The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

HIV in Rural Vermont

Through our Health Sciences capstone, we are serving as public health interns at the Pride Center of Vermont. The Pride Center provides sexual health education materials, activities, a wide range of resources, and a safe space for the LGBTQ+ community. The main demographic that this community center works with is within Chittenden county. An estimated 5% of adult Vermonters identify as lesbian, gay, bisexual, or transgender. People aged 18-24 are most likely to identify as LGBTQ+ and about 8% of high school students identify as lesbian, gay, or bisexual (Vermont State Health Assessment, 2018). The majority of services for the LGBTQ+ community in Vermont are located in the greater Burlington area. An issue of focus for The Pride Center is to increase access to services for rural communities in Vermont, with a focus on people living with HIV however they lack major funding. Knowing this, we will assess the rates of HIV in rural areas of Vermont in addition to taking an inventory of current efforts locally and best practices in the literature on reaching rural populations. By the conclusion of our internships, we formulate a proposal for the Pride Center of Vermont on how to successfully expand into rural areas of Vermont. We would like to present at the 2019 Student Research Conference on our service learning research. Sources: -http://www.healthvermont.gov/sites/default/files/documents/pdf/ID_HIV_2016VermontHIVEpiProfile.pdf Vermont State Health Assessment, 201

Personalized fludarabine dosing to reduce nonrelapse mortality in hematopoietic stem-cell transplant recipients receiving reduced intensity conditioning

Patients undergoing hematopoietic cell transplantation (HCT) with reduced intensity conditioning (RIC) commonly receive fludarabine. Higher exposure of F-ara-A, the active component of fludarabine, has been associated with a greater risk of non-relapse mortality (NRM). We sought to develop a model for fludarabine dosing in adult HCT recipients that would allow for precise dose targeting and predict adverse clinical outcomes. We developed a pharmacokinetic model from 87 adults undergoing allogeneic RIC HCT that predicts F-ara-A population clearance (Clpop) accounting for ideal body weight and renal function. We then applied the developed model to an independent cohort of 240 patients to identify whether model predictions were associated with NRM and acute graft vs host disease (GVHD). Renal mechanisms accounted for 35.6% of total F-ara-A Clpop. In the independent cohort the hazard ratio of NRM at day 100 was significantly higher in patients with predicted F-ara-A clearance (Clpred) <8.50 L/hr (p<0.01) and area under the curve (AUCpred)>6.00 μg*hr/mL (p=0.01). A lower Clpred was also associated with more NRM at month 6 (p=0.01) and trended towards significance at 12 months (p=0.05). In multivariate analysis, low fludarabine clearance trended towards higher risk of acute GVHD (p=0.05). We developed a model that predicts an individual's systemic F-ara-A exposure accounting for kidney function and weight. This model may provide guidance in dosing in overweight individuals and those with altered kidney function