A Case–Crossover Study of Wintertime Ambient Air Pollution and Infant Bronchiolitis

We examined the association of infant bronchiolitis with acute exposure to ambient air pollutants. DESIGN: We employed a time-stratified case–crossover method and based the exposure windows on a priori, biologically based hypotheses. PARTICIPANTS: We evaluated effects in 19,901 infants in the South Coast Air Basin of California in 1995–2000 with a hospital discharge record for bronchiolitis in the first year of life (International Classification of Diseases, 9th Revision, CM466.1). EVALUATIONS/MEASUREMENTS: Study subjects’ ZIP code was linked to ambient air pollution monitors to derive exposures. We estimated the risk of bronchiolitis hospitalization associated with increases in wintertime ambient air pollutants using conditional logistic regression. RESULTS: We observed no increased risk after acute exposure to particulate matter ≤ 2.5 μm in aerodynamic diameter (PM(2.5)), carbon monoxide, or nitrogen dioxide. PM(2.5) exposure models suggested a 26–41% increased risk in the most premature infants born at gestational ages between 25 and 29 weeks; however, these findings were based on very small numbers. CONCLUSIONS: We found little support for a link between acute increases in ambient air pollution and infant bronchiolitis except modestly increased risk for PM(2.5) exposure among infants born very prematurely. In these infants, the periods of viral acquisition and incubation concurred with the time of increased risk. RELEVANCE TO PROFESSIONAL PRACTICE: We present novel data for the infant period and the key respiratory disease of infancy, bronchiolitis. Incompletely explained trends in rising bronchiolitis hospitalization rates and increasing number of infants born prematurely underscore the importance of evaluating the impact of ambient air pollution in this age group in other populations and studies

Determination of free 25(OH)D concentrations and their relationships to total 25(OH)D in multiple clinical populations

Context : The optimal measure of vitamin D(D) status is unknown. Objective : Directly measure circulating free 25(OH)D concentrations and relationships to total 25(OH)D in a clinically diverse sample of humans. Design : Cross-sectional analysis Setting : Seven academic sites Patients : 1661 adults: (healthy(n=211), pre-diabetic(n=479), outpatients(n=783), cirrhotic(n=90), pregnant(n=20), nursing home(n=79)) Interventions : Merge research data on circulating free 25(OH)D (directly measured immunoassay), total 25(OH)D (LC/MS/MS), D binding protein (DBP by radial (polyclonal) immunodiffusion assay)), albumin, creatinine, iPTH and DBP haplotype Main outcome measures : Distribution of free 25(OH)D (ANOVA with Bonferroni correction for post hoc comparisons) and relationships between free and total 25(OH)D (mixed effects modeling incorporating clinical condition, DBP haplotype with sex, race, eGFR, BMI and other covariates). Results : Free 25(OH)D was 4.7±1.8 pg/mL (mean ±SD) in healthy and 4.3 ±1.9 pg/mL in outpatients with 0.5-8.1 pg/mL and 0.9-8.1 pg/mL encompassing 95% of healthy and outpatients, respectively. Free 25(OH)D was higher in cirrhotics (7.1 ±3.0 pg/mL, pnursing home>prediabetic > outpatient > pregnant), and BMI (lesser effect) as covariates affecting relationships but not eGFR, sex, race or DBP haplotype. Conclusions : Total 25(OH)D, health condition, race and DBP haplotype affected free 25(OH)D, but only health conditions and BMI affected relationships between total and free 25(OH) D. Clinical importance of free 25(OH)D needs to be established in studies assessing outcomes

Safety and tolerability of sitagliptin in patients with type 2 diabetes: a pooled analysis

