Systems approach to assessing and improving local human research Institutional Review Board performance.

ObjectiveTo quantifying the interdependency within the regulatory environment governing human subject research, including Institutional Review Boards (IRBs), federally mandated Medicare coverage analysis and contract negotiations.MethodsOver 8000 IRB, coverage analysis and contract applications initiated between 2013 and 2016 were analyzed using traditional and machine learning analytics for a quality improvement effort to improve the time required to authorize the start of human research studies.ResultsStaffing ratios, study characteristics such as the number of arms, source of funding and number and type of ancillary reviews significantly influenced the timelines. Using key variables, a predictive algorithm identified outliers for a workflow distinct from the standard process. Improved communication between regulatory units, integration of common functions, and education outreach improved the regulatory approval process.ConclusionsUnderstanding and improving the interdependencies between IRB, coverage analysis and contract negotiation offices requires a systems approach and might benefit from predictive analytics

Route of administration affects corticosteroid sensitivity of a combined ovalbumin and lipopolysaccharide model of asthma exacerbation in guinea-pigs

Lipopolysaccharide (LPS) contributes to asthma exacerbations and development of inhaled corticosteroid insensitivity. Complete resistance to systemic corticosteroids is rare and most patients lie on a continuum of steroid responsiveness. The objective of this study was to examine the sensitivity of combined ovalbumin- (Ova) and LPS-induced functional and inflammatory responses to inhaled and systemic corticosteroid in conscious guinea-pigs, to test the hypothesis that the route of administration affects its sensitivity. Guinea-pigs were sensitised to Ova and challenged with inhaled Ova alone or combined with LPS. Airways function was determined by measuring specific airways conductance via whole-body plethysmography. Airways hyperresponsiveness to histamine was determined pre- and 24h post-Ova challenge. Airways inflammation and underlying mechanisms were determined from bronchoalveolar lavage cell counts and lung tissue cytokines. Vehicle or dexamethasone was administered by once-daily intraperitoneal injection (5, 10 or 20 mg/kg) or twice-daily inhalation (4 or 20 mg/ml) for 6 days before Ova challenge or Ova with LPS. LPS exacerbated Ova-induced responses, elongating early asthmatic responses (EAR), prolonging bronchoconstriction by histamine and further elevating airways inflammation. Intraperitoneal dexamethasone (20 mg/kg) significantly reduced the elongated EAR and airways inflammation but not the increased bronchoconstriction to histamine. In contrast, inhaled dexamethasone (20 mg/ml), which inhibited responses to Ova alone, did not significantly reduce functional and inflammatory responses to combined Ova and LPS. Combined Ova and LPS-induced functional and inflammatory responses are insensitive to inhaled but only partially sensitive to systemic dexamethasone. These results suggest that the route of corticosteroid administration may be important in determining the sensitivity of asthmatic responses to these agents

Evidence for a stratigraphic basis for the Anthropocene

The Anthropocene was proposed as a term (Crutzen and Stoermer 2000) before consideration was given to the nature of the key signatures, contrasting with standard procedures for defining such units. The term is being widely used in both popular and scientific publications before a decision is made as to whether it warrants formalisation and definition of a Global Stratigraphic Section and Point (GSSP). The deliberate human modification of the landscape and its subsurface, and the creation of human-generated novel sedimentary deposits, minerals, and landforms, are characteristic features of the development of Earth’s surface and near surface, which has accelerated in the past two centuries. The large-scale intentional excavation, transportation, and deposition of mixtures of rock and soil to form anthropogenic deposits and landforms represent a new geological process that could be used as a diagnostic signature of the Anthropocene

Comparative Metabolism of Benzo(a)pyrene by Ovarian Microsomes of Various Species

Knowledge of the ability of the female reproductive system to metabolize polycyclic aromatic hydrocarbons (PAHs) is critical to the diagnosis and management of female infertility and for risk assessment purposes. The PAHs are a family of widespread pollutants that are released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, PAHs become activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. The extent of susceptibility to PAH exposure may depend on the ability of animals to metabolize these chemicals. The present study has been undertaken to assess whether any differences exist among mammals in the metabolism of benzo(a)pyrene (BaP), a prototypical PAH compound

Comparative Metabolism of Benzo(a)pyrene by Ovarian Microsomes of Various Species

Knowledge of the ability of the female reproductive system to metabolize polycyclic aromatic hydrocarbons (PAHs) is critical to the diagnosis and management of female infertility and for risk assessment purposes. The PAHs are a family of widespread pollutants that are released into the environment from automobile exhausts, cigarette smoke, burning of refuse, industrial emissions, and hazardous waste sites. In exposed animals, PAHs become activated to reactive metabolites that interfere with target organ function and as a consequence cause toxicity. The extent of susceptibility to PAH exposure may depend on the ability of animals to metabolize these chemicals. The present study has been undertaken to assess whether any differences exist among mammals in the metabolism of benzo(a)pyrene (BaP), a prototypical PAH compound

Humans are the most significant global geomorphological driving force of the 21st Century

The transformation of the Earth’s land surface by mineral extraction and construction is on a scale greater than natural erosive terrestrial geological processes. Mineral extraction statistics can be used as a proxy to measure the size of the total anthropogenic global sediment flux related to mineral extraction and construction. It is demonstrated that the annual direct anthropogenic contribution to the global production of sediment in 2015 was conservatively some 316 Gt (150 km3), a figure more than 24 times greater than the sediment supplied annually by the world’s major rivers to the oceans. The major long-term acceleration in anthropogenic sediment flux started just after the Second World War and anthropogenic sediment flux overtook natural fluvial sediment flux in the mid-1950s. Humans are now the major global geological driving force and an important component of earth system processes in landscape evolution. The changing magnitude of anthropogenic sediments and landforms over time are significant factors in the characterisation of the proposed new epoch of geological time - the Anthropocene