Showing papers by "University of London published in 2004"
TL;DR: This paper provides updated and extended guidance, based on the 2010 version of the CONSORT statement and the 2008consORT statement for the reporting of abstracts, on how to report the results of cluster randomised controlled trials.
Abstract: The Consolidated Standards of Reporting Trials (CONSORT) statement was developed to improve the reporting of randomised controlled trials. It was initially published in 1996 and focused on the reporting of parallel group randomised controlled trials. The statement was revised in 2001, with a further update in 2010. A separate CONSORT statement for the reporting of abstracts was published in 2008. In earlier papers we considered the implications of the 2001 version of the CONSORT statement for the reporting of cluster randomised trial. In this paper we provide updated and extended guidance, based on the 2010 version of the CONSORT statement and the 2008 CONSORT statement for the reporting of abstracts.
2,655 citations
TL;DR: Exemestane therapy after two to three years ofTamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxIFen treatment.
Abstract: background Tamoxifen, taken for five years, is the standard adjuvant treatment for postmenopausal women with primary, estrogen-receptor–positive breast cancer. Despite this treatment, however, some patients have a relapse. methods We conducted a double-blind, randomized trial to test whether, after two to three years of tamoxifen therapy, switching to exemestane was more effective than continuing tamoxifen therapy for the remainder of the five years of treatment. The primary end point was disease-free survival. results Of the 4742 patients enrolled, 2362 were randomly assigned to switch to exemestane, and 2380 to continue to receive tamoxifen. After a median follow-up of 30.6 months, 449 first events (local or metastatic recurrence, contralateral breast cancer, or death) were reported — 183 in the exemestane group and 266 in the tamoxifen group. The unadjusted hazard ratio in the exemestane group as compared with the tamoxifen group was 0.68 (95 percent confidence interval, 0.56 to 0.82; P<0.001 by the log-rank test), representing a 32 percent reduction in risk and corresponding to an absolute benefit in terms of disease-free survival of 4.7 percent (95 percent confidence interval, 2.6 to 6.8) at three years after randomization. Overall survival was not significantly different in the two groups, with 93 deaths occurring in the exemestane group and 106 in the tamoxifen group. Severe toxic effects of exemestane were rare. Contralateral breast cancer occurred in 20 patients in the tamoxifen group and 9 in the exemestane group (P=0.04). conclusions Exemestane therapy after two to three years of tamoxifen therapy significantly improved disease-free survival as compared with the standard five years of tamoxifen treatment.
1,731 citations
TL;DR: In this article, a load theory of attention in which distractor rejection depends on the level and type of load involved in current processing was tested, and it was shown that whereas high perceptual load reduces distractor interference, working memory load or dual-task coordination load increases distractor interferences.
Abstract: A load theory of attention in which distractor rejection depends on the level and type of load involved in current processing was tested. A series of experiments demonstrates that whereas high perceptual load reduces distractor interference, working memory load or dual-task coordination load increases distractor interference. These findings suggest 2 selective attention mechanisms: a perceptual selection mechanism serving to reduce distractor perception in situations of high perceptual load that exhaust perceptual capacity in processing relevant stimuli and a cognitive control mechanism that reduces interference from perceived distractors as long as cognitive control functions are available to maintain current priorities (low cognitive load). This theory resolves the long-standing early versus late selection debate and clarifies the role of cognitive control in selective attention.
1,420 citations
TL;DR: It is concluded that more detailed research is needed to fractionate the executive system in autism by assessing a wide range of executive functions as well as their neuroanatomical correlates in the same individuals across the lifespan.
1,242 citations
TL;DR: Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent, and the safest or least expensive antiemetic interventions should be used first.
