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OBJECTIVE: Neuronal loss, a key substrate of irreversible disability in multiple sclerosis (MS), is a recognised feature of MS cortical pathology of which the cause remains unknown. Fibrin(ogen) deposition is neurotoxic in animal models of MS, but has not been evaluated in human progressive MS cortex. The aim of this study was to investigate the extent and distribution of fibrin(ogen) in progressive MS cortex and elucidate its relationship with neurodegeneration. METHODS: A post-mortem cohort of pathologically confirmed MS (n=47) and control (n=10) cases was used. The extent and distribution of fibrin(ogen) was assessed and related to measures of demyelination, inflammation, and neuronal density. In a subset of cases (MS, n=20; control, n=10), the expression of plasminogen activator inhibitor (PAI-1), a key enzyme in the fibrinolytic cascade, was assessed and related to the extent of fibrin(ogen). RESULTS: Motor cortical fibrin(ogen) deposition was significantly overrepresented in MS compared to control cases in all compartments studied (i.e. extracellular (p=0.001), cell body (p=0.003) and neuritic/glial-processes (p=0.004)). MS cases with high levels of extracellular fibrin(ogen) had significantly up-regulated PAI-1 expression in all cortical layers assessed (p

Risk prediction models, developed to estimate the probability of an individual developing a particular outcome, are frequently published. Few are adequately validated resulting in a large number of prediction models not used in practice. Data are often measured with some degree of error. This error can influence the performance of a prediction model. The impact of either random or systematic error in a particular covariate, the covariate’s strength or the sample size at which this measurement error could become negligible on model performance is unknown. This simulation study investigates the impact of measurement error and its relationship to sample size and a covariate’s strength on calibration (i.e. how close observed and predicted probabilities are, and quantified by the calibration slope and Brier score), discrimination (i.e. how well the model differentiates between individuals with and without the outcome, and quantified by the c-index and D statistic), and explained variation (e.g. R2).

Importance Acute sore throat poses a significant burden on primary care and is a source of inappropriate antibiotic prescribing. Corticosteroids could be an alternative symptomatic treatment. Objective To assess the clinical effectiveness of oral corticosteroids for acute sore throat in the absence of antibiotics. Design, Setting, and Participants Double-blind, placebo-controlled randomized trial (April 2013-February 2015; 28-day follow-up completed April 2015) conducted in 42 family practices in South and West England, enrolled 576 adults recruited on the day of presentation to primary care with acute sore throat not requiring immediate antibiotic therapy. Interventions Single oral dose of 10 mg of dexamethasone (n = 293) or identical placebo (n = 283). Main Outcomes and Measures Primary: proportion of participants experiencing complete resolution of symptoms at 24 hours. Secondary: complete resolution at 48 hours, duration of moderately bad symptoms (based on a Likert scale, 0, normal; 6, as bad as it could be), visual analog symptom scales (0-100 mm; 0, no symptom to 100, worst imaginable), health care attendance, days missed from work or education, consumption of delayed antibiotics or other medications, adverse events. Results Among 565 eligible participants who were randomized (median age, 34 years [interquartile range, 26.0-45.5 year]; 75.2% women; 100% completed the intervention), 288 received dexamethasone; 277, placebo. At 24 hours, 65 participants (22.6%) in the dexamethasone group and 49 (17.7%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 4.7% (95% CI, −1.8% to 11.2%) and a relative risk of 1.28 (95% CI; 0.92 to 1.78; P = .14). At 24 hours, participants receiving dexamethasone were not more likely than those receiving placebo to have complete symptom resolution. At 48 hours, 102 participants (35.4%) in the dexamethasone group vs 75 (27.1%) in the placebo group achieved complete resolution of symptoms, for a risk difference of 8.7% (95% CI, 1.2% to 16.2%) and a relative risk of 1.31 (95% CI, 1.02 to 1.68; P = .03). This difference also was observed in participants not offered delayed antibiotic prescription, for a risk difference of 10.3% (95% CI, 0.6% to 20.1%) and a relative risk of 1.37 (95% CI, 1.01 to 1.87; P = .046). There were no significant differences in any other secondary outcomes. Conclusions and Relevance Among adults presenting to primary care with acute sore throat, a single dose of oral dexamethasone compared with placebo did not increase the proportion of patients with resolution of symptoms at 24 hours. However, there was a significant difference at 48 hours.

[This corrects the article DOI: 10.1186/s41512-016-0001-y.].

The monitoring or follow-up of a person subjected to a health care intervention is a daily routine nursing activity. In the chronic patient the monitoring or follow-up is a core activity and forms a part of the ritual in the periodic visits. In spite of the high percentage workload and use of resources that patient follow up represents within the health system, it is a poorly investigated area. In the present article we examine the differences between a test versus a monitoring strategy, the conditions that justify the monitoring, the methodology to evaluate a follow-up strategy,, as well as creating initiatives to improve monitoring (MaDOx) worldwide. © 2009 Elsevier España, S.L. All rights reserved.

