationships, the medicines culture in care homes or the generic health-related quality of life of residents. Discussion This study will establish the effectiveness of a new model of multi-professional clinical medication reviews in care homes, using novel approaches to recruitment and consent. It is the first study to undertake an examination of direct patient outcomes, together with an economic analysis. Trial Registration ISRCTN: ISRCTN90761620

Abstract Background A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model. Method In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model. Results The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP-A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free β-hCG with or without nuchal translucency. Conclusion The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.

Abstract Background There is a need for greater understanding of the impact of multiple sclerosis (MS) from the perspective of individuals with the condition. The South West Impact of MS Project (SWIMS) has been designed to improve understanding of disease impact using a patient-centred approach. The purpose is to (1) develop improved measurement instruments for clinical trials, (2) evaluate longitudinal performance of a variety of patient-reported outcome measures, (3) develop prognostic predictors for use in individualising drug treatment for patients, particularly early on in the disease course. Methods This is a patient-centred, prospective, longitudinal study of multiple sclerosis and clinically isolated syndrome (CIS) in south west England. The study area comprises two counties with a population of approximately 1.7 million and an estimated 1,800 cases of MS. Self-completion questionnaires are administered to participants every six months (for people with MS) or 12 months (CIS). Here we present descriptive statistics of the baseline data provided by 967 participants with MS. Results Seventy-five percent of those approached consented to participate. The male:female ratio was 1.00:3.01 (n = 967). Average (standard deviation) age at time of entry to SWIMS was 51.6 (11.5) years (n = 961) and median (interquartile range) time since first symptom was 13.3 (6.8 to 24.5) years (n = 934). Fatigue was the most commonly reported symptom, with 80% of participants experiencing fatigue at baseline. Although medication use for symptom control was common, there was little evidence of effectiveness, particularly for fatigue. Nineteen percent of participants were unable to classify their subtype of MS. When patient-reported subtype was compared to neurologist assessment for a sample of participants (n = 396), agreement in disease sub-type was achieved in 63% of cases. There were 836 relapses, reported by 931 participants, in the twelve months prior to baseline. Twenty-three percent of the relapsing-remitting group and 12% of the total sample were receiving disease-modifying therapy at baseline. Conclusions Demographics of this sample were similar to published data for the UK. Overall, the results broadly reflect clinical experience in confirming high symptom prevalence, with relatively little complete symptom relief. Participants often had difficulty in defining MS relapses and their own MS type.

Abstract Background Conjugated linoleic acid (cis-9, trans-11 CLA) and trans-11 vaccenic acid (VA) are found naturally in ruminant-derived foods. CLA has been shown to have numerous potential health related effects and has been extensively investigated. More recently, we have shown that VA has lipid-lowering properties associated with reduced hepatic lipidogenesis and chylomicron secretion in the JCR:LA-cp rat. The aim of this study was to evaluate potential additional hypolipidemic effects of purified forms of CLA and VA in an animal model of the metabolic syndrome (the JCR:LA-cp rat). Methods Twenty four obese JCR:LA-cp rats were randomized and assigned to one of three nutritionally adequate iso-caloric diets containing 1% w/w cholesterol and 15% w/w fat for 16 wk: 1) control diet (CD), 2) 1.0% w/w cis-9, trans-11 CLA (CLA), 3) 1.0% w/w VA and 1% w/w cis-9, trans-11 CLA (VA+CLA). Lean rats were fed the CD to represent normolipidemic conditions. Results Fasting plasma triglyceride (TG), total cholesterol and LDL-cholesterol concentrations were reduced in obese rats fed either the CLA diet or the VA+CLA diet as compared to the obese control group (p < 0.05, p < 0.001; p < 0.001, p < 0.01; p < 0.01, p < 0.001, respectively). The VA+CLA diet reduced plasma TG and LDL-cholesterol to the level of the normolipidemic lean rats and further decreased nonesterified fatty acids compared to the CLA diet alone. Interestingly, rats fed the VA+CLA diet had a higher food intake but lower body weight than the CLA fed group (P < 0.05). Liver weight and TG content were lower in rats fed either CLA (p < 0.05) or VA+CLA diets (p < 0.001) compared to obese control, consistent with a decreased relative protein abundance of hepatic acetyl-CoA carboxylase in both treatment groups (P < 0.01). The activity of citrate synthase was increased in liver and adipose tissue of rats fed, CLA and VA+CLA diets (p < 0.001) compared to obese control, suggesting increased mitochondrial fatty acid oxidative capacity. Conclusion We demonstrate that the hypolipidemic effects of chronic cis-9, trans-11 CLA supplementation on circulating dyslipidemia and hepatic steatosis are enhanced by the addition of VA in the JCR:LA-cp rat.

