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Journal of Experimental Botany Jul 2024Linear mixed models (LMMs) are a commonly used method for genome-wide association studies (GWAS) that aim to detect associations between genetic markers and phenotypic...
Linear mixed models (LMMs) are a commonly used method for genome-wide association studies (GWAS) that aim to detect associations between genetic markers and phenotypic measurements in a population of individuals while accounting for population structure and cryptic relatedness. In a standard GWAS, hundreds of thousands to millions of statistical tests are performed, requiring control for multiple hypothesis testing. Typically, static corrections that penalize the number of tests performed are used to control for the family-wise error rate, which is the probability of making at least one false positive. However, it has been shown that in practice this threshold is too conservative for normally distributed phenotypes and not stringent enough for non-normally distributed phenotypes. Therefore, permutation-based LMM approaches have recently been proposed to provide a more realistic threshold that takes phenotypic distributions into account. In this work, we will discuss the advantages of permutation-based GWAS approaches, including new simulations and results from a re-analysis of all publicly available Arabidopsis thaliana phenotypes from the AraPheno database.
PubMed: 38954539
DOI: 10.1093/jxb/erae280 -
Environmental Geochemistry and Health Jul 2024Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological...
Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.
Topics: Pakistan; Rivers; Agricultural Irrigation; Drinking Water; Water Quality; Water Pollutants, Chemical; Environmental Monitoring
PubMed: 38954066
DOI: 10.1007/s10653-024-02026-y -
Pediatric Pulmonology Jul 2024Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter... (Review)
Review
BACKGROUND
Several techniques can be used to assess bronchodilator response (BDR) in preschool-aged children, including spirometry, respiratory oscillometry, the interrupter technique, and specific airway resistance. However, there has not been a systematic comparison of BDR thresholds across studies yet.
METHODS
A systematic review was performed on all studies up to May 2023 measuring a bronchodilator effect in children 2-6 years old using one of these techniques (PROSPERO CRD42021264659). Studies were identified using MEDLINE, Cochrane, EMBASE, CINAHL via EBSCO, Web of Science databases, and reference lists of relevant manuscripts.
RESULTS
Of 1224 screened studies, 43 were included. Over 85% were from predominantly European ancestry populations, and only 22 studies (51.2%) calculated a BDR cutoff based on a healthy control group. Five studies included triplicate testing with a placebo to account for the within-subject intrasession repeatability. A relative BDR was most consistently reported by the included studies (95%) but varied widely across all techniques. Various statistical methods were used to define a BDR, with six studies using receiver operating characteristic analyses to measure the discriminative power to distinguish healthy from wheezy and asthmatic children.
CONCLUSION
A BDR in 2- to 6-year-olds cannot be universally defined based on the reviewed literature due to inconsistent methodology and cutoff calculations. Further studies incorporating robust methods using either distribution-based or clinical anchor-based approaches to define BDR are required.
PubMed: 38953717
DOI: 10.1002/ppul.27112 -
Biometrical Journal. Biometrische... Jul 2024In biomedical research, the simultaneous inference of multiple binary endpoints may be of interest. In such cases, an appropriate multiplicity adjustment is required...
In biomedical research, the simultaneous inference of multiple binary endpoints may be of interest. In such cases, an appropriate multiplicity adjustment is required that controls the family-wise error rate, which represents the probability of making incorrect test decisions. In this paper, we investigate two approaches that perform single-step -value adjustments that also take into account the possible correlation between endpoints. A rather novel and flexible approach known as multiple marginal models is considered, which is based on stacking of the parameter estimates of the marginal models and deriving their joint asymptotic distribution. We also investigate a nonparametric vector-based resampling approach, and we compare both approaches with the Bonferroni method by examining the family-wise error rate and power for different parameter settings, including low proportions and small sample sizes. The results show that the resampling-based approach consistently outperforms the other methods in terms of power, while still controlling the family-wise error rate. The multiple marginal models approach, on the other hand, shows a more conservative behavior. However, it offers more versatility in application, allowing for more complex models or straightforward computation of simultaneous confidence intervals. The practical application of the methods is demonstrated using a toxicological dataset from the National Toxicology Program.
Topics: Models, Statistical; Biometry; Biomedical Research; Sample Size; Endpoint Determination; Humans
PubMed: 38953619
DOI: 10.1002/bimj.202300197 -
Frontiers in Nutrition 2024The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019.
