Impact of changes in protective behaviors and out-of-household activities by age on COVID-19 transmission and hospitalization in Chicago, Illinois.

PURPOSE: Even with an efficacious vaccine, protective behaviors (social distancing, masking) are essential for preventing COVID-19 transmission and could become even more important if current or future variants evade immunity from vaccines or prior infection. METHODS: We created an agent-based model representing the Chicago population and conducted experiments to determine the effects of varying adult out-of-household activities (OOHA), school reopening, and protective behaviors across age groups on COVID-19 transmission and hospitalizations. RESULTS: From September-November 2020, decreasing adult protective behaviors and increasing adult OOHA both substantially impacted COVID-19 outcomes; school reopening had relatively little impact when adult protective behaviors and OOHA were maintained. As of November 1, 2020, a 50% reduction in young adult (age 18-40) protective behaviors resulted in increased latent infection prevalence per 100,000 from 15.93 (IQR 6.18, 36.23) to 40.06 (IQR 14.65, 85.21) and 19.87 (IQR 6.83, 46.83) to 47.74 (IQR 18.89, 118.77) with 15% and 45% school reopening. Increasing adult (age ≥18) OOHA from 65% to 80% of prepandemic levels resulted in increased latent infection prevalence per 100,000 from 35.18 (IQR 13.59, 75.00) to 69.84 (IQR 33.27, 145.89) and 38.17 (IQR 15.84, 91.16) to 80.02 (IQR 30.91, 186.63) with 15% and 45% school reopening. Similar patterns were observed for hospitalizations. CONCLUSIONS: In areas without widespread vaccination coverage, interventions to maintain adherence to protective behaviors, particularly among younger adults and in out-of-household settings, remain a priority for preventing COVID-19 transmission.

Graph-Guided Regularized Regression of Pacific Ocean Climate Variables to Increase Predictive Skill of Southwestern U.S. Winter Precipitation.

Understanding the physical drivers of seasonal hydroclimatic variability and improving predictive skill remains a challenge with important socioeconomic and environmental implications for many regions around the world. Physics-based deterministic models show limited ability to predict precipitation as the lead time increases, due to imperfect representation of physical processes and incomplete knowledge of initial conditions. Similarly, statistical methods drawing upon established climate teleconnections have low prediction skill due to the complex nature of the climate system. Recently, promising data-driven approaches have been proposed, but they often suffer from overparameterization and overfitting due to the short observational record, and they often do not account for spatiotemporal dependencies among covariates (i.e., predictors such as sea surface temperatures). This study addresses these challenges via a predictive model based on a graph-guided regularizer that simultaneously promotes similarity of predictive weights for highly correlated covariates and enforces sparsity in the covariate domain. This approach both decreases the effective dimensionality of the problem and identifies the most predictive features without specifying them a priori. We use large ensemble simulations from a climate model to construct this regularizer, reducing the structural uncertainty in the estimation. We apply the learned model to predict winter precipitation in the southwestern United States using sea surface temperatures over the entire Pacific basin, and demonstrate its superiority compared to other regularization approaches and statistical models informed by known teleconnections. Our results highlight the potential to combine optimally the space-time structure of predictor variables learned from climate models with new graph-based regularizers to improve seasonal prediction.

A case of Robin sequence, microgastria, radiohumeral synostosis, femoral deficiency, and other unusual findings: a newly recognized syndrome?

In this report, we describe an 8-year-old male with Robin sequence, bilateral radiohumeral synostosis, microgastria, cryptorchidism, dislocated hips, proximal femoral deficiency, and an autism spectrum disorder. This combination of findings has not been previously reported. Features of particular interest are the radiohumeral synostosis and microgastria, both of which are rare defects, and to our knowledge, have not been reported to occur together. We propose that the patient has a newly recognized syndrome consisting of the aforementioned features, the etiology of which is unknown.

NAHR-mediated copy-number variants in a clinical population: mechanistic insights into both genomic disorders and Mendelizing traits.

We delineated and analyzed directly oriented paralogous low-copy repeats (DP-LCRs) in the most recent version of the human haploid reference genome. The computationally defined DP-LCRs were cross-referenced with our chromosomal microarray analysis (CMA) database of 25,144 patients subjected to genome-wide assays. This computationally guided approach to the empirically derived large data set allowed us to investigate genomic rearrangement relative frequencies and identify new loci for recurrent nonallelic homologous recombination (NAHR)-mediated copy-number variants (CNVs). The most commonly observed recurrent CNVs were NPHP1 duplications (233), CHRNA7 duplications (175), and 22q11.21 deletions (DiGeorge/velocardiofacial syndrome, 166). In the ∼25% of CMA cases for which parental studies were available, we identified 190 de novo recurrent CNVs. In this group, the most frequently observed events were deletions of 22q11.21 (48), 16p11.2 (autism, 34), and 7q11.23 (Williams-Beuren syndrome, 11). Several features of DP-LCRs, including length, distance between NAHR substrate elements, DNA sequence identity (fraction matching), GC content, and concentration of the homologous recombination (HR) hot spot motif 5'-CCNCCNTNNCCNC-3', correlate with the frequencies of the recurrent CNVs events. Four novel adjacent DP-LCR-flanked and NAHR-prone regions, involving 2q12.2q13, were elucidated in association with novel genomic disorders. Our study quantitates genome architectural features responsible for NAHR-mediated genomic instability and further elucidates the role of NAHR in human disease.

Genotype-phenotype correlation in interstitial 6q deletions: a report of 12 new cases.

Interstitial deletions of 6q are associated with variable phenotypes, including growth retardation, dysmorphic features, upper limb malformations, and Prader-Willi (PW)-like features. Only a minority of cases in the literature have been characterized with high resolution techniques, making genotype-phenotype correlations difficult. We report 12 individuals with overlapping, 200-kb to 16.4-Mb interstitial deletions within 6q15q22.33 characterized by microarray-based comparative genomic hybridization to better correlate deletion regions with specific phenotypes. Four individuals have a PW-like phenotype, though only two have deletion of SIM1, the candidate gene for this feature. Therefore, other genes on 6q may contribute to this phenotype including multiple genes on 6q16 and our newly proposed candidate, the transcription cofactor gene VGLL2 on 6q22.2. Two individuals present with movement disorders as a major feature, and ataxia is present in a third. The 4.1-Mb 6q22.1q22.2 critical region for movement disorders includes the cerebellar-expressed candidate gene GOPC. Observed brain malformations include thick corpus callosum in two subjects, cerebellar vermal hypoplasia in two subjects, and cerebellar atrophy in one subject. Seven subjects' deletions overlap a ~250-kb cluster of four genes on 6q22.1 including MARCKS, HDAC2, and HS3ST5, which are involved in neural development. Two subjects have only this gene cluster deleted, and one deletion was apparently de novo, suggesting at least one of these genes plays an important role in development. Although the phenotypes associated with 6q deletions can vary, using overlapping deletions to delineate critical regions improves genotype-phenotype correlation for interstitial 6q deletions.