Background Testing for carcino-embryonic antigen (CEA) in the blood is a recommended part of follow-up to detect recurrence of colorectal cancer following primary curative treatment. There is substantial clinical variation in the cut-off level applied to trigger further investigation. Objectives To determine the diagnostic performance of different blood CEA levels in identifying people with colorectal cancer recurrence in order to inform clinical practice. Search methods We conducted all searches to January 29 2014. We applied no language limits to the searches, and translated non-English manuscripts. We searched for relevant reviews in the MEDLINE, EMBASE, MEDION and DARE databases. We searched for primary studies (including conference abstracts) in the Cochrane Central Register of Controlled Trials (CENTRAL), in MEDLINE, EMBASE, and the Science Citation Index and Conference Proceedings Citation Index – Science. We identified ongoing studies by searching WHO ICTRP and the ASCO meeting library. Selection criteria We included cross-sectional diagnostic test accuracy studies, cohort studies, and randomised controlled trials (RCTs) of post-resection colorectal cancer follow-up that compared CEA to a reference standard. We included studies only if we could extract 2 x 2 accuracy data. We excluded case-control studies, as the ratio of cases to controls is determined by the study design, making the data unsuitable for assessing test accuracy. Data collection and analysis Two review authors (BDN, IP) assessed the quality of all articles independently, discussing any disagreements. Where we could not reach consensus, a third author (BS) acted as moderator. We assessed methodological quality against QUADAS-2 criteria. We extracted binary diagnostic accuracy data from all included studies as 2 x 2 tables. We conducted a bivariate meta-analysis. We used the xtmelogit command in Stata to produce the pooled estimates of sensitivity and specificity and we also produced hierarchical summary ROC plots. Main results In the 52 included studies, sensitivity ranged from 41% to 97% and specificity from 52% to 100%. In the seven studies reporting the impact of applying a threshold of 2.5 µg/L, pooled sensitivity was 82% (95% confidence interval (CI) 78% to 86%) and pooled specificity 80% (95% CI 59% to 92%). In the 23 studies reporting the impact of applying a threshold of 5 µg/L, pooled sensitivity was 71% (95% CI 64% to 76%) and pooled specificity 88% (95% CI 84% to 92%). In the seven studies reporting the impact of applying a threshold of 10 µg/L, pooled sensitivity was 68% (95% CI 53% to 79%) and pooled specificity 97% (95% CI 90% to 99%). Authors' conclusions CEA is insufficiently sensitive to be used alone, even with a low threshold. It is therefore essential to augment CEA monitoring with another diagnostic modality in order to avoid missed cases. Trying to improve sensitivity by adopting a low threshold is a poor strategy because of the high numbers of false alarms generated. We therefore recommend monitoring for colorectal cancer recurrence with more than one diagnostic modality but applying the highest CEA cut-off assessed (10 µg/L).

CONTEXT: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. OBJECTIVE: To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. DATA SOURCES: Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. STUDY SELECTION: Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. DATA EXTRACTION: Reviewers with methodological expertise conducted data extraction independently. RESULTS: The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks

BACKGROUND: Material or financial incentives may be used in an attempt to reinforce behaviour change, including smoking cessation. They have been widely used in workplace smoking cessation programmes, and to a lesser extent within community programmes. Quit and Win contests are the subject of a companion review. OBJECTIVES: To determine whether competitions and incentives lead to higher long-term quit rates. We also set out to examine the relationship between incentives and participation rates. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group Specialized Register, with additional searches of MEDLINE (January 1966 to September 2004), EMBASE (1980 to 2004/8), CINAHL (1982 to 2004/8) and PsycINFO (1872 to 2004/6). Search terms included incentive*, competition*, contest*, reward*, prize*, contingent payment*, deposit contract*. SELECTION CRITERIA: We considered randomized controlled trials, allocating individuals, workplaces, groups within workplaces, or communities to experimental or control conditions. We also considered controlled studies with baseline and post-intervention measures. DATA COLLECTION AND ANALYSIS: Data were extracted by one author and checked by the second. We contacted study authors for additional data where necessary. The main outcome measure was abstinence from smoking for at least six months from the start of the intervention. We used the most rigorous definition of abstinence in each trial, and biochemically validated rates where available. Where possible we performed meta-analysis using a generic inverse variance model, grouped by timed endpoints, but not pooled across the subgroups. MAIN RESULTS: Fifteen studies met our inclusion criteria. None of the studies demonstrated significantly higher quit rates for the incentives group than for the control group beyond the six-month assessment. There was no clear evidence that participants who committed their own money to the programme did better than those who did not, or that different types of incentives were more or less effective. There is some evidence that although cessation rates have not been shown to differ significantly, recruitment rates can be improved by rewarding participation, which may be expected to deliver higher absolute numbers of successful quitters. Cost effectiveness analysis is not appropriate to this review, since the efficacy of the intervention has not been demonstrated. AUTHORS' CONCLUSIONS: Incentives and competitions do not appear to enhance long-term cessation rates, with early success tending to dissipate when the rewards are no longer offered. Rewarding participation and compliance in contests and cessation programmes may have more potential to deliver higher absolute numbers of quitters.