Abstract Background Given the immuno-modulatory activity of native haemozoin (Hz), the effects of constitutive Hz components on immune response are of interest. Recently, gene expression changes mediated by HNE and the synthetic analogue of Hz, beta-haematin (BH), were identified and implicated a significant role for lipid peroxidation products in Hz's activity. The study presented herein examines gene expression changes in response to 15(S)-hydroxyeicosatetraenoic acid (HETE) in a model macrophage cell line. Methods LPS-stimulated RAW 264.7 macrophage-like cells were treated with 40 μM 15(S)-HETE for 24 h, and microarray analysis was used to identify global gene expression alterations. Fold changes were calculated relative to LPS-stimulated cells and those genes altered at least 1.8-fold (p value ≤ 0.025) were considered to be differentially expressed. Expression levels of a subset of genes were assessed by qRT-PCR and used to confirm the microarray results. Results Network analysis revealed that altered genes were primarily associated with "lipid metabolism" and "small molecule biochemistry". While several genes associated with PPAR-gamma receptor-mediated signaling were differentially expressed, a number of genes indicated the activation of secondary signaling cascades. Genes related to cytoadherence (cell-cell and cell-matrix), leukocyte extravasation, and inflammatory response were also differentially regulated by treatment, supporting a potential role for 15(S)-HETE in malaria pathogenesis. Conclusion These results add insight and detail to 15-HETE's effects on gene expression in macrophage-like cells. Data indicate that while 15-HETE exerts biological activity and may participate in Hz-mediated immuno-modulation, the gene expression changes are modest relative to those altered by the lipid peroxidation product HNE.

Abstract Many western industrialized countries are currently suffering from a crisis in health human resources, one that involves a debate over the recruitment and licensing of foreign-trained doctors and nurses. The intense public policy interest in foreign-trained medical personnel, however, is not new. During the 1960s, western countries revised their immigration policies to focus on highly-trained professionals. During the following decade, hundreds of thousands of health care practitioners migrated from poorer jurisdictions to western industrialized countries to solve what were then deemed to be national doctor and nursing 'shortages' in the developed world. Migration plummeted in the 1980s and 1990s only to re-emerge in the last decade as an important debate in global health care policy and ethics. This paper will examine the historical antecedents to this ethical debate. It will trace the early articulation of the idea of a 'brain drain', one that emerged from the loss of NHS doctors to other western jurisdictions in the 1950s and 1960s. Only over time did the discussion turn to the 'manpower' losses of 'third world countries', but the inability to track physician migration, amongst other variables, muted any concerted ethical debate. By contrast, the last decade's literature has witnessed a dramatically different ethical framework, informed by globalization, the rise of South Africa as a source donor country, and the ongoing catastrophe of the AIDS epidemic. Unlike the literature of the early 1970s, recent scholarship has focussed on a new framework of global ethics.

Abstract Background Self-administered questionnaires are becoming increasingly common in general practice. Much research has explored methods to increase response rates but comparatively few studies have explored the effect of questionnaire administration on reported answers. Methods The aim of this study was to determine the effect on responses of returning patient questionnaires to the respondents' medical practice or an independent researcher to questions relating to adherence and satisfaction with a GP consultation. One medical practice in Waveney primary care trust, Suffolk, England participated in this randomised trial. Patients over 18 years initiated on a new long-term medication during a consultation with a GP were randomly allocated to return a survey from their medical practice to either their medical practice or an independent researcher. The main outcome measures were self reported adherence, satisfaction with information about the newly prescribed medicine, the consultation and involvement in discussions. Results 274 (47%) patients responded to the questionnaire (45% medical practice, 48% independent researcher (95% CI -5 to 11%, p = 0.46)) and the groups appeared demographically comparable, although the high level of non-response limits the ability to assess this. There were no significant differences between the groups with respect to total adherence or any of the satisfaction scales. Five (4%) patients reported altering doses of medication in the medical practice group compared with 18 (13%) in the researcher group (P = 0.009, Fisher's exact test). More patients in the medical practice group reported difficulties using their medication compared to the researcher group (46 (35%) v 30 (21%); p = 0.015, Fisher's exact test). Conclusion Postal satisfaction questionnaires do not appear to be affected by whether they are returned to the patient's own medical practice or an independent researcher. However, returning postal questionnaires relating to detailed patient behaviours may be subject to response biases and further work is needed to explore this phenomena.

