Bivariate Linear Models Research Articles

Sociodemographic and dietary determinants of glyphosate exposure in a NYC-based pregnancy cohort

Previous studies have provided evidence for associations between glyphosate and aminomethylphosphonic acid (AMPA) exposure and adverse birth outcomes. However, few pregnancy cohort studies have investigated dietary and other determinants of glyphosate and AMPA exposure. We aimed to identify dietary and sociodemographic factors that predict glyphosate and AMPA exposure in a contemporary, urban pregnancy cohort in the US. The study included 725 pregnant participants from the New York University Children's Health and Environment Study (NYU CHES) in New York City. Urinary concentrations of glyphosate and AMPA, determined by high-performance liquid chromatography and tandem mass spectrometry, were analyzed in urine collected from NYU CHES participants across three prenatal time points. The Diet Health Questionnaire II was completed to capture dietary intake during the prenatal period. Descriptive statistics and bivariate linear models were used to assess determinants of urinary glyphosate and AMPA concentrations. Median urinary glyphosate and AMPA levels were 0.36 ng/mL and 0.37 ng/mL, respectively. Lower glyphosate levels were associated with younger age, obesity, public insurance, being single, and lower educational attainment. Nuts, seeds and whole grain intake was associated with increased urinary glyphosate concentrations. Urinary glyphosate concentrations were lower in summer than in winter. The study findings highlight widespread exposure to glyphosate and AMPA in this pregnancy cohort, with nuts/seeds and whole grains identified as possible dietary sources of exposure. High detection rates in the study population necessitate further research on dietary exposure patterns and perinatal outcomes to inform targeted interventions and reduce exposure in vulnerable populations.

Effect of a correlated competing risk on marginal survival estimation in an accelerated failure time model

In problems with a time to event outcome, subjects may experience competing events, which censor the outcome of interest. Cox’s partial likelihood estimator treating competing events as independent censoring is commonly used to examine group differences in clinical trials but fails to adjust for omitted covariates and can bias the assessment of marginal benefit. A bivariate normal linear model generating latent data with dependent censoring is used to assess this bias. Our R-package bnc provides maximum penalized likelihood (MPL) parameter estimation using a novel EM algorithm. Using bnc, we study the properties of such MPL estimation. Simulation results for two-sample survival comparisons of time to an event of interest, with independent censoring accompanied by censoring from a correlated competing risk, are presented. Key parameters—means, hazard ratios, and correlation—are estimated. These results demonstrated that, despite ill-conditioning in models generating correlated competing risks, estimates of marginal effects are reliable. Bivariate normal models were fitted in a trial of head and neck cancer. Model fits help with clinical interpretation while also supplementing other standard methods for follow-up that are terminated by intervening risks.

Estimation of Genetic Parameters for Litter Size and Growth Traits in a Prolific Line of Tunisian Barbarine Sheep

This study aimed to assess genetic parameters for ewe productivity in a Tunisian Barbarine sheep line. The traits studied were litter size (LS), birth weight (BW), weight at 90 days (W90), and average daily gain between 10 and 30 days (ADG13). A total of 3804 growth and 2726 lambing records were used. Bivariate linear and threshold animal models were fitted and analyzed using the Gibbs sampling methodology. Heritabilities for LS obtained with univariate threshold, bivariate linear, and threshold models were around 0.15, higher than the estimate obtained by a univariate linear model (0.09 ± 0.03). Direct heritability for growth traits remained consistent across models, except for W90 in the bivariate linear threshold model. Maternal heritability for growth traits was higher than direct heritability, ranging from 0.07 to 0.15, except for BW. The covariances between the direct and maternal effects of growth traits were slightly negative. Repeatability oscillated between 0.16 and 0.62. Direct genetic correlations between LS and the other traits were negative, varying from −0.18 (LS-BW) to −0.83 (LS-W90). Our results suggest that the threshold model may be the most appropriate for LS. A selection index including LS and growth traits may be proposed for routine genetic evaluation in this population.