The global burden, trends, and inequalities of individuals with developmental and intellectual disabilities attributable to iodine deficiency from 1990 to 2019 and its prediction up to 2030.
OBJECTIVE
The objective of this study was to assess the global burden of disease for developmental and intellectual disabilities caused by iodine deficiency from 1990 to 2019.
METHODS
Using data from the global burden of disease (GBD) 2019, we conducted a cross-country inequity analysis to examine the worldwide burden of developmental and intellectual disabilities caused by the issue of iodine deficiency from 1990 to 2019. Absolute and relative inequality were assessed by the slope index of inequality and the concentration index, respectively. After summarising the latest evidence, we also projected the age-standardized prevalence and years lived with disability (YLD) rates up to 2030 using the BAPC and INLA packages in R statistical software.
RESULTS
In 2019, the global age-standardized prevalence and YLD rates for developmental and intellectual disabilities due to iodine deficiency were 22.54 per 100,000 population (95% UI 14.47 to 29.23) and 4.12 per 100,000 population (95% UI 2.25 to 6.4), respectively. From 1990 to 2019, the age-standardized prevalence and YLD rates of developmental and intellectual disabilities due to iodine deficiency decreased significantly. Geographic distribution showed that areas with lower socio-demographic indices (SDI) were the most affected. The correlation between higher SDI and lower prevalence highlights the role of economic and social factors in the prevalence of the disease. Cross-national inequity analysis shows that disparities persist despite improvements in health inequalities. In addition, projections suggest that the disease burden may decline until 2030.
CONCLUSION
This research underscores the necessity for targeted interventions, such as enhancing iodine supplementation and nutritional education, especially in areas with lower SDI. We aim to provide a foundation for policymakers further to research effective preventative and potential alternative treatment strategies.
PubMed: 38953045
DOI: 10.3389/fnut.2024.1366525 -
PeerJ 2024The volcano rabbit () is a lagomorph endemic to the central mountains of the Trans-Mexican Volcanic Belt and is classified as threatened at extinction risk. It is a...
The volcano rabbit () is a lagomorph endemic to the central mountains of the Trans-Mexican Volcanic Belt and is classified as threatened at extinction risk. It is a habitat specialist in bunchgrass communities. The annual wildfires that occur throughout its distribution range are a vulnerability factor for the species. However, the effects of wildfires on volcano rabbit populations are not fully understood. We evaluated the occupancy and change in the volcano rabbit relative abundance index in the burned bunchgrass communities of the Ajusco-Chichinautzin Mountain Range during an annual cycle of wildfire events. Additionally, we assessed the factors that favor and limit occupation and reoccupation by the volcano rabbit using the relative abundance index in burned plots as an indicator of these processes. The explanatory factors for the response of the volcano rabbit were its presence in the nearby unburned bunchgrasses, the height of three species of bunchgrass communities, the proportion of different types of vegetation cover within a 500 m radius around the burned plots, heterogeneity of the vegetation cover, and the extent of the wildfire. Statistical analyses indicated possible reoccupation in less than a year in burned bunchgrass communities adjacent to unburned bunchgrass communities with volcano rabbits. The relative abundance index of volcano rabbits was not favored when the maximum height of the bunchgrass community was less than 0.77 m. When the vegetation around the burned plots was dominated by forest (cover >30% of the buffer) and the fire was extensive, the number of latrines decreased per month but increased when the bunchgrass and shrub cover was greater around the burned plots. While the statistical results are not conclusive, our findings indicate a direction for future projects, considering extensive monitoring to obtain a greater number of samples that contribute to consolidating the models presented.
Topics: Animals; Wildfires; Mexico; Ecosystem; Lagomorpha; Rabbits; Poaceae
PubMed: 38952973
DOI: 10.7717/peerj.17510 -
Nigerian Medical Journal : Journal of... 2023Being a frequently used approach by otorhinolaryngologists, Endoscopic sinus surgery (ESS) has been useful in the surgical management of different sinonasal conditions...
BACKGROUND
Being a frequently used approach by otorhinolaryngologists, Endoscopic sinus surgery (ESS) has been useful in the surgical management of different sinonasal conditions in this era. Although ESS is most commonly performed for inflammatory and infectious sinus diseases since its introduction in the 1960s by Prof. Messserklinger and Wigand, the current advancement in instrumentation has led to an increase in its indications. This study therefore aimed at auditing the ESS done at a tertiary hospital in our settings.
