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

Limits on the OH Molecule in the Smith High Velocity Cloud

We have used the Green Bank Telescope (GBT) to search for the OH molecule at several locations in the Smith Cloud, one of the most prominent of the high-velocity clouds that surround the Milky Way. Five positions with a high HI column density were selected as targets for individual pointings, along with a square degree around a molecular cloud detected with the Planck telescope near the tip of the Smith Cloud. Gas in the Galactic disk with similar values of $N_{HI}$ has detectable OH emission. Although we found OH at velocities consistent with the foreground Aquila molecular cloud, nothing was found at the velocity of the Smith Cloud to an rms level of 0.7 mK (T$_b$) in a 1 km $s^1$ channel. The three positions that give the strictest limits on OH are analyzed in detail. Their combined data imply a $5\sigma$ limit on $N(H_2) / N_{HI} \leq 0.03$ scaled by a factor dependent on the OH excitation temperature and background continuum $T_{ex}/(T_{ex}-T_{bg})$. There is no evidence for far-infrared emission from dust within the Smith Cloud. These results are consistent with expectations for a low-metallicity diffuse cloud exposed to the radiation field of the Galactic halo rather than a product of a galactic fountain.Comment: Accepted for The Astrophysical Journal 21 pages, 4 figures, 5 table

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