Retrograde tibiotalocalcaneal nailing for the treatment of acute ankle fractures in the elderly: a systematic review and meta-analysis.

Introduction: Fragility ankle fractures are traditionally managed conservatively or with open reduction internal fixation. Tibiotalocalcaneal (TTC) nailing is an alternative option for the geriatric patient. This meta-analysis provides the most detailed analysis of TTC nailing for fragility ankle fractures.

Personalized Model to Predict Keratoconus Progression From Demographic, Topographic, and Genetic Data.

Purpose: To generate a prognostic model to predict keratoconus progression to corneal crosslinking (CXL).

Design: Retrospective cohort study.

Methods: We recruited 5025 patients (9341 eyes) with early keratoconus between January 2011 and November 2020.

Factors associated with mortality in older patients sustaining pelvic or acetabular fractures.

Introduction: This study aimed to investigate potential factors, including delay to surgical stabilisation, affecting mortality in older patients sustaining pelvic or acetabular (PA) fractures.

Materials And Methods: A retrospective review of the Trauma Audit and Research Network (TARN) database was performed to identify older patients (aged 65 and over) sustaining PA fractures treated surgically in a UK Major Trauma Centre (MTC) between 2015 and 2019. Chi-squared and Fisher tests were used to compare 1-year mortality rates following operative intervention between patients treated within 72 h and after 72 h.

Specificity and positive predictive value of SARS-CoV-2 nucleic acid amplification testing in a low-prevalence setting.

Objectives: When the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is low, many positive test results are false positives. Confirmatory testing reduces overdiagnosis and nosocomial infection and enables real-world estimates of test specificity and positive predictive value. This study estimates these parameters to evaluate the impact of confirmatory testing and to improve clinical diagnosis, epidemiological estimation and interpretation of vaccine trials.

Systematic review on the outcomes of poller screw augmentation in intramedullary nailing of long bone fracture.

Various technical tips have been described on the placement of poller screws during intramedullary (IM) nailing; however studies reporting outcomes are limited. Overall there is no consistent conclusion about whether intramedullary nailing alone, or intramedullary nails augmented with poller screws is more advantageous.We conducted a systematic review of PubMed, EMBASE, and Cochrane databases.

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists.

Stochastic search and joint fine-mapping increases accuracy and identifies previously unreported associations in immune-mediated diseases.

Thousands of genetic variants are associated with human disease risk, but linkage disequilibrium (LD) hinders fine-mapping the causal variants. Both lack of power, and joint tagging of two or more distinct causal variants by a single non-causal SNP, lead to inaccuracies in fine-mapping, with stochastic search more robust than stepwise. We develop a computationally efficient multinomial fine-mapping (MFM) approach that borrows information between diseases in a Bayesian framework.

simGWAS: a fast method for simulation of large scale case-control GWAS summary statistics.

Motivation: Methods for analysis of GWAS summary statistics have encouraged data sharing and democratized the analysis of different diseases. Ideal validation for such methods is application to simulated data, where some 'truth' is known. As GWAS increase in size, so does the computational complexity of such evaluations; standard practice repeatedly simulates and analyses genotype data for all individuals in an example study.

Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

Genome-wide association studies (GWAS) have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs) is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases.

Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls.

Determining whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent data sets.

Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.

Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci.

Integration of disease association and eQTL data using a Bayesian colocalisation approach highlights six candidate causal genes in immune-mediated diseases.

The genes and cells that mediate genetic associations identified through genome-wide association studies (GWAS) are only partially understood. Several studies that have investigated the genetic regulation of gene expression have shown that disease-associated variants are over-represented amongst expression quantitative trait loci (eQTL) variants. Evidence for colocalisation of eQTL and disease causal variants can suggest causal genes and cells for these genetic associations.

A method for gene-based pathway analysis using genomewide association study summary statistics reveals nine new type 1 diabetes associations.

Pathway analysis can complement point-wise single nucleotide polymorphism (SNP) analysis in exploring genomewide association study (GWAS) data to identify specific disease-associated genes that can be candidate causal genes. We propose a straightforward methodology that can be used for conducting a gene-based pathway analysis using summary GWAS statistics in combination with widely available reference genotype data. We used this method to perform a gene-based pathway analysis of a type 1 diabetes (T1D) meta-analysis GWAS (of 7,514 cases and 9,045 controls).