A description of the methodology used in an overview of reviews to evaluate evidence on the treatment, harms, diagnosis/ classification, prognosis and outcomes used in the management of neck pain

Background: Neck Pain (NP) is a common musculoskeletal disorder and the literature provides conflicting evidence about its management. Objective: To describe the methodology used to conduct an overview of reviews (OvR) and to characterize the distribution and risk of bias profiles across the evidence for all areas of NP management. Methods: Standard systematic review (SR) methodology was employed. MEDLINE, CINAHL, EMBASE, ILC, Cochrane CENTRAL, and LILACS were searched from 2000 to March 2012; Narrative and SR and clinical practice guidelines (CPG) evaluating the efficacy of treatment (benefits and harms), diagnosis/classification, prognosis, and outcomes were eligible. For treatment, articles were limited to SRs from 2005 forward. Risk of bias of SR was assessed with the AMSTAR; the AGREE II was used to critically appraise the CPGs. Results: From 2476 articles, 508 were eligible for full text screening. A total of 341 articles were included. Treatment (n=117) had the greatest yield. Other clinical areas had less literature (diagnosis=54, prognosis=16, outcomes=27, harms=16). There were no SR for classification and narrative reviews were problematic for this topic. There was great overlap across different databases within each clinical area except for those for outcome measures. Risk of bias assessment using the AMSTAR of eligible SRs showed a similar trend across different clinical areas. Conclusion: A summary of methods used to review the literature in five clinical areas of NP management have been described. The challenges of selecting and synthesizing eligible articles in an OvR required customized solutions across different areas of clinical focus

An ICON overview on physical modalities for neck pain and associated disorders

Introduction: Neck pain is common, can be disabling and is costly to society. Physical modalities are often included in neck rehabilitation programs. Interventions may include thermal, electrotherapy, ultrasound, mechanical traction, laser and acupuncture. Definitive knowledge regarding optimal modalities and dosage for neck pain management is limited. Purpose: To systematically review existing literature to establish the evidence-base for recommendations on physical modalities for acute to chronic neck pain. Methods: A comprehensive computerized and manual search strategy from January 2000 to July 2012, systematic review methodological quality assessment using AMSTAR, qualitative assessment using a GRADE approach and recommendation presentation was included. Systematic or meta-analyses of studies evaluating physical modalities were eligible. Independent assessment by at least two review team members was conducted. Data extraction was performed by one reviewer and checked by a second. Disagreements were resolved by consensus. Results: Of 103 reviews eligible, 20 were included and 83 were excluded. Short term pain relief - Moderate evidence of benefit: acupuncture, intermittent traction and laser were shown to be better than placebo for chronic neck pain. Moderate evidence of no benefit: pulsed ultrasound, infrared light or continuous traction was no better than placebo for acute whiplash associated disorder, chronic myofascial neck pain or subacute to chronic neck pain. There was no added benefit when hot packs were combined with mobilization, manipulation or electrical muscle stimulation for chronic neck pain, function or patient satisfaction at six month follow-up. Conclusions: The current state of the evidence favours acupuncture, laser and intermittent traction for chronic neck pain. Some electrotherapies show little benefit for chronic neck pain. Consistent dosage, improved design and long term follow-up continue to be the recommendations for future research

What is the experience of receiving healthcare for neck pain?

This study used a descriptive phenomenological approach to describe the experience of finding and receiving health services for neck pain. Nineteen participants (18 females, 1 male) with neck pain (>3 months) were interviewed using a semi-structured questionnaire guide. Interviews were recorded, transcribed and coded. Two overarching themes described the experience: complexity in finding effective health care; and the need for informative, personalized, respectful communication. Complexity in finding effective health care was attributed to the variable approach and effectiveness of different health professionals, the need to experiment with care to find what works, the need to differentiate temporary versus permanent treatment effects, concerns about treatment side effects and the sense that financial factors influence personal treatment choices and provider behaviours. The need for informative, personalized, respectful communications was broken down into the following subthemes: the importance of being listened to, seen and believed; the need for useful information; and a desire to have outcomes formally tracked as a means of individualizing treatment. Overall, patients struggled to navigate the variable health services and providers that were available and that provided variable outcomes. They often did so through a trial and error approach. As such, patients remain open to unproven, even controversial treatment options. Research evidence was not a key ingredient in patient decision-making about accessing health services. The environmental, personal, health behavior factors interacted to contribute to health service utilization and would increase the burden of these for both the individual and society at large. The effectiveness of neck pain interventions is dependent on complex interactions between the context, individual, and health care provider, therefore, physiological responses cannot be considered as being distinct from these determinants