Abstract: background Untreated, one third of patients who undergo surgery will have postoperative nausea and vomiting. Although many trials have been conducted, the relative benefits of prophylactic antiemetic interventions given alone or in combination remain unknown. methods We enrolled 5199 patients at high risk for postoperative nausea and vomiting in a randomized, controlled trial of factorial design that was powered to evaluate interactions among as many as three antiemetic interventions. Of these patients, 4123 were randomly assigned to 1 of 64 possible combinations of six prophylactic interventions: 4 mg of ondansetron or no ondansetron; 4 mg of dexamethasone or no dexamethasone; 1.25 mg of droperidol or no droperidol; propofol or a volatile anesthetic; nitrogen or nitrous oxide; and remifentanil or fentanyl. The remaining patients were randomly assigned with respect to the first four interventions. The primary outcome was nausea and vomiting within 24 hours after surgery, which was evaluated blindly. results Ondansetron, dexamethasone, and droperidol each reduced the risk of postoperative nausea and vomiting by about 26 percent. Propofol reduced the risk by 19 percent, and nitrogen by 12 percent; the risk reduction with both of these agents (i.e., total intravenous anesthesia) was thus similar to that observed with each of the antiemetics. All the interventions acted independently of one another and independently of the patients’ baseline risk. Consequently, the relative risks associated with the combined interventions could be estimated by multiplying the relative risks associated with each intervention. Absolute risk reduction, though, was a critical function of patients’ baseline risk. conclusions Because antiemetic interventions are similarly effective and act independently, the safest or least expensive should be used first. Prophylaxis is rarely warranted in low-risk patients, moderate-risk patients may benefit from a single intervention, and multiple interventions should be reserved for high-risk patients.
1,210 citations
TL;DR: The findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events, by contrast with influenza, tetanus, and pneumococcal vaccinations, which do not produce a detectable increase inThe risk ofascular events.
Abstract: BACKGROUND: There is evidence that chronic inflammation may promote atherosclerotic disease. We tested the hypothesis that acute infection and vaccination increase the short-term risk of vascular events. METHODS: We undertook within-person comparisons, using the case-series method, to study the risks of myocardial infarction and stroke after common vaccinations and naturally occurring infections. The study was based on the United Kingdom General Practice Research Database, which contains computerized medical records of more than 5 million patients. RESULTS: A total of 20,486 persons with a first myocardial infarction and 19,063 persons with a first stroke who received influenza vaccine were included in the analysis. There was no increase in the risk of myocardial infarction or stroke in the period after influenza, tetanus, or pneumococcal vaccination. However, the risks of both events were substantially higher after a diagnosis of systemic respiratory tract infection and were highest during the first three days (incidence ratio for myocardial infarction, 4.95; 95 percent confidence interval, 4.43 to 5.53; incidence ratio for stroke, 3.19; 95 percent confidence interval, 2.81 to 3.62). The risks then gradually fell during the following weeks. The risks were raised significantly but to a lesser degree after a diagnosis of urinary tract infection. The findings for recurrent myocardial infarctions and stroke were similar to those for first events. CONCLUSIONS: Our findings provide support for the concept that acute infections are associated with a transient increase in the risk of vascular events. By contrast, influenza, tetanus, and pneumococcal vaccinations do not produce a detectable increase in the risk of vascular events.
1,161 citations
TL;DR: In this article, the small subunit ribosomal RNA and the circumsporozoite protein genes were sequenced for eight isolates that had been microscopically identified as P knowlesi by microscopy.
1,100 citations
Journal Article•
TL;DR: Real-time RT-PCR remains a research tool, and it is important to recognize the considerable pitfalls associated with transcriptome analysis, with the successful application of RTPCR depending on careful experimental design, application, and validation.