METHODOLOGY
This was a retrospective descriptive cross-sectional study which was conducted at Muhimbili National Hospital. It involved all patients who underwent ESS in the department of otorhinolaryngology. Information was extracted from patients' files, ledger, and admission books. The obtained data were analyzed using a statistical package for social sciences (SPSS) version 22. Descriptive statistics were performed to present the frequency distribution of the demographic characteristics, indications for ESS, and mean for the length of hospital stay.
RESULTS
Out of 1261 surgeries done during the study period, 6.7% (84/1261) were endoscopic sinus surgeries. Of patients who underwent ESS, an almost equal proportion of males and females was found and ages ranged from 8 to 71 years with a mean age of 32 .2 ±16 .9 years. The commonest indication for ESS was sinonasal polyposis at 50.0% (42/84) followed by chronic rhinosinusitis at 20.4% (17/84). The majority of patients 52.4% (44/84) had a hospital stay of 1-3 days. The mean length of postoperative hospital stay following ESS in this study was found to be 2.8 days.
CONCLUSION
Endoscopic sinus surgeries accounted for 6.7% of all surgeries with sinonasal polyposis being the commonest indication and the estimated mean length of postoperative hospital stay being 3 days.
PubMed: 38952879
DOI: 10.60787/NMJ-64-4-325 -
MedRxiv : the Preprint Server For... May 2024HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which...
INTRODUCTION
HIV drug resistance poses a challenge to the United Nation's goal of ending the HIV/AIDS epidemic. The integrase strand transfer inhibitor (InSTI) dolutegravir, which has a higher resistance barrier, was endorsed by the World Health Organization in 2019 for first-, second-, and third-line antiretroviral therapy (ART). This multiplicity of roles of dolutegravir in ART may facilitate the emergence of dolutegravir resistance.
METHODS AND ANALYSIS
DTG RESIST is a multicentre longitudinal study of adults and adolescents living with HIV in sub-Saharan Africa, Asia, and South and Central America who experienced virologic failure on dolutegravir-based ART. At the time of virologic failure whole blood will be collected and processed to prepare plasma or dried blood spots. Laboratories in Durban, Mexico City and Bangkok will perform genotyping. Analyses will focus on (i) individuals who experienced virologic failure on dolutegravir, and (ii) on those who started or switched to such a regimen and were at risk of virologic failure. For population (i), the outcome will be any InSTI drug resistance mutations, and for population (ii) virologic failure defined as a viral load >1000 copies/mL. Phenotypic testing will focus on non-B subtype viruses with major InSTI resistance mutations. Bayesian evolutionary models will explore and predict treatment failure genotypes. The study will have intermediate statistical power to detect differences in resistance mutation prevalence between major HIV-1 subtypes; ample power to identify risk factors for virologic failure and limited power for analysing factors associated with individual InSTI drug resistance mutations.
ETHICS AND DISSEMINATION
The research protocol was approved by the Biomedical Research Ethics Committee at the University of KwaZulu-Natal, South Africa, and the Ethics Committee of the Canton of Bern, Switzerland. All sites participate in IeDEA and have obtained ethics approval from their local ethics committee to conduct the additional data collection.
REGISTRATION
NCT06285110.
STRENGTHS AND LIMITATIONS OF THIS STUDY
- DTG RESIST is a large international study to prospectively examine emergent dolutegravir resistance in diverse settings characterised by different HIV-1 subtypes, provision of ART, and guidelines on resistance testing. - Embedded within the International epidemiology Databases to Evaluate AIDS (IeDEA), DTG RESIST will benefit from harmonized clinical data across participating sites and expertise in clinical, epidemiological, biological, and computational fields. - Procedures for sequencing and assembling genomes from different HIV-1 strains will be developed at the heart of the HIV epidemic, by the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), in Durban, South Africa. Phenotypic testing, Genome Wide Association Study (GWAS) methods and Bayesian evolutionary models will explore and predict treatment failure genotypes. - A significant limitation is the absence of genotypic resistance data from participants before they started dolutegravir treatment, as collecting and bio-banking pre-treatment samples was not feasible at most IeDEA sites. Consistent and harmonized data on adherence to treatment are also lacking. - The distribution of HIV-1 subtypes across different sites is uncertain, which may limit the statistical power of the study in analysing patterns and risk factors for dolutegravir resistance. The results from GWAS and Bayesian modelling analyses will be preliminary and hypothesis-generating.
PubMed: 38952780
DOI: 10.1101/2024.05.23.24307850 -
International Journal of Nursing... Jun 2024Incidents affecting patient safety can cause unnecessary injury to a patient. It is generally accepted that incident reporting can improve patient safety. In Ethiopian...