Genetic evaluation for stillbirth and preweaning mortality in Australian dairy cattle

The welfare of calves is important to both farmers and consumers. Practices that increase the proportion of calves born alive and enable them to thrive through to weaning contribute to improved sustainability. Stillbirths (SB) are calvings where the calf dies at birth or within 24 h after birth. Preweaning mortality (PWM) refers to calves that die after the first day of life but before weaning based on termination data. Both SB and PWM are binary traits characterized by low heritability. Data collection for these traits is incomplete, compared with traits such as milk yield in cows. Despite these challenges, genetic variation can be measured and used to produce breeding tools, such as EBVs, to reduce calf mortality over time. The aim of this study was to compare the performance of various linear models to predict SB and PWM traits in Holstein and Jersey cattle and evaluate their applicability for industry-wide use in the Australian dairy industry. Calving records from around 2.25 million Holstein and Jersey dams were obtained from DataGene's Central Data Repository from the year 2000 onward, to calculate genetic parameters. About 7% of calves were recorded as SB in the period from 2000 to 2021 (n = 1.48 million calvings). The prevalence of PWM was much lower than SB during the same period at 2% (n = 0.89 million calves). Genetic parameters were estimated for SB direct, SB maternal, and PWM using bivariate linear models with calving ease (CE) as the second trait in the model. The heritability of these calf traits was low and varied between 1% and 5% depending on the breed, trait, and model. In Holstein cattle, heritabilities were 2% for PWM and SB direct and 1% for SB maternal, whereas in Jersey cattle heritabilities were 5% for PWM, 2% for SB direct, and 1% for SB maternal. The genetic trends for both SB direct and SB maternal in Holstein cattle indicate improvement in both traits, whereas there was no apparent increase or decrease in PWM in the past 2 decades. The coefficient of genetic variation for SB direct and PWM was between 11.7% and 23.0% in Holstein and Jersey cattle, demonstrating considerable genetic variation in calf survival traits as a first step to using genetic selection to increase the proportion of calves born alive and calves weaned. A focus on improved calf and calving recording practices is expected to increase the reliability of genetic predictions.

Well-Being, Loneliness, and Quality of Relationships Before and During the COVID-19 Pandemic in Botswana

This paper explored the determinants of well-being, quality of relationships (QOR), and loneliness among people of Botswana before and during the novel COVID-19 pandemic. It also examined whether there were significant differences between participants’ well-being, loneliness, and QOR before and during the COVID-19 pandemic. Factors associated with the well-being, loneliness, and QOR of the Botswana population before and during the COVID-19 pandemic were also explored. A cross-sectional design was used to collect information on the three variables before and during the COVID-19 pandemic using online platforms. Convenience sampling was used to recruit participants ( N = 422) using the WHO-5, Three-Item Loneliness Scale, and the Relationship Quality Index (RQI). Data were analyzed using bivariate and multivariate mixed-effects linear models. Age, relationship status, concern about own and family health, difficulty switching on and off media reporting on COVID, change in lifestyle, participation in sports, and resting were significantly associated with well-being ( p < .001) and loneliness ( p < .05). Sleep was associated with QOR. There were significant differences in the well-being, QOR, and loneliness scores before COVID-19 conditions and during COVID-19 conditions. Stakeholders should take cognizance of the impact of predictor variables on well-being and loneliness to mitigate the impact of current and future pandemics.

Application of deep learning with bivariate models for genomic prediction of sow lifetime productivity-related traits.

Pig breeders cannot obtain phenotypic information at the time of selection for sow lifetime productivity (SLP). They would benefit from obtaining genetic information of candidate sows. Genomic data interpreted using deep learning (DL) techniques could contribute to the genetic improvement of SLP to maximize farm profitability because DL models capture nonlinear genetic effects such as dominance and epistasis more efficiently than conventional genomic prediction methods based on linear models. This study aimed to investigate the usefulness of DL for the genomic prediction of two SLP-related traits; lifetime number of litters (LNL) and lifetime pig production (LPP). Two bivariate DL models, convolutional neural network (CNN) and local convolutional neural network (LCNN), were compared with conventional bivariate linear models (i.e., genomic best linear unbiased prediction, Bayesian ridge regression, Bayes A, and Bayes B). Phenotype and pedigree data were collected from 40,011 sows that had husbandry records. Among these, 3,652 pigs were genotyped using the PorcineSNP60K BeadChip. The best predictive correlation for LNL was obtained with CNN (0.28), followed by LCNN (0.26) and conventional linear models (approximately 0.21). For LPP, the best predictive correlation was also obtained with CNN (0.29), followed by LCNN (0.27) and conventional linear models (approximately 0.25). A similar trend was observed with the mean squared error of prediction for the SLP traits. This study provides an example of a CNN that can outperform against the linear model-based genomic prediction approaches when the nonlinear interaction components are important because LNL and LPP exhibited strong epistatic interaction components. Additionally, our results suggest that applying bivariate DL models could also contribute to the prediction accuracy by utilizing the genetic correlation between LNL and LPP.

