Ambient Fine Particulate Matter Exposure and Myocardial Ischemia in the Environmental Epidemiology of Arrhythmogenesis in the Women’s Health Initiative (EEAWHI) Study

BackgroundAmbient particulate matter (PM) air pollution is associated with coronary heart disease, but the pathways underlying the association remain to be elucidated.MethodsWe studied the association between PM and ischemia among 57,908 Women’s Health Initiative clinical trial participants from 1999–2003. We used the Minnesota Code criteria to identify ST-segment and T-wave abnormalities, and estimated T amplitude (microvolt) from resting, standard 12-lead electrocardiogram (ECG). We used U.S. Environmental Protection Agency’s monitor data to estimate concentrations of PM < 2.5 μm (PM2.5) at geocoded participant addresses over 6 days before the ECGs (lag0 through lag5). We excluded 2,379 women with ECG QRS duration ≥ 120 msec.ResultsOverall, 6% of the remaining 55,529 women (52–90 years of age; 83% non-Hispanic white) had ST abnormalities and 16% had T abnormalities. Lead-specific T amplitude was normally distributed (range of means from −14 to 349 μV). PM2.5 (mean ± SD) averaged over lag0–2 was 14 ± 7 μg/m3. In logistic and linear regression models adjusted for demographic, clinical, temporal, and climatic factors, a 10-μg/m3 increase in lag0–2 PM2.5 was associated with a 4% [95% confidence interval (CI), −3%, to 10%] increase in the odds of ST abnormality and a 5% (95% CI, 0% to 9%) increase in the odds of T abnormality. We observed corresponding decreases in T amplitude in all exam sites and leads except lead V1, reaching a minimum of −2 μV (95% CI, −5 to 0 μV) in lead V3.ConclusionsShort-term PM2.5 exposure is associated with ECG evidence of myocardial ischemia among postmenopausal women. The principal manifestations include subclinical but potentially arrhythmogenic ST–T abnormalities and decreases in T amplitude

Short Lag Times for Invasive Tropical Plants: Evidence from Experimental Plantings in Hawai'i

Background: The lag time of an invasion is the delay between arrival of an introduced species and its successful spread in a new area. To date, most estimates of lag times for plants have been indirect or anecdotal, and these estimates suggest that plant invasions are often characterized by lag times of 50 years or more. No general estimates are available of lag times for tropical plant invasions. Historical plantings and documentation were used to directly estimate lag times for tropical plant invasions in Hawai’i. Methodology/Principal Findings: Historical planting records for the Lyon Arboretum dating back to 1920 were examined to identify plants that have since become invasive pests in the Hawaiian Islands. Annual reports describing escape from plantings were then used to determine the lag times between initial plantings and earliest recorded spread of the successful invaders. Among 23 species that eventually became invasive pests, the average lag time between introduction and first evidence of spread was 14 years for woody plants and 5 years for herbaceous plants. Conclusions/Significance: These direct estimates of lag times are as much as an order of magnitude shorter than previous, indirect estimates, which were mainly based on temperate plants. Tropical invaders may have much shorter lag times than temperate species. A lack of direct and deliberate observations may have also inflated many previous lag time estimates. Although there have been documented cases of long lag times due to delayed arrival of a mutualist or environmenta

Conserved presence of G-quadruplex forming sequences in the Long Terminal Repeat Promoter of Lentiviruses

