1,963 research outputs found
Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California.
BackgroundAmbient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain.ObjectiveWe determined the impact of residential traffic on mortality during treatment of active TB.MethodsFrom 2000-2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests.ResultsParticipants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002].ConclusionsResidential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699
Fasting Insulin, Adiponectin, hs-CRP Levels, and The Components of Metabolic Syndrome
ABSTRACT 3, 5, 7, 7, 4
Histone Deacetylase Inhibitors Prevent Pulmonary Endothelial Hyperpermeability and Acute Lung Injury By Regulating Heat Shock Protein 90 Function
Transendothelial hyperpermeability caused by numerous agonists is dependent on heat shock protein 90 (Hsp90) and leads to endothelial barrier dysfunction (EBD). Inhibition of Hsp90 protects and restores transendothelial permeability. Hyperacetylation of Hsp90, as by inhibitors of histone deacetylase (HDAC), suppresses its chaperone function and mimics the effects of Hsp90 inhibitors. In this study we assessed the role of HDAC in mediating lipopolysaccharide (LPS)-induced transendothelial hyperpermeability and acute lung injury (ALI). We demonstrate that HDAC inhibition protects against LPS-mediated EBD. Inhibition of multiple HDAC by the general inhibitors panobinostat or trichostatin provided protection against LPS-induced transendothelial hyperpermeability, acetylated and suppressed Hsp90 chaperone function, and attenuated RhoA activity and signaling crucial to endothelial barrier function. Treatment with the HDAC3-selective inhibitor RGFP-966 or the HDAC6-selective inhibitor tubastatin A provided partial protection against LPS-mediated transendothelial hyperpermeability. Similarly, knock down of HDAC3 and HDAC6 by specific small-interfering RNAs provided significant protection against LPS-induced EBD. Furthermore, combined pharmacological inhibition of both HDAC3 and -6 attenuated the inflammation, capillary permeability, and structural abnormalities associated with LPS-induced ALI in mice. Together these data indicate that HDAC mediate increased transendothelial hyperpermeability caused by LPS and that inhibition of HDAC protects against LPS-mediated EBD and ALI by suppressing Hsp90-dependent RhoA activity and signaling
Measuring co-authorship and networking-adjusted scientific impact
Appraisal of the scientific impact of researchers, teams and institutions
with productivity and citation metrics has major repercussions. Funding and
promotion of individuals and survival of teams and institutions depend on
publications and citations. In this competitive environment, the number of
authors per paper is increasing and apparently some co-authors don't satisfy
authorship criteria. Listing of individual contributions is still sporadic and
also open to manipulation. Metrics are needed to measure the networking
intensity for a single scientist or group of scientists accounting for patterns
of co-authorship. Here, I define I1 for a single scientist as the number of
authors who appear in at least I1 papers of the specific scientist. For a group
of scientists or institution, In is defined as the number of authors who appear
in at least In papers that bear the affiliation of the group or institution. I1
depends on the number of papers authored Np. The power exponent R of the
relationship between I1 and Np categorizes scientists as solitary (R>2.5),
nuclear (R=2.25-2.5), networked (R=2-2.25), extensively networked (R=1.75-2) or
collaborators (R<1.75). R may be used to adjust for co-authorship networking
the citation impact of a scientist. In similarly provides a simple measure of
the effective networking size to adjust the citation impact of groups or
institutions. Empirical data are provided for single scientists and
institutions for the proposed metrics. Cautious adoption of adjustments for
co-authorship and networking in scientific appraisals may offer incentives for
more accountable co-authorship behaviour in published articles.Comment: 25 pages, 5 figure
Effects of systematic asymmetric discounting on physician-patient interactions: a theoretical framework to explain poor compliance with lifestyle counseling
BACKGROUND: This study advances the use of a utility model to model physician-patient interactions from the perspectives of physicians and patients. PRESENTATION OF THE HYPOTHESIS: In cases involving acute care, patient counseling involves a relatively straightforward transfer of information from the physician to a patient. The patient has less information than the physician on the impact the condition and its treatment have on utility. In decisions involving lifestyle changes, the patient may have more information than the physician on his/her utility of consumption; moreover, differences in discounting future health may contribute significantly to differences between patients' preferences and physicians' recommendations. TESTING THE HYPOTHESIS: The expectation of differences in internal discount rate between patients and their physicians is discussed. IMPLICATIONS OF THE HYPOTHESIS: This utility model provides a conceptual basis for the finding that educational approaches alone may not effect changes in patient behavior and suggests other economic variables that could be targeted in the attempt to produce healthier behavior
