Project description:Objectives Universities have turned to SARS-CoV-2 models to examine campus reopening strategies. While these studies have explored a variety of modeling techniques, none have used empirical data. Methods In this study, we use an empirical proximity network of college freshmen obtained using smartphone Bluetooth to simulate the spread of the virus. We investigate the role of immunization, testing, isolation, mask wearing, and social distancing in the presence of implementation challenges and imperfect compliance. Results We show that frequent testing could drastically reduce the spread of the virus if levels of immunity are low, but its effects are limited if immunity is more ubiquitous. Furthermore, moderate levels of mask wearing and social distancing could lead to additional reductions in cumulative incidence, but their benefit decreases rapidly as immunity and testing frequency increase. However, if immunity from vaccination is imperfect or declines over time, scenarios not studied here, frequent testing and other interventions may play more central roles. Conclusions Our findings suggest that although regular testing and isolation are powerful tools, they have limited benefit if immunity is high or other interventions are widely adopted. If universities can attain even moderate levels of vaccination, masking, and social distancing, they may be able to relax the frequency of testing to once every four weeks.
Project description:Universities have turned to SARS-CoV-2 models to examine campus reopening strategies1-9. While these studies have explored a variety of modeling techniques, all have relied on simulated data. Here, we use an empirical proximity network of college freshmen10, ascertained using smartphone Bluetooth, to simulate the spread of the virus. We investigate the role of testing, isolation, mask wearing, and social distancing in the presence of implementation challenges and imperfect compliance. Here we show that while frequent testing can drastically reduce spread if mask wearing and social distancing are not widely adopted, testing has limited impact if they are ubiquitous. Furthermore, even moderate levels of immunity can significantly reduce new infections, especially when combined with other interventions. Our findings suggest that while testing and isolation are powerful tools, they have limited benefit if other interventions are widely adopted. If universities can attain high levels of masking and social distancing, they may be able to relax testing frequency to once every two to four weeks.
Project description:Declining success rates coupled with increased costs is leading to an inevitable breaking point in the drug development pipeline. Can we avoid it by incorporating the vast mechanistic understanding of drug action? A recent review highlights this dilemma and proposes "quantitative logic gate" modeling as a solution.(1) The goal of this commentary is to contrast this approach with mechanistic biochemical network models, which, although alluded to by Kiruoac and Onsum, requires a closer analysis.
Project description:Passive surveillance data had signaled the possibility of gastrointestinal adverse events occurring after the administration of high-dose inactivated influenza vaccine (IIV-HD). However, in a large, prospective randomized clinical trial, rates of serious gastrointestinal events were no greater among IIV-HD recipients than among those who received a standard-dose influenza vaccine.
Project description:The ongoing COVID-19 pandemic still requires fast and effective efforts from all fronts, including epidemiology, clinical practice, molecular medicine, and pharmacology. A comprehensive molecular framework of the disease is needed to better understand its pathological mechanisms, and to design successful treatments able to slow down and stop the impressive pace of the outbreak and harsh clinical symptomatology, possibly via the use of readily available, off-the-shelf drugs. This work engages in providing a wider picture of the human molecular landscape of the SARS-CoV-2 infection via a network medicine approach as the ground for a drug repurposing strategy. Grounding on prior knowledge such as experimentally validated host proteins known to be viral interactors, tissue-specific gene expression data, and using network analysis techniques such as network propagation and connectivity significance, the host molecular reaction network to the viral invasion is explored and exploited to infer and prioritize candidate target genes, and finally to propose drugs to be repurposed for the treatment of COVID-19. Ranks of potential target genes have been obtained for coherent groups of tissues/organs, potential and distinct sites of interaction between the virus and the organism. The normalization and the aggregation of the different scores allowed to define a preliminary, restricted list of genes candidates as pharmacological targets for drug repurposing, with the aim of contrasting different phases of the virus infection and viral replication cycle.
Project description:Living near major roadways has been associated with increased risk of cardiovascular events, but little is known about its impact on renal function.We calculated the estimated glomerular filtration rate (eGFR) for 1103 consecutive Boston-area patients hospitalised with confirmed acute ischaemic stroke between 1999 and 2004. We used linear regression to evaluate the association between eGFR and categories of residential distance to major roadway (0 to ?50, >50 to ?100, >100 to ?200, >200 to ?400, >400 to ?1000 and >1000 m) adjusting for age, sex, race, smoking, comorbid conditions, treatment with ACE inhibitor and neighbourhood-level socioeconomic characteristics. In a second analysis, we considered the log of distance to major roadway as a continuous variable.Patients living closer to a major roadway had lower eGFR than patients living farther away (Ptrend=0.01). Comparing patients living 50 m versus 1000 m from a major roadway was associated with a 3.9 ml/min/1.73 m(2) lower eGFR (95% CI 1.0 to 6.7; p=0.007): a difference comparable in magnitude to the reduction in eGFR observed for a 4-year increase in age in population-based studies. The magnitude of this association did not differ significantly across categories of age, sex, race, history of hypertension, diabetes or socioeconomic status.Living near a major roadway is associated with lower eGFR in a cohort of patients presenting with acute ischaemic stroke. If causal, these results imply that exposures associated with living near a major roadway contribute to reduced renal function, an important risk factor for cardiovascular events.