<p>Abstract</p> <p>Background</p> <p>Sitagliptin, a highly selective dipeptidyl peptidase-4 inhibitor, is the first in a new class of oral antihyperglycemic agents (AHAs) for the treatment of patients with type 2 diabetes. Type 2 diabetes is a life-long disease requiring chronic treatment and management. Therefore, robust assessment of the long-term safety and tolerability of newer therapeutic agents is of importance. The purpose of this analysis was to assess the safety and tolerability of sitagliptin by pooling 12 large, double-blind, Phase IIb and III studies up to 2 years in duration. Methods: This analysis included 6139 patients with type 2 diabetes receiving either sitagliptin 100 mg/day (N = 3415) or a comparator agent (placebo or an active comparator) (N = 2724; non-exposed group). The 12 studies from which this pooled population was drawn represent the double-blind, randomized, Phase IIB and III studies that included patients treated with the clinical dose of sitagliptin (100 mg/day) for at least 18 weeks up to 2 years and that were available in a single safety database as of November 2007. These 12 studies assessed sitagliptin as monotherapy, initial combination therapy with metformin, or add-on combination therapy with other oral AHAs (metformin, pioglitazone, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone). Patients in the non-exposed group were taking placebo, pioglitazone, metformin, sulfonylurea, sulfonylurea + metformin, or metformin + rosiglitazone. This safety analysis used patient-level data from each study to evaluate clinical and laboratory adverse experiences.</p> <p>Results</p> <p>For clinical adverse experiences, the incidence rates of adverse experiences overall, serious adverse experiences, and discontinuations due to adverse experiences were similar in the sitagliptin and non-exposed groups. The incidence rates of specific adverse experiences were also generally similar in the two groups, with the exception of an increased incidence rate of hypoglycemia observed in the non-exposed group. The incidence rates of drug-related adverse experiences overall and discontinuations due to drug-related adverse experiences were higher in the non-exposed group, primarily due to the increased incidence rate of hypoglycemia in this group. For cardiac- and ischemia-related adverse experiences (including serious events), there were no meaningful between-group differences. No meaningful differences between groups in laboratory adverse experiences, either summary measures or specific adverse experiences, were observed.</p> <p>Conclusion</p> <p>In patients with type 2 diabetes, sitagliptin 100 mg/day was well tolerated in clinical trials up to 2 years in duration.</p

Proposal of a framework for evaluating military surveillance systems for early detection of outbreaks on duty areas

<p>Abstract</p> <p>Background</p> <p>In recent years a wide variety of epidemiological surveillance systems have been developed to provide early identification of outbreaks of infectious disease. Each system has had its own strengths and weaknesses. In 2002 a Working Group of the Centers for Disease Control and Prevention (CDC) produced a framework for evaluation, which proved suitable for many public health surveillance systems. However this did not easily adapt to the military setting, where by necessity a variety of different parameters are assessed, different constraints placed on the systems, and different objectives required. This paper describes a proposed framework for evaluation of military syndromic surveillance systems designed to detect outbreaks of disease on operational deployments.</p> <p>Methods</p> <p>The new framework described in this paper was developed from the cumulative experience of British and French military syndromic surveillance systems. The methods included a general assessment framework (CDC), followed by more specific methods of conducting evaluation. These included Knowledge/Attitude/Practice surveys (KAP surveys), technical audits, ergonomic studies, simulations and multi-national exercises. A variety of military constraints required integration into the evaluation. Examples of these include the variability of geographical conditions in the field, deployment to areas without prior knowledge of naturally-occurring disease patterns, the differences in field sanitation between locations and over the length of deployment, the mobility of military forces, turnover of personnel, continuity of surveillance across different locations, integration with surveillance systems from other nations working alongside each other, compatibility with non-medical information systems, and security.</p> <p>Results</p> <p>A framework for evaluation has been developed that can be used for military surveillance systems in a staged manner consisting of initial, intermediate and final evaluations. For each stage of the process parameters for assessment have been defined and methods identified.</p> <p>Conclusion</p> <p>The combined experiences of French and British syndromic surveillance systems developed for use in deployed military forces has allowed the development of a specific evaluation framework. The tool is suitable for use by all nations who wish to evaluate syndromic surveillance in their own military forces. It could also be useful for civilian mobile systems or for national security surveillance systems.</p

Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

Boolean Dynamics with Random Couplings

This paper reviews a class of generic dissipative dynamical systems called N-K models. In these models, the dynamics of N elements, defined as Boolean variables, develop step by step, clocked by a discrete time variable. Each of the N Boolean elements at a given time is given a value which depends upon K elements in the previous time step. We review the work of many authors on the behavior of the models, looking particularly at the structure and lengths of their cycles, the sizes of their basins of attraction, and the flow of information through the systems. In the limit of infinite N, there is a phase transition between a chaotic and an ordered phase, with a critical phase in between. We argue that the behavior of this system depends significantly on the topology of the network connections. If the elements are placed upon a lattice with dimension d, the system shows correlations related to the standard percolation or directed percolation phase transition on such a lattice. On the other hand, a very different behavior is seen in the Kauffman net in which all spins are equally likely to be coupled to a given spin. In this situation, coupling loops are mostly suppressed, and the behavior of the system is much more like that of a mean field theory. We also describe possible applications of the models to, for example, genetic networks, cell differentiation, evolution, democracy in social systems and neural networks.Comment: 69 pages, 16 figures, Submitted to Springer Applied Mathematical Sciences Serie