Psychological wellbeing among parents of a child living with a serious chronic illness: A cross-sectional survey study.

Parents of a child with a chronic illness can experience greater distress than the average population, yet little is understood about differences between illness groups. This cross-sectional survey study aimed to compare parents' psychological distress and perceived wellbeing across five chronic illnesses. Parents from one Australian pediatric hospital completed the Kessler Psychological Distress Scale and seven purpose-designed items about their wellbeing. Data from 106 parents (cancer = 48, cystic fibrosis [CF] = 27, kidney disease = 12, gastrointestinal condition/disorder = 9, developmental and epileptic encephalopathy [DEE] = 10) was analysed using bivariate Pearson's Correlation and linear mixed-effects models. Parents' distress scores differed between groups (F(4,80) = 2.50, p = .049), with the DEE group reporting higher distress than the CF group (mean difference = 6.76, 95% CI [0.11, 13.42]). Distress scores were moderately correlated to parents' perceptions of their child's health and their own wellbeing. Parents' self-reported coping with their child's condition/treatments differed (F(4,81) = 3.24, p = .016), with the DEE group rating their coping as poorer than the CF group (mean difference = -25.32, 95% CI [-46.52, 4.11]). Across all groups, parents reported unmet needs, particularly for psychosocial support and practical/financial assistance. Support interventions may be most effective if tailored to the child's illness, with greater support potentially needed for parents who have a child with DEE and/or severe comorbidities.

Longitudinal association between muscle and bone loss: Results of US and Japanese cohort studies.

Muscle and bone are physiologically interconnected, but joint changes of muscle and bone with aging, and whether the muscle-bone changes are different by sex and by country has been little studied. We examined longitudinal associations of bone mineral density (BMD) and muscle mass or muscle strength in community-dwelling 65years or older in the United States and Japan. The present analytic sample included 1129 women and men from the Baltimore Longitudinal Study of Aging (BLSA) (mean age, 74.5±7.5years; women, 49.8%) and 1998 women and men from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) (mean age, 70.0±4.5years; women, 51.4%). Median follow-up was 4.6 (min-max, 0-15.4) years in the BLSA and 4.0 (min-max, 0-13.4) years in the NILS-LSA. We selected visits at which participants had BMD (whole body, pelvic, femoral neck, trochanter, and Ward's triangle BMDs) and muscle mass [appendicular lean mass, (ALM)] measured by DXA scan. In each bone site, we ran cohort-specific bivariate linear mixed-effects models adjusted for baseline age, sex, body height, body weight, fat mass, education year, and smoking status. Race was an additional adjustment in the BLSA. Additionally, we performed sex-specific analyses. In the BLSA, the rate of change in ALM positively correlated with the rate of change in the whole body (rho=0.30, P<0.0001) and pelvic BMD (rho=0.24, P<0.0001), but not in trochanter, femoral neck, or Ward's triangle BMD (P>0.05). In the NILS-LSA, ALM positively correlated with the rate of change in all bone sites (rho ranged from 0.20 to 0.71, P<0.01). In women, ALM positively correlated with the rate of change in all bone sites in both cohorts (in the NILS-LSA, rho ranged from 0.35 to 0.91, P<0.01; in the BLSA, rho ranged from 0.26 to 0.56, P<0.05) except for femoral neck BMD in the BLSA. In men, ALM positively correlated with pelvic, trochanter, and Ward's triangle BMD in the NILS-LSA (rho ranged from 0.45 to 0.68, P<0.0001), and whole body and trochanter BMD in the BLSA (both, rho=0.20, P<0.05). Muscle loss co-occurred with bone loss in both cohorts, but the association in the NILS-LSA tended to be stronger than in the BLSA, and the association was higher in women than in men, implying that the association may differ by sex and country.

Changes to the shape, orientation and packing of red cells as a function of retinal capillary size.

