Volatile Organic Compounds and Pulmonary Function in the Third National Health and Nutrition Examination Survey, 1988–1994

BACKGROUND: Volatile organic compounds (VOCs) are present in much higher concentrations indoors, where people spend most of their time, than outdoors and may have adverse health effects. VOCs have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations; no studies have addressed their relationship with respiratory outcomes. OBJECTIVE: We examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. METHODS: We used data from 953 adult participants (20–59 years of age) in the Third National Health and Nutrition Examination Survey (1988–1994) who had VOC blood measures as well as pulmonary function measures. Linear regression models were used to evaluate the relationship between 11 VOCs and measures of pulmonary function. RESULTS: After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was associated with reduced pulmonary function. Participants in the highest decile of 1,4-DCB concentration had decrements of −153 mL [95% confidence interval (CI), −297 to −8] in forced expiratory volume in 1 sec and −346 mL/sec (95% CI, −667 to −24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile. CONCLUSIONS: Exposure to 1,4-DCB, a VOC related to the use of air fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S. general population, may result in reduced pulmonary function. This common exposure may have long-term adverse effects on respiratory health

Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication

Background: Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. Methods: The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. Results: When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. Conclusions: In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population

Cosmogenic neutron production at the Sudbury Neutrino Observatory

Neutrons produced in nuclear interactions initiated by cosmic-ray muons present an irreducible background to many rare-event searches, even in detectors located deep underground. Models for the production of these neutrons have been tested against previous experimental data, but the extrapolation to deeper sites is not well understood. Here we report results from an analysis of cosmogenically produced neutrons at the Sudbury Neutrino Observatory. A specific set of observables are presented, which can be used to benchmark the validity of geant4 physics models. In addition, the cosmogenic neutron yield, in units of 10-4 cm2/(g·μ), is measured to be 7.28±0.09(stat)-1.12+1.59(syst) in pure heavy water and 7.30±0.07(stat)-1.02+1.40(syst) in NaCl-loaded heavy water. These results provide unique insights into this potential background source for experiments at SNOLAB

Left gaze bias in humans, rhesus monkeys and domestic dogs

While viewing faces, human adults often demonstrate a natural gaze bias towards the left visual field, that is, the right side of the viewee’s face is often inspected first and for longer periods. Using a preferential looking paradigm, we demonstrate that this bias is neither uniquely human nor limited to primates, and provide evidence to help elucidate its biological function within a broader social cognitive framework. We observed that 6-month-old infants showed a wider tendency for left gaze preference towards objects and faces of different species and orientation, while in adults the bias appears only towards upright human faces. Rhesus monkeys showed a left gaze bias towards upright human and monkey faces, but not towards inverted faces. Domestic dogs, however, only demonstrated a left gaze bias towards human faces, but not towards monkey or dog faces, nor to inanimate object images. Our findings suggest that face- and species-sensitive gaze asymmetry is more widespread in the animal kingdom than previously recognised, is not constrained by attentional or scanning bias, and could be shaped by experience to develop adaptive behavioural significance

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Ecosystem Services in Conservation Planning: Targeted Benefits vs. Co-Benefits or Costs?

There is growing support for characterizing ecosystem services in order to link conservation and human well-being. However, few studies have explicitly included ecosystem services within systematic conservation planning, and those that have follow two fundamentally different approaches: ecosystem services as intrinsically-important targeted benefits vs. substitutable co-benefits. We present a first comparison of these two approaches in a case study in the Central Interior of British Columbia. We calculated and mapped economic values for carbon storage, timber production, and recreational angling using a geographical information system (GIS). These ‘marginal’ values represent the difference in service-provision between conservation and managed forestry as land uses. We compared two approaches to including ecosystem services in the site-selection software Marxan: as Targeted Benefits, and as Co-Benefits/Costs (in Marxan's cost function); we also compared these approaches with a Hybrid approach (carbon and angling as targeted benefits, timber as an opportunity cost). For this analysis, the Co-Benefit/Cost approach yielded a less costly reserve network than the Hybrid approach (1.6% cheaper). Including timber harvest as an opportunity cost in the cost function resulted in a reserve network that achieved targets equivalently, but at 15% lower total cost. We found counter-intuitive results for conservation: conservation-compatible services (carbon, angling) were positively correlated with each other and biodiversity, whereas the conservation-incompatible service (timber) was negatively correlated with all other networks. Our findings suggest that including ecosystem services within a conservation plan may be most cost-effective when they are represented as substitutable co-benefits/costs, rather than as targeted benefits. By explicitly valuing the costs and benefits associated with services, we may be able to achieve meaningful biodiversity conservation at lower cost and with greater co-benefits

First Neutrino Observations from the Sudbury Neutrino Observatory

The first neutrino observations from the Sudbury Neutrino Observatory are presented from preliminary analyses. Based on energy, direction and location, the data in the region of interest appear to be dominated by 8B solar neutrinos, detected by the charged current reaction on deuterium and elastic scattering from electrons, with very little background. Measurements of radioactive backgrounds indicate that the measurement of all active neutrino types via the neutral current reaction on deuterium will be possible with small systematic uncertainties. Quantitative results for the fluxes observed with these reactions will be provided when further calibrations have been completed.Comment: Latex, 7 pages, 10 figures, Invited paper at Neutrino 2000 Conference, Sudbury, Canada, June 16-21, 2000 to be published in the Proceeding

Electron Antineutrino Search at the Sudbury Neutrino Observatory

Upper limits on the \nuebar flux at the Sudbury Neutrino Observatory have been set based on the \nuebar charged-current reaction on deuterium. The reaction produces a positron and two neutrons in coincidence. This distinctive signature allows a search with very low background for \nuebar's from the Sun and other potential sources. Both differential and integral limits on the \nuebar flux have been placed in the energy range from 4 -- 14.8 MeV. For an energy-independent \nu_e --> \nuebar conversion mechanism, the integral limit on the flux of solar \nuebar's in the energy range from 4 -- 14.8 MeV is found to be \Phi_\nuebar <= 3.4 x 10^4 cm^{-2} s^{-1} (90% C.L.), which corresponds to 0.81% of the standard solar model 8B \nu_e flux of 5.05 x 10^6 cm^{-2} s^{-1}, and is consistent with the more sensitive limit from KamLAND in the 8.3 -- 14.8 MeV range of 3.7 x 10^2 cm^{-2} s^{-1} (90% C.L.). In the energy range from 4 -- 8 MeV, a search for \nuebar's is conducted using coincidences in which only the two neutrons are detected. Assuming a \nuebar spectrum for the neutron induced fission of naturally occurring elements, a flux limit of Phi_\nuebar <= 2.0 x 10^6 cm^{-2} s^{-1}(90% C.L.) is obtained.Comment: submitted to Phys. Rev.

The role of ethnicity in the attainment and experiences of graduates in distance education

In the UK, the attainment of White graduates (as measured by the class of honours that they have been awarded) tends to be higher than that of graduates from other ethnic groups. This is apparent, in particular, in graduates who have taken courses by distance learning with the Open University. Analysis of data from Open University graduates over three successive years yielded no evidence that the latter trend could be attributed to confounded demographic variables. A postal survey found little variation in perceptions of academic quality or reports of personal development among Open University graduates from different ethnic groups. Quantitative variations in the attainment of graduates from different ethnic groups are not necessarily reflected in qualitative variations in their experience of distance education