Abstract: Polymerase chain reaction (PCR)-based assays can target either DNA (the genome) or RNA (the transcriptome). Targeting the genome generates robust data that are informative and, most importantly, generally applicable. This is because the information contained within the genome is context-independent; i.e., generally, every normal cell contains the same DNA sequence--the same mutations and polymorphisms. The transcriptome, on the other hand, is context-dependent; i.e., the mRNA complement and level varies with physiology, pathology, or development. This makes the information contained within the transcriptome intrinsically flexible and variable. If this variability is combined with the technical limitations inherent in any reverse-transcription (RT)-PCR assay, it can be difficult to achieve not just a technically accurate but a biologically relevant result. Template quality, operator variability, the RT step itself, and subjectivity in data analysis and reporting are just a few technical aspects that make real-time RT-PCR appear to be a fragile assay that makes accurate data interpretation difficult. There can be little doubt that in the future, transcriptome-based analysis will become a routine technique. However, for the time being it remains a research tool, and it is important to recognize the considerable pitfalls associated with transcriptome analysis, with the successful application of RTPCR depending on careful experimental design, application, and validation.
1,073 citations
TL;DR: The findings raise the possibility that this infection was transfusion transmitted in the recipient of Variant Creutzfeldt-Jakob disease, and the age of the patient was well beyond that of most vCJD cases, so the chance of observing a case of vC JD in a recipient in the absence of transfusions transmitted infection is about 1 in 15000 to 1 in 30000.
1,066 citations
TL;DR: Transmission electron microscopy analysis was performed at the microscopy facility of the Institute of Biomedical Problems and was cofinanced by CNRS, R=gion Alsace, Louis Pasteur University, and the Association de la Recherche pour le Cancer.
Abstract: [*] Dipl.-Chem. D. Pantarotto, Prof. M. Prato Dipartimento di Scienze Farmaceutiche Universit di Trieste 34127 Trieste (Italy) Fax: (+39)040-5272 E-mail: prato@univ.trieste.it Dipl.-Chem. R. Singh, Dipl.-Chem. D. McCarthy, Dr. K. Kostarelos Centre for Drug Delivery Research and Electron Microscopy Unit The School of Pharmacy University of London London WC1N 1AX (United Kingdom) Fax: (+39)207-7535942 E-mail: kostas.kostarelos@ulsop.ac.uk Dipl.-Chem. D. Pantarotto, Dr. J.-P. Briand, Dr. A. Bianco Institut de Biologie Mol=culaire et Cellulaire UPR9021 CNRS Immunologie et Chimie Th=rapeutiques 67084 Strasbourg (France) Fax: (+33)388-610-680 E-mail: A.Bianco@ibmc.u-strasbg.fr Dr. M. Erhardt Institut de Biologie Mol=culaire des Plantes 67084 Strasbourg (France) [**] This work was supported by the Centre National de la Recherche Scientifique (CNRS), Universit di Trieste, and Ministero dell’Istruzione, dell’ Universit e della Ricerca (MIUR; cofin 2002, prot. 2002032171). Transmission electron microscopy (TEM) analysis was performed at the microscopy facility of the Institute of Biomedical Problems and was cofinanced by CNRS, R=gion Alsace, Louis Pasteur University, and the Association de la Recherche pour le Cancer. The authors wish to acknowledge C. D. Partidos for helpful and stimulating discussions. We thank Mr. Claudio Gamboz (Centro Servizi Polivalenti di Ateneo (CSPA), Universit di Trieste) for his great help with the TEM measurements. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Communications
1,047 citations
TL;DR: The forthcoming Ministerial Summit on Health Research seeks to help define a learning agenda for health systems, so that by 2015, substantial progress will have been made to reducing the system constraints to achieving the MDGs.
TL;DR: Although 'diseases of affluence' are increasing in developing countries, infectious diseases still impose the greatest health burden and simple, accurate and stable diagnostic tests are essential to combat these diseases.
Abstract: Although 'diseases of affluence', such as diabetes and cardiovascular disease, are increasing in developing countries, infectious diseases still impose the greatest health burden. Annually, just under 1 million people die from malaria, 4.3 million from acute respiratory infections, 2.9 million from enteric infections and 5 million from AIDS and tuberculosis. Other sexually transmitted infections and tropical parasitic infections are responsible for hundreds of thousands of deaths and an enormous burden of morbidity. More than 95% of these deaths occur in developing countries. Simple, accurate and stable diagnostic tests are essential to combat these diseases, but are usually unavailable or inaccessible to those who need them.
