SimPEL: Simulation‐based power estimation for sequencing studies of low‐prevalence conditions

Power estimations are important for optimizing genotype‐phenotype association study designs. However, existing frameworks are designed for common disorders, and thus ill‐suited for the inherent challenges of studies for low‐prevalence conditions such as rare diseases and infrequent adverse drug reactions. These challenges include small sample sizes and the need to leverage genetic annotation resources in association analyses for the purpose of ranking potential causal genes. We present SimPEL, a simulation‐based program providing power estimations for the design of low‐prevalence condition studies. SimPEL integrates the usage of gene annotation resources for association analyses. Customizable parameters, including the penetrance of the putative causal allele and the employed pathogenic scoring system, allow SimPEL to realistically model a large range of study designs. To demonstrate the effects of various parameters on power, we estimated the power of several simulated designs using SimPEL and captured power trends in agreement with observations from current literature on low‐frequency condition studies. SimPEL, as a tool, provides researchers studying low‐frequency conditions with an intuitive and highly flexible avenue for statistical power estimation. The platform‐independent “batteries included” executable and default input files are available at https://github.com/precisionomics/SimPEL .     

Implementation of the redesigned Community Health Fund in the Dodoma region of Tanzania: A qualitative study of views from rural communities

The need to understand how an intervention is received by the beneficiary community is well recognised and particularly neglected in the micro–health insurance (MHI) domain. This study explored the views and reactions of the beneficiary community of the redesigned Community Health Fund (CHF) implemented in the Dodoma region of Tanzania. We collected data from focus group discussions with 24 groups of villagers (CHF members and nonmembers) and in‐depth interviews with 12 key informants (enrolment officers and health care workers). The transcribed material was analysed thematically. We found that participants highly appreciate the scheme, but to be resolved are the challenges posed by the implementation strategies adopted. The responses of the community were nested within a complex pathway relating to their interaction with the implementation strategies and their ongoing reflections regarding the benefits of the scheme. Community reactions ranged from accepting to rejecting the scheme, demanding the right to receive benefit packages once enrolled, and dropping out of the scheme when it failed to meet their expectations. Reported drivers of the responses included intensity of CHF communication activities, management of enrolment procedures, delivery of benefit packages, critical features of the scheme, and contextual factors (health system and socio‐political context). This study highlights that scheme design and implementation strategies that address people's needs, voices, and values can improve uptake of MHI interventions. The study adds to the knowledge base on implementing MHI initiatives and could promote interests in assessing the response to interventions within the MHI domain and beyond.     

The role of glutamate receptors in attention‐deficit/hyperactivity disorder: From physiology to disease

Attention‐deficit hyperactivity disorder (ADHD) is the most common psychiatric disorder in children and adolescents, which is characterized by behavioral problems such as attention deficit, hyperactivity, and impulsivity. As the receptors of the major excitatory neurotransmitter in the mammalian central nervous system (CNS), glutamate receptors (GluRs) are strongly linked to normal brain functioning and pathological processes. Extensive investigations have been made about the structure, function, and regulation of GluR family, describing evidences that support the disruption of these mechanisms in mental disorders, including ADHD. In this review, we briefly described the family and function of GluRs in the CNS, and discussed what is recently known about the role of GluRs in ADHD, that including GluR genes, animal models, and the treatment, which would help us further elucidate the etiology of ADHD.