Prioritizing Risks and Uncertainties from Intentional Release of Selected Category A Pathogens

This paper synthesizes available information on five Category A pathogens (Bacillus anthracis, Yersinia pestis, Francisella tularensis, Variola major and Lassa) to develop quantitative guidelines for how environmental pathogen concentrations may be related to human health risk in an indoor environment. An integrated model of environmental transport and human health exposure to biological pathogens is constructed which 1) includes the effects of environmental attenuation, 2) considers fomite contact exposure as well as inhalational exposure, and 3) includes an uncertainty analysis to identify key input uncertainties, which may inform future research directions. The findings provide a framework for developing the many different environmental standards that are needed for making risk-informed response decisions, such as when prophylactic antibiotics should be distributed, and whether or not a contaminated area should be cleaned up. The approach is based on the assumption of uniform mixing in environmental compartments and is thus applicable to areas sufficiently removed in time and space from the initial release that mixing has produced relatively uniform concentrations. Results indicate that when pathogens are released into the air, risk from inhalation is the main component of the overall risk, while risk from ingestion (dermal contact for B. anthracis) is the main component of the overall risk when pathogens are present on surfaces. Concentrations sampled from untracked floor, walls and the filter of heating ventilation and air conditioning (HVAC) system are proposed as indicators of previous exposure risk, while samples taken from touched surfaces are proposed as indicators of future risk if the building is reoccupied. A Monte Carlo uncertainty analysis is conducted and input-output correlations used to identify important parameter uncertainties. An approach is proposed for integrating these quantitative assessments of parameter uncertainty with broader, qualitative considerations to identify future research priorities

Chromosomal radiosensitivity in head and neck cancer patients: evidence for genetic predisposition?

The association between chromosomal radiosensitivity and genetic predisposition to head and neck cancer was investigated in this study. In all, 101 head and neck cancer patients and 75 healthy control individuals were included in the study. The G2 assay was used to measure chromosomal radiosensitivity. The results demonstrated that head and neck cancer patients had a statistically higher number of radiation-induced chromatid breaks than controls, with mean values of 1.23 and 1.10 breaks per cell, respectively (P<0.001). Using the 90th percentile of the G2 scores of the healthy individuals as a cutoff value for chromosomal radiosensitivity, 26% of the cancer patients were radiosensitive compared with 9% of the healthy controls (P=0.008). The mean number of radiation-induced chromatid breaks and the proportion of radiosensitive individuals were highest for oral cavity cancer patients (1.26 breaks per cell, 38%) and pharynx cancer patients (1.27 breaks per cell, 35%). The difference between patients and controls was most pronounced in the lower age group (⩽50 years, 1.32 breaks per cell, 38%) and in the non- and light smoking patient group (⩽10 pack-years, 1.28 breaks per cell, 46%). In conclusion, enhanced chromosomal radiosensitivity is a marker of genetic predisposition to head and neck cancer, and the genetic contribution is highest for oral cavity and pharynx cancer patients and for early onset and non- and light smoking patients

Test structure for thermal monitoring

International audienceThe paper is dealing with thermal test structures for CMOS ICs. A new temperature sensor/test structure is proposed: the Thermal Feedback Oscillator (TFO). Detailed design considerations are presented together with experimental results. Moreover the paper discusses general questions of the "design for thermal testability" (DfTT) principle including both the problems of placement of the test structures and possible solutions for the read-out of the test data

Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib.

BackgroundObservational studies have shown reduced risk of Alzheimer dementia in users of nonsteroidal anti-inflammatory drugs.ObjectiveTo evaluate the effects of naproxen sodium and celecoxib on cognitive function in older adults.DesignRandomized, double-masked chemoprevention trial.SettingSix US memory clinics.ParticipantsMen and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment.InterventionsCelecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively.Main outcome measuresSeven tests of cognitive function and a global summary score measured annually.ResultsLongitudinal analyses showed lower global summary scores over time for naproxen compared with placebo (- 0.05 SDs; P = .02) and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo (- 0.33 points for celecoxib [P = .04] and - 0.36 points for naproxen [P = .02]). Restriction of analyses to measures collected from persons without dementia attenuated the treatment group differences. Analyses limited to measures obtained while participants were being issued study drugs produced results similar to the intention-to-treat analyses.ConclusionsUse of naproxen or celecoxib did not improve cognitive function. There was weak evidence for a detrimental effect of naproxen

Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib.

BackgroundObservational studies have shown reduced risk of Alzheimer dementia in users of nonsteroidal anti-inflammatory drugs.ObjectiveTo evaluate the effects of naproxen sodium and celecoxib on cognitive function in older adults.DesignRandomized, double-masked chemoprevention trial.SettingSix US memory clinics.ParticipantsMen and women aged 70 years and older with a family history of Alzheimer disease; 2117 of 2528 enrolled had follow-up cognitive assessment.InterventionsCelecoxib (200 mg twice daily), naproxen sodium (220 mg twice daily), or placebo, randomly allocated in a ratio of 1:1:1.5, respectively.Main outcome measuresSeven tests of cognitive function and a global summary score measured annually.ResultsLongitudinal analyses showed lower global summary scores over time for naproxen compared with placebo (- 0.05 SDs; P = .02) and lower scores on the Modified Mini-Mental State Examination over time for both treatment groups compared with placebo (- 0.33 points for celecoxib [P = .04] and - 0.36 points for naproxen [P = .02]). Restriction of analyses to measures collected from persons without dementia attenuated the treatment group differences. Analyses limited to measures obtained while participants were being issued study drugs produced results similar to the intention-to-treat analyses.ConclusionsUse of naproxen or celecoxib did not improve cognitive function. There was weak evidence for a detrimental effect of naproxen