Abstract Background Birth weight is a composite of skeletal size and soft tissue. These components are likely to have different growth patterns. The aim of this paper is to investigate the association between established determinants of birth weight and these separate components. Methods Weight, length, crown-rump, knee-heel, head circumference, arm circumference, and skinfold thicknesses were measured at birth in 699 healthy, term, UK babies recruited as part of the Exeter Family Study of Childhood Health. Corresponding measurements were taken on both parents. Principal components analysis with varimax rotation was used to reduce these measurements to two independent components each for mother, father and baby: one highly correlated with measures of fat, the other with skeletal size. Results Gestational age was significantly related to skeletal size, in both boys and girls (r = 0.41 and 0.52), but not fat. Skeletal size at birth was also associated with parental skeletal size (maternal: r = 0.24 (boys), r = 0.39 (girls) ; paternal: r = 0.16 (boys), r = 0.25 (girls)), and maternal smoking (0.4 SD reduction in boys, 0.6 SD reduction in girls). Fat was associated with parity (first borns smaller by 0.45 SD in boys; 0.31 SD in girls), maternal glucose (r = 0.18 (boys); r = 0.27 (girls)) and maternal fat (r = 0.16 (boys); r = 0.36 (girls)). Conclusion Principal components analysis with varimax rotation provides a useful method for reducing birth weight to two more meaningful components: skeletal size and fat. These components have different associations with known determinants of birth weight, suggesting fat and skeletal size may have different regulatory mechanisms, which would be important to consider when studying the associations of birth weight with later adult disease.

Abstract Background Since the publication of the first draft of the human genome in 2000, bioinformatic data have been accumulating at an overwhelming pace. Currently, more than 3 million sequences and 35 thousand structures of proteins and nucleic acids are available in public databases. Finding correlations in and between these data to answer critical research questions is extremely challenging. This problem needs to be approached from several directions: information science to organize and search the data; information visualization to assist in recognizing correlations; mathematics to formulate statistical inferences; and biology to analyze chemical and physical properties in terms of sequence and structure changes. Results Here we present MultiSeq, a unified bioinformatics analysis environment that allows one to organize, display, align and analyze both sequence and structure data for proteins and nucleic acids. While special emphasis is placed on analyzing the data within the framework of evolutionary biology, the environment is also flexible enough to accommodate other usage patterns. The evolutionary approach is supported by the use of predefined metadata, adherence to standard ontological mappings, and the ability for the user to adjust these classifications using an electronic notebook. MultiSeq contains a new algorithm to generate complete evolutionary profiles that represent the topology of the molecular phylogenetic tree of a homologous group of distantly related proteins. The method, based on the multidimensional QR factorization of multiple sequence and structure alignments, removes redundancy from the alignments and orders the protein sequences by increasing linear dependence, resulting in the identification of a minimal basis set of sequences that spans the evolutionary space of the homologous group of proteins. Conclusion MultiSeq is a major extension of the Multiple Alignment tool that is provided as part of VMD, a structural visualization program for analyzing molecular dynamics simulations. Both are freely distributed by the NIH Resource for Macromolecular Modeling and Bioinformatics and MultiSeq is included with VMD starting with version 1.8.5. The MultiSeq website has details on how to download and use the software: http://www.scs.uiuc.edu/~schulten/multiseq/

Abstract Background The association between infertility and sperm disomy is well documented. Results vary but most report that men with severely compromised semen parameters have a significantly elevated proportion of disomic sperm. The relationship between individual semen parameters and segregation of specific chromosome pairs is however less well reported as is the variation of disomy levels in individual men. Methods In order to address these questions the technique of fluorescent in-situ hybridisation (FISH) was utilised to determine the disomy levels of chromosomes X, Y and 21 in 43 sperm samples from 19 infertile males. The results generated from this study were analysed using logistic regression. Results In this study we compared levels of sperm concentration, motility and morphology with levels of sperm disomy for chromosome 21 and the sex chromosomes. Our results suggest that there is considerable variation in disomy levels for certain men. They also suggest that oligozoospermic males have significantly elevated levels of sex chromosome disomy but not disomy 21; they suggest that severe asthenozoospermic males have significantly elevated levels of disomy 21 but not sex chromosome disomy. Surprisingly, severe teratozoopsermic males appeared to have significantly lower levels of sperm disomy for both the sex chromosomes and chromosome 21. Conclusion We suggest that the association between sex chromosome disomy and oligozoospermia may be due to reduced recombination in the XY pairing region and discuss the relevance of our findings for the correlations between sperm disomy and sperm motility and morphology.