TL;DR: The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation, and recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities.
Abstract: Anthropogenic land use changes drive a range of infectious disease outbreaks and emergence events and modify the transmission of endemic infections. These drivers include agricultural encroachment, deforestation, road construction, dam building, irrigation, wetland modification, mining, the concentration or expansion of urban environments, coastal zone degradation, and other activities. These changes in turn cause a cascade of factors that exacerbate infectious disease emergence, such as forest fragmentation, disease introduction, pollution, poverty, and human migration. The Working Group on Land Use Change and Disease Emergence grew out of a special colloquium that convened international experts in infectious diseases, ecology, and environmental health to assess the current state of knowledge and to develop recommendations for addressing these environmental health challenges. The group established a systems model approach and priority lists of infectious diseases affected by ecologic degradation. Policy-relevant levels of the model include specific health risk factors, landscape or habitat change, and institutional (economic and behavioral) levels. The group recommended creating Centers of Excellence in Ecology and Health Research and Training, based at regional universities and/or research institutes with close links to the surrounding communities. The centers' objectives would be 3-fold: a) to provide information to local communities about the links between environmental change and public health; b) to facilitate fully interdisciplinary research from a variety of natural, social, and health sciences and train professionals who can conduct interdisciplinary research; and c) to engage in science-based communication and assessment for policy making toward sustainable health and ecosystems.
TL;DR: Different in vitro and in vivo screens for antimalarial drug discovery are suggested and a streamlined process for evaluating new compounds on the path from drug discovery to development is recommended.
Abstract: Increased efforts in antimalarial drug discovery are urgently needed. The goal must be to develop safe and affordable new drugs to counter the spread of malaria parasites that are resistant to existing agents. Drug efficacy, pharmacology and toxicity are important parameters in the selection of compounds for development, yet little attempt has been made to review and standardize antimalarial drug-efficacy screens. Here, we suggest different in vitro and in vivo screens for antimalarial drug discovery and recommend a streamlined process for evaluating new compounds on the path from drug discovery to development.
TL;DR: The model can be estimated in any software package that estimates GLMs with user‐defined link functions and utilizes the theory of generalized linear models for assessing goodness‐of‐fit and studying regression diagnostics.
Abstract: Four approaches to estimating a regression model for relative survival using the method of maximum likelihood are described and compared. The underlying model is an additive hazards model where the total hazard is written as the sum of the known baseline hazard and the excess hazard associated with a diagnosis of cancer. The excess hazards are assumed to be constant within pre-specified bands of follow-up. The likelihood can be maximized directly or in the framework of generalized linear models. Minor differences exist due to, for example, the way the data are presented (individual, aggregated or grouped), and in some assumptions (e.g. distributional assumptions). The four approaches are applied to two real data sets and produce very similar estimates even when the assumption of proportional excess hazards is violated. The choice of approach to use in practice can, therefore, be guided by ease of use and availability of software. We recommend using a generalized linear model with a Poisson error structure based on collapsed data using exact survival times. The model can be estimated in any software package that estimates GLMs with user-defined link functions (including SAS, Stata, S-plus, and R) and utilizes the theory of generalized linear models for assessing goodness-of-fit and studying regression diagnostics.
TL;DR: In this paper, a critical review assesses whether evaluation studies can answer three key questions about behaviour change interventions: "Do they work?" "How well" and "How do they work?".
Abstract: This critical review assesses whether evaluation studies can answer three key questions about behaviour change interventions: ‘Do they work? How well do they work? How do they work?’ Reviews of intervention evaluations are examined, particularly those addressing decreasing unprotected sexual intercourse and smoking. Selection of outcome measures and calculation of effect sizes are discussed. The article also considers the extent to which evaluation reports specify (i) discrete intervention techniques and (ii) psychological mechanisms that account for observed behavioural change. It is concluded that intervention descriptions are often not specific about the techniques employed and that there is no clear correspondence between theoretical inspiration and adoption of particular change techniques. The review calls for experimental testing of specific theory-based techniques, separately and in combination.
