Modeling community COVID-19 transmission risk associated with U.S. universities.

The ongoing COVID-19 pandemic is among the worst in recent history, resulting in excess of 520,000,000 cases and 6,200,000 deaths worldwide. The United States (U.S.) has recently surpassed 1,000,000 deaths. Individuals who are elderly and/or immunocompromised are the most susceptible to serious sequelae. Rising sentiment often implicates younger, less-vulnerable populations as primary introducers of COVID-19 to communities, particularly around colleges and universities. Adjusting for more than 32 key socio-demographic, economic, and epidemiologic variables, we (1) implemented regressions to determine the overall community-level, age-adjusted COVID-19 case and mortality rate within each American county, and (2) performed a subgroup analysis among a sample of U.S. colleges and universities to identify any significant preliminary mitigation measures implemented during the fall 2020 semester. From January 1, 2020 through March 31, 2021, a total of 22,385,335 cases and 374,130 deaths were reported to the CDC. Overall, counties with increasing numbers of university enrollment showed significantly lower case rates and marginal decreases in mortality rates. County-level population demographics, and not university level mitigation measures, were the most significant predictor of adjusted COVID-19 case rates. Contrary to common sentiment, our findings demonstrate that counties with high university enrollments may be more adherent to public safety measures and vaccinations, likely contributing to safer communities.

Dynamics of data availability in disease modeling: An example evaluating the trade-offs of ultra-fine-scale factors applied to human West Nile virus disease models in the Chicago area, USA.

BACKGROUND: Since 1999, West Nile virus (WNV) has moved rapidly across the United States, resulting in tens of thousands of human cases. Both the number of human cases and the minimum infection rate (MIR) in vector mosquitoes vary across time and space and are driven by numerous abiotic and biotic forces, ranging from differences in microclimates to socio-demographic factors. Because the interactions among these multiple factors affect the locally variable risk of WNV illness, it has been especially difficult to model human disease risk across varying spatial and temporal scales. Cook and DuPage Counties, comprising the city of Chicago and surrounding suburbs, experience some of the highest numbers of human neuroinvasive cases of WNV in the United States. Despite active mosquito control efforts, there is consistent annual WNV presence, resulting in more than 285 confirmed WNV human cases and 20 deaths from the years 2014-2018 in Cook County alone. METHODS: A previous Chicago-area WNV model identified the fifty-five most high and low risk locations in the Northwest Mosquito Abatement District (NWMAD), an enclave » the size of the combined Cook and DuPage county area. In these locations, human WNV risk was stratified by model performance, as indicated by differences in studentized residuals. Within these areas, an additional two-years of field collections and data processing was added to a 12-year WNV dataset that includes human cases, MIR, vector abundance, and land-use, historical climate, and socio-economic and demographic variables, and was assessed by an ultra-fine-scale (1 km spatial x 1 week temporal resolution) multivariate logistic regression model. RESULTS: Multivariate statistical methods applied to the ultra-fine-scale model identified fewer explanatory variables while improving upon the fit of the previous model. Beyond MIR and climatic factors, efforts to acquire additional covariates only slightly improved model predictive performance. CONCLUSIONS: These results suggest human WNV illness in the Chicago area may be associated with fewer, but increasingly critical, key variables at finer scales. Given limited resources, these findings suggest large variations in model performance occur, depending on covariate availability, and provide guidance in variable selection for optimal WNV human illness modeling.

Light Harvesting with Guide-Slide Superabsorbing Condensed-Matter Nanostructures.

We establish design principles for light-harvesting antennae whose energy capture scales superlinearly with system size. Controlling the absorber dipole orientations produces sets of "guide-slide" states that promote steady-state superabsorbing characteristics in noisy condensed-matter nanostructures. Inspired by natural photosynthetic complexes, we discuss the example of ringlike dipole arrangements and show that, in our setup, vibrational relaxation enhances rather than impedes performance. Remarkably, the superabsorption effect proves to be robust to O(5%) disorder simultaneously for all relevant system parameters, showing promise for experimental exploration across a broad range of platforms.

Assessing human risk of illness with West Nile virus mosquito surveillance data to improve public health preparedness.