Abstract Background HTLV-I is associated with adult T-cell leukemia, and both HTLV-I and -II are associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Several published reports suggest that HTLV-I may lead to decreased survival, but HTLV-II has not previously been associated with mortality. Results We examined deaths among 138 HTLV-I, 358 HTLV-II, and 759 uninfected controls enrolled in a prospective cohort study of U.S. blood donors followed biannually since 1992. Proportional hazards models yielded hazard ratios (HRs) for the association between mortality and HTLV infection, controlling for sex, race/ethnicity, age, income, educational level, blood center, smoking, injection drug use history, alcohol intake, hepatitis C status and autologous donation. After a median follow-up of 8.6 years, there were 45 confirmed subject deaths. HTLV-I infection did not convey a statistically significant excess risk of mortality (unadjusted HR 1.9, 95%CI 0.8–4.4; adjusted HR 1.9, 95%CI 0.8–4.6). HTLV-II was associated with death in both the unadjusted model (HR 2.8, 95%CI 1.5–5.5) and in the adjusted model (HR 2.3, 95%CI 1.1–4.9). No single cause of death appeared responsible for the HTLV-II effect. Conclusions After adjusting for known and potential confounders, HTLV-II infection is associated with increased mortality among healthy blood donors. If replicated in other cohorts, this finding has implications for both HTLV pathogenesis and counseling of infected persons.

Abstract Background We report the characterisation of the variable large protein (vlp) gene expressed by clinical isolate A1 of Borrelia recurrentis; the agent of the life-threatening disease louse-borne relapsing fever. Methods The major vlp protein of this isolate was characterised and a DNA probe created. Use of this together with standard molecular methods was used to determine the location of the vlp1B. recurrentis A1 gene in both this and other isolates. Results This isolate was found to carry silent and expressed copies of the vlp1B. recurrentis A1 gene on plasmids of 54 kbp and 24 kbp respectively, whereas a different isolate, A17, had only the silent vlp1B. recurrentis A17 on a 54 kbp plasmid. Silent and expressed vlp1 have identical mature protein coding regions but have different 5' regions, both containing different potential lipoprotein leader sequences. Only one form of vlp1 is transcribed in the A1 isolate of B. recurrentis, yet both 5' upstream sequences of this vlp1 gene possess features of bacterial promoters. Conclusion Taken together these results suggest that antigenic variation in B. recurrentis may result from recombination of variable large and small protein genes at the junction between lipoprotein leader sequence and mature protein coding region. However, this hypothetical model needs to be validated by further identification of expressed and silent variant protein genes in other B. recurrentis isolates.

This study reports the performance of 7 types of consumer grade passive Electronic Radon Integrating Monitors, ERIM (AlphaE, AER Plus, Canary, Corentium Pro, Radon Scout Home, Ramon and Wave) and passive etched track radon detectors. All monitors and passive radon detectors were exposed side by side for 2 periods of 3 months under controlled conditions in the UKHSA radon chamber and in a stainless steel container to an average radon concentration of 4781 Bq m -3 and 166 Bq m -3 , respectively. The performance of each individual monitor was compared with Atmos 12DPX and AlphaGUARD P30 reference instruments. The performance of the monitors was evaluated by estimating the biased, precision and measurement errors of each type. It was found that UKHSA passive radon detectors showed excellent performance (measurement error < 10%) at both higher and lower exposures. The AlphaE, Canary and Ramon showed excellent performance, with measurement error <10%, when they were exposed to radon concentrations between 4000 Bq m -3 and 6000 Bq m -3 in the UKHSA radon chamber. However, when the monitors were exposed to radon levels below the UK radon Action Level of 200 Bq m -3 , the only ERIM which had a measurement error <10% was the Radon Scout Home. All other monitors showed a significant decrease in their performance with measurement errors ranging between 20% and 50%. The calibration factor, which is the ratio between the measured value (background is subtracted) and the reference value, was also studied. It was found that the calibration factors of individual monitors changed significantly. Calibration measurements in 2019 and in 2023 found that the percentage change varied between -46% and +63%. This shows the importance of initial and regular calibration, and maintenance of the monitors., (Creative Commons Attribution license.)