G-quadruplexes (G4s) are secondary structures of nucleic acids that epigenetically regulate cellular processes. In the human immunodeficiency lentivirus 1 (HIV-1), dynamic G4s are located in the unique viral LTR promoter. Folding of HIV-1 LTR G4s inhibits viral transcription; stabilization by G4 ligands intensifies this effect. Cellular proteins modulate viral transcription by inducing/unfolding LTR G4s. We here expanded our investigation on the presence of LTR G4s to all lentiviruses. G4s in the 5'-LTR U3 region were completely conserved in primate lentiviruses. A G4 was also present in a cattle-infecting lentivirus. All other non-primate lentiviruses displayed hints of less stable G4s. In primate lentiviruses, the possibility to fold into G4s was highly conserved among strains. LTR G4 sequences were very similar among phylogenetically related primate viruses, while they increasingly differed in viruses that diverged early from a common ancestor. A strong correlation between primate lentivirus LTR G4s and Sp1/NF\u3baB binding sites was found. All LTR G4s folded: their complexity was assessed by polymerase stop assay. Our data support a role of the lentiviruses 5'-LTR G4 region as control centre of viral transcription, where folding/unfolding of G4s and multiple recruitment of factors based on both sequence and structure may take place

An evaluation of Canada's Compassionate Care Benefit from a family caregiver's perspective at end of life

<p>Abstract</p> <p>Background</p> <p>The goal of Canada's Compassionate Care Benefit (CCB) is to enable family members and other loved ones who are employed to take a temporary <it>secured </it>leave to care for a terminally ill individual at end of life. Successful applicants of the CCB can receive up to 55% of their average insured earnings, up to a maximum of CDN$435 per week, over a six week period to provide care for a gravely ill family member at risk of death within a six month period, as evidenced by a medical certificate. The goal of this study is to evaluate the CCB from the perspective of family caregivers providing care to individuals at end of life. There are three specific research objectives. Meeting these objectives will address our study purpose which is to make policy-relevant recommendations informed by the needs of Canadian family caregivers and input from other key stakeholders who shape program uptake. Being the first study that will capture family caregivers' experiences and perceptions of the CCB and gather contextual data with front-line palliative care practitioners, employers, and human resources personnel, we will be in a unique position to provide policy solutions/recommendations that will address concerns raised by numerous individuals and organizations.</p> <p>Methods</p> <p>We will achieve the research goal and objectives through employing utilization-focused evaluation as our methodology, in-depth interviews and focus groups as our techniques of data collection, and constant comparative as our technique of data analysis. Three respondent groups will participate: (1) family caregivers who are providing or who have provided end of life care via phone interview; (2) front-line palliative care practitioners via phone interview; and (3) human resources personnel and employers via focus group. Each of these three groups has a stake in the successful administration of the CCB. A watching brief of policy documents, grey literature, media reports, and other relevant items will also be managed throughout data collection.</p> <p>Discussion</p> <p>We propose to conduct this study over a three year period beginning in October, 2006 and ending in October, 2009.</p

Primary care incidence and treatment of four neuropathic pain conditions: A descriptive study, 2002–2005

<p>Abstract</p> <p>Background</p> <p>Between 1992 and 2001 the UK general practice incidence of post-herpetic neuralgia and trigeminal neuralgia declined, whilst the incidence of painful diabetic neuropathy increased. The most common first line treatments were compound analgesics. As therapeutic options have subsequently changed, this study presents updated data on incidence and prescribing patterns in neuropathic pain.</p> <p>Methods</p> <p>A descriptive analysis of the epidemiology and prescription treatment at diagnosis of incident post-herpetic neuralgia (n = 1,923); trigeminal neuralgia (1,862); phantom limb pain (57) and painful diabetic neuropathy (1,444) using computerised UK general practice records (THIN): May 2002 to July 2005.</p> <p>Results</p> <p>Primary care incidences per 100,000 person years observation of 28 (95% confidence interval (CI) 27–30) for post-herpetic neuralgia, 27 (95%CI 26–29) for trigeminal neuralgia, 0.8 (95%CI 0.6–1.1) for phantom limb pain and 21 (95%CI 20–22) for painful diabetic neuropathy are reported. The most common initial treatments were tricyclic antidepressants (post-herpetic neuralgia) or antiepileptics (trigeminal neuralgia and painful diabetic neuropathy) and opioid analgesics (phantom limb pain). The mean number of changes before a stable drug regimen was 1.2 to 1.5 for trigeminal neuralgia, painful diabetic neuropathy and post-herpetic neuralgia, and 2.4 for phantom limb pain.</p> <p>Conclusion</p> <p>The incidence of phantom limb pain and post-herpetic neuralgia are decreasing whilst painful diabetic neuropathy plateaued and trigeminal neuralgia remained constant. Despite more frequent use of antidepressants and antiepileptics for first line treatment, as opposed to conventional non-opioid analgesics, changes to therapy are common before a stable regimen is reached.</p

