A missing dimension in measures of vaccination impacts

Immunological protection, acquired from either natural infection or vaccination, varies among hosts, reflecting underlying biological variation and affecting population-level protection. Owing to the nature of resistance mechanisms, distributions of susceptibility and protection entangle with pathogen dose in a way that can be decoupled by adequately representing the dose dimension. Any infectious processes must depend in some fashion on dose, and empirical evidence exists for an effect of exposure dose on the probability of transmission to mumps-vaccinated hosts [1], the case-fatality ratio of measles [2], and the probability of infection and, given infection, of symptoms in cholera [3]. Extreme distributions of vaccine protection have been termed leaky (partially protects all hosts) and all-or-nothing (totally protects a proportion of hosts) [4]. These distributions can be distinguished in vaccine field trials from the time dependence of infections [5]. Frailty mixing models have also been proposed to estimate the distribution of protection from time to event data [6], [7], although the results are not comparable across regions unless there is explicit control for baseline transmission [8]. Distributions of host susceptibility and acquired protection can be estimated from dose-response data generated under controlled experimental conditions [9]–[11] and natural settings [12], [13]. These distributions can guide research on mechanisms of protection, as well as enable model validity across the entire range of transmission intensities. We argue for a shift to a dose-dimension paradigm in infectious disease science and community health

Patient safety culture measurement in general practice. Clinimetric properties of 'SCOPE'

<p>Abstract</p> <p>Background</p> <p>A supportive patient safety culture is considered to be an essential condition for improving patient safety. Assessing the current safety culture in general practice may be a first step to target improvements. To that end, we studied internal consistency and construct validity of a safety culture questionnaire for general practice (SCOPE) which was derived from a comparable questionnaire for hospitals (Dutch-HSOPS).</p> <p>Methods</p> <p>The survey was conducted among caregivers of Dutch general practice as part of an ongoing quality accreditation process using a 46 item questionnaire. We conducted factor analyses and studied validity by calculating correlations between the subscales and testing the hypothesis that respondents' <it>patient safety grade </it>of their practices correlated with their scores on the questionnaire.</p> <p>Results</p> <p>Of 72 practices 294 respondents completed the questionnaire. Eight factors were identified concerning <it>handover and teamwork, support and fellowship, communication openness, feedback and learning from error, intention to report events, adequate procedures and staffing, overall perceptions of patient safety </it>and <it>expectations and actions of managers</it>. Cronbach's alpha of the factors rated between 0.64 and 0.85. The subscales intercorrelated moderately, except for the factor about intention to report events. Respondents who graded patient safety highly scored significantly higher on the questionnaire than those who did not.</p> <p>Conclusions</p> <p>The SCOPE questionnaire seems an appropriate instrument to assess patient safety culture in general practice. The clinimetric properties of the SCOPE are promising, but future research should confirm the factor structure and construct of the SCOPE and delineate its responsiveness to changes in safety culture over time.</p

An overview of the current status of CMB observations

In this paper we briefly review the current status of the Cosmic Microwave Background (CMB) observations, summarising the latest results obtained from CMB experiments, both in intensity and polarization, and the constraints imposed on the cosmological parameters. We also present a summary of current and future CMB experiments, with a special focus on the quest for the CMB B-mode polarization.Comment: Latest CMB results have been included. References added. To appear in "Highlights of Spanish Astrophysics V", Proceedings of the VIII Scientific Meeting of the Spanish Astronomical Society (SEA) held in Santander, 7-11 July, 200

Bone Marrow–Harvesting Technique Influences Functional Heterogeneity of Mesenchymal Stem/Stromal Cells and Cartilage Regeneration

