Population Structure Analyses Provide Insight into the Source Populations Underlying Rural Isolated Communities in Illinois

We have previously hypothesized that relatively small and isolated rural communities may experience founder effects, defined as the genetic ramifications of small population sizes at the time of a community’s establishment. To explore this, we used an Illumina Infinium Omni2.5Exome-8 chip to collect data from 157 individuals from four Illinois communities, three rural and one urban. Genetic diversity estimates of 999,259 autosomal markers suggested that the reduction in heterozygosity due to shared ancestry was approximately 0, indicating a randomly mating population. An eigenanalysis, which is similar to a principal component analysis but ran on a genetic coancestry matrix, conducted in the SNPRelate R package revealed that the majority of these individuals formed one cluster with a few putative outliers obscuring population variation. An additional eigenanalysis on the same markers in a combined data set including the 2,504 individuals in the 1000 Genomes database found that most of the 157 Illinois individuals clustered into one group in close proximity to individuals of European descent. A final eigenanalysis of the Illinois individuals with the 503 individuals of European descent (within the 1000 Genomes Project) revealed two clusters of individuals and likely two source populations; one British and one consisting of multiple European subpopulations. We therefore demonstrate the feasibility of examining genetic relatedness across Illinois populations and assessing the number of source populations using publicly available databases. When assessed, it becomes possible for population structure information to contribute to the understanding of genetic history in rural populations

Bilan sédimentaire et gestion de la recharge. De l'évaluation des enjeux à la détermination des nouvelles orientations de gestion par les forestiers dans les périmètres RTM drômois : le cas du bassin de la Drôme et ses possibilités de transposabilité.

L'homme depuis la fin du 18e siècle n'a jamais cessé de mener des actions pour lutter contre les inondations et l'érosion des berges, accroître les domaines agricoles dans les fonds de vallées, assainir les plaines alluviales, lutter contre l'érosion de

Identifying Areas with Disproportionate Local Health Department Services Relative to Opioid Overdose, HIV and Hepatitis C Diagnosis Rates: A Study of Rural Illinois

Background: U.S. rural populations have been disproportionately affected by the syndemic of opioid-use disorder (OUD) and the associated increase in overdoses and risk of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) transmission. Local health departments (LHDs) can play a critical role in the response to this syndemic. We utilized two geospatial approaches to identify areas of discordance between LHD service availability and disease burden to inform service prioritization in rural settings.Methods: We surveyed rural Illinois LHDs to assess their OUD-related services, and calculated county-level opioid overdose, HIV, and hepatitis C diagnosis rates. Bivariate choropleth maps were created to display LHD service provision relative to disease burden in rural Illinois counties. Results: Most rural LHDs provided limited OUD-related services, although many LHDs provided HIV and HCV testing. Bivariate mapping showed rural counties with limited OUD treatment and HIV services and with corresponding higher outcome/disease rates to be dispersed throughout Illinois. Additionally, rural counties with limited LHD-offered hepatitis C services and high hepatitis C diagnosis rates were geographically concentrated in southern Illinois. Conclusions: Bivariate mapping can enable geographic targeting of resources to address the opioid crisis and related infectious disease by identifying areas with low LHD services relative to high disease burden

The Problem of the Color Line: Spatial Access to Hospital Services for Minoritized Racial and Ethnic Groups

Examining how spatial access to health care varies across geography is key to documenting structural inequalities in the United States. In this article and the accompanying StoryMap, our team identified ZIP Code Tabulation Areas (ZCTAs) with the largest share of minoritized racial and ethnic populations and measured distances to the nearest hospital offering emergency services, trauma care, obstetrics, outpatient surgery, intensive care, and cardiac care. In rural areas, ZCTAs with high Black or American Indian/Alaska Native representation were significantly farther from services than ZCTAs with high White representation. The opposite was true for urban ZCTAs, with high White ZCTAs being farther from most services. These patterns likely result from a combination of housing policies that restrict housing opportunities and federal health policies that are based on service provision rather than community need. The findings also illustrate the difficulty of using a single metric—distance—to investigate access to care on a national scale

Carotid Ultrasound Boundary Study (CUBS): An Open Multicenter Analysis of Computerized Intima–Media Thickness Measurement Systems and Their Clinical Impact

Common carotid intima–media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts’ manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan–Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.1

CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics

Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins—high physical stability, specificity and low production costs—with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development

Engineering Bispecificity into a Single Albumin-Binding Domain

Bispecific antibodies as well as non-immunoglobulin based bispecific affinity proteins are considered to have a very high potential in future biotherapeutic applications. In this study, we report on a novel approach for generation of extremely small bispecific proteins comprised of only a single structural domain. Binding to tumor necrosis factor-α (TNF-α) was engineered into an albumin-binding domain while still retaining the original affinity for albumin, resulting in a bispecific protein composed of merely 46 amino acids. By diversification of the non albumin-binding side of the three-helix bundle domain, followed by display of the resulting library on phage particles, bispecific single-domain proteins were isolated using selections with TNF-α as target. Moreover, based on the obtained sequences from the phage selection, a second-generation library was designed in order to further increase the affinity of the bispecific candidates. Staphylococcal surface display was employed for the affinity maturation, enabling efficient isolation of improved binders as well as multiparameter-based sortings with both TNF-α and albumin as targets in the same selection cycle. Isolated variants were sequenced and the binding to albumin and TNF-α was analyzed. This analysis revealed an affinity for TNF-α below 5 nM for the strongest binders. From the multiparameter sorting that simultaneously targeted TNF-α and albumin, several bispecific candidates were isolated with high affinity to both antigens, suggesting that cell display in combination with fluorescence activated cell sorting is a suitable technology for engineering of bispecificity. To our knowledge, the new binders represent the smallest engineered bispecific proteins reported so far. Possibilities and challenges as well as potential future applications of this novel strategy are discussed