Associations between common genetic variants and income provide insights about the socio-economic health gradient.

We conducted a genome-wide association study on income among individuals of European descent (N = 668,288) to investigate the relationship between socio-economic status and health disparities. We identified 162 genomic loci associated with a common genetic factor underlying various income measures, all with small effect sizes (the Income Factor). Our polygenic index captures 1-5% of income variance, with only one fourth due to direct genetic effects.

The Effects of Hospital Delivery Volume and Travel Time on Perinatal Mortality and Delivery in Transit: Causal Inference with Triangulation.

Background: Hospital regionalization involves balancing hospital volume and travel time. We investigated how hospital volume and travel time affect perinatal mortality and the risk of delivery in transit using three different study designs.

Methods: This nationwide cohort study used data from the Medical Birth Registry of Norway (1999-2016) and Statistics Norway.

Patients with neurological or psychiatric complications of COVID-19 have worse long-term functional outcomes: COVID-CNS-A multicentre case-control study.

It is established that patients hospitalised with COVID-19 often have ongoing morbidity affecting activity of daily living (ADL), employment, and mental health. However, little is known about the relative outcomes in patients with COVID-19 neurological or psychiatric complications. We conducted a UK multicentre case-control study of patients hospitalised with COVID-19 (controls) and those who developed COVID-19 associated acute neurological or psychiatric complications (cases).

Highly Optimized CNS Penetrant Inhibitors of EGFR Exon20 Insertion Mutations.

Despite recent advances in the inhibition of EGFR (epidermal growth factor receptor), there remains a clinical need for new EGFR Exon20 insertion (Ex20Ins) inhibitors that spare EGFR WT. Herein, we report the discovery and optimization of two chemical series leading to ether and biaryl as potent, selective, and brain-penetrant inhibitors of Ex20Ins mutants. Building on our earlier discovery of alkyne which allowed access to CNS property space for an Ex20Ins inhibitor, we utilized structure-based design to move to lower lipophilicity and lower CL compounds while maintaining a WT selectivity margin.

Non-invasive assessment of intracranial compliance in idiopathic intracranial hypertension: an MRI-ICP study.

Background/objectives: Idiopathic intracranial hypertension (IIH) is a disease which threatens vision and causes disabling headaches, affecting women of childbearing age with obesity. It is characterised by raised intracranial pressure (ICP), measured invasively either with lumbar punctures or intracranially-inserted monitors. There is an unmet clinical need to develop non-invasive means to assess ICP.