Project description:BACKGROUND:Traffic-related air pollution (TRAP) has been linked with several adverse health outcomes, including preterm birth and low birth weight, which are both related to onset of puberty. No studies to date have investigated the association between TRAP and altered pubertal timing. OBJECTIVE:Determine the association between residential proximity to traffic, as a marker of long-term TRAP exposure, and age at pubertal onset in a longitudinal study of girls. METHODS:We analyzed data for 437 girls at the CYGNET study site of the Breast Cancer and Environment Research Program. TRAP exposure was assessed using several measures of residential proximity to traffic based on address at study entry. Using accelerated failure time models, we calculated time ratios (TRs) and their corresponding 95% confidence intervals (CIs) for specified traffic metrics and pubertal onset, defined as stage 2 or higher for breast or pubic hair development (respectively, B2+ and PH2+). Models were adjusted for race/ethnicity, household income, and cotinine levels. RESULTS:At baseline, 71% of girls lived within 150m of a major road. The median age of onset was 10.3years for B2+ and 10.9years for PH2+. Living within 150m downwind of a major road was associated with earlier onset of PH2+ (TR 0.96, 95% CI 0.93, 0.99). Girls in the highest quintile of either distance-weighted traffic density, annual average daily traffic, and/or traffic density also reached PH2+ earlier than girls in the lowest quintiles. CONCLUSIONS:In this first study to assess the association between residential proximity to traffic and pubertal onset we found girls with higher exposure reached one pubertal milestone several months earlier than low exposed girls, even after consideration of likely confounders. Results should be expanded in larger epidemiological studies, and with measured levels of air pollutants.
Project description:BackgroundWe investigated whether residing near more green space might reduce the risk of preeclampsia.MethodsParticipants were women who delivered a live, singleton birth between 1998 and 2011 in eight counties of the San Joaquin Valley in California. There were 7276 cases of preeclampsia divided into mild, severe, or superimposed on preexisting hypertension. Controls were 197,345 women who did not have a hypertensive disorder and delivered between 37 and 41 weeks. Green space was estimated from satellite data using Normalized Difference Vegetation Index (NDVI), an index calculated from surface reflectance at the visible and near-infrared wavelengths. Values closer to 1 denote a higher density of green vegetation. Average NDVI was calculated within a 50 m, 100 m, and 500 m buffer around each woman's residence. Odds ratios and 95% confidence intervals were estimated comparing the lowest and highest quartiles of mean NDVI to the interquartile range comparing each preeclampsia phenotype, divided into early (20-31 weeks) and late (32-36 weeks) preterm birth, to full-term controls.ResultsWe observed an inverse association in the 500 m buffer for women in the top quartile of NDVI and a positive association for women in the lowest quartile of NDVI for women with superimposed preeclampsia. There were no associations in the 50 and 100 m buffers.ConclusionWithin a 500 m buffer, more green space was inversely associated with superimposed preeclampsia. Future work should explore the mechanism by which green space may protect against preeclampsia.
Project description:BackgroundEffective vaccines, improved testing technologies, and decreases in COVID-19 incidence prompt an examination of the choices available to residential college administrators seeking to safely resume in-person campus activities in fall 2021.ObjectiveTo help college administrators design and evaluate customized COVID-19 safety plans.DesignDecision analysis using a compartmental epidemic model to optimize vaccination, testing, and other nonpharmaceutical interventions depending on decision makers' preferences, choices, and assumptions about epidemic severity and vaccine effectiveness against infection, transmission, and disease progression.SettingU.S. residential colleges.ParticipantsHypothetical cohort of 5000 persons (students, faculty, and staff) living and working in close proximity on campus.MeasurementsCumulative infections over a 120-day semester.ResultsUnder base-case assumptions, if 90% coverage can be attained with a vaccine that is 85% protective against infection and 25% protective against asymptomatic transmission, the model finds that campus activities can be resumed while holding cumulative cases below 5% of the population without the need for routine, asymptomatic testing. With 50% population coverage using such a vaccine, a similar cap on cumulative cases would require either daily asymptomatic testing of unvaccinated persons or a combination of less frequent testing and resumption of aggressive distancing and other nonpharmaceutical prevention policies. Colleges returning to pre-COVID-19 campus activities without either broad vaccination coverage or high-frequency testing put their campus population at risk for widespread viral transmission.LimitationUncertainty in data, particularly vaccine effectiveness (preventive and transmission); no distinguishing between students and employees; and assumes limited community intermixing.ConclusionVaccination coverage is the most powerful tool available to residential college administrators seeking to achieve a safe return to prepandemic operations this fall. Given the breadth of potential outcomes in the face of uncontrollable and uncertain factors, even colleges with high vaccination rates should be prepared to reinstitute or expand testing and distancing policies on short notice.Primary funding sourceNational Institute on Drug Abuse.
Project description:Significant elevations in the risk of childhood leukemia have been associated with environmental exposure to gasoline; aromatic hydrocarbons from refinery pollution, petroleum waste sites, and mobile sources (automobile exhaust); paints, paint products, and thinners; and secondary cigarette smoke in the home. These higher risks have also been associated with parental exposure to benzene, gasoline, motor vehicle-related jobs, painting, and rubber solvents. These exposures and jobs have 1 common chemical exposure-benzene, a recognized cause of acute leukemia in adults-and raise the question of whether children represent a subpopulation in which a higher risk of leukemia is associated with very low level exposure to environmental benzene.