TL;DR: A review of studies of executive function in autism spectrum disorder is presented in this paper, where the focus is on planning, inhibition, shifting set, generativity, and action monitoring.
TL;DR: C cervical screening has prevented an epidemic that would have killed about one in 65 of all British women born since 1950 and culminated in about 6000 deaths per year in this country, at a cost per life saved of about pound 36000.
TL;DR: It is proposed that variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution and that this has resulted in a genetically diverse pathogenic species.
Abstract: Burkholderia pseudomallei is a recognized biothreat agent and the causative agent of melioidosis. This Gram-negative bacterium exists as a soil saprophyte in melioidosis-endemic areas of the world and accounts for 20% of community-acquired septicaemias in northeastern Thailand where half of those affected die. Here we report the complete genome of B. pseudomallei, which is composed of two chromosomes of 4.07 megabase pairs and 3.17 megabase pairs, showing significant functional partitioning of genes between them. The large chromosome encodes many of the core functions associated with central metabolism and cell growth, whereas the small chromosome carries more accessory functions associated with adaptation and survival in different niches. Genomic comparisons with closely and more distantly related bacteria revealed a greater level of gene order conservation and a greater number of orthologous genes on the large chromosome, suggesting that the two replicons have distinct evolutionary origins. A striking feature of the genome was the presence of 16 genomic islands (GIs) that together made up 6.1% of the genome. Further analysis revealed these islands to be variably present in a collection of invasive and soil isolates but entirely absent from the clonally related organism B. mallei. We propose that variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution and that this has resulted in a genetically diverse pathogenic species.
TL;DR: MTR is affected by myelin content in MS white matter, and the extent of gliosis was detected using morphometric and digital imaging techniques.
Abstract: Several quantitative magnetic resonance (MR) measures are used to investigate multiple sclerosis (MS) in vivo. Precise quantitative investigation of the histopathological correlates of such measures has, to date, been limited. This study investigates the relationship of quantitative measures of myelin content, axonal density, and gliosis with quantitative MR measures in postmortem (PM) MS tissue. MR imaging (MRI) was performed on a 1.5T scanner and T1-relaxation time (T1-RT) and magnetization transfer ratio (MTR) maps were acquired in fresh PM brain of 20 MS subjects. Myelin content, axonal counts, and the extent of gliosis all were quantified using morphometric and digital imaging techniques. MRI and pathological data were in most cases coregistered using stereotactic navigation. Using multiple regression analysis, we detected significant correlations between myelin content (Tr(myelin)) and MTR (r = -0.84, p < 0.001) and myelin content and axonal count (-0.80, p < 0.001); MTR correlated with T1-RT (r = -0.79, p < 0.001). No association was detected between the extent of gliosis and either MR measure. MTR was significantly higher in remyelinated than demyelinated lesions (means: 30.0 [standard deviation, 2.9] vs 23.8 [standard deviation, 4.3], p = 0.008). In conclusion, MTR is affected by myelin content in MS white matter.
TL;DR: In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults, with a failure to treat alternative causes of severe infection.
