Restricted Maximum Likelihood Research Articles

SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure

The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

Tomato families possessing resistance to late blight also display high-quality fruit

In recent years, several efforts have been made to develop tomato cultivars displaying both late blight resistance and good organoleptic fruit quality. Selection indexes are considered the best option to perform genotype selection when many different traits are being considered to select genotypes as close to the desired ideotype as possible. Therefore, this study aimed at selecting late blight-resistant tomato families based on their fruit quality attributes using factor analysis and ideotype-design / best linear unbiased predictor (FAI-BLUP) index. For this purpose, we assessed the fruit quality parameters of 81 F3:5 tomato families previously selected as late blight resistant. The tomato cultivars Thaise, Argos, and Liberty were included in the trial as checks. The experimental arrangement consisted of complete randomized blocks with three replicates. Each plot was formed by five plants, three of which were used in the fruit quality assessment. The quality parameters assessed were fruit diameter, fruit length, fruit color (L, a*, C, and H), fruit firmness, titratable acidity, soluble solids content, hydrogen potential, and SS:TA ratio. Fruit quality data were analyzed using the mixed model methodology via REML/BLUP (restricted residual maximum likelihood / best linear unbiased prediction) to obtain BLUPs that were further subjected to the FAI-BLUP selection index. The FAI-BLUP was efficient in selecting late blight-resistant tomato genotypes based on their fruit quality attributes. Fourteen tomato families were classified as closest to the desirable ideotype for fruit quality. These genotypes should move on to the following stages of the tomato breeding program.

Overnutrition is a risk factor for iron, but not for zinc or vitamin A deficiency in children and young people: a systematic review and meta-analysis

IntroductionTraditionally associated with undernutrition, increasing evidence suggests micronutrient deficiencies can coexist with overnutrition. Therefore, this work aimed to systematically review the associations between iron, zinc and vitamin A (VA) status...

Resistance to natural tick infestation varies with age and coat and hair traits in a tropically adapted beef cattle breed

Rhipicephalus (Boophilus) microplus causes considerable livestock production losses. Knowledge of the traits that influence tick resistance contributes to the development of breeding strategies designed to improve herd productivity. Within this context, this study evaluated the resistance of Caracu, a tropically adapted cattle breed, to R. microplus. Tick count, hair length, coat thickness, and coat color were evaluated in 202 naturally tick-infested females (cows and heifers) over a period of 18 months. Blood samples were collected from all animals during the winter season for hematological analysis. Data were analyzed using Pearson correlations, generalized linear models, and principal component analysis. Correlation coefficients of tick count with coat color, coat thickness, and hair length were estimated within each season. Hematological parameters were only included in the winter season analysis and were analyzed by the restricted maximum likelihood method using log-transformed data. No differences in blood parameters were observed between animals with and without ticks. However, tick count was negatively correlated with erythrocytes (−0.29) and hematocrit (−0.24) and positively correlated with mean corpuscular hemoglobin (0.21) and mean corpuscular hemoglobin concentration (0.25). These findings suggest that higher tick counts lead to a decrease in erythrocytes but also to an increase in the amount of hemoglobin per erythrocyte, which could reduce the damage caused by low erythrocyte levels due to tick hematophagy, delaying or preventing anemia. Although tick infestation on pasture was demonstrated by the infestation of all staff members during herd management, none of the animals exhibited high tick counts, providing evidence of resistance of Caracu animals to R. microplus. Tick infestation was influenced by age class (cows > heifers), season (spring and summer > fall and winter), coat thickness (>1.5 mm > <1.5 mm), and hair length (>6 mm > <6 mm). Three components were extracted by principal component analysis, which accounted for 69.46% of data variance. The findings of this study will contribute to the development of efficient strategies aimed at reducing economic losses due to tick infestation and could be applied in animal breeding to select for tick resistance traits, reducing chemical control strategies and consequently improving sustainable livestock production.

