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It is well known that supplemental oxygen used to treat preterm infants in respiratory distress is associated with permanently disrupting lung development and the host response to influenza A virus (IAV). However, many infants who go home with normally functioning lungs are also at risk for hyperreactivity after a respiratory viral infection. We recently reported a new, low-dose hyperoxia mouse model (40% for 8 days; 40×8) that causes a transient change in lung function that resolves, rendering 40×8 adult animals functionally indistinguishable from room air controls. Here we report that when infected with IAV, 40×8 mice display an early transient activation of TGFβ signaling and later airway hyperreactivity associated with peribronchial inflammation (profibrotic macrophages) and fibrosis compared with infected room air controls, suggesting neonatal oxygen induced hidden molecular changes that prime the lung for hyperreactive airways disease. Although searching for potential activators of TGFβ signaling, we discovered that thrombospondin-1 (TSP-1) is elevated in naïve 40×8 mice compared with controls and localized to lung megakaryocytes and platelets before and during IAV infection. Elevated TSP-1 was also identified in human autopsy samples of former preterm infants with bronchopulmonary dysplasia. These findings reveal how low doses of oxygen that do not durably change lung function may prime it for hyperreactive airways disease by changing expression of genes, such as TSP-1, thus helping to explain why former preterm infants who have normal lung function are susceptible to airway obstruction and increased morbidity after viral infection.

Ataxia-telangiectasia (A-T), caused by mutations in the A-T mutated ( ATM) gene, is a neurodegenerative disorder affecting ∼1 in 40,000–100,000 children. Recurrent respiratory infections are a common and challenging comorbidity, often leading to the development of bronchiectasis in individuals with A-T. The role of ATM in development of immune memory in response to recurrent respiratory viral infections is not well understood. Here, we infect wild-type (WT) and Atm-null mice with influenza A virus (IAV; HKx31, H3N2) and interrogate the immune memory with secondary infections designed to challenge the B cell memory response with homologous infection (HKx31) and the T cell memory response with heterologous infection (PR8, H1N1). Although Atm-null mice survived primary and secondary infections, they lost more weight than WT mice during secondary infections. This enhanced morbidity to secondary infections was not attributed to failure to effectively clear virus during the primary IAV infection. Instead, Atm-null mice developed persistent peribronchial inflammation, characterized in part by clusters of B220+B cells. Additionally, levels of select serum antibodies to hemagglutinin-specific IAV were significantly lower in Atm-null than WT mice. These findings reveal that Atm is required to mount a proper memory response to a primary IAV infection, implying that vaccination of children with A-T by itself may not be sufficiently protective against respiratory viral infections.

The Paris Climate Agreement aims to hold global-mean temperature well below 2 °C and to pursue efforts to limit it to 1.5 °C above preindustrial levels. While it is recognized that there are benefits for human health in limiting global warming to 1.5 °C, the magnitude with which those societal benefits will be accrued remains unquantified. Crucial to public health preparedness and response is the understanding and quantification of such impacts at different levels of warming. Using dengue in Latin America as a study case, a climate-driven dengue generalized additive mixed model was developed to predict global warming impacts using five different global circulation models, all scaled to represent multiple global-mean temperature assumptions. We show that policies to limit global warming to 2 °C could reduce dengue cases by about 2.8 (0.8-7.4) million cases per year by the end of the century compared with a no-policy scenario that warms by 3.7 °C. Limiting warming further to 1.5 °C produces an additional drop in cases of about 0.5 (0.2-1.1) million per year. Furthermore, we found that by limiting global warming we can limit the expansion of the disease toward areas where incidence is currently low. We anticipate our study to be a starting point for more comprehensive studies incorporating socioeconomic scenarios and how they may further impact dengue incidence. Our results demonstrate that although future climate change may amplify dengue transmission in the region, impacts may be avoided by constraining the level of warming.

Climate change is projected to have significant effects on the distribution of species globally, but research into the implications in parts of Africa has been limited. Using species distribution modelling, this study models climate change-related risks to the terrestrial biodiversity (birds, mammals, reptiles, amphibians and plants) of Kenya’s economically-important and ecologically diverse Tana River Basin. Large reductions in species richness are projected with just 2°C warming (relative to preindustrial levels) with birds and plants seeing the greatest impact. Potential climate refugia for biodiversity are identified within the basin, but often overlap with areas already converted to agriculture or set aside for agricultural expansion, and the majority are outside protected areas. Similarly, some protected areas contain no projected refugia at higher levels of global warming, showing they may be insufficient to protect the basin’s biodiversity as climate changes. However, risks to biodiversity are much smaller if the Paris Agreement’s goal of limiting global warming to ‘well below 2°C’ warming, rather than 2°C only, is met. The potential for refugia for plants and animals decreases strongly with warming. For example, 82% of the basin remaining climatically suitable for at least 75% of the plants currently present at 1.5°C warming, as compared with 23% at 2°C and 3% at 4.5°C. This research provides the first assessment of the combined effects of development plans and climate change on biodiversity of the Tana River Basin, including identifying potential areas for restoration, and contributes to a greater understanding of biodiversity protection and adaptation options in Kenya.