The free diameter of a red blood cell exceeds the lumen diameter of capillaries in the central nervous system, requiring significant deformation of cells. However the deformations undertaken in vivo are not well established due to the difficulty in observing cellular capillary flow in living human tissue. Here, we used high resolution adaptive optics imaging to non-invasively track 17,842 red blood cells in transit through 121 unique capillary segments of diameter 8 µm or less in the retina of 3 healthy human subjects. Within each vessel, a 2D en face profile was generated for the "average cell", whose shape was then inferred in 3D based on the key assumption of a circular capillary cross-section. From this we estimated the average volume, surface area, orientation, and separation between red cells within each capillary tube. Our results showed a network filtration effect, whereby narrower vessels were more likely to contain smaller cells (defined by surface area, which is thought not to vary during a cell's passage through the vascular system). A bivariate linear model showed that for larger cells in narrower vessels: cells re-orient themselves to align with the flow axis, their shape becomes more elongated, there are longer gaps between successive cells, and remarkably, that cell volume is less which implies the ejection of water from cells to facilitate capillary transit. Taken together, these findings suggest that red cells pass through retinal capillaries with some reluctance. A biphasic distribution for cell orientation and separation was evident, indicating a "tipping point" for vessels narrower than approx. 5 µm. This corresponds closely to the typical capillary lumen diameter, and may maximize sensitivity of cellular flow to small changes in diameter. We suggest that the minimization of unnecessary oxygen exchange, and hence of damage via reactive oxygen pathways, may have provided evolutionary pressure to ensure that capillary lumens are generally narrower than red blood cells.

Atmospheric dependence of the direct, diffuse, and global clear-sky conversion ratios between solar photosynthetic active irradiance and photon flux

The ratio of the global solar photosynthetic active radiation (PAR) photon flux (in μmol/m2s) to global solar PAR irradiance (in W/m2) is of interest to convert one into another. This ratio is usually considered as a constant value close to its extraterrestrial value, 4.55μmol/J. However, this ratio depends on the spectral composition of solar radiation at ground level and it is different for the diffuse and beam components of solar irradiance. Under clear-sky conditions, the three PAR ratios (global, beam and diffuse) are determined by the local atmospheric composition and the relative air mass. In this work, the SMARTS spectral irradiance model with MERRA-2 atmospheric inputs is used to evaluate the dependence of these ratios under clear-sky conditions with air mass, aerosol optical depth (AOD), precipitable water vapor and ozone column. The accuracy of the SMARTS beam spectral irradiance is previously assessed using local spectroradiometer measurements. The clear-sky ratios for the diffuse and direct components increase with increasing air mass, while the global ratio shows only a weak air mass dependence. The clear-sky ratios can be modeled with simple bi-variate linear models in air mass and AOD. These results can be used in similar climatic regions to convert PAR flux to PAR irradiance and vice versa with increased accuracy for the global, direct, and diffuse radiation under cloud-free conditions.

A framework to characterise the reproducibility of meta-analysis results with its application to direct oral anticoagulants in the acute treatment of venous thromboembolism.

The number of meta-analyses of aggregate data has dramatically increased due to the facility of obtaining data from publications and the development of free, easy-to-use, and specialised statistical software. Even when meta-analyses include the same studies, their results may vary owing to different methodological choices. Assessment of the replication of meta-analysis provides an example of the variation of effect 'naturally' observed between multiple research projects. Reproducibility of results has mostly been reported using graphical descriptive representations. A quantitative analysis of such results would enable (i) breakdown of the total observed variability with quantification of the variability generated by the replication process and (ii) identification of which variables account for this variability, such as methodological quality or the statistical analysis procedures used. These variables might explain systematic mean differences between results and dispersion of the results. To quantitatively characterise the reproducibility of meta-analysis results, a bivariate linear mixed-effects model was developed to simulate both mean results and their corresponding uncertainty. Results were assigned to several replication groups, those assessing the same studies, outcomes, treatment indication and comparisons classified in the same replication group. A nested random effect structure was used to break down the total variability within each replication group and between these groups to enable calculation of an intragroup correlation coefficient and quantification of reproducibility. Determinants of variability were investigated by modelling both mean and variance parameters using covariates. The proposed model was applied to the example of meta-analyses evaluating direct oral anticoagulants in the acute treatment of venous thromboembolism.