Estimation of heritability with genomic information by method R.

Estimating heritabilities with large genomic models by established methods such as restricted maximum likelihood (REML) or Bayesian via Gibbs sampling is computationally expensive. Alternatively, heritability can be estimated indirectly by method R and by maximum predictivity, referred to as MaxPred here, at a much lower computing cost. By method R, the heritability used for predictions with whole and partial data is considered the best estimate when the predictions based on partial data are unbiased relative to those with the complete data. By MaxPred, the heritability estimate is the one that maximizes predictivity. This study compared heritability estimation with genomic information using average information REML (AI-REML), method R and MaxPred. A simulated population was generated with ten generations of 5000 animals each and an effective population size of 80. Each animal had one record for a trait with a heritability of 0.3, a phenotypic variance of 10.0 and was genotyped at 50 k SNP. In method R, the heritability estimate is found when the expectation of a regression coefficient is equal to one. The regression is the EBV of selection candidates calculated with the whole dataset regressed on the EBV of candidates calculated from a partial dataset. In this study, we used the GBLUP framework and therefore, GEBV was calculated. The partial dataset was created by removing the last generation of phenotypes. Predictivity was defined as the correlation between the adjusted phenotypes of the selection candidates and their GEBV calculated from the partial data. We estimated the heritability for populations that included between three and 10 generations. In every scenario, predictivity increased as more data was used and was the highest at the simulated heritability. However, the predictivity for all data subsets and all heritabilities compared did not differ more than 0.01, suggesting MaxPred is not the best indication for heritability estimation. For the whole dataset, the heritability was estimated as 0.30 ± 0.01, 0.26 ± 0.01 and 0.30 ± 0.04 for AI-REML without genomics, AI-REML with genomics and method R with genomics, respectively. Heritability estimation with genomics by method R reduced timing by 83%, implying a reduction in computing time from 9.5 to 1.6 h, on average, compared to AI-REML with genomics. Method R has the potential to estimate heritabilities with large genomic information at a low cost when many generations of animals are present; however, the standard error can be high when only a few iterations are used.

A mediation analysis framework based on variance component to remove genetic confounding effect.

Identification of pleiotropy at the single nucleotide polymorphism (SNP) level provides valuable insights into shared genetic signals among phenotypes. One approach to study these signals is through mediation analysis, which dissects the total effect of a SNP on the outcome into a direct effect and an indirect effect through a mediator. However, estimated effects from mediation analysis can be confounded by the genetic correlation between phenotypes, leading to inaccurate results. To address this confounding effect in the context of genetic mediation analysis, we propose a restricted-maximum-likelihood (REML)-based mediation analysis framework called REML-mediation, which can be applied to either individual-level or summary statistics data. Simulations demonstrated that REML-mediation provides unbiased estimates of the true cross-trait causal effect, assuming certain assumptions, albeit with a slightly inflated standard error compared to traditional linear regression. To validate the effectiveness of REML-mediation, we applied it to UK Biobank data and analyzed several mediator-outcome trait pairs along with their corresponding sets of pleiotropic SNPs. REML-mediation successfully identified and corrected for genetic confounding effects in these trait pairs, with correction magnitudes ranging from 7% to 39%. These findings highlight the presence of genetic confounding effects in cross-trait epidemiological studies and underscore the importance of accounting for them in data analysis.

Small Sample Methods in Multilevel Analysis

Bayesian methods have been said to solve small sample problems in frequentist methods by reflecting prior knowledge in the prior distribution. However, there are dangers in strongly reflecting prior knowledge or situations where much prior knowledge cannot be used. In order to address the issue, in this article, we considered to apply two Bayesian methods, one with weakly informative prior for random effect parameters (BayesW) and another with non-informative prior (BayesN) and compared their performance of parameter recovery with restricted maximum likelihood (REML) method, a frequentist-based estimation method commonly used in multilevel analysis. Specifically, we conducted two simulation studies using a two-level linear multilevel model and compared the performance of the BayesW, the BayesN, and the REML in various conditions that include scenarios of small sample data with a combination of small sample size both at level-1 and level-2. The results showed that the REML performed better than the BayesW, which showed overall better performance than the BayesN, in terms of convergence, bias, and coverage in some small sample scenarios. Therefore, based on the results of the present study, it is recommended to use the REML when adapting the two-level linear multilevel model and analyzing real-world data with small samples.

