Toward a diagnostic toolkit for linear models with Gaussian-process distributed random effects

Gaussian processes (GPs) are widely used as distributions of random effects in linear mixed models, which are fit using the restricted likelihood or the closely-related Bayesian analysis. This article addresses two problems. First, we propose tools for understanding how data determine estimates in these models, using a spectral basis approximation to the GP under which the restricted likelihood is formally identical to the likelihood for a gamma-errors GLM with identity link. Second, to examine the data's support for a covariate and to understand how adding that covariate moves variation in the outcome y out of the GP and error parts of the fit, we apply a linear-model diagnostic, the added variable plot (AVP), both to the original observations and to projections of the data onto the spectral basis functions. The spectral- and observation-domain AVPs estimate the same coefficient for a covariate but emphasize low- and high-frequency data features respectively and thus highlight the covariate's effect on the GP and error parts of the fit respectively. The spectral approximation applies to data observed on a regular grid; for data observed at irregular locations, we propose smoothing the data to a grid before applying our methods. The methods are illustrated using the forest-biomass data of Finley et al.~(2008)

Feasibility and tolerability of whole-body, low-intensity vibration and its effects on muscle function and bone in patients with dystrophinopathies: a pilot study.

IntroductionDystrophinopathies are X-linked muscle degenerative disorders that result in progressive muscle weakness complicated by bone loss. This study's goal was to evaluate feasibility and tolerability of whole-body, low-intensity vibration (WBLIV) and its potential effects on muscle and bone in patients with Duchenne or Becker muscular dystrophy.MethodsThis 12-month pilot study included 5 patients (age 5.9-21.7 years) who used a low-intensity Marodyne LivMD plate vibrating at 30-90 Hz for 10 min/day for the first 6 months. Timed motor function tests, myometry, and peripheral quantitative computed tomography were performed at baseline and at 6 and 12 months.ResultsMotor function and lower extremity muscle strength remained either unchanged or improved during the intervention phase, followed by deterioration after WBLIV discontinuation. Indices of bone density and geometry remained stable in the tibia.ConclusionsWBLIV was well tolerated and appeared to have a stabilizing effect on lower extremity muscle function and bone measures. Muscle Nerve 55: 875-883, 2017

Assessing the Accuracy of Normal Approximations

1 online resource (PDF, 48 pages

Are there any known health risks to early introduction of solids to an infant's diet?

Few studies support an association between early introduction of solid food and atopic conditions, obesity, or any other illness (strength of recommendation [SOR]: B, cohort studies with mixed results). Very weak evidence suggests an increased risk of atopic dermatitis. A single cohort study found an association between early gluten exposure and increased risk of celiac disease in high-risk infants, who carry the HLA-DR3 or DR4 allele (SOR: B, single cohort study)

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic sub-Saharan Africa, where the greatest sickle-cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, and hydroxyurea-associated neutropenia could worsen infections. NOHARM (Novel use Of Hydroxyurea in an African Region with Malaria) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda, comparing hydroxyurea to placebo at 20 ± 2.5 mg/kg per day for 12 months. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events (AEs), clinical and laboratory effects, and hematological toxicities. Children received either hydroxyurea (N = 104) or placebo (N = 103). Malaria incidence did not differ between children on hydroxyurea (0.05 episodes per child per year; 95% confidence interval [0.02, 0.13]) vs placebo (0.07 episodes per child per year [0.03, 0.16]); the hydroxyurea/placebo malaria incidence rate ratio was 0.7 ([0.2, 2.7]; P = .61). Time to infection also did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%; P = .001). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, with decreased leukocytes and reticulocytes. Serious AEs, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Three deaths occurred (2 hydroxyurea, 1 placebo, and none from malaria). Hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased severe malaria, infections, or AEs. Hydroxyurea provides SCA-related laboratory and clinical efficacy, but optimal dosing and monitoring regimens for Africa remain undefined. This trial was registered at www.clinicaltrials.gov as #NCT01976416