Abstract: OBJECTIVE: To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission. DESIGN: Prospective observational study of children and adults over the course a year. SETTING: 10 hospitals in north east Tanzania. PARTICIPANTS: 17,313 patients were admitted to hospital; of these 4474 (2851 children aged under 5 years) fulfilled criteria for severe disease. MAIN OUTCOME MEASURE: Details of the treatment given and outcome. Altitudes of residence (a proxy for transmission intensity) measured with a global positioning system. RESULTS: Blood film microscopy showed that 2062 (46.1%) of people treated for malaria had Plasmodium falciparum (slide positive). The proportion of slide positive cases fell with increasing age and increasing altitude of residence. Among 1086 patients aged > or = 5 years who lived above 600 metres, only 338 (31.1%) were slide positive, while in children < 5 years living in areas of intense transmission (< 600 metres) most (958/1392, 68.8%) were slide positive. Among 2375 people who were slide negative, 1571 (66.1%) were not treated with antibiotics and of those, 120 (7.6%) died. The case fatality in slide negative patients was higher (292/2412, 12.1%) than for slide positive patients (142/2062, 6.9%) (P < 0.001). Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children. CONCLUSIONS: In Tanzania, malaria is commonly overdiagnosed in people presenting with severe febrile illness, especially in those living in areas with low to moderate transmission and in adults. This is associated with a failure to treat alternative causes of severe infection. Diagnosis needs to be improved and syndromic treatment considered. Routine hospital data may overestimate mortality from malaria by over twofold.
TL;DR: Evidence is provided that the human disgust emotion may be an evolved response to objects in the environment that represent threats of infectious disease.
Abstract: Disgust is a powerful human emotion that has been little studied until recently. Current theories do not coherently explain the purpose of disgust, nor why a wide range of stimuli can provoke a similar emotional response. Over 40 000 individuals completed a web-based survey using photo stimuli. Images of objects holding a potential disease threat were reported as significantly more disgusting than similar images with little or no disease relevance. This pattern of response was found across all regions of the world. Females reported higher disgust sensitivity than males; there was a constant decline in disgust sensitivity over the life course; and the bodily fluids of strangers were found more disgusting than those of close relatives. These data provide evidence that the human disgust emotion may be an evolved response to objects in the environment that represent threats of infectious disease.
TL;DR: The potential for innate immune mechanisms directed against Plasmodium parasites both to contribute to protection from malaria and to modulate adaptive immune responses is considered.
Abstract: Malaria is a major cause of disease and death in tropical countries. A safe and effective vaccine is essential to achieve significant and sustained reductions in malaria-related morbidity and mortality. Driven by this need, research on the immunology of malaria has tended to focus on adaptive immunity. The potential for innate immune mechanisms to provide rapid protection against malaria has been largely neglected. On the basis of data from animal models, and clinical and epidemiological studies, this review considers the potential for innate immune mechanisms directed against Plasmodium parasites both to contribute to protection from malaria and to modulate adaptive immune responses.
TL;DR: Analysis of longitudinal data from the first two cohorts showed that long-term outcomes for adolescents with conduct problems were closely similar, providing evidence that observed trends were unaffected by possible changes in reporting thresholds.
Abstract: BACKGROUND:
Existing evidence points to a substantial rise in psychosocial disorders affecting young people over the past 50 years (Rutter & Smith, 1995). However, there are major methodological challenges in providing conclusive answers about secular changes in disorder. Comparisons of rates of disorder at different time points are often affected by changes in diagnostic criteria, differences in assessment methods, and changes in official reporting practices. Few studies have examined this issue using the same instruments at each time point.
METHODS:
The current study assessed the extent to which conduct, hyperactive and emotional problems have become more common over a 25-year period in three general population samples of UK adolescents. The samples used in this study were the adolescent sweeps of the National Child Development Study and the 1970 Birth Cohort Study, and the 1999 British Child and Adolescent Mental Health Survey. Comparable questionnaires were completed by parents of 15-16-year-olds at each time point (1974, 1986, and 1999).
RESULTS AND CONCLUSIONS:
Results showed a substantial increase in adolescent conduct problems over the 25-year study period that has affected males and females, all social classes and all family types. There was also evidence for a recent rise in emotional problems, but mixed evidence in relation to rates of hyperactive behaviour. Further analyses using longitudinal data from the first two cohorts showed that long-term outcomes for adolescents with conduct problems were closely similar. This provided evidence that observed trends were unaffected by possible changes in reporting thresholds.