Do statistical heterogeneity methods impact the results of meta- analyses? A meta epidemiological study.

Orthodontic systematic reviews (SRs) use different methods to pool the individual studies in a meta-analysis when indicated. However, the number of studies included in orthodontic meta-analyses is relatively small. This study aimed to evaluate the direction of estimate changes of orthodontic meta-analyses (MAs) using different between-study variance methods considering the level of heterogeneity when few trials were pooled. Search and study selection: Systematic reviews (SRs) published over the last three years, from the 1st of January 2020 to the 31st of December 2022, in six main orthodontic journals with at least one MA pooling five or lesser primary studies were identified. Data collection and analysis: Data were extracted from each eligible MA, which was replicated in a random effect model using DerSimonian and Laird (DL), Paule-Mandel (PM), Restricted maximum-likelihood (REML), Hartung Knapp and Sidik Jonkman (HKSJ) methods. The results were reported using median and interquartile range (IQR) for continuous data and frequencies for categorical data and analyzed using non-parametric tests. The Boruta algorithm was used to assess the significant predictors for the significant change in the confidence interval between the different methods compared to the DL method, which was only feasible using the HKSJ method. 146 MAs were included, most applying the random effect model (n = 111; 76%) and pooling continuous data using mean difference (n = 121; 83%). The median number of studies was three (range 2, 4), and the overall statistical heterogeneity (I2 ranged from 0 to 99% with a median of 68%). Close to 60% of the significant findings became non-significant when HKSJ was applied compared to the DL method and when the heterogeneity was present I2>0%. On the other hand, 30.43% of the non-significant meta-analyses using the DL method became significant when HKSJ was used when the heterogeneity was absent I2 = 0%. Orthodontic MAs with few studies can produce different results based on the between-study variance method and the statistical heterogeneity level. Compared to DL, HKSJ method is overconservative when I2 is greater than 0% and may result in false positive findings when the heterogeneity is absent.

Reliability generalization meta-analysis of orthorexia nervosa using the ORTO-11/12/15/R scale in all populations and language versions

BackgroundThe ORTO scale was developed in 2004 as a self-report questionnaire to assess symptoms of orthorexia nervosa (ON). ON is an unhealthy preoccupation with eating healthy food. The scale aims to measure obsessive attitudes and behaviors related to the selection, purchase, preparation, and consumption of pure, healthy food. Since its development, the ORTO-15 has been adapted into several shorter versions. The objective was to conduct a reliability generalization meta-analysis of the ORTO scale and its variant versions in all populations and languages.MethodsA systematic literature search was conducted to identify studies reporting the internal consistency of ORTO. Random-effect models were used to evaluate summary statistics of reliability coefficients, weighting the coefficients by the inverse variance using the restricted maximum likelihood method. The heterogeneity among the reliability coefficients was evaluated and assessed using numerous statistical metrics. The tau (τ), tau2 (τ2), I2, H2, R2, df, and the Q-statistic are among those obtained. Meta-regression analyses were used to examine moderators such as age and sex.ResultsTwenty-one studies (k = 21) involving 11,167 participants (n = 11,167) were analyzed. The overall effect estimate on internal consistency was 0.59 (95% CI 0.49–0.68), with a minimum reliability coefficient of 0.23 and a maximum reliability coefficient of 0.83. The heterogeneity statistics were found to have an I2 of 99.31%, which suggested high heterogeneity owing to a decrease in the confidence interval (95% CI) and an increase in variability. Sensitivity analysis revealed that a few studies strongly influenced the overall estimate. Egger’s test suggested possible publication bias. Neither age nor sex significantly moderated reliability via meta-regression.ConclusionsThe ORTO scale has a relatively low pooled reliability coefficient. Alternative ON assessment tools with enhanced psychometric properties are needed. Clinicians should not base diagnoses or treatment decisions on ORTO alone. Comprehensive psychiatric assessment is essential for accurate ON evaluation.