Background/objectives: Giant cell arteritis (GCA) is an inflammatory vascular disease in which prompt and accurate diagnosis is critical. The efficacy of temporal artery biopsy (TAB) is limited by 'skip' lesions and a delay in histological analysis. This first-in-man ex-vivo study aims to assess the accuracy of optical frequency domain imaging (OFDI) in diagnosing GCA., Subjects/methods: 29 TAB samples of patients with suspected GCA were submerged in 0.9% sodium chloride and an OFDI catheter was passed through the lumen to create cross-sectional images prior to histological analysis. The specimens were then preserved in formalin for histological examination. Mean intimal thickness (MIT) on OFDI was measured, and the presence of both multinucleate giant cells (MNGCs) and fragmentation of the internal elastic lamina (FIEL) was assessed and compared with histology, used as the diagnostic gold standard., Results: MIT in patients with/without histological evidence of GCA was 0.425 mm (±0.43) and 0.13 mm (±0.06) respectively compared with 0.215 mm (±0.09) and 0.135 mm (±0.07) on OFDI. MIT measured by OFDI was significantly higher in patients with histologically diagnosed arteritis compared to those without (p = 0.0195). For detecting FIEL and MNGCs, OFDI had a sensitivity of 75% and 28.6% and a specificity of 100% and 77.3% respectively. Applying diagnostic criteria of MIT > 0.20 mm, or the presence of MNGCs or FIEL, the sensitivity of detecting histological arteritis using OFDI was 91.4% and the specificity 94.1%., Conclusions: OFDI provided rapid imaging of TAB specimens achieving a diagnostic accuracy comparable to histological examination. In-vivo imaging may allow imaging of a longer arterial section., (© 2024. The Author(s).)

Importance: Hospitalizations related to opioid use disorder (OUD) represent an opportunity to initiate medication for OUD (MOUD)., Objective: To assess whether starting MOUD after a hospitalization or emergency department (ED) visit is associated with the odds of fatal and nonfatal opioid overdose at 6 and 12 months., Design, Setting, and Participants: This population-based cohort study used data from the Oregon Comprehensive Opioid Risk Registry, which links all payer claims data to other administrative health datasets, for individuals aged 18 years or older who had diagnosis codes related to OUD recorded at an index ED visit or hospitalization from January 2017 to December 2019. Data were analyzed between May 2023 and January 2024., Exposures: Receipt of MOUD within the 7 days after an OUD-related hospital visit., Main Outcomes and Measures: The primary outcome was fatal or nonfatal overdose at 6 and 12 months after discharge. Sample characteristics, including age, sex, insurance plan, number of comorbidities, and opioid-related overdose events, were stratified by receipt or nonreceipt of MOUD within 7 days after an OUD-related hospital visit. A logistic regression model was used to investigate the association between receipt of MOUD and having an opioid overdose event., Results: The study included 22 235 patients (53.1% female; 25.0% aged 25-39 years) who had an OUD-related hospital visit during the study period. Overall, 1184 patients (5.3%) received MOUD within 7 days of their ED visit or hospitalization. Of these patients, 683 (57.7%) received buprenorphine, 463 (39.1%) received methadone, and 46 (3.9%) received long-acting injectable naltrexone. Patients who received MOUD within 7 days after discharge had lower adjusted odds of fatal or nonfatal overdose at 6 months compared with those who did not (adjusted odds ratio [AOR], 0.63; 95% CI, 0.41-0.97). At 12 months, there was no difference in adjusted odds of fatal or nonfatal overdose between these groups (AOR, 0.79; 95% CI, 0.58-1.08). Patients had a lower risk of fatal or nonfatal overdose at 6 months associated with buprenorphine use (AOR, 0.50; 95% CI, 0.27-0.95) but not with methadone use (AOR, 0.57; 95% CI, 0.28-1.17)., Conclusions and Relevance: In this cohort study of individuals with an OUD-related hospital visit, initiation of MOUD was associated with reduced odds of opioid-related overdose at 6 months. Hospitals should consider implementing programs and protocols to offer initiation of MOUD to patients with OUD who present for care.