BACKGROUND
Incidents affecting patient safety can cause unnecessary injury to a patient. It is generally accepted that incident reporting can improve patient safety. In Ethiopian public hospitals, especially in the Hadiya zone, patient safety-related incidents are commonly witnessed, but there is no evidence of reporting behavior among healthcare professionals.
PURPOSE
This study aimed to assess patient safety incident reporting behavior and its associated factors among healthcare professionals working in public hospitals in the Hadiya zone, South Nation's, Nationalities, and Peoples' Region, Ethiopia, in 2021.
METHOD
A cross-sectional study design was employed, among 345 healthcare professionals working in public hospitals in the Hadiya zone from August 1-30, 2021. A simple random sampling technique was used to select study participants, and a structured self-administered questionnaire which is adapted from a Hospital survey on patient safety survey and literature was used to collect the data. The data were entered into a data attraction template prepared using the Epi data software and then exported to the SPSS version 25 software for analysis. Descriptive analyses were conducted to determine the general characteristics and distributions of the data collected. An inferential statistical analysis was conducted using the logistic regression model to identify associations between outcome and predictor variables. The odds ratio with the 95 % confidence interval was used to test the associations between the outcome variable and predictor variables. Finally, statistical significance was set at p-value < 0.05.
RESULTS
From the total of 354 healthcare professionals expected, 334 participants, which gave a response rate of 94.4 %, had completed and returned the questionnaire. The result shows that overall patient safety incident reporting behavior among healthcare professionals was 28.7 % (95 % Confidence Interval (CI): (24.6, 33.2). Being a nurse professional [Adjusted Odd Ratio (AOR): 5.48, 95 % CI: (1.67, 17.80)], having job training [AOR: 2.87, 95 % CI: (1.46, 6.28)], having a team within the units [AOR=2.79, 95 %CI: (1.23, 6.28)], communication openness [AOR=2.78, 95 %CI: (1.44, 5.37)], and management support [AOR=2.8, 95 %CI; (1.40, 5.60)] were found to factor significantly associated with patient safety incident reporting behaviour.
CONCLUSION
This study revealed that the incident-reporting behavior among healthcare professionals was low compared to previous studies. Being a nurse professional, having an on -job training, having a team within the unit, communication openness, perception of the time reporting takes, fear of administration sanction and management support were factors associated with their patient safety incident reporting behavior. Managers should focus on patient safety incidents, prepare continuous training programs, and provide open communication to improve patient safety incident reporting.
PubMed: 38952573
DOI: 10.1016/j.ijnsa.2024.100209 -
Frontiers in Aging Neuroscience 2024Studying the spatiotemporal patterns of amyloid accumulation in the brain over time is crucial in understanding Alzheimer's disease (AD). Positron Emission Tomography...
INTRODUCTION
Studying the spatiotemporal patterns of amyloid accumulation in the brain over time is crucial in understanding Alzheimer's disease (AD). Positron Emission Tomography (PET) imaging plays a pivotal role because it allows for the visualization and quantification of abnormal amyloid beta (Aβ) load in the living brain, providing a powerful tool for tracking disease progression and evaluating the efficacy of anti-amyloid therapies. Generative artificial intelligence (AI) can learn complex data distributions and generate realistic synthetic images. In this study, we demonstrate for the first time the potential of Generative Adversarial Networks (GANs) to build a low-dimensional representation space that effectively describes brain amyloid load and its dynamics.
METHODS
Using a cohort of 1,259 subjects with AV45 PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we develop a 3D GAN model to project images into a latent representation space and generate back synthetic images. Then, we build a progression model on the representation space based on non-parametric ordinary differential equations to study brain amyloid evolution.
RESULTS
We found that global SUVR can be accurately predicted with a linear regression model only from the latent representation space ( = 0.08 ± 0.01). We generated synthetic PET trajectories and illustrated predicted Aβ change in four years compared with actual progression.
DISCUSSION
Generative AI can generate rich representations for statistical prediction and progression modeling and simulate evolution in synthetic patients, providing an invaluable tool for understanding AD, assisting in diagnosis, and designing clinical trials. The aim of this study was to illustrate the huge potential that generative AI has in brain amyloid imaging and to encourage its advancement by providing use cases and ideas for future research tracks.
PubMed: 38952479
DOI: 10.3389/fnagi.2024.1410844