Carcass characteristics and meat quality of cull cows from different genetic groups

We aimed to evaluate the quality of the carcass and meat of cull cows from different genetic groups. It was considered 48 cows being 16 of the Nellore breed (NEL), 16 ½Angus ½Nellore (ANGNEL), and 16 ½Caracu ½Nellore (CARNEL), slaughtered at the end of eight pregnancy seasons, with approximately 11 years of age. For carcass analysis, body weight at slaughter (SW), hot carcass weight (HCW), carcass yield (CY), carcass finishing (CF), fat distribution (FDIST), cold storage conformation (CSC), marbling (MAR), subcutaneous fat thickness (SFT), ribeye area (REA), internal depth (INTD), external depth (EXTD), carcass length (CL), physiological maturity (FMAT), muscle color (COLOR) and texture (TEXT). For meat analysis, samples taken from the Longissimus muscle were analyzed after zero and 14 days of maturation for exudation losses (ExuL at 0 and 14 days), cooking losses (CookL), pH (pH at 0 and 14 days), color components of meat (L*, a* and b* 0 and 14 days) and shear force (SF at 0 and 14 days), the ether extract (EE) of the samples was also evaluated according to the genetic group of the cull cows. The Means were compared according to the adjusted Tukey-Kramer test (α = 0.05). The data were evaluated for the presence of outliers, homogeneity of variance, and normality of residuals. The effects of genetic groups on the described characteristics were evaluated by restricted maximum likelihood (REML) analysis, adjusting a mixed model containing the effects of cow age, genetic group, and slaughter date. NEL and ANGNEL cows presented higher SFT results when compared to CARNEL cows. The REA, INTD, and EXTD, ANGNEL and CARNEL cows obtained greater results when compared to NEL cows group. There was no significant effect on the genetic group of cull cows for the variables CY, CF, FDIST, CSC, MARM, FMAT, COLOR and TEXT. A significant difference was observed only for the L* characteristic (0 and 14 days of maturation), in which NEL cows presented darker meat than ANGNEL, with CARNEL cows having intermediate results. The ANGNEL cull cows have higher slaughter weights, and carcass weights, and AOL and EGS with better carcass finish. Cull cows slaughtered at an advanced age, between 10 and 11 years old, have similar meat quality. We recommend the meat maturation process for 14 days to improve the tenderness of the meat from cull cows, since in this 14-day meat maturation process, calpains degrade the myofibrillar proteins at certain internal points of the molecules and improve the tenderness of the meat, regardless of the genetic group.

Genetic parameters for ewe lifetime productivity traits in Central Anatolian Merino sheep