The Atacama Cosmology Telescope: Data Characterization and Map Making

We present a description of the data reduction and mapmaking pipeline used for the 2008 observing season of the Atacama Cosmology Telescope (ACT). The data presented here at 148 GHz represent 12% of the 90 TB collected by ACT from 2007 to 2010. In 2008 we observed for 136 days, producing a total of 1423 hours of data (11 TB for the 148 GHz band only), with a daily average of 10.5 hours of observation. From these, 1085 hours were devoted to a 850 deg^2 stripe (11.2 hours by 9.1 deg) centered on a declination of -52.7 deg, while 175 hours were devoted to a 280 deg^2 stripe (4.5 hours by 4.8 deg) centered at the celestial equator. We discuss sources of statistical and systematic noise, calibration, telescope pointing, and data selection. Out of 1260 survey hours and 1024 detectors per array, 816 hours and 593 effective detectors remain after data selection for this frequency band, yielding a 38% survey efficiency. The total sensitivity in 2008, determined from the noise level between 5 Hz and 20 Hz in the time-ordered data stream (TOD), is 32 micro-Kelvin sqrt{s} in CMB units. Atmospheric brightness fluctuations constitute the main contaminant in the data and dominate the detector noise covariance at low frequencies in the TOD. The maps were made by solving the least-squares problem using the Preconditioned Conjugate Gradient method, incorporating the details of the detector and noise correlations. Cross-correlation with WMAP sky maps, as well as analysis from simulations, reveal that our maps are unbiased at multipoles ell > 300. This paper accompanies the public release of the 148 GHz southern stripe maps from 2008. The techniques described here will be applied to future maps and data releases.Comment: 20 pages, 18 figures, 6 tables, an ACT Collaboration pape

Extensive telomere erosion is consistent with localised clonal expansions in Barrett’s metaplasia

Barrett’s oesophagus is a premalignant metaplastic condition that predisposes patients to the development of oesophageal adenocarcinoma. However, only a minor fraction of Barrett’s oesophagus patients progress to adenocarcinoma and it is thus essential to determine bio-molecular markers that can predict the progression of this condition. Telomere dysfunction is considered to drive clonal evolution in several tumour types and telomere length analysis provides clinically relevant prognostic and predictive information. The aim of this work was to use high-resolution telomere analysis to examine telomere dynamics in Barrett’s oesophagus. Telomere length analysis of XpYp, 17p, 11q and 9p, chromosome arms that contain key cancer related genes that are known to be subjected to copy number changes in Barrett’s metaplasia, revealed similar profiles at each chromosome end, indicating that no one specific telomere is likely to suffer preferential telomere erosion. Analysis of patient matched tissues (233 samples from 32 patients) sampled from normal squamous oesophagus, Z-line, and 2 cm intervals within Barrett’s metaplasia, plus oesophago-gastric junction, gastric body and antrum, revealed extensive telomere erosion in Barrett’s metaplasia to within the length ranges at which telomere fusion is detected in other tumour types. Telomere erosion was not uniform, with distinct zones displaying more extensive erosion and more homogenous telomere length profiles. These data are consistent with an extensive proliferative history of cells within Barrett’s metaplasia and are indicative of localised clonal growth. The extent of telomere erosion highlights the potential of telomere dysfunction to drive genome instability and clonal evolution in Barrett’s metaplasia

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe