Strategies to reduce the harmful effects of extreme heat events: A four-city study

Extreme heat events (EHEs) are becoming more intense, more frequent and longer lasting in the 21st century. These events can disproportionately impact the health of low-income, minority, and urban populations. To better understand heat-related intervention strategies used by four U.S. cities, we conducted 73 semi-structured interviews with government and non-governmental organization leaders representing public health, general social services, emergency management, meteorology, and the environmental planning sectors in Detroit, MI; New York City, NY; Philadelphia, PA and Phoenix, AZ—cities selected for their diverse demographics, climates, and climate adaptation strategies. We identified activities these leaders used to reduce the harmful effects of heat for residents in their city, as well as the obstacles they faced and the approaches they used to evaluate these efforts. Local leaders provided a description of how local context (e.g., climate, governance and city structure) impacted heat preparedness. Despite the differences among study cities, political will and resource access were critical to driving heat-health related programming. Upon completion of our interviews, we convened leaders in each city to discuss these findings and their ongoing efforts through day-long workshops. Our findings and the recommendations that emerged from these workshops could inform other local or national efforts towards preventing heat-related morbidity and mortality

Pilot Study of Delayed ICOS/ICOS-L Blockade With alphaCD40 to Modulate Pathogenic Alloimmunity in a Primate Cardiac Allograft Model

Background: Inducible costimulator (ICOS) is rapidly upregulated with T-cell stimulation and may represent an escape pathway for T-cell costimulation in the setting of CD40/CD154 costimulation blockade. Induction treatment exhibited no efficacy in a primate renal allograft model, but rodent transplant models suggest that the addition of delayed ICOS/ICOS-L blockade may prolong allograft survival and prevent chronic rejection. Here, we ask whether ICOS-Ig treatment, timed to anticipate ICOS upregulation, prolongs NHP cardiac allograft survival or attenuates pathogenic alloimmunity. Methods: Cynomolgus monkey heterotopic cardiac allograft recipients were treated with alphaCD40 (2C10R4, d0-90) either alone or with the addition of delayed ICOS-Ig (d63-110). Results: Median allograft survival was similar between ICOS-Ig + alphaCD40 (120 days, 120-125 days) and alphaCD40 (124 days, 89-178 days) treated animals, and delayed ICOS-Ig treatment did not prevent allograft rejection in animals with complete CD40 receptor coverage. Although CD4(+) TEM cells were decreased in peripheral blood (115 +/- 24) and mLNs (49 +/- 1.9%) during ICOS-Ig treatment compared with monotherapy (214 +/- 27%, P = 0.01; 72 +/- 9.9%, P = 0.01, respectively), acute and chronic rejection scores and kinetics of alloAb elaboration were similar between groups. Conclusions: Delayed ICOS-Ig treatment with the reagent tested is probably ineffective in modulating pathogenic primate alloimmunity in this model

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Development and validation of PediaTrac™: A web-based tool to track developing infants

OBJECTIVE: PediaTrac™, a 363-item web-based tool to track infant development, administered in modules of ∼40-items per sampling period, newborn (NB), 2--, 4--, 6--, 9-- and 12--months was validated. Caregivers answered demographic, medical, and environmental questions, and questions covering the sensorimotor, feeding/eating, sleep, speech/language, cognition, social-emotional, and attachment domains. METHODS: Expert Panel Reviews and Cognitive Interviews (CI) were conducted to validate the item bank. Classical Test Theory (CTT) and Item Response Theory (IRT) methods were employed to examine the dimensionality and psychometric properties of PediaTrac with pooled longitudinal and cross-sectional cohorts (N = 132). RESULTS: Intraclass correlation coefficients (ICC) for the Expert Panel Review revealed moderate agreement at 6 -months and good reliability at other sampling periods. ICC estimates for CI revealed moderate reliability regarding clarity of the items at NB and 4 months, good reliability at 2--, 9-- and 12--months and excellent reliability at 6 -months. CTT revealed good coefficient alpha estimates (α ≥ 0.77 for five of the six ages) for the Social-Emotional/Communication, Attachment (α ≥ 0.89 for all ages), and Sensorimotor (α ≥ 0.75 at 6-months) domains, revealing the need for better targeting of sensorimotor items. IRT modeling revealed good reliability (r = 0.85-0.95) for three distinct domains (Feeding/Eating, Social-Emotional/Communication and Attachment) and four subdomains (Feeding Breast/Formula, Feeding Solid Food, Social-Emotional Information Processing, Communication/Cognition). Convergent and discriminant construct validity were demonstrated between our IRT-modeled domains and constructs derived from existing developmental, behavioral and caregiver measures. Our Attachment domain was significantly correlated with existing measures at the NB and 2-month periods, while the Social-Emotional/Communication domain was highly correlated with similar constructs at the 6-, 9- and 12-month periods. CONCLUSION: PediaTrac has potential for producing novel and effective estimates of infant development via the Sensorimotor, Feeding/Eating, Social-Emotional/Communication and Attachment domains