Rapidly increasing population size, recent breaks in production and supply chains, due to pandemics, and those further expected because of climate change emphasize the compelling importance of animal productivity. Traits associated with the productivity of ewes have a direct impact on the overall productivity, profitability and efficiency of sheep farms. Therefore, the objective of the current study was to estimate the variance components, heritabilities as well as genetic and phenotypic correlations, for traits associated with the lifetime productivity of Central Anatolian Merino ewes. Birth and weaning records of lambs for each ewe as well as environmental factors such as sex and birth type were utilized for deriving ewe lifetime productivity traits. Genetic parameter estimations involved observations from 3101 Central Anatolian Merino ewes, encompassing mean and total lamb birth weight per ewe (MBW and TBW), mean and total lamb weaning weight per ewe (MWW and TWW), and the mean and total number of lambs weaned (MNLW and TNLW). This analysis utilized a pedigree comprising 13229 animals. Average Information Restricted Maximum Likelihood (AIREML) based Animal Linear Mixed Model estimations for the decomposition of (co)variance components were implemented based on pedigree-derived numerator relationship matrix by also accounting for the number of parities as a fixed factor. Low to moderate heritability estimates, ranging between 0.29 and 0.42, were observed for the lifetime productivity traits of the breed. A wide range of genetic and phenotypic correlations (between −0.56 and 0.99) was observed among the traits of interest. The outcomes of the study are anticipated to significantly enhance the global sheep production systems by uncovering the essential parameters for incorporating ewe’s lifetime reproductive performance and productivity into the selection indices. This will also benefit Central Anatolian Merino farmers, who form a large proportion of sheep producers in Turkey.

Evaluation of models for estimation of genetic parameters for post-weaning body measurements and their association with yearling weight in Nellore sheep.

The objective of this study was to obtain (co) variance components and genetic parameter estimates for post-weaning body measurements such as body length (BL), height at withers (HW), and chest girth (HG) recorded at six (SBL, SHW, and SHG), nine (NBL, NHW, and NHG) and twelve (YBL, YHW, and YHG) months of age along with yearling weight (YW) in Nellore sheep maintained at livestock research station, Palamaner, Andhra Pradesh, India and also the association among body measurements with YW was studied. Data on 2,076 Nellore sheep (descended from 75 sires and 522 dams) recorded between 2007 and 2016 (10 years) were utilized in the study. Lambing year, sex of lamb, season of lambing and parity of dam were included in the model as fixed effects and ewe weight was kept as a covariate. Analyses were conducted with six animal models with different combinations of direct and maternal genetic effects using restricted maximum likelihood procedure. Best model for each trait was determined based on Akaike's information criterion. Moderate estimates of direct heritability were obtained for the studied traits viz., BL (0.02 to 0.24), HW (0.31 to 0.49), and CG (0.08 to 0.35) and their corresponding maternal heritability estimates were in the range of 0.00 to 0.07 (BL), 0.13 to 0.17 (HW), and 0.07 to 0.13 (CG), respectively. Positive direct genetic and phenotypic correlations among the traits and they ranged from 0.07 (YBL-YW) to 0.99 (SBL-SHG, SHG-YW, and NBL-YBL) and 0.01 (SBL-YBL) to 0.99 (NBL-NHG), respectively. Further, the genetic correlations among all the body measurements and YW were positive and ranged from 0.07 (YW and YBL) to 0.99 (YW and SHG). There was a strong association of chest girth at six months with YW. Further, it is indicated that moderate improvement of post-weaning body measurements in Nellore sheep would be possible through selection.

Genetic background of hematological parameters in Holstein cattle based on genome-wide association and RNA sequencing analyses