Human influence on climate in the 2014 southern England winter floods and their impacts

A succession of storms reaching Southern England in the winter of 2013/2014 caused severe floods and £451 million insured losses. In a large ensemble of climate model simulations, we find that, as well as increasing the amount of moisture the atmosphere can hold, anthropogenic warming caused a small but significant increase in the number of January days with westerly flow, both of which increased extreme precipitation. Hydrological modelling indicates this increased extreme 30-day-average Thames river flows, and slightly increased daily peak flows, consistent with the understanding of the catchment’s sensitivity to longer-duration precipitation and changes in the role of snowmelt. Consequently, flood risk mapping shows a small increase in properties in the Thames catchment potentially at risk of riverine flooding, with a substantial range of uncertainty, demonstrating the importance of explicit modelling of impacts and relatively subtle changes in weather-related risks when quantifying present-day effects of human influence on climate

The Glycan Shield of HIV Is Predominantly Oligomannose Independently of Production System or Viral Clade

The N-linked oligomannose glycans of HIV gp120 are a target for both microbicide and vaccine design. The extent of cross-clade conservation of HIV oligomannose glycans is therefore a critical consideration for the development of HIV prophylaxes. We measured the oligomannose content of virion-associated gp120 from primary virus from PBMCs for a range of viral isolates and showed cross-clade elevation (62–79%) of these glycans relative to recombinant, monomeric gp120 (∼30%). We also confirmed that pseudoviral production systems can give rise to notably elevated gp120 oligomannose levels (∼98%), compared to gp120 derived from a single-plasmid viral system using the HIVLAI backbone (56%). This study highlights differences in glycosylation between virion-associated and recombinant gp120

Postherpetic Neuralgia: Role of Gabapentin and Other Treatment Modalities

Postherpetic neuralgia (PHN) is a chronic and painful condition that may occur after a herpes zoster infection. The frequency of PHN after untreated zoster varies widely. Age is the most important risk factor for development of PHN. The condition occurs in an estimated 50% of patients older than 50 years. The pain of PHN can be severe and debilitating and is frequently associated with allodynia. Although in most patients pain remits within the first year, it may persist for a lifetime. Tricyclic antidepressants (TCAs), topical agents, opioids, and gabapentin, a structural Γ-amino butyric acid (GABA) analogue, are the only agents that have demonstrated efficacy in randomized clinical trials for treatment of both the shooting and the burning form of pain associated with PHN. TCAs are among the most commonly used classes of agents for treating PHN and are effective in a significant proportion of patients. However, various adverse events can limit treatment. These side effects tend to be more acute in the elderly, the population most likely to suffer from PHN. Topical agents have led to mild to moderate improvement in patients with PHN but are usually ineffective as monotherapy for this condition. Until recently, carbamazepine was the only antiepileptic drug evaluated for the treatment of PHN. Over the past few years, however, gabapentin has received increasing attention as a useful treatment for neuropathic pain. Gabapentin lacks significant drug-drug interactions and has a favorable safety profile, which makes it particularly useful for treatment of PHN.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65597/1/j.1528-1157.1999.tb00933.x.pd

Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure

<p>Abstract</p> <p>Background</p> <p>Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging.</p> <p>Methods</p> <p>Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations.</p> <p>Results</p> <p>Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race.</p> <p>Conclusion</p> <p>The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations.</p