The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

Population-Based Precision Cancer Screening: A Symposium on Evidence, Epidemiology, and Next Steps

Precision medicine, an emerging approach for disease treatment that takes into account individual variability in genes, environment, and lifestyle, is under consideration for preventive interventions, including cancer screening. On September 29, 2015, the National Cancer Institute sponsored a symposium entitled “Precision Cancer Screening in the General Population: Evidence, Epidemiology, and Next Steps”. The goal was two-fold: to share current information on the evidence, practices, and challenges surrounding precision screening for breast, cervical, colorectal, lung, and prostate cancers, and to allow for in-depth discussion among experts in relevant fields regarding how epidemiology and other population sciences can be used to generate evidence to inform precision screening strategies. Attendees concluded that the strength of evidence for efficacy and effectiveness of precision strategies varies by cancer site, that no one research strategy or methodology would be able or appropriate to address the many knowledge gaps in precision screening, and that issues surrounding implementation must be researched as well. Additional discussion needs to occur to identify the high priority research areas in precision cancer screening for pertinent organs and to gather the necessary evidence to determine whether further implementation of precision cancer screening strategies in the general population would be feasible and beneficial

Patterns of impact resulting from a 'sit less, move more' web-based program in sedentary office employees.

PURPOSE: Encouraging office workers to 'sit less and move more' encompasses two public health priorities. However, there is little evidence on the effectiveness of workplace interventions for reducing sitting, even less about the longer term effects of such interventions and still less on dual-focused interventions. This study assessed the short and mid-term impacts of a workplace web-based intervention (Walk@WorkSpain, W@WS; 2010-11) on self-reported sitting time, step counts and physical risk factors (waist circumference, BMI, blood pressure) for chronic disease. METHODS: Employees at six Spanish university campuses (n=264; 42±10 years; 171 female) were randomly assigned by worksite and campus to an Intervention (used W@WS; n=129; 87 female) or a Comparison group (maintained normal behavior; n=135; 84 female). This phased, 19-week program aimed to decrease occupational sitting time through increased incidental movement and short walks. A linear mixed model assessed changes in outcome measures between the baseline, ramping (8 weeks), maintenance (11 weeks) and follow-up (two months) phases for Intervention versus Comparison groups. RESULTS: A significant 2 (group) × 2 (program phases) interaction was found for self-reported occupational sitting (F[3]=7.97, p=0.046), daily step counts (F[3]=15.68, p=0.0013) and waist circumference (F[3]=11.67, p=0.0086). The Intervention group decreased minutes of daily occupational sitting while also increasing step counts from baseline (446±126; 8,862±2,475) through ramping (+425±120; 9,345±2,435), maintenance (+422±123; 9,638±3,131) and follow-up (+414±129; 9,786±3,205). In the Comparison group, compared to baseline (404±106), sitting time remained unchanged through ramping and maintenance, but decreased at follow-up (-388±120), while step counts diminished across all phases. The Intervention group significantly reduced waist circumference by 2.1cms from baseline to follow-up while the Comparison group reduced waist circumference by 1.3cms over the same period. CONCLUSIONS: W@WS is a feasible and effective evidence-based intervention that can be successfully deployed with sedentary employees to elicit sustained changes on "sitting less and moving more"

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Blood cultures in ambulatory outpatients

BACKGROUND: Blood cultures are a gold standard specific test for diagnosing many infections. However, the low yield may limit their usefulness, particularly in low-risk populations. This study was conducted to assess the utility of blood cultures drawn from ambulatory outpatients. METHODS: Blood cultures drawn at community-based collection sites in the Calgary Health Region (population 1 million) in 2001 and 2002 were included in this study. These patients were analyzed by linkages to acute care health care databases for utilization of acute care facilities within 2 weeks of blood culture draw. RESULTS: 3102 sets of cultures were drawn from 1732 ambulatory outpatients (annual rate = 89.4 per 100,000 population). Significant isolates were identified from 73 (2.4%) sets of cultures from 51 patients, including Escherichia coli in 18 (35%) and seven (14%) each of Staphylococcus aureus and Streptococcus pneumoniae. Compared to patients with negative cultures, those with positive cultures were older (mean 49.6 vs. 40.1 years, p < 0.01), and more likely to subsequently receive care at a regional emergency department, outpatient antibiotic clinic, or hospital (35/51 vs. 296/1681, p < 0.0001). Of the 331 (19%) patients who received acute care treatment, those with positive cultures presented sooner after community culture draw (median 2 vs. 3 days, p < 0.01) and had longer median treatment duration (6 vs. 2 days, p < 0.01). CONCLUSION: Blood cultures drawn in outpatient settings are uncommonly positive, but may define patients for increased intensity of therapy. Strategies to reduce utilization without excluding patients with positive cultures need to be developed for this patient population