Hematological parameters refer to the assessment of changes in the number and distribution of blood cells, including leukocytes (LES), erythrocytes (ERS), and platelets (PLS), which are essential for the early diagnosis of hematological system disorders and other systemic diseases in livestock. In this context, the primary objectives of this study were to investigate the genomic background of 19 hematological parameters in Holstein cattle, focusing on LES, ERS, and PLS blood components. Genetic and phenotypic (co)variances of hematological parameters were calculated based on the Average Information Restricted Maximum Likelihood (AIREML) method and 1,610 genotyped individuals and 5,499 hematological parameter records from 4,543 cows. Furthermore, we assessed the genetic relationship between these hematological parameters and other economically important traits in dairy cattle breeding programs. We also carried out genome-wide association studies and candidate gene analyses. Blood samples from 21 primiparous cows were used to identify candidate genes further through RNA sequencing (RNA-seq) analyses. Hematological parameters generally exhibited low-to-moderate heritabilities ranging from 0.01 to 0.29, with genetic correlations between them ranging from -0.88 ± 0.09 (between mononuclear cell ratio and lymphocyte cell ratio) to 0.99 ± 0.01 (between white blood cell count and granulocyte cell count). Furthermore, low to moderate approximate genetic correlations between hematological parameters with one longevity, 4 fertility, and 5 health traits were observed. One-hundred-and-99 significant single nucleotide polymorphisms (SNP) located primarily on the Bos taurus autosomes (BTA) BTA4, BTA6, and BTA8 were associated with 16 hematological parameters. Based on the RNA-seq analyses, 6,687 genes were significantly downregulated and 4,119 genes were upregulated when comparing 2 groups of cows with high and low phenotypic values. By integrating genome-wide association studies (GWAS), RNA-seq, and previously published results, the main candidate genes associated with hematological parameters in Holstein cattle were ACRBP, ADAMTS3, CANT1, CCM2L, CNN3, CPLANE1, GPAT3, GRIP2, PLAGL2, RTL6, SOX4, WDFY3, and ZNF614. Hematological parameters are heritable and moderately to highly genetically correlated among themselves. The large number of candidate genes identified based on GWAS and RNA-seq indicate the polygenic nature and complex genetic determinism of hematological parameters in Holstein cattle.

Genetic association between fat-to-protein ratio and traits of economic interest in early lactation Holstein cows in Brazil.

The aims of this study were to estimate the genetic parameters for fat-to-protein ratio (F:P) within the first 90days of lactation and to examine their genetic associations with daily milk yield (MY), somatic cell score (SCS), and calving interval between the first and second calving (IFSC) and between the second and third calving (ISTC) during the first three lactations of Holstein cows. We utilized 200,626 production-related data officially recorded from 77,436 cows milked two or three times a day from 2012 to 2022, sourced from the Holstein Cattle Breeders Association of Paraná State, Brazil. The (co)variance components were estimated using animal models, adopting the restricted maximum likelihood (REML) method with single-trait analysis (for heritability and repeatability) and two-trait analysis (for genetic and phenotypic correlations), per lactation. Regardless of lactation number, heritability estimates were relatively low, ranging from 0.08 ± 0.005 to 0.10 ± 0.003 for F:P; 0.08 ± 0.01 to 0.18 ± 0.005 for MY; 0.04 ± 0.01 to 0.07 ± 0.004 for SCS; and 0.03 ± 0.01 for both IFSC and ISTC. Repeatability estimates within the same lactation were low for F:P (ranging from 0.17 ± 0.002 to 0.19 ± 0.03), high for MY (between 0.50 ± 0.003 and 0.53 ± 0.002), and moderate to high for SCS (between 0.39 ± 0.003 and 0.44 ± 0.004). Genetic correlations between F:P and MY ranged from -0.26 ± 0.03 to -0.15 ± 0.02; F:P and SCS, from -0.06 ± 0.03 to -0.03 ± 0.08; F:P and IFSC, 0.31 ± 0.01; F:P and ISTC, 0.20 ± 0.01; MY and IFSC, 0.24 ± 0.05; and MY and ISTC, 0.13 ± 0.08. The fat-to-protein ratio during early lactation showed low genetic variability, regardless of lactation number. Furthermore, it was genetically correlated with MY, IFSC, and ISTC, although there is an antagonistic and unfavorable correlation between traits that can limit genetic progress.

Impact of trial attrition rates on treatment effect estimates in chronic inflammatory diseases: A meta-epidemiological study.

