De novo pathogenic variants in CACNA1E cause developmental and epileptic encephalopathy with contractures, macrocephaly, and dyskinesias
Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the α1-subunit of the voltage-gated CaV2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission.
Optimizing and evaluating biomarker combinations as trial-level general surrogates
We extend the method proposed in a recent work by the Authors for trial-level general surrogate evaluation to allow combinations of biomarkers and provide a procedure for finding the "best" combination of biomarkers based on the absolute prediction error summary of surrogate quality. We use a nonparametric Bayesian model that allows us to select an optimal subset of biomarkers without having to consider a large number of explicit model specifications for that subset.
Limited marginal utility of deep sequencing for HIV drug resistance testing in the age of integrase inhibitors
HIV drug resistance genotyping is a critical tool in the clinical management of HIV infections. Although resistance genotyping has traditionally been conducted using Sanger sequencing, next-generation sequencing (NGS) is emerging as a powerful tool due to its ability to detect lower frequency alleles. However, the clinical value added from NGS approaches to antiviral resistance testing remains to be demonstrated.
Fatty acid biomarkers of dairy fat consumption and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies
We aimed to investigate prospective associations of circulating or adipose tissue odd-chain fatty acids 15:0 and 17:0 and trans-palmitoleic acid, t16:1n-7, as potential biomarkers of dairy fat intake, with incident type 2 diabetes (T2D). In a large meta-analysis that pooled the findings from 16 prospective cohort studies, higher levels of 15:0, 17:0, and t16:1n-7 were associated with a lower risk of T2D.
Do medical conditions predispose to the development of chronic back pain? A longitudinal co-twin control study of middle-aged males with 11-year follow-up
Poor general health predicts the transition to chronic back pain (CBP), but the role of specific medical conditions in the development of CBP is unclear. The study aim was to examine the association of medical conditions with the development of CBP ("incident CBP"), while controlling for familial factors, including genetics.
It's time to make the time to viral suppression after HIV diagnosis a metric of HIV care success
An academic-practice partnership at the University of Washington School of Public Health: The Student Epidemic Action Leaders (SEAL) team
In 2015, the University of Washington School of Public Health, Department of Epidemiology established the Student Epidemic Action Leaders (SEAL) team to provide public health students with experience in field epidemiology in state and local public health communicable disease divisions. The University of Washington Department of Epidemiology developed the SEAL team in collaboration with the Washington State Department of Health to offer public health graduate students opportunities to contribute to the real-time needs of public health agencies during a communicable disease event and/or preparedness event.
Implications of epigenetic drift in colorectal neoplasia
Many normal tissues undergo age-related drift in DNA methylation, providing a quantitative measure of tissue age. Here we identify and validate 781 CpG-islands (CGI) that undergo significant methylomic drift in 232 normal colorectal tissues and show that these CGI continue to drift in neoplasia while retaining significant correlations across samples.
Quadrivalent HPV vaccine in HIV-1-infected early adolescent girls and boys in Kenya: Month 7 and 12 post vaccine immunogenicity and correlation with immune status
In sub-Saharan Africa, a generation of HIV-1-infected children is approaching the age of sexual debut and becoming at risk for HPV infection and its sequelae. We assessed safety and immunogenicity of the quadrivalent HPV (qHPV) vaccine in HIV-1-infected adolescents.
Increase in HSV shedding at initiation of antiretroviral therapy (ART) and decrease in shedding over time on ART in HIV and HSV-2 infected persons
HIV-infected persons with chronic herpesvirus infections may experience paradoxical worsening after initiation of antiretroviral therapy (ART), but the impact of longer term ART is unclear. We evaluated the relationships between genital herpes simplex virus (HSV) shedding and ART initiation and time on therapy in HIV and HSV-2 infected persons.