A quantitative analysis of transmission efficiency versus intensity for malaria

The relationship between malaria transmission intensity and efficiency is important for malaria epidemiology, for the design of randomized control trials that measure transmission or incidence as end points, and for measuring and modelling malaria transmission and control. Five kinds of studies published over the past century were assembled and reanalysed to quantify malaria transmission efficiency and describe its relation to transmission intensity, to understand the causes of inefficient transmission and to identify functions suitable for modelling mosquito-borne disease transmission. In this study, we show that these studies trace a strongly nonlinear relationship between malaria transmission intensity and efficiency that is parsimoniously described by a model of heterogeneous biting. When many infectious bites are concentrated on a few people, infections and parasite population structure will be highly aggregated affecting the immunoepidemiology of malaria, the evolutionary ecology of parasite life history traits and the measurement and stratification of transmission for control using entomological and epidemiological data

Evolutionary conservation of lampbrush-like loops in drosophilids

<p>Abstract</p> <p>Background</p> <p>Loopin-1 is an abundant, male germ line specific protein of <it>Drosophila melanogaster</it>. The polyclonal antibody T53-F1 specifically recognizes Loopin-1 and enables its visualization on the Y-chromosome lampbrush-like loop named kl-3 during primary spermatocyte development, as well as on sperm tails. In order to test lampbrush-like loop evolutionary conservation, extensive phase-contrast microscopy and immunostaining with T53-F1 antibody was performed in other drosophilids scattered along their genealogical tree.</p> <p>Results</p> <p>In the male germ line of all species tested there are cells showing giant nuclei and intranuclear structures similar to those of <it>Drosophila melanogaster </it>primary spermatocytes. Moreover, the antibody T53-F1 recognizes intranuclear structures in primary spermatocytes of all drosophilids analyzed. Interestingly, the extent and conformation of the staining pattern is species-specific. In addition, the intense staining of sperm tails in all species suggests that the terminal localization of Loopin-1 and its orthologues is conserved. A comparison of these cytological data and the data coming from the literature about sperm length, amount of sperm tail entering the egg during fertilization, shape and extent of both loops and primary spermatocyte nuclei, seems to exclude direct relationships among these parameters.</p> <p>Conclusion</p> <p>Taken together, the data reported strongly suggest that lampbrush-like loops are a conserved feature of primary spermatocyte nuclei in many, if not all, drosophilids. Moreover, the conserved pattern of the T53-F1 immunostaining indicates that a Loopin-1-like protein is present in all the species analyzed, whose localization on lampbrush-like loops and sperm tails during spermatogenesis is evolutionary conserved.</p

The Influence of Object Relative Size on Priming and Explicit Memory

We investigated the effects of object relative size on priming and explicit memory for color photos of common objects. Participants were presented with color photos of pairs of objects displayed in either appropriate or inappropriate relative sizes. Implicit memory was assessed by speed of object size ratings whereas explicit memory was assessed by an old/new recognition test. Study-to-test changes in relative size reduced both priming and explicit memory and had large effects for objects displayed in large vs. small size at test. Our findings of substantial size-specific influences on priming with common objects under some but not other conditions are consistent with instance views of object perception and priming but inconsistent with structural description views

Krill Excretion Boosts Microbial Activity in the Southern Ocean

Antarctic krill are known to release large amounts of inorganic and organic nutrients to the water column. Here we test the role of krill excretion of dissolved products in stimulating heterotrophic bacteria on the basis of three experiments where ammonium and organic excretory products released by krill were added to bacterial assemblages, free of grazers. Our results demonstrate that the addition of krill excretion products (but not of ammonium alone), at levels expected in krill swarms, greatly stimulates bacteria resulting in an order-of-magnitude increase in growth and production. Furthermore, they suggest that bacterial growth rate in the Southern Ocean is suppressed well below their potential by resource limitation. Enhanced bacterial activity in the presence of krill, which are major sources of DOC in the Southern Ocean, would further increase recycling processes associated with krill activity, resulting in highly efficient krill-bacterial recycling that should be conducive to stimulating periods of high primary productivity in the Southern Ocean.This research is a contribution to projects ICEPOS (REN2002-04165-CO3-O2) and ATOS (POL2006-00550/CTM), funded by the Spanish Ministry of Science and Innovation