Surveillance for West Nile virus (WNV) and other mosquito-borne pathogens involves costly and time-consuming collection and testing of mosquito samples. One difficulty faced by public health personnel is how to interpret mosquito data relative to human risk, thus leading to a failure to fully exploit the information from mosquito testing. The objective of our study was to use the information gained from historic West Nile virus mosquito testing to determine human risk relative to mosquito infection and to assess the usefulness of our mosquito infection forecasting models to give advance warning. We compared weekly mosquito infection rates from 2004 to 2013 to WNV case numbers in Illinois. We then developed a weather-based forecasting model to estimate the WNV mosquito infection rate one to 3 weeks ahead of mosquito testing both statewide and for nine regions of Illinois. We further evaluated human illness risk relative to both the measured and the model-estimated infection rates to provide guidelines for public health messages. We determined that across 10 years, over half of human WNV cases occurred following the 29 (of 210) weeks with the highest mosquito infection rates. The values forecasted by the models can identify those time periods, but model results and data availability varied by region with much stronger results obtained from regions with more mosquito data. The differences among the regions may be related to the amount of surveillance or may be due to diverse landscape characteristics across Illinois. We set the stage for better use of all surveillance options available for WNV and described an approach to modelling that can be expanded to other mosquito-borne illnesses.

Effect of Replacing Race With Apolipoprotein L1 Genotype in Calculation of Kidney Donor Risk Index.

Renal allografts from deceased African American donors with two apolipoprotein L1 gene (APOL1) renal-risk variants fail sooner than kidneys from donors with fewer variants. The Kidney Donor Risk Index (KDRI) was developed to evaluate organ offers by predicting allograft longevity and includes African American race as a risk factor. Substituting APOL1 genotype for race may refine the KDRI. For 622 deceased African American kidney donors, we applied a 10-fold cross-validation approach to estimate contribution of APOL1 variants to a revised KDRI. Cross-validation was repeated 10 000 times to generate distribution of effect size associated with APOL1 genotype. Average effect size was used to derive the revised KDRI weighting. Mean current-KDRI score for all donors was 1.4930 versus mean revised-KDRI score 1.2518 for 529 donors with no or one variant and 1.8527 for 93 donors with two variants. Original and revised KDRIs had comparable survival prediction errors after transplantation, but the spread in Kidney Donor Profile Index based on presence or absence of two APOL1 variants was 37 percentage points. Replacing donor race with APOL1 genotype in KDRI better defines risk associated with kidneys transplanted from deceased African American donors, substantially improves KDRI score for 85-90% of kidneys offered, and enhances the link between donor quality and recipient need.

Predicting West Nile Virus Infection Risk From the Synergistic Effects of Rainfall and Temperature.

Mosquito-based surveillance is a practical way to estimate the risk of transmission of West Nile virus (WNV) to people. Variations in temperature and precipitation play a role in driving mosquito infection rates and transmission of WNV, motivating efforts to predict infection rates based on prior weather conditions. Weather conditions and sequential patterns of meteorological events can have particularly important, but regionally distinctive, consequences for WNV transmission, with high temperatures and low precipitation often increasing WNV mosquito infection. Predictive models that incorporate weather can thus be used to provide early indications of the risk of WNV infection. The purpose of this study was first, to assess the ability of a previously published model of WNV mosquito infection to predict infection for an area within the region for which it was developed, and second, to improve the predictive ability of this model by incorporating new weather factors that may affect mosquito development. The legacy model captured the primary trends in mosquito infection, but it was improved considerably when calibrated with local mosquito infection rates. The use of interaction terms between precipitation and temperature improved model performance. Specifically, temperature had a stronger influence than rainfall, so that lower than average temperature greatly reduced the effect of low rainfall on increased infection rates. When rainfall was lower, high temperature had an even stronger positive impact on infection rates. The final model is practical, stable, and operationally valid for predicting West Nile virus infection rates in future weeks when calibrated with local data.

Genome-wide meta-analyses of smoking behaviors in African Americans.

The identification and exploration of genetic loci that influence smoking behaviors have been conducted primarily in populations of the European ancestry. Here we report results of the first genome-wide association study meta-analysis of smoking behavior in African Americans in the Study of Tobacco in Minority Populations Genetics Consortium (n = 32,389). We identified one non-coding single-nucleotide polymorphism (SNP; rs2036527[A]) on chromosome 15q25.1 associated with smoking quantity (cigarettes per day), which exceeded genome-wide significance (ß = 0.040, s.e. = 0.007, P = 1.84 × 10(-8)). This variant is present in the 5'-distal enhancer region of the CHRNA5 gene and defines the primary index signal reported in studies of the European ancestry. No other SNP reached genome-wide significance for smoking initiation (SI, ever vs never smoking), age of SI, or smoking cessation (SC, former vs current smoking). Informative associations that approached genome-wide significance included three modestly correlated variants, at 15q25.1 within PSMA4, CHRNA5 and CHRNA3 for smoking quantity, which are associated with a second signal previously reported in studies in European ancestry populations, and a signal represented by three SNPs in the SPOCK2 gene on chr10q22.1. The association at 15q25.1 confirms this region as an important susceptibility locus for smoking quantity in men and women of African ancestry. Larger studies will be needed to validate the suggestive loci that did not reach genome-wide significance and further elucidate the contribution of genetic variation to disparities in cigarette consumption, SC and smoking-attributable disease between African Americans and European Americans.