Hind feet position score: A novel trait to genetically reduce lameness incidence

Lameness is an important health and welfare issue that causes considerable economic losses in dairy herds. The objective of this study was to investigate whether the hind feet position score (HFPS) can be used as an auxiliary trait for genetic evaluation of lameness. The HFPS is evaluated by visual scoring of the position of both the hind-digits to the mid-line of the cow's body. The higher the heel height of the lateral claw, the higher is the HFPS, and the higher is the risk for development of lameness. In total, 3,478 records from 1,064 Fleckvieh cows from 35 farms were obtained between September 1, 2021, and March 5, 2022. Data collection was carried out by the regional milk recording organizations. Hind feet position was scored visually by trained personnel during routine milk performance testing in the milking parlor using a 3-class scoring system: score 1 = 0° to <17° indicating a balanced heel height of both the medial and the lateral claw; score 2 = angle of 17° to 24°; score 3 = angle of >24°. After all cows had been milked, locomotion scoring was performed for each animal using a 5-class scoring system with locomotion scores ranging between 1 (normal) and 5 (severely lame). Using HFPS, sensitivity and specificity were 69.5% and 66.8%, respectively, for detecting lameness defined by locomotion score ≥2. For genetic analyses, a bivariate linear animal model was fitted with fixed effects of herd, parity, lactation stage, and classifier, and random effects of animal and permanent environment. Heritabilities for HFPS and locomotion score were 0.07 and 0.10, respectively, and the genetic correlation between the 2 traits studied was 0.80. These results suggest that the HFPS could be used for genetic evaluations to reduce lameness incidence in dairy cattle.

Genetic parameters for health traits and their association with fertility and milk production in Chinese Holsteins.

Herd health is one of the key problems influencing the efficiency of the dairy industry. Genetic selection, with a focus on animal health, is important for herd improvement. This study aimed to estimate genetic parameters for health traits and their correlations with fertility and milk production traits in dairy cattle. Based on records from 58,549 lactating cows calved between 2015 and 2021, a total of 24 health traits (six composite health traits and 18 independent health traits), four fertility traits and five milk production traits were analysed. First, linear and threshold animal models were used to estimate the variance components and heritabilities of the health traits. Second, a bivariate linear animal model was used to estimate genetic correlations among all 24 health traits. Finally, a bivariate linear animal model based on records from the first lactation was used to estimate the correlations between health traits and fertility or milk production traits. The results showed that all health traits had low heritabilities, ranging from 0.002 (0.001) to 0.048 (0.004) in the linear model and from <0.001 (0.021) to 0.226 (0.035) in the threshold model. Genetic correlations between health traits across categories were generally low, whereas the relatively high genetic correlations were found between health traits within the same category. In this study, only a few significant and moderate genetic correlations were observed between health traits and fertility or milk production traits. Clinical mastitis showed relatively moderate correlations with fertility traits, ranging from 0.277 (0.113) (interval from first to last insemination) to 0.401 (0.104) (calving interval). Moreover, there were moderate genetic correlations between hoof health and milk production traits. The results from the current study will support balanced dairy breeding to genetically improve disease resistance in dairy cows.

The Effect of Continuous Liver Normothermic Machine Perfusion on the Severity of Histological Bile Duct Injury.

Static Cold Storage (SCS) injures the bile duct, while the effect of Normothermic Machine Perfusion (NMP) is unknown. In a sub-study of the COPE trial on liver NMP, we investigated the impact of preservation type on histological bile duct injury score (BDIS). Transplants with at least one bile duct biopsy, either at end of preservation or 1h post-reperfusion, were considered. BDIS was determined by assessing peribiliary glands injury, stromal and mural loss, haemorrhage, and thrombosis. A bivariate linear model compared BDIS (estimate, CI) between groups. Sixty-five transplants and 85 biopsies were analysed. Twenty-three grafts were preserved with SCS and 42 with NMP, with comparable baseline characteristics except for a shorter cold ischemic time in NMP. The BDIS increased over time regardless of preservation type (p = 0.04). The BDIS estimate was higher in NMP [8.02 (7.40-8.65)] than in SCS [5.39 (4.52-6.26), p < 0.0001] regardless of time. One patient in each group developed ischemic cholangiopathy, with a BDIS of 6 for the NMP-preserved liver. In six other NMP grafts, BDIS ranged 7-12 without development of ischemic cholangiopathy. In conclusion, BDIS increases over time, and the higher BDIS in NMP did not increase ischemic cholangiopathy. Thus, BDIS may overestimate this risk after liver NMP.