The objective of this meta-epidemiological study was to explore the impact of attrition rates on treatment effect estimates in randomised trials of chronic inflammatory diseases (CID) treated with biological and targeted synthetic disease-modifying drugs. We sampled trials from Cochrane reviews. Attrition rates and primary endpoint results were retrieved from trial publications; Odds ratios (ORs) were calculated from the odds of withdrawing in the experimental intervention compared to the control comparison groups (i.e., differential attrition), as well as the odds of achieving a clinical response (i.e., the trial outcome). Trials were combined using random effects restricted maximum likelihood meta-regression models and associations between estimates of treatment effects and attrition rates were analysed. From 37 meta-analyses, 179 trials were included, and 163 were analysed (301 randomised comparisons; n = 62,220 patients). Overall, the odds of withdrawal were lower in the experimental compared to control groups (random effects summary OR = 0.45, 95% CI, 0.41-0.50). The corresponding overall treatment effects were large (random effects summary OR = 4.43, 95% CI 3.92-4.99) with considerable heterogeneity across interventions and clinical specialties (I2 = 85.7%). The ORs estimating treatment effect showed larger treatment benefits when the differential attrition was more prominent with more attrition in the control group (OR = 0.73, 95% CI 0.55-0.96). Higher attrition rates from the control arm are associated with larger estimated benefits of treatments with biological or targeted synthetic disease-modifying drugs in CID trials; differential attrition may affect estimates of treatment benefit in randomised trials.

Stereotactic Body and Conventional Radiotherapy for Painful Bone Metastases

Conventional external beam radiotherapy (cEBRT) and stereotactic body radiotherapy (SBRT) are commonly used treatment options for relieving metastatic bone pain. The effectiveness of SBRT compared with cEBRT in pain relief has been a subject of debate, and conflicting results have been reported. To compare the effectiveness associated with SBRT vs cEBRT for relieving metastatic bone pain. A structured search was performed in the PubMed, Embase, and Cochrane databases on June 5, 2023. Additionally, results were added from a new randomized clinical trial (RCT) and additional unpublished data from an already published RCT. Comparative studies reporting pain response after SBRT vs cEBRT in patients with painful bone metastases. Two independent reviewers extracted data from eligible studies. Data were extracted for the intention-to-treat (ITT) and per-protocol (PP) populations. The study is reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Overall and complete pain response at 1, 3, and 6 months after radiotherapy, according to the study's definition. Relative risk ratios (RRs) with 95% CIs were calculated for each study. A random-effects model using a restricted maximum likelihood estimator was applied for meta-analysis. There were 18 studies with 1685 patients included in the systematic review and 8 RCTs with 1090 patients were included in the meta-analysis. In 7 RCTs, overall pain response was defined according to the International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE). The complete pain response was reported in 6 RCTs, all defined according to the ICPRE. The ITT meta-analyses showed that the overall pain response rates did not differ between cEBRT and SBRT at 1 (RR, 1.14; 95% CI, 0.99-1.30), 3 (RR, 1.19; 95% CI, 0.96-1.47), or 6 (RR, 1.22; 95% CI, 0.96-1.54) months. However, SBRT was associated with a higher complete pain response at 1 (RR, 1.43; 95% CI, 1.02-2.01), 3 (RR, 1.80; 95% CI, 1.16-2.78), and 6 (RR, 2.47; 95% CI, 1.24-4.91) months after radiotherapy. The PP meta-analyses showed comparable results. In this systematic review and meta-analysis, patients with painful bone metastases experienced similar overall pain response after SBRT compared with cEBRT. More patients had complete pain alleviation after SBRT, suggesting that selected subgroups will benefit from SBRT.

The effect of oral synbiotics on the gut microbiota and inflammatory biomarkers in healthy adults: a systematic review and meta-analysis