Overview of the Rapid Response data.

The Type I Diabetes Genetics Consortium (T1DGC) Rapid Response Workshop was established to evaluate published candidate gene associations in a large collection of affected sib-pair (ASP) families. We report on our quality control (QC) and preliminary family-based association analyses. A random sample of blind duplicates was analyzed for QC. Quality checks, including examination of plate-panel yield, marker yield, Hardy-Weinberg equilibrium, mismatch error rate, Mendelian error rate, and allele distribution across plates, were performed. Genotypes from 2324 families within nine cohorts were obtained from a panel of 21 candidate genes, including 384 single-nucleotide polymorphisms on two genotyping platforms performed at the Broad Institute Center for Genotyping and Analysis (Cambridge, MA, USA). The T1DGC Rapid Response project, following rigorous QC procedures, resulted in a 2297 family, 9688 genotyped individual database on a single-candidate gene panel. The available data include 9005 individuals with genotype data from both platforms and 683 individuals genotyped (276 in Illumina; 407 in Sequenom) on only one platform.

Overview of the MHC fine mapping data.

AIM: The aim of this study was to perform quality control (QC) and initial family-based association analyses on the major histocompatibility complex (MHC) single nucleotide polymorphism (SNP) and microsatellite marker data for the MHC Fine Mapping Workshop through the Type 1 Diabetes Genetics Consortium (T1DGC). METHODS: A random sample of blind duplicates was sent for analysis of QC. DNA samples collected from participants were shipped to the genotyping laboratory from several T1DGC DNA Repository sites. Quality checks including examination of plate-panel yield, marker yield, Hardy-Weinberg equilibrium, mismatch error rate, Mendelian error rate and allele distribution across plates were performed. RESULTS: Genotypes from 2325 families within nine cohorts were obtained and subjected to QC procedures. The MHC project consisted of three marker panels - two 1536 SNP sets (Illumina Golden Gate platform performed at the Wellcome Trust Sanger Institute, Cambridge, UK) and one 66 microsatellite marker panel (performed at deCODE). In the raw SNP data, the overall concordance rate was 99.1% (+/-0.02). CONCLUSIONS: The T1DGC MHC Fine Mapping project resulted in a 2300 family, 9992 genotyped individuals database comprising of two 1536 SNP panels and a 66 microsatellite panel to densely cover the 4 Mb MHC core region for use in statistical genetic analyses.

Lack of aggregation of ischemic stroke subtypes within affected sibling pairs.

OBJECTIVE: To establish whether subtypes of ischemic stroke aggregate within ischemic stroke-affected sibling pairs more than expected by chance alone. METHODS: This retrospective family study was based on a pooled analysis of two cohorts of male and female adult sibling pairs with symptomatic ischemic stroke. One hospital-based cohort of 404 individuals (first proband seen August 30, 1999) was recruited from the United States and Canada, and another population-based cohort of 198 individuals (first proband seen April 17, 1997) was recruited from Umeå, Sweden. Subtype diagnoses were based on Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. RESULTS: Agreement for subtype diagnoses within families was poor (mean +/- asymptotic SE kappa = 0.17 +/- 0.04). Occurrence of one ischemic stroke subtype in a proband was not associated with a greater likelihood of that subtype being the qualifying stroke subtype in the sibling. Comparable levels of agreement were seen when restricting the analysis to same-sex sibling pairs (kappa = 0.22 +/- 0.05) to sibling pairs in which the proband's stroke occurred before the age of 65 years (kappa = 0.16 +/- 0.05) or to pairs in which the proband's stroke occurred at or after the age of 65 years (kappa = 0.19 +/- 0.05). CONCLUSIONS: The subtype of ischemic stroke in a proband was a poor determinant of the subtype of ischemic stroke in the respective sibling. This suggests that many genetic risk factors for ischemic stroke may not be specific for one subtype.

Leukaemia and aplastic anaemia in patients irradiated for ankylosing spondylitis. 1957.