Background: Connective tissue progenitors (CTPs) from native bone marrow (BM) or their culture-expanded progeny, often referred to as mesenchymal stem/stromal cells, represents a promising strategy for treatment of cartilage injuries. But the cartilage regeneration capacity of these cells remains unpredictable because of cell heterogeneity. Hypothesis: The harvest technique of BM may highly influence stem cell heterogeneity and, thus, cartilage formation because these cells have distinct spatial localization within BM from the same bone. Study Design: Controlled laboratory study. Methods: CTPs obtained from the femur of patients undergoing total hip replacement by 2 harvest techniques—BM aspiration and BM collection—after bone rasping were immunophenotyped by flow cytometry and evaluated for chondrogenic ability. The spatial localization of different CTP subsets in BM was verified by immunohistochemistry. Results: Cells from the BM after rasping were significantly more chondrogenic than the donor-matched aspirate, whereas no notable difference in their osteogenic or adipogenic potential was observed. The authors then assessed whether distinct immunophenotypically defined CTP subsets were responsible for the different chondrogenic capacity. Cells directly isolated from BM after rasping contained a higher percentage (mean, 7.2-fold) of CD45–CD2711CD561 CTPs as compared with BM aspirates. The presence of this subset in the harvested BM strongly correlated with chondrogenic ability, showing that CD2711CD561 cells are enriched in chondroprogenitors. Furthermore, evaluation of these CTP subsets in BM revealed that CD2711CD561 cells were localized in the bone-lining regions whereas CD2711CD56– cells were found in the perivascular regions. Since the iliac crest remains a frequent site of BM harvest for musculoskeletal regeneration, the authors also compared the spatial distribution of these subsets in trabeculae of femoral head and iliac crest and found CD2711CD561 bone-lining cells in both tissues. Conclusion: Chondrogenically distinct CTP subsets have distinct spatial localization in BM; hence, the harvest technique of BM determines the efficiency of cartilage formation. Clinical Relevance: The harvest technique of BM may be of major importance in determining the clinical success of BM mesenchymal stem/stromal cells in cartilage repair

Influenza pandemic preparedness: motivation for protection among small and medium businesses in Australia

<p>Abstract</p> <p>Background</p> <p>Community-wide preparedness for pandemic influenza is an issue that has featured prominently in the recent news media, and is currently a priority for health authorities in many countries. The small and medium business sector is a major provider of private sector employment in Australia, yet we have little information about the preparedness of this sector for pandemic influenza. This study aimed to investigate the association between individual perceptions and preparedness for pandemic influenza among small and medium business owners and managers.</p> <p>Methods</p> <p>Semi-structured face-to-face interviews were conducted with 201 small and medium business owners or managers in New South Wales and Western Australia. Eligible small or medium businesses were defined as those that had less than 200 employees. Binomial logistic regression analysis was used to identify the predictors of having considered the impact of, having a plan for, and needing help to prepare for pandemic influenza.</p> <p>Results</p> <p>Approximately 6 per cent of participants reported that their business had a plan for pandemic influenza, 39 per cent reported that they had not thought at all about the impact of pandemic influenza on their business, and over 60 per cent stated that they required help to prepare for a pandemic. Beliefs about the severity of pandemic influenza and the ability to respond were significant independent predictors of having a plan for pandemic influenza, and the perception of the risk of pandemic influenza was the most important predictor of both having considered the impact of, and needing help to prepare for a pandemic.</p> <p>Conclusion</p> <p>Our findings suggest that small and medium businesses in Australia are not currently well prepared for pandemic influenza. We found that beliefs about the risk, severity, and the ability to respond effectively to the threat of pandemic influenza are important predictors of preparedness. Campaigns targeting small and medium businesses should emphasise the severity of the consequences to their businesses if a pandemic were to occur, and, at the same time, reassure them that there are effective strategies capable of being implemented by small and medium businesses to deal with a pandemic.</p

Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human hepatocellular carcinoma and their prognostic significance

<p>Abstract</p> <p>Background</p> <p>Organic cation transporters (OCT) are responsible for the uptake and intracellular inactivation of a broad spectrum of endogenous substrates and detoxification of xenobiotics and chemotherapeutics. The transporters became pharmaceutically interesting, because OCTs are determinants of the cytotoxicity of platin derivates and the transport activity has been shown to correlate with the sensitivity of tumors towards tyrosine kinase inhibitors. No data exist about the relevance of OCTs in hepatocellular carcinoma (HCC).</p> <p>Methods</p> <p>OCT1 (<it>SLC22A1</it>) and OCT3 (<it>SLC22A3</it>) mRNA expression was measured in primary human HCC and corresponding non neoplastic tumor surrounding tissue (TST) by real time PCR (n = 53). Protein expression was determined by western blot analysis and immunofluorescence. Data were correlated with the clinicopathological parameters of HCCs.</p> <p>Results</p> <p>Real time PCR showed a downregulation of <it>SLC22A1 </it>and <it>SLC22A3 </it>in HCC compared to TST (p ≤ 0.001). A low <it>SLC22A1 </it>expression was associated with a worse patient survival (p < 0.05). Downregulation was significantly associated with advanced HCC stages, indicated by a higher number of T3 tumors (p = 0.025) with a larger tumor diameter (p = 0.035), a worse differentiation (p = 0.001) and higher AFP-levels (p = 0.019). In accordance, <it>SLC22A1 </it>was less frequently downregulated in tumors with lower stages who underwent transarterial chemoembolization (p < 0.001) and liver transplantation (p = 0.001). Tumors with a low <it>SLC22A1 </it>expression (< median) showed a higher <it>SLC22A3 </it>expression compared to HCC with high <it>SLC22A1 </it>expression (p < 0.001). However, there was no significant difference in tumor characteristics according to the level of the <it>SLC22A3 </it>expression.</p> <p>In the western blot analysis we found a different protein expression pattern in tumor samples with a more diffuse staining in the immunofluorescence suggesting that especially OCT1 is not functional in advanced HCC.</p> <p>Conclusion</p> <p>The downregulation of OCT1 is associated with tumor progression and a worse patient survival.</p

