An essential step in ensuring the toxicological safety of ingredients in consumer products is the evaluation of their skin sensitising potential. Where skin exposure is low, it is possible to conduct ...a risk assessment using the Dermal Sensitisation Threshold (DST), a process similar to that of the Threshold of Toxicological Concern. This paper describes work building on that previously published, whose aim was to produce a more robust tool for assessing the safety of consumer products. This consisted of expanding the Local Lymph Node Assay dataset used to define the original DST and classifying chemicals in the dataset according to their mechanistic chemistry domains. A DST of 900
μg/cm
2 was derived for chemicals classified as non-reactive and non-proreactive. This value was benchmarked against human potency data for 58 fragrance allergens and was lower than the measured No Expected Sensitisation Levels for those classified as non-reactive. Use of this DST will help to eliminate the need for animal testing of non-reactive and non-proreactive chemicals where skin exposure is sufficiently low. For chemicals where a Quantitative Risk Assessment based on the DST does not give an adequate margin of safety, and those classified as reactive, a case-by-case risk assessment will be required.
The role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded ...and multigenerational households and COVID-19 in New York City (NYC).
Cohort study.
We conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as the proportion of the estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was an adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), the prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering.
39,923 suspected COVID-19 cases were presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (βinteraction = 0.99, 95% CI: 0.99–1.00).
Overcrowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of the surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.
Despite potential harm that can result from polypharmacy, real-world data on polypharmacy in the setting of heart failure (HF) are limited. We sought to address this knowledge gap by studying older ...adults hospitalized for HF derived from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke).
We examined 558 older adults aged ≥65 years with adjudicated HF hospitalizations from 380 hospitals across the United States. We collected and examined data from the REGARDS baseline assessment, medical charts from HF-adjudicated hospitalizations, the American Hospital Association annual survey database, and Medicare's Hospital Compare website. We counted the number of medications taken at hospital admission and discharge; and classified each medication as HF-related, non-HF cardiovascular-related, or noncardiovascular-related.
The vast majority of participants (84% at admission and 95% at discharge) took ≥5 medications; and 42% at admission and 55% at discharge took ≥10 medications. The prevalence of taking ≥10 medications (polypharmacy) increased over the study period. As the number of total medications increased, the number of noncardiovascular medications increased more rapidly than the number of HF-related or non-HF cardiovascular medications.
Defining polypharmacy as taking ≥10 medications might be more ideal in the HF population as most patients already take ≥5 medications. Polypharmacy is common both at admission and hospital discharge, and its prevalence is rising over time. The majority of medications taken by older adults with HF are noncardiovascular medications. There is a need to develop strategies that can mitigate the negative effects of polypharmacy among older adults with HF.
Connected and automated vehicles (CAVs) are poised to reshape transportation and mobility by replacing humans as the driver and service provider. While the primary stated motivation for vehicle ...automation is to improve safety and convenience of road mobility, this transformation also provides a valuable opportunity to improve vehicle energy efficiency and reduce emissions in the transportation sector. Progress in vehicle efficiency and functionality, however, does not necessarily translate to net positive environmental outcomes. Here, we examine the interactions between CAV technology and the environment at four levels of increasing complexity: vehicle, transportation system, urban system, and society. We find that environmental impacts come from CAV-facilitated transformations at all four levels, rather than from CAV technology directly. We anticipate net positive environmental impacts at the vehicle, transportation system, and urban system levels, but expect greater vehicle utilization and shifts in travel patterns at the society level to offset some of these benefits. Focusing on the vehicle-level improvements associated with CAV technology is likely to yield excessively optimistic estimates of environmental benefits. Future research and policy efforts should strive to clarify the extent and possible synergetic effects from a systems level to envisage and address concerns regarding the short- and long-term sustainable adoption of CAV technology.
We sought to determine the associations between baseline chronic medical conditions and future risk of sepsis.
Longitudinal cohort study using the 30,239 community-dwelling participants of the ...REGARDS cohort. We determined associations between baseline chronic medical conditions and incident sepsis episodes, defined as hospitalization for an infection with the presence of infection plus two or more systemic inflammatory response syndrome criteria.
Over the mean observation time of 4.6 years (February 5, 2003 through October 14, 2011), there were 975 incident cases of sepsis. Incident sepsis episodes were associated with older age (p<0.001), white race (HR 1.39; 95% CI: 1.22-1.59), lower education (p<0.001) and income (p<0.001), tobacco use (p<0.001), and alcohol use (p = 0.02). Incident sepsis episodes were associated with baseline chronic lung disease (adjusted HR 2.43; 95% CI: 2.05-2.86), peripheral artery disease (2.16; 1.58-2.95), chronic kidney disease (1.99; 1.73-2.29), myocardial infarction 1.79 (1.49-2.15), diabetes 1.78 (1.53-2.07), stroke 1.67 (1.34-2.07), deep vein thrombosis 1.63 (1.29-2.06), coronary artery disease 1.61 (1.38-1.87), hypertension 1.49 (1.29-1.74), atrial fibrillation 1.48 (1.21-1.81) and dyslipidemia 1.16 (1.01-1.34). Sepsis risk increased with the number of chronic medical conditions (p<0.001).
Individuals with chronic medical conditions are at increased risk of future sepsis events.