The early appearance of broadly neutralizing antibodies (bNAbs) in serum is associated with spontaneous hepatitis C virus (HCV) clearance, but to date, the majority of bNAbs have been isolated from chronically infected donors. Most of these bNAbs use the V H 1-69 gene segment and target the envelope glycoprotein E2 front layer. Here, we performed longitudinal B cell receptor (BCR) repertoire analysis on an elite neutralizer who spontaneously cleared multiple HCV infections. We isolated 10,680 E2-reactive B cells, performed BCR sequencing, characterized monoclonal B cell cultures, and isolated bNAbs. In contrast to what has been seen in chronically infected donors, the bNAbs used a variety of V H genes and targeted at least three distinct E2 antigenic sites, including sites previously thought to be non-neutralizing. Diverse front-layer-reactive bNAb lineages evolved convergently, acquiring breadth-enhancing somatic mutations. These findings demonstrate that HCV clearance-associated bNAbs are genetically diverse and bind distinct antigenic sites that should be the target of vaccine-induced bNAbs., Competing Interests: Declaration of interests J.R.B. and C.O.O. have filed a provisional patent 63/470,326 related to monoclonal antibodies described in this manuscript., (Copyright © 2024. Published by Elsevier Inc.)

Climate change is significantly impacting agricultural production worldwide. Peanuts provide food and nutritional security to millions of people across the globe because of its high nutritive values. Drought and heat stress alone or in combination cause substantial yield losses to peanut production. The stress, in addition, adversely impact nutritional quality. Peanuts exposed to drought stress at reproductive stage are prone to aflatoxin contamination, which imposes a restriction on use of peanuts as health food and also adversely impact peanut trade. A comprehensive understanding of the impact of drought and heat stress at physiological and molecular levels may accelerate the development of stress tolerant productive peanut cultivars adapted to a given production system. Significant progress has been achieved towards the characterization of germplasm for drought and heat stress tolerance, unlocking the physiological and molecular basis of stress tolerance, identifying significant marker-trait associations as well major QTLs and candidate genes associated with drought tolerance, which after validation may be deployed to initiate marker-assisted breeding for abiotic stress adaptation in peanut. The proof of concept about the use of transgenic technology to add value to peanuts has been demonstrated. Advances in phenomics and artificial intelligence to accelerate the timely and cost-effective collection of phenotyping data in large germplasm/breeding populations have also been discussed. Greater focus is needed to accelerate research on heat stress tolerance in peanut. A suits of technological innovations are now available in the breeders toolbox to enhance productivity and nutritional quality of peanuts in harsh environments. A holistic breeding approach that considers drought and heat-tolerant traits to simultaneously address both stresses could be a successful strategy to produce climate-resilient peanut genotypes with improved nutritional quality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Puppala, Nayak, Sanz-Saez, Chen, Devi, Nivedita, Bao, He, Traore, Wright, Pandey and Sharma.)

Importance: Previous studies that examined the role of household opioid prescriptions in opioid overdose risk were limited to commercial claims, did not include fatal overdoses, and had limited inclusion of household prescription characteristics. Broader research is needed to expand understanding of the risk of overdose., Objective: To assess the role of household opioid availability and other household prescription factors associated with individuals' odds of fatal or nonfatal opioid overdose., Design, Setting, and Participants: A retrospective cohort study assessing patient outcomes from January 1, 2015, through December 31, 2018, was conducted on adults in the Oregon Comprehensive Opioid Risk Registry database in households of at least 2 members. Data analysis was performed between October 16, 2020, and January 26, 2023., Exposures: Household opioid prescription availability and household prescription characteristics., Main Outcomes and Measures: Opioid overdoses were captured from insurance claims, death records, and hospital discharge data. Household opioid prescription availability and prescription characteristics for individuals and households were modeled as 6-month cumulative time-dependent measures, updated monthly. To assess the association between household prescription availability, household prescription characteristics, and overdose, multilevel logistic regression models were developed, adjusting for demographic, clinical, household, and prescription characteristics., Results: The sample included 1 691 856 individuals in 1 187 140 households, of which most were women (53.2%), White race (70.7%), living in metropolitan areas (75.8%), and having commercial insurance (51.8%), no Elixhauser comorbidities (69.5%), and no opioid prescription fills in the study period (57.0%). A total of 28 747 opioid overdose events were observed during the study period (0.0526 per 100 person-months). Relative to individuals without personal or household opioid fills, the odds of opioid-related overdose increased by 60% when another household member had an opioid fill in the past 6 months (adjusted odds ratio [aOR], 1.60; 95% CI, 1.54-1.66) and were highest when both the individual and another household member had opioid fills in the preceding 6 months (aOR, 6.25; 95% CI, 6.09-6.40)., Conclusions and Relevance: In this cohort study of adult Oregon residents in households of at least 2 members, the findings suggest that household prescription availability is associated with increased odds of opioid overdose for others in the household, even if they do not have their own opioid prescription. These findings underscore the importance of educating patients about proper opioid disposal and the risks of household opioids.