Factors associated with mental health outcomes after COVID-19: A 24-month follow-up longitudinal study

ObjectiveInvestigate the proportion of mental health outcomes (MHOs) and associated factors in COVID-19 survivors during a 24-month follow-up period. MethodAn observational, prospective study was performed in a teaching hospital in Barranquilla, Colombia, from April 1, 2020, to August 30, 2022. A cohort of 1565 COVID-19 survivors was recruited after discharge from the emergency room (ER), inpatient floor (IF), and intensive care unit (ICU) services and followed for 24 -months. The clinical assessment included screening scales for symptoms of anxiety, depressive, post-traumatic stress disorder (PTSD), and insomnia. Sociodemographic and clinical factors were also collected to identify possible associated factors. Descriptive, bivariate and mixed random-effect linear models were performed. ResultsA total of 1565 patients were included, of whom 785 (50.35%) were men. A large proportion of patients with mental symptoms were identified. After 24-months, the proportions of anxiety, depression, PTSD, and insomnia symptoms remained high at 16.55%, 21.79%, 35.27%, and 23.86%, respectively. Social factors, location of hospital stays, physical comorbidities, and the severity of COVID-19 were significantly associated with anxiety, depression, PTSD, and insomnia symptoms. ConclusionsCOVID-19's 2-year deleterious impacts on mental health, as well as the variables influencing these findings, have been documented. These results should aid in the development of public health initiatives to reduce morbidity rates in post-COVID-19 patients.

Longitudinal Relationships of White Matter Hyperintensities and Alzheimer Disease Biomarkers Across the Adult Life Span.

White matter hyperintensities (WMH) correlate with Alzheimer disease (AD) biomarkers cross-sectionally and modulate AD pathogenesis. Longitudinal changes have been reported for AD biomarkers, including concentrations of CSF β-amyloid (Aβ) 42, Aβ40, total tau and phosphorylated tau181, standardized uptake value ratio from the molecular imaging of cerebral fibrillar Aβ with PET using [11C] Pittsburgh Compound-B, MRI-based hippocampal volume, and cortical thickness. Correlations between established AD biomarkers and the longitudinal change for WMH have not been fully evaluated, especially among cognitively normal individuals across the adult life span. We jointly analyzed the longitudinal data of WMH volume and each of the established AD biomarkers and cognition from 371 cognitively normal individuals whose baseline age spanned from 19.6 to 88.20 years from 4 longitudinal studies of aging and AD. A 2-stage algorithm was applied to identify the inflection point of baseline age whereby older participants had an accelerated longitudinal change in WMH volume, in comparison with the younger participants. The longitudinal correlations between WMH volume and AD biomarkers were estimated from the bivariate linear mixed-effects models. A longitudinal increase in WMH volume was associated with a longitudinal increase in PET amyloid uptake and a decrease in MRI hippocampal volume, cortical thickness, and cognition. The inflection point of baseline age in WMH volume was identified at 60.46 (95% CI 56.43-64.49) years, with the annual increase for the older participants (83.12 [SE = 10.19] mm3 per year) more than 13 times faster (p < 0.0001) than that for the younger participants (6.35 [SE = 5.63] mm3 per year). Accelerated rates of change among the older participants were similarly observed in almost all the AD biomarkers. Longitudinal correlations of WMH volume with MRI, PET amyloid biomarkers, and cognition seemed to be numerically stronger for the younger participants, but not significantly different from those for the older participants. Carrying APOE ε4 alleles did not alter the longitudinal correlations between WMH and AD biomarkers. Longitudinal increases in WMH volume started to accelerate around a baseline age of 60.46 years and correlated with the longitudinal change in PET amyloid uptake, MRI structural outcomes, and cognition.