Abstract Context Prior research has explored the effect of synbiotics, the combination of probiotics and prebiotics, on the gut microbiota in clinical populations. However, evidence related to the effect of synbiotics on the gut microbiota in healthy adults has not been reviewed to date. Objective A systematic review and meta-analysis was conducted to comprehensively investigate the effect of synbiotics on the gut microbiota and inflammatory markers in populations of healthy adults. Data Sources Scopus, PubMed, Web of Science, ScienceDirect, MEDLINE, CINAHL, and The Cochrane Library were systematically searched to retrieve randomized controlled trials examining the primary outcome of gut microbiota or intestinal permeability changes after synbiotic consumption in healthy adults. Secondary outcomes of interest were short-chain fatty acids, inflammatory biomarkers, and gut microbiota diversity. Data Extraction Weighted (WMD) or standardized mean difference (SMD) outcome data were pooled in restricted maximum likelihood models using random effects. Twenty-seven articles reporting on 26 studies met the eligibility criteria (n = 1319). Data Analysis Meta-analyses of 16 studies showed synbiotics resulted in a significant increase in Lactobacillus cell count (SMD, 0.74; 95% confidence interval [CI], 0.15, 1.33; P = 0.01) and propionate concentration (SMD, 0.22; 95% CI, 0.02, 0.43; P = 0.03) compared with controls. A trend for an increase in Bifidobacterium relative abundance (WMD, 0.97; 95% CI, 0.42, 2.52; P = 0.10) and cell count (SMD, 0.82; 95% CI, 0.13, 1.88; P = 0.06) was seen. No significant differences in α-diversity, acetate, butyrate, zonulin, IL-6, CRP, or endotoxins were observed. Conclusion This review demonstrates that synbiotics modulate the gut microbiota by increasing Lactobacillus and propionate across various healthy adult populations, and may result in increased Bifidobacterium. Significant variations in synbiotic type, dose, and duration should be considered as limitations when applying findings to clinical practice. Systematic Review Registration PROSPERO no. CRD42021284033.

Adverse neonatal outcomes in pregnant women with asthma: An updated systematic review and meta-analysis.

A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma. Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes. We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*). Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma. The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined. A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance. Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma.

Load and recovery monitoring in Swiss top-level youth soccer players: Exploring the associations of a new web application-based score with recognised load measures

Load and recovery monitoring in Swiss top-level youth soccer players: Exploring the associations of a new web application-based score with recognised load measures

Sex-specific genetic parameter estimates of body weight in Mazandaran indigenous chickens.

Body weight is an economically important trait in poultry that shows sexual dimorphism (SD). In the present study, variation in SD in Mazandaran native chickens was investigated in terms of the (Co) variance components and genetic parameters of body weight between males and females. Studied traits were body weights at hatch (BW1), 8 weeks (BW8) and 12 weeks of age (BW12). Also, for weight at sexual maturity (WSM) covariance components were only estimated in females. Cross-sex direct and maternal correlations were also estimated for studied traits except for WSM. For this purpose, a deep 21-generation pedigree and body weight data (57,576 BW1, 72,925 BW8, 62,727 BW12 and, 42,496 WSM) were used. Evaluation of SD of body weight was performed using six bivariate animal models with and without considering the genetic and permanent maternal environmental effects under the restricted maximum likelihood method in WOMBAT software. Model with direct additive genetic effects and maternal genetic effects without covariance between them was identified as the best model for BW1 and BW8. The Model including direct additive genetic effects and permanent maternal environmental effects was the best model for BW12 and WSM. Direct heritability (h2 ) estimates for BW1, BW8 and, BW12 were, respectively, 0.05 ± 0.013, 0.17 ± 0.02 and, 0.25 ± 0.03 in males and, 0.05 ± 0.012, 0.15 ± 0.01 and 0.21 ± 0.01 in females. Also, the direct heritability of WSM based on univariate analysis in females was estimated to be 0.40 ± 0.01. Maternal heritability ( ) varied from 0.39 ± 0.01 (BW1) to 0.04 ± 0.009 (BW8) in males, and 0.36 ± 0.10 (BW1) to 0.04 ± 0.006 (BW8) in females. The correlation between direct genetic effects between males and females for BW1 was not significantly different from one. The direct genetic correlation between the two sexes for BW8 and BW12 was significantly different from 1 concluding that these traits are dimorphic in terms of direct genetic effects and therefore independent selection in both sexes is possible.