Bridging the gap between the economic evaluation literature and daily practice in occupational health: a qualitative study among decision-makers in the healthcare sector

Background: Continued improvements in occupational health can only be ensured if decisions regarding the implementation and continuation of occupational health and safety interventions (OHS interventions) are based on the best available evidence. To ensure that this is the case, scientific evidence should meet the needs of decision-makers. As a first step in bridging the gap between the economic evaluation literature and daily practice in occupational health, this study aimed to provide insight into the occupational health decision-making process and information needs of decision-makers.Methods: An exploratory qualitative study was conducted with a purposeful sample of occupational health decision-makers in the Ontario healthcare sector. Eighteen in-depth interviews were conducted to explore the process by which occupational health decisions are made and the importance given to the financial implications of OHS interventions. Twenty-five structured telephone interviews were conducted to explore the sources of information used during the decision-making process, and decision-makers' knowledge on economic evaluation methods. In-depth interview data were analyzed according to the constant comparative method. For the structured telephone interviews, summary statistics were prepared.Results: The occupational health decision-making process generally consists of three stages: initiation stage, establishing the need for an intervention; pre-implementation stage, developing an intervention and its business case in order to receive senior management approval; and implementation and evaluation stage, implementing and evaluating an intervention. During this process, information on the financial implications of OHS interventions was found to be of great importance, especially the employer's costs and benefits. However, scientific evidence was rarely consulted, sound ex-post program evaluations were hardly ever performed, and there seemed to be a need to advance the economic evaluation skill set of decision-makers.Conclusions: Financial information is particularly important at the front end of implementation decisions, and can be a key deciding factor of whether to go forward with a new OHS intervention. In addition, it appears that current practice in occupational health in the healthcare sector is not solidly grounded in evidence-based decision-making and strategies should be developed to improve this. © 2013 van Dongen et al.; licensee BioMed Central Ltd

Practice Induces Function-Specific Changes in Brain Activity

Practice can have a profound effect on performance and brain activity, especially if a task can be automated. Tasks that allow for automatization typically involve repeated encoding of information that is paired with a constant response. Much remains unknown about the effects of practice on encoding and response selection in an automated task.To investigate function-specific effects of automatization we employed a variant of a Sternberg task with optimized separation of activity associated with encoding and response selection by means of m-sequences. This optimized randomized event-related design allows for model free measurement of BOLD signals over the course of practice. Brain activity was measured at six consecutive runs of practice and compared to brain activity in a novel task.Prompt reductions were found in the entire cortical network involved in encoding after a single run of practice. Changes in the network associated with response selection were less robust and were present only after the third run of practice.This study shows that automatization causes heterogeneous decreases in brain activity across functional regions that do not strictly track performance improvement. This suggests that cognitive performance is supported by a dynamic allocation of multiple resources in a distributed network. Our findings may bear importance in understanding the role of automatization in complex cognitive performance, as increased encoding efficiency in early stages of practice possibly increases the capacity to otherwise interfering information

Composition Influences the Pathway but not the Outcome of the Metabolic Response of Bacterioplankton to Resource Shifts

Bacterioplankton community metabolism is central to the functioning of aquatic ecosystems, and strongly reactive to changes in the environment, yet the processes underlying this response remain unclear. Here we explore the role that community composition plays in shaping the bacterial metabolic response to resource gradients that occur along aquatic ecotones in a complex watershed in Québec. Our results show that the response is mediated by complex shifts in community structure, and structural equation analysis confirmed two main pathways, one involving adjustments in the level of activity of existing phylotypes, and the other the replacement of the dominant phylotypes. These contrasting response pathways were not determined by the type or the intensity of the gradients involved, as we had hypothesized, but rather it would appear that some compositional configurations may be intrinsically more plastic than others. Our results suggest that community composition determines this overall level of community plasticity, but that composition itself may be driven by factors independent of the environmental gradients themselves, such that the response of bacterial communities to a given type of gradient may alternate between the adjustment and replacement pathways. We conclude that community composition influences the pathways of response in these bacterial communities, but not the metabolic outcome itself, which is driven by the environment, and which can be attained through multiple alternative configurations