Surgical adhesive glue to repair first-degree perineal tears in vaginal birth: A randomised controlled clinical trial

BackgroundPerineal tears in vaginal birth are highly prevalent and may be related to physical and psychological trauma. Surgical glues are an alternative repair method to avoid the pain that may be caused by perineal repairs with sutures. ObjectiveTo evaluate the effectiveness of surgical adhesive glue in reducing perineal pain when compared to sutures in first-degree perineal tears resulting from vaginal birth. DesignOpen-label parallel-group randomised controlled trial. SettingAn alongside birth centre in Sao Paulo, Brazil. Participants84 intrapartum women with first-degree perineal tears needing repair. MethodsIn the experimental group (n = 42), the perineal tears were repaired with Epiglu® surgical glue (ethyl-2-cyanoacrylate); in the control group (n = 42), the tears were repaired with Vicryl Rapide® (polyglactin 910) sutures. The primary outcome was the intensity of perineal pain after birth measured by a numeric pain rating scale ranging from 0 to 10 points. The secondary outcomes were healing, measured by the “Redness, Oedema, Ecchymosis, Discharge, and Approximation" scale; women's satisfaction with the perineal repair, measured by a visual analogue scale; and the time necessary to complete the repair. Data were collected during postpartum hospitalisation and 10–20 days after discharge, from December 2020 to May 2021. Data were analysed using bivariate analysis and linear models by intention-to-treat. Results36–48 h after birth, the mean of perineal pain was 0.2 (95% Confidence Interval [CI] 0.1–0.8) in the experimental group and 0.9 (95% CI 0.5–1.5) in the control group; the perineal healing score was 0.7 (95% CI 0.4–1.2) and 0.8 (95% CI 0.5–1.2), in the experimental and control groups, respectively; satisfaction was higher among women in the experimental group (88.1% versus 83.3% in the control group). After discharge, the mean of perineal pain was 0.1 (95% CI 0.0–0.5) in the experimental group and 1.4 (95% CI 0.8–2.2) in the control group; the perineal healing score was 0.0 (95% CI 0) and 1.0 (95% CI 0.7–1.3) in the experimental and control groups, respectively. Satisfaction was higher in the experimental group (94.9% versus 75.0%). The longitudinal analysis showed statistically significant differences between the groups regarding perineal pain and women's satisfaction. The average time necessary for perineal repair was 6.0 (95% CI 4.7–8.7) minutes in the experimental group and 9.7 (95% CI 8.3–11.5) in the control group (p < 0.001). ConclusionsSurgical glue resulted in less perineal pain, faster repair, and greater satisfaction than perineal sutures after birth. The healing process was similar in both cases. Tweetable abstractSurgical glue was less painful and promoted greater satisfaction after birth compared to sutures in women with first-degree perineal tears. RegistrationRegistered on The Brazilian Clinical Trials Registry number RBR-52y5tq (http://www.ensaiosclinicos.gov.br/rg/RBR-52y5tq/), on July 16, 2020. The first recruitment was on December 17, 2020.

Identification of the genetic basis of sow pelvic organ prolapse.

Introduction: Pelvic organ prolapse (POP) is one contributor to recent increases in sow mortality that have been observed in some populations and environments, leading to financial losses and welfare concerns. Methods: With inconsistent previous reports, the objective here was to investigate the role of genetics on susceptibility to POP, using data on 30,429 purebred sows, of which 14,186 were genotyped (25K), collected from 2012 to 2022 in two US multiplier farms with a high POP incidence of 7.1% among culled and dead sows and ranging from 2% to 4% of all sows present by parity. Given the low incidence of POP for parities 1 and >6, only data from parities 2 to 6 were retained for analyses. Genetic analyses were conducted both across parities, using cull data (culled for POP versus another reason), and by parity, using farrowing data. (culled for POP versus culled for another reason or not culled). Results and Discussion: Estimates of heritability from univariate logit models on the underlying scale were 0.35 0.02 for the across-parity analysis and ranged from 0.41 0.03 in parity 2 to 0.15 0.07 in parity 6 for the by-parity analyses. Estimates of genetic correlations of POP between parities based on bivariate linear models indicated a similar genetic basis of POP across parities but less similar with increasing distance between parities. Genome wide association analyses revealed six 1Mb windows that explained more than 1% of the genetic variance in the across-parity data. Most regions were confirmed in several by-parity analyses. Functional analyses of the identified genomic regions showed a potential role of several genes on chromosomes 1, 3, 7, 10, 12, and 14 in susceptibility to POP, including the Estrogen Receptor gene. Gene set enrichment analyses showed that genomic regions that explained more variation for POP were enriched for several terms from custom transcriptome and gene ontology libraries. Conclusion: The influence of genetics on susceptibility to POP in this population and environment was confirmed and several candidate genes and biological processes were identified that can be targeted to better understand and mitigate the incidence of POP.