Source Citation Hayward G, Thompson MJ, Perera R, et al. Corticosteroids as standalone or add-on treatment for sore throat. Cochrane Database Syst Rev. 2012;(10):CD008268. 23076943

Cochrane Review: School-based programmes for preventing smoking Thomas RE, McLellan J, Perera R. School-based programmes for preventing smoking. Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD001293. DOI: 10.1002/14651858.CD001293.pub3. This companion piece to the review, "School/based programmes for preventing smoking," contains the following pieces: The abstract of the review A commentary of one or more of the review authors, explaining why the review team felt the review was an important once to produce A review of clinical practice guidelines from the American Academy of Pediatrics, the Canadian Paediatric Society and the National Institute for Health and Care Excellence (NICE), United Kingdom Some other recently published references on this topic © 2013 The Cochrane Collaboration. Published by John Wiley and Sons, Ltd.

The development of monitoring technologies particularly suitable to be used with novel CFRP strengthening techniques has gained great attention in recent years. However, in spite of the high performance of these advanced composite materials in the strengthening and repairing of structures in service, they are usually associated with brittle and sudden failure mainly caused by debonding phenomena, originated either at the CFRP-plate end or at the intermediate areas in the vicinity of flexural cracks in the RC beam. Thus, it is highly recommended for these structures to be monitored in order to ensure their integrity while in service. Specifically, the feasibility of smart sensing technologies such as Fiber Bragg Grating (FBG) sensors and piezo-impedance transducers (PZT) has been studied. To the knowledge of the authors, none serious study has been carried out until now concerned to the topic of damage detection due to debonding in rehabilitated structures with CFRP composites., El desarrollo de tecnologías de monitorización aplicables junto con las novedosas técnicas de refuerzo basadas en materiales CFRP ha recibido una atención creciente los últimos años. Sin embargo, a pesar del alto rendimiento de estos avanzados materiales compuestos en la reparación y refuerzo de estructuras en servicio, están habitualmente asociados a fallos frágiles y repentinos causados principalmente por fenómenos de despegue, originados bien en los extremos del refuerzo, bien en áreas intermedias en las proximidades de grietas de flexión existentes en la viga. Por tanto, es altamente recomendable monitorizar estas soluciones estructurales de cara a garantizar su integridad en servicio. Específicamente, se ha estudiado la viabilidad de sensores inteligentes tales como los sensores Fiber Bragg Grating (FBG) o los transductores piezoeléctricos (PZT). Hasta donde los autores saben, no se han realizado estudios serios hasta la fecha abordando la detección de daño debido al despegue en estructuras reforzadas con compuestos CFRP.

Performance, satisfaction and safety indicators are commonly measured on a percentage scale. Such indicators are often subject to ceiling or floor effects and performance may be inherently non-linear: for example, improving from 85% to 95% may be more difficult and require more effort than improving from 55% to 65%. As such, analysis of these indicators is not always straightforward and standard linear analysis may be problematic. We present the most common approach to dealing with this problem: a logit transformation of the score, following which standard linear analysis can be conducted on the transformed score. We also demonstrate how estimates can be back-transformed to percentages for easier communication of findings. In this paper we discuss the benefits of this method, algebraically describe the relevant steps in the transformation process, provide guidance on interpretation and provide a tool for analysis.

Fish is crucial to food and nutrition security in Solomon Islands, and demand is expected to increase due to a growing population. However, it is projected that current capture fisheries production will not meet this growing demand. Aquaculture has the potential to mitigate the capture fishery shortfall, and the Government of Solomon Islands is prioritizing aquaculture as a solution to meet future food and income needs. Aquaculture in Solomon Islands is still in early development. Mozambique tilapia (Oreochromis mossambicus) is farmed for household consumption, but its prolific reproductive rate and resulting slow growth limit its potential as a commercial aquaculture species. More productive fish species that are not indigenous to Solomon Islands but are successfully farmed overseas could be introduced; however, such a decision needs to take into account the potential ecological or social impacts. For land-based pond aquaculture, the only indigenous species that has been farmed extensively elsewhere is milkfish (Chanos chanos). This report presents a feasibility assessment for milkfish farming in Solomon Islands. It synthesizes the current knowledge about milkfish farming and presents results of a 4-year study on the potential for milkfish aquaculture in Solomon Islands. Australian Centre for International Agricultural Research Developing inland aquaculture in Solomon Islands

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