Reported here is a seminal study of leukaemia among patients who had been treated with x-rays for ankylosing spondylitis. The findings were first published in a Medical Research Council (MRC) report in 1957. The report is now published in a scientific journal for the first time, 50 years after it first appeared.

Correlation of proband and sibling stroke latency: the SWISS Study.

The authors found a correlation between the age at which probands experience an incident stroke and the age at which their siblings experience an incident stroke (r = 0.68; p < 0.0001). Proband-sibling incident stroke latency correlations were observed in analyses restricted to siblings concordant for smoking (r = 0.68; p < 0.0001), diabetes (r = 0.73; p < 0.0001), and hypertension (r = 0.63; p < 0.0001). In the authors' cohort of affected sibling pairs, inherited factors were important determinants of incident ischemic stroke latency.

NMR solution structure of a potent cyclic nonapeptide inhibitor of ICAM-1-mediated leukocyte adhesion produced by homologous amino acid substitution.

We have previously described a disulfide-linked cyclic nonapeptide (inhibitory peptide-01, IP01), with the sequence CLLRMRSIC, which binds to intercellular adhesion molecule-1 (ICAM-1), and blocks binding to its counter-structure, the integrin alphaLbeta2 (leukocyte functional antigen-1, LFA-1) (Sillerud et al., J. Peptide Res. 62, 2003: 97). We now report the optimization of this peptide by means of single homologous amino acid substitutions to yield a new peptide (IP02-K6; CLLRMKSAC) which shows an approximately sixfold improvement in inhibitory activity of multivalent leukocyte binding (inhibition constant for 50% inhibition, IC50 = 90 microm) compared with IP01 (IC50 = 580 microm). This improvement in activity gives IP02-K6 potent in vivo activity in a murine model of ischemia reperfusion injury (Merchant et al., Am. J. Physiol. Heart Circ. 284, 2003: H1260). In order to determine the structural features relevant to ICAM-1-binding, we have determined the structure of IP02-K6 using proton nuclear magnetic resonance (NMR) spectroscopy and restrained molecular modeling. In our previously reported study of solution models of IP01, we observed three interconverting conformations during low-temperature molecular dynamics simulation. In the present study, we find a single conformation of IP02-K6 similar to one of the previously found conformations of IP01 (family C). In particular, an R4-S7 beta-turn is present in similar proportions in both conformation C of IP01 and in IP02-K6; this motif is important in binding to ICAM-1 because this turn enables the IP02-K6 backbone to drape over proline-36 on ICAM-1. The NMR-derived solution model of IP02-K6 was found to dock at the alphaLbeta2-binding site on ICAM-1 with no changes in peptide backbone conformation. This docking model displaced five of the 15 alphaLbeta2 residues at the ICAM-1-binding site and provided a rationale for understanding the quantitative relationship between IP02-K6 structure and biologic activity.

Sniffing human sex-steroid derived compounds modulates mood, memory and autonomic nervous system function in specific behavioral contexts.

We asked whether the effects of exposure to two human sex-steroid derived compounds were context dependent. The effects of sniffing 4,16-androstadien-3-one (AND) and 1,3,5(10),16-estratetraen-3-ol (EST) on mood, memory, and autonomic nervous system responses were explored in 72 participants. Subjects were tested with AND, EST, or a Control compound within four mood contexts: neutral, sexually aroused, sad and happy. These moods were successfully induced using selected film segments (P < 0.0001). During the neutral context, none of the compounds affected mood or autonomic nervous system function. However, compound effects were significantly increased within arousing contexts. During the sexually arousing context, both compounds increased sexual arousal (P < 0.029). During the sad context, AND maintained positive mood in women (P< 0.050) and increased negative mood in men (P < 0.031). Memory for events during the sad context was impaired by AND in women (P < 0.047) but not in men. Finally, effects of AND on physiology were observed during the sexually arousing context whereby AND increased skin temperature in both sexes (P < 0.022) but reduced abdominal respiration rate in men only (P < 0.034). These results suggest that sex-steroidal compounds modulate mood, memory and autonomic nervous system responses and increase their significance within specific behavioral contexts. These findings lend support to a specific role for these compounds in chemical communication between humans.

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28. Multipoint mode-of-inheritance-free linkage analyses were performed using the GENEHUNTER software. Some evidence of prostate cancer was detected to HPC1 using all families with a maximum NPL Z score of 1.12 near marker D1S413 (P=0.13). Increased evidence of linkage was observed in the 24 families with prostate cancer diagnosis prior to age 65 years and in the 20 families with male-to-male transmission. Some evidence of prostate cancer linkage was also detected at markers mapping to PCAP, HPC20, and HPCX. Continued collection and analysis of African American prostate cancer families will lead to an improved understanding of inherited susceptibility in this high-risk group.

Sex-steroid derived compounds induce sex-specific effects on autonomic nervous system function in humans.

The physiological and psychological effects of 2 human sex-steroid derived compounds, 4.16-androstadien-3-one (AND) and l,3,5(10),16-estratetraen-3-ol(EST) were measured in 24 subjects who participated in a within-subjects, double-blind experiment. A dissociation was evident in the physiological effects of AND, in that it increased physiological arousal in women but decreased it in men. EST did not significantly affect physiological arousal in women or men. Neither compound significantly affected mood. AND is an androgen derivative that is the most prevalent androstene in human male sweat, male axillary hair, and on the male axillary skin surface. The authors argue that AND's opposite effects on physiology in men and women further implicate this compound in chemical communication between humans.

Iris yellow spot virus on Onion in Colorado.

A new disease was found in September 2001 on greenhouse-produced onion transplants of cv. Colorado 6 grown in a field in Larimer County in northern Colorado. Symptoms included straw-colored, dry, tan, spindle- or diamond-shaped lesions on the leaves and scapes of onion plants. Infected plants were scattered (less than 5% incidence) throughout the outer perimeter of the sprinkler-irrigated field. Iris yellow spot virus (IYSV) in two collections each with 4 to 6 symptomatic onion plants was confirmed with western blot assays by James Moyer of North Carolina State University. Western blot showed a faint band from protein extracts of infected Nicotiana benethimiana. Western blot assay is the most definitive method of identification. IYSV can be mechanically transmitted to N. benethimiana, but it cannot be recovered and transmitted back to onion, and it is difficult to detect in infected onion plants. IYSV is a tospovirus that is transmitted by various species of thrips, including onion thrips and western flower thrips (1). The host range for this disease includes onion, leek, and iris. IYSV has been reported previously on onion in Israel, Brazil, and Idaho (2). There are no reports that this disease affects bulb quality or marketability; however, heavy losses of onion bulb production are reported (1). University and industry personnel in other onion-growing areas of the country are encouraged to monitor onion and other host fields for evidence and distribution of IYSV. References: (1) A. Kritzman et al. Plant Dis. 85:838, 2001. (2) L. Pozzer et al. Plant Dis. 83:345, 1999.

Barley yellow rust in North America.

Yellow rust of barley is an invasive disease that was found in the past 10 years in North America. The causal agent, Puccinia striiformis f. sp. hordei, was introduced into Colombia, South America, from Europe in 1975. It spread to all major barley-producing areas in South America by 1982. In 1988 it was found in Mexico and in 1991 in Texas. Since then it has been found in all major barley-producing areas of the American West. Originally described as race (R) 24, barley yellow rust in North America is now known to be a very heterogeneous population. Resistance has been identified, evaluated, and is being introduced into commercial malting and other barley cultivars. Cultural and chemical controls are effective and available. An integrated approach using general field resistance and other tactics is described for sustainable management of barley yellow rust.

The scented brain: pheromonal responses in humans.

Using PET, Savic et al., in this issue of Neuron, found a sexually dimorphic neural response to two putative human pheromones. The specific regions activated combined with the pronounced sex difference depict a pheromonal-type brain response in humans. Here, we preview this finding and suggest that human pheromones exist.

Genetic linkage and transmission disequilibrium of marker haplotypes at chromosome 1q41 in human systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies to a wide range of self-antigens. Recent genome screens have implicated numerous chromosomal regions as potential SLE susceptibility loci. Among these, the 1q41 locus is of particular interest, because evidence for linkage has been found in several independent SLE family collections. Additionally, the 1q41 locus appears to be syntenic with a susceptibility interval identified in the NZM2410 mouse model for SLE. Here, we report the results of genotyping of 11 microsatellite markers within the 1q41 region in 210 SLE sibpair and 122 SLE trio families. These data confirm the modest evidence for linkage at 1q41 in our family collection (LOD = 1.21 at marker D1S2616). Evidence for significant linkage disequilibrium in this interval was also found. Multiple markers in the region exhibit transmission disequilibrium, with the peak single marker multiallelic linkage disequilibrium noted at D1S490 (pedigree disequilibrium test [PDT] global P value = 0.0091). Two- and three-marker haplotypes from the 1q41 region similarly showed strong transmission distortion in the collection of 332 SLE families. The finding of linkage together with significant transmission disequilibrium provides strong evidence for a susceptibility locus at 1q41 in human SLE.