Nitrogen and carbon stable isotope analysis sheds light on trophic competition between two syntopic land iguana species from Galápagos

Coexistence between closely related species can lead to intense competition for resources. Stable isotope analysis (SIA) is a reliable tool to estimate the extent of species competition. We employed SIA to evaluate niche partitioning among two syntopic species of Galápagos land iguanas: Conolophus subcristatus and C. marthae. Samples were collected on Wolf Volcano, Isabela Island, where C. marthae is endemic and syntopic with C. subcristatus. We determined δ13C and δ15N ratios and described the isotopic niche of each species using corrected standard ellipse area (SEAc). We tested for differentiation between the isotopic niches, while controlling for sex, body size, spatial location of samples and mean annual primary productivity at capture points, using bivariate linear models. Despite the extensive overlap of the isotopic niches, we found species and sex to be a significant, interacting predictor of a sample’s location in the δ13C, δ15N space, indicating the existence of niche partitioning mechanisms acting between species and sexes. We also found that body size and productivity at the capture points, compounded with yet undetermined spatial effects, explain ca. 75% of the differences observed between species and sexes, providing evidence for differential microhabitat and food-items usage. Our study provides essential baselines for evaluating conservation actions for C. marthae, such as the potential translocation to a sanctuary area free of competition from C. subcristatus.

Genomic analyses of claw disorders in Holstein cows: Genetic parameters, trait associations, and genome-wide associations considering interactions of SNP and heat stress.

The aim of the present study was an in-depth genomic analysis to understand the genomic mechanisms of the 3 claw disorders dermatitis digitalis (DD), interdigital hyperplasia (HYP), and sole ulcer (SU). In this regard, we estimated genetic parameters based on genomic relationship matrices, performed genome-wide association studies, annotated potential candidate genes, and inferred genetic associations with breeding goal traits considering the most important chromosomal segments. As a further novelty of this study, we inferred possible SNP × heat stress interactions for claw disorders. The study consisted of 17,264 first-lactation Holstein Friesian cows kept in 50 large-scale contract herds. The disease prevalence was 15.96, 2.36, and 8.20% for DD, HYP, and SU, respectively. The remaining breeding goal traits consisted of type traits of the feet and leg composite, female fertility, health traits, and 305-d production traits. The final genotype data set included 44,474 SNPs from the 17,264 genotyped cows. Heritabilities for DD, HYP, and SU were estimated in linear and threshold models considering the genomic relationship matrix (G matrix). Genetic correlations with breeding goal traits based on G were estimated in a series of bivariate linear models, which were verified via SNP effect correlations for specific chromosome segments (i.e., segments harboring potential candidate genes for DD, HYP, and SU). Genome-wide association studies were performed for all traits in a case-control design by applying a single SNP linear mixed model. Furthermore, for DD, HYP, and SU, we modeled SNP × heat stress interactions in genome-wide association studies. Single nucleotide polymorphism-based heritabilities were 0.04 and 0.08 for DD, 0.03 and 0.10 for SU, and 0.03 and 0.23 for HYP from linear and threshold models, respectively. The genetic correlations between DD, HYP, and SU with conformation traits from the feet and leg composite were positive throughout, indicating the value of indirect selection on conformation traits to improve claw health. Genetic correlations between DD, SU, and HYP with other breeding goal traits indicated impaired female fertility, impaired udder health status, and productivity decline of diseased cows. Genetic correlations among DD, SU, and HYP were moderate to large, indicating that different claw disorders have similar genetic mechanisms. Nevertheless, we identified disease-specific potential candidate genes, and genetic associations based on the surrounding SNPs partly differed from the genetic correlations. Especially for candidate genes contributing to 2 traits simultaneously, correlations based on SNP effects from the respective chromosome segment were close to 1 or to -1. In this regard, we annotated the candidate genes KRT33A and KRT33B for HYP and DD, KIF27 for HYP and calving to first insemination, and MAN1A1 for SU and the production traits. For SNP × heat stress interactions, we identified significant SNPs on BTA 2, 4, 5, 7, 8, 9, 13, 22, 25, and 28, and we annotated the potential candidate genes FSIP2, CLCN1, ADGRV1, DOP1A, THBD, and RHOBTB1. Results indicate gene-specific mechanisms of the claw disorders only in specific environments.