Background This report was produced for the Canadian Task Force on Preventive Health Care to provide guidelines on screening for abdominal aortic aneurysm (AAA) with ultrasound scan. Purpose The aim of this systematic review is to examine the evidence on benefits and harms of AAA screening. Search strategy This systematic review considered studies from the most recent United States Preventive Services Task Force review on AAA screening and passed through the screening process with citations identified in our search up to April 2015 (PROSPERO Registration #CRD42015019047). Results For benefits of one-time AAA screening in men compared with controls, pooled analyses from four randomized controlled trials with moderate quality evidence showed significant reductions in AAA-related mortality and AAA rupture rate up to 13 to 15 years of follow-up with 42% reduction (risk ratio [RR], 0.58; 95% confidence interval [CI], 0.39-0.88; number needed to screen = 212) and 38% reduction (RR, 0.62; 95% CI, 0.45-0.86; number needed to screen = 200), respectively. The effect of on all-cause mortality was marginally significant for longer follow-up. The Chichester trial examined the benefits of one-time AAA screening in women and found no significant differences between screening and control arms for up to 10 years of follow-up (RR, 0.88; 95% CI, 0.72-1.07). For consequences of one-time AAA screening in men compared with controls, there was a significant increase in the total number of AAA-related procedures over a follow-up of 13 to 15 years (2.16 times more likely) compared with controls. For harms of one-time AAA screening, no significant differences were observed in 30-day postoperative mortality for elective and emergency operations with compared control groups. Evidence from the Multicenter Aneurysm Screening Study trial using 13-year follow-up data showed that one-time AAA screening with ultrasound scan was potentially associated with an overdiagnosis of 45% (95% CI, 42%-47%) among screen-detected men. Conclusions Population-based screening for AAA with ultrasound scan in asymptomatic men aged 65 years and older showed statistically significant reductions in AAA-related mortality and rupture and, hence, avoids unnecessary AAA-related deaths. The current evidence showed no benefit of one-time AAA screening in woman. Limited evidence is available on the benefits of repeat AAA screening and targeted screening approaches based on risk factors for AAA. Future research should explore the differential benefits of AAA screening based on risk factors that increase risk for developing AAA.

To evaluate the effectiveness of colorectal cancer (CRC) screening in asymptomatic adults. A search was conducted of the Medline, Embase, and the Cochrane Library databases. A targeted search of PubMed was conducted for on-topic randomized controlled trials (RCTs). Meta-analysis across 4 RCTs for guaiac fecal occult blood testing (gFOBT) and flexible sigmoidoscopy (FS) screening showed a reduction of 18% (risk ratio [RR], 0.82; 95% CI [CI], 0.73-0.92) and 26% (RR, 0.74; 95% CI, 0.67-0.83) in CRC mortality for the screening group compared to controls, respectively. The number needed to screen (NNS) were 377 (95% CI, 249-887) and 864 (95% CI, 672-1266) for gFOBT and FS screening, respectively. A reduction of 8% and 27% in incidence of late-stage CRC was also observed for gFOBT and FS screening, respectively, but both had no significant effect on all-cause mortality. A single RCT found that screening with immunochemical fecal occult blood test (iFOBT) had no significant impact on CRC mortality (RR, 0.88; 95% CI, 0.72-1.07). Screening with FS has potential harms such as perforation, major and minor bleeding, and death from the procedure or from follow-up colonoscopy. gFOBT and FS screening reduce CRC mortality and incidence of late-stage disease. The absolute effect and NNS were much more favorable for older adults (≥ 60 years), suggesting that a targeted screening approach may avoid exposing younger adults to the harms of CRC screening, from which they are unlikely to derive any significant benefit. Although there is insufficient RCT evidence on the impact of iFOBT on mortality outcomes. compared to gFOBT, this test showed higher sensitivity and comparable specificity, indicating the need to update and reevaluate the evidence in light of future high-quality research. The protocol for this systematic review have been published with PROSPERO 2014: CRD42014009777.