Aim The campos de altitude are a series of cool-humid, grass-dominated formations restricted to the highest summits of the southeastern Brazilian Highlands. Relatively little is known of the ecology, ...biogeography, or developmental history of this archipelago of mountaintop formations. This contribution presents an overview of our present state of knowledge with respect to the past and present physical environment and vegetation of the campos de altitude. The aim is (1) to introduce an international audience to the natural history of these diminutive yet important ecosystems, and (2) to provide the background for a series of forthcoming contributions that will treat the ecology of the campos de altitude and explore physical and biotic relationships between these `Brazilian páramos' and similar formations in the high mountains of equatorial South and Central America. Location Beginning at altitudes of 1800-2000 m, the campos de altitude are found atop the highest summits of the main ranges of the southeastern Brazilian Highlands, between the states of Santa Catarina and Minas Gerais/Espírito Santo. Methods Drawing upon both original data and previously published results, this contribution reviews what we presently know about the physical environment and vegetation of the campos de altitude, in the context of geographic setting, geology, palaeoclimatology and palaeobotany, modern climate, modern vegetation, and conservation. Results and main conclusions Uplift of the southeastern Brazilian ranges to altitudes high enough to support orographic grasslands may have occurred as early as the middle- to late-Tertiary; pollen records show that campos de altitude have been extant on southeastern summits at least since the Late Pleistocene. The present-day climate of the campos de altitude is cool and (per) humid, but patterns of rainfall, temperature, and frost are distinctly seasonal. Although the flora of the campos de altitude is highly diverse and characterized by a high degree of endemism, the campos de altitude maintain strong floristic similarities to equatorial alpine formations of the Andean and Central American Cordillera; these similarities also extend to climate, soils, and vegetation physiognomy. Anthropogenic fires and grazing are widespread in the campos de altitude and probably contribute significantly to the modern structure of vegetation communities.
Guidelines recommend lifestyle modification for patients with coronary heart disease (CHD). Few data demonstrate which lifestyle modifications, if sustained, reduce recurrent CHD and mortality risk ...in cardiac patients after the postacute rehabilitation phase. We determined the association between ideal lifestyle factors and recurrent CHD and all-cause mortality in REasons for Geographic and Racial Differences in Stroke study participants with CHD (n = 4,174). Ideal lifestyle factors (physical activity ≥4 times/week, nonsmoking, highest quartile of Mediterranean diet score, and waist circumference <88 cm for women and <102 cm for men) were assessed through questionnaires and an in-home study visit. There were 447 recurrent CHD events and 745 deaths over a median 4.3 and 4.5 years, respectively. After multivariable adjustment, physical activity ≥4 versus no times/week and non-smoking versus current smoking were associated with reduced hazard ratios (HRs; 95% confidence interval CI) for recurrent CHD (HR 0.69, 95% CI 0.54 to 0.89 and HR 0.50, 95% CI 0.39 to 0.64, respectively) and death (HR 0.71, 95% CI 0.59 to 0.86 and HR 0.53, 95% CI 0.44 to 0.65, respectively). The multivariable-adjusted HRs (and 95% CIs) for recurrent CHD and death comparing the highest versus lowest quartile of Mediterranean diet adherence were 0.77 (95% CI 0.55 to 1.06) and 0.84 (95% CI 0.67 to 1.07), respectively. Neither outcome was associated with waist circumference. Comparing participants with 1, 2, and 3 versus 0 ideal lifestyle factors (non-smoking, physical activity ≥4 times/week, and highest quartile of Mediterranean diet score), the HRs (and 95% CIs) were 0.60 (95% CI 0.44 to 0.81), 0.49 (95% CI 0.36 to 0.67), and 0.38 (95% CI 0.21 to 0.67), respectively, for recurrent CHD and 0.65 (95% CI 0.51 to 0.83), 0.57 (95% CI 0.43 to 0.74), and 0.41 (95% CI 0.26 to 0.64), respectively, for death. In conclusion, maintaining smoking cessation, physical activity, and Mediterranean diet adherence is important for secondary CHD prevention.
•The Dermal Sensitisation Threshold applies TTC principals to skin sensitisation.•The DST is useful for both non-reactive and protein reactive chemicals.•The DST along with structural alerts defines ...a threshold of low sensitisation risk.
The evaluation of chemicals for their skin sensitising potential is an essential step in ensuring the safety of ingredients in consumer products. Similar to the Threshold of Toxicological Concern, the Dermal Sensitisation Threshold (DST) has been demonstrated to provide effective risk assessments for skin sensitisation in cases where human exposure is low. The DST was originally developed based on a Local Lymph Node Assay (LLNA) dataset and applied to chemicals that were not considered to be directly reactive to skin proteins, and unlikely to initiate the first mechanistic steps leading to the induction of sensitisation. Here we have extended the DST concept to protein reactive chemicals. A probabilistic assessment of the original DST dataset was conducted and a threshold of 64μg/cm2 was derived. In our accompanying publication, a set of structural chemistry based rules was developed to proactively identify highly reactive and potentially highly potent materials which should be excluded from the DST approach. The DST and rule set were benchmarked against a test set of chemicals with LLNA/human data. It is concluded that by combining the reactive DST with knowledge of chemistry a threshold can be established below which there is no appreciable risk of sensitisation for protein-reactive chemicals.
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