TL;DR: It is shown that the Internet topology at the autonomous system (AS) level has a rich-club phenomenon, which is a simple qualitative way to differentiate between power law topologies and provides a criterion for new network models.
Abstract: We show that the Internet topology at the autonomous system (AS) level has a rich-club phenomenon. The rich nodes, which are a small number of nodes with large numbers of links, are very well connected to each other. The rich-club is a core tier that we measured using the rich-club connectivity and the node-node link distribution. We obtained this core tier without any heuristic assumption between the ASs. The rich-club phenomenon is a simple qualitative way to differentiate between power law topologies and provides a criterion for new network models. To show this, we compared the measured rich-club of the AS graph with networks obtained using the Baraba/spl acute/si-Albert (BA) scale-free network model, the Fitness BA model and the Inet-3.0 model.
TL;DR: In this article, the authors synthesize the existing evaluation research on whole-school programs to determine the overall effectiveness of this approach and find that the majority of programs evaluated to date have yielded nonsignificant outcomes on measures of self-re- ported victimization and bullying, and only a small number have yielded positive outcomes.
Abstract: Bullying is a serious problem in schools, and school authorities need effective solutions to resolve this problem. There is growing interest in the whole- school approach to bullying. Whole-school programs have multiple components that operate simultaneously at different levels in the school community. This ar- ticle synthesizes the existing evaluation research on whole-school programs to determine the overall effectiveness of this approach. The majority of programs evaluated to date have yielded nonsignificant outcomes on measures of self-re- ported victimization and bullying, and only a small number have yielded positive outcomes. On the whole, programs in which implementation was systematically monitored tended to be more effective than programs without any monitoring.
TL;DR: It is demonstrated that inhibition of a specific glycine receptor subtype (GlyR α3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization and may provide a previously unrecognized molecular target in pain therapy.
Abstract: Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR alpha3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR alpha3 is distinctly expressed in superficial layers of the spinal cord dorsal horn. Mice deficient in GlyR alpha3 not only lack the inhibition of glycinergic neurotransmission by PGE2 seen in wild-type mice but also show a reduction in pain sensitization induced by spinal PGE2 injection or peripheral inflammation. Thus, GlyR alpha3 may provide a previously unrecognized molecular target in pain therapy.
TL;DR: A review and meta-analysis of published reports of occupational epidemiologic studies providing a more secure basis for risk assessment than was previously available and limited information on total dust exposure did not suggest that dust exposure was an important confounder or modified the effect.
Abstract: Typical polycyclic aromatic hydrocarbon mixtures are established lung carcinogens, but the quantitative exposure-response relationship is less clear. To clarify this relationship we conducted a review and meta-analysis of published reports of occupational epidemiologic studies. Thirty-nine cohorts were included. The average estimated unit relative risk (URR) at 100 Mu g/m (superscript)3(/superscript) years benzo[a]pyrene was 1.20 [95% confidence interval (CI), 1.11-1.29] and was not sensitive to particular studies or analytic methods. However, the URR varied by industry. The estimated means in coke ovens, gasworks, and aluminum production works were similar (1.15-1.17). Average URRs in other industries were higher but imprecisely estimated, with those for asphalt (17.5; CI, 4.21-72.78) and chimney sweeps (16.2; CI, 1.64-160.7) significantly higher than the three above. There was no statistically significant variation of URRs within industry or in relation to study design (including whether adjusted for smoking), or source of exposure information. Limited information on total dust exposure did not suggest that dust exposure was an important confounder or modified the effect. These results provide a more secure basis for risk assessment than was previously available.
TL;DR: Six overlapping mechanisms that could be responsible for change are proposed: reduced vigilance; reduced avoidance; reduced self-focused attention; mindfulness; increased attentional control; increased self-esteem.
TL;DR: Cosegregation of parkinsonism and POLG mutations in seven families suggests that when defective, this gene can underlie mendelian transmission of Parkinsonism.