Complex-Distance Potential Theory and Hyperbolic Equations
An extension of potential theory in R^n is obtained by continuing the
Euclidean distance function holomorphically to C^n. The resulting Newtonian
potential is generated by an extended source distribution D(z) in C^n whose
restriction to R^n is the delta function. This provides a natural model for
extended particles in physics. In C^n, interpreted as complex spacetime, D(z)
acts as a propagator generating solutions of the wave equation from their
initial values. This gives a new connection between elliptic and hyperbolic
equations that does not assume analyticity of the Cauchy data. Generalized to
Clifford analysis, it induces a similar connection between solutions of
elliptic and hyperbolic Dirac equations. There is a natural application to the
time-dependent, inhomogeneous Dirac and Maxwell equations, and the
`electromagnetic wavelets' introduced previously are an example.Comment: 25 pages, submited to Proceedings of 5th Intern. Conf. on Clifford
Algebras, Ixtapa, June 24 - July 4, 199
Imaging Single Retrovirus Entry through Alternative Receptor Isoforms and Intermediates of Virus-Endosome Fusion
A large group of viruses rely on low pH to activate their fusion proteins that merge the viral envelope with an endosomal membrane, releasing the viral nucleocapsid. A critical barrier to understanding these events has been the lack of approaches to study virus-cell membrane fusion within acidic endosomes, the natural sites of virus nucleocapsid capsid entry into the cytosol. Here we have investigated these events using the highly tractable subgroup A avian sarcoma and leukosis virus envelope glycoprotein (EnvA)-TVA receptor system. Through labeling EnvA pseudotyped viruses with a pH-sensitive fluorescent marker, we imaged their entry into mildly acidic compartments. We found that cells expressing the transmembrane receptor (TVA950) internalized the virus much faster than those expressing the GPI-anchored receptor isoform (TVA800). Surprisingly, TVA800 did not accelerate virus uptake compared to cells lacking the receptor. Subsequent steps of virus entry were visualized by incorporating a small viral content marker that was released into the cytosol as a result of fusion. EnvA-dependent fusion with TVA800-expressing cells occurred shortly after endocytosis and delivery into acidic endosomes, whereas fusion of viruses internalized through TVA950 was delayed. In the latter case, a relatively stable hemifusion-like intermediate preceded the fusion pore opening. The apparent size and stability of nascent fusion pores depended on the TVA isoforms and their expression levels, with TVA950 supporting more robust pores and a higher efficiency of infection compared to TVA800. These results demonstrate that surface receptor density and the intracellular trafficking pathway used are important determinants of efficient EnvA-mediated membrane fusion, and suggest that early fusion intermediates play a critical role in establishing low pH-dependent virus entry from within acidic endosomes
Serum methylarginines and spirometry-measured lung function in older adults
Rationale: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans.
Objectives: This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures.
Methods: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study.
The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity.
Measurements and Main Results: In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function.
Conclusions: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function
Pulsar spins from an instability in the accretion shock of supernovae
Rotation-powered radio pulsars are born with inferred initial rotation
periods of order 300 ms (some as short as 20 ms) in core-collapse supernovae.
In the traditional picture, this fast rotation is the result of conservation of
angular momentum during the collapse of a rotating stellar core. This leads to
the inevitable conclusion that pulsar spin is directly correlated with the
rotation of the progenitor star. So far, however, stellar theory has not been
able to explain the distribution of pulsar spins, suggesting that the birth
rotation is either too slow or too fast. Here we report a robust instability of
the stalled accretion shock in core-collapse supernovae that is able to
generate a strong rotational flow in the vicinity of the accreting
proto-neutron star. Sufficient angular momentum is deposited on the
proto-neutron star to generate a final spin period consistent with
observations, even beginning with spherically symmetrical initial conditions.
This provides a new mechanism for the generation of neutron star spin and
weakens, if not breaks, the assumed correlation between the rotational periods
of supernova progenitor cores and pulsar spin.Comment: To be published in Natur
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