Human SCGB1A1 protein has been shown to be significantly reduced in BAL, sputum, and serum from humans with asthma as compared with healthy individuals. However, the mechanism of this reduction and its functional impact have not been entirely elucidated. By mining online datasets, we found that the mRNA of SCGB1A1 was significantly repressed in brushed human airway epithelial cells from individuals with asthma, and this repression appeared to be associated with reduced expression of FOXA2. Consistently, both Scgb1A1 and FoxA2 were downregulated in an ovalbumin-induced mouse model of asthma. Furthermore, compared with wild-type mice, Scgb1a1 knockout mice had increased airway hyperreactivity and inflammation when they were exposed to ovalbumin, confirming the antiinflammatory role of Scgb1a1 in protection against asthma phenotypes. To search for potential asthma-related stimuli of SCGB1A1 repression, we tested T-helper cell type 2 cytokines. Both IL-4 and IL-13 repressed epithelial expression of SCGB1A1 and FOXA2. Importantly, infection of epithelial cells with human rhinovirus similarly reduced expression of these two genes, which suggests that FOXA2 may be the common regulator of SCGB1A1. To establish the causal role of reduced FOXA2 in SCGB1A1 repression, we demonstrated that FOXA2 was required for SCGB1A1 expression at baseline. FOXA2 overexpression was sufficient to drive promoter activity and expression of SCGB1A1 and was also able to restore the repressed SCGB1A1 expression in IL-13–treated or rhinovirus-infected cells. Taken together, these findings suggest that low levels of epithelial SCGB1A1 in asthma are caused by reduced FOXA2 expression.

ObjectiveTo compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.DesignSystematic review with bayesian meta-analysis and network meta-analysis.Data sourcesMedline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.Eligibility criteria for study selectionExperimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.Results27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).ConclusionsUsing the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.Protocol registrationProspero CRD42017056389.

The United Nations' Paris Agreement includes the aim of pursuing efforts to limit global warming to only 1.5 °C above pre-industrial levels. However, it is not clear what the resulting climate would look like across the globe and over time. Here we show that trajectories towards a '1.5 °C warmer world' may result in vastly different outcomes at regional scales, owing to variations in the pace and location of climate change and their interactions with society's mitigation, adaptation and vulnerabilities to climate change. Pursuing policies that are considered to be consistent with the 1.5 °C aim will not completely remove the risk of global temperatures being much higher or of some regional extremes reaching dangerous levels for ecosystems and societies over the coming decades.

Tuberculosis has historically thrived in some of the most impoverished and marginalized populations; however, research into why lower socio-economic populations are at a higher risk of contracting diseases remains to be a topic lacking exploration. This is becoming a more prevalent issue as multi-drug resistant Tuberculosis (MDR-TB) and extensively-drug resistant Tuberculosis (XDR-TB) are on the rise in individuals living in poverty. The main research question that will be addressed in this paper is: How do socio-economic inequalities play a role in rising incidence rates of Tuberculosis in South Africa, and what are the future challenges in dealing with MDR-TB and XDR-TB? South Africa is a particularly important country of focus because of the racial inequity that has resulted in economic disparity, and a large percentage of the population living below the poverty line. Reviews of existing literature on Tuberculosis and correlations to poverty will be critically analyzed and applied, as well as the use of government documents, including Statistics South Africa, and the World Health Organization. A cross-cultural comparison of Canada and South Africa will be included to highlight the long-term effects of marginalization societal stratification. The health care policies dealing with treatment will also be discussed, with a specific focus on social epidemiology. This paper will argue that long-term racial inequalities in South Africa has result in economic disparity, through which Black Africans and people of Colour are more susceptible to contracting TB, MDR-TB, and insufficient health resources to support them.

Aim The evidence for self-management programmes in older adults varies in methodological approaches, and disease criteria. Using predetermined methodological criteria, we evaluated the effect of diabetes-specific self-management programme interventions in older adults. Methods The EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials databases were searched from January 1980 to November 2013, as were reference lists from systematic reviews, meta-analyses and clinical practice guidelines. A total of 13 trials met the selection criteria, which included 4517 older adult participants; 2361 participants randomized to a diabetes self-management programme and 2156 to usual care. Results The pooled effect on HbA1c was a reduction of –2 mmol/mol (–0.2%; 95% CI –0.3 to –0.1); tailored interventions [–3 mmol/mol (–0.2%; 95% CI –0.4 to –0.1)] or programmes with a psychological emphasis [–3 mmol/mol (–0.2; 95% CI –0.4 to –0.1)] were most effective. A pooled treatment effect on total cholesterol was a 5.81 mg/dl reduction (95% CI –10.33 to –1.29) and non-significant reductions in systolic and diastolic blood pressure. Conclusions Diabetes self-management programmes for older adults demonstrate a small reduction in HbA1c, lipids and blood pressure. These findings may be of greater clinical relevance when offered in conjunction with other therapies.

Background: Childhood obesity is a public health concern. One-third of North American children and youth are overweight or obese. We reviewed the evidence of behavioural and pharmacological weight-management interventions on body mass index (BMI), BMI z-score and the prevalence of overweight and obesity in children and youth. Methods: We updated the search of a previous review. We searched 4 databases up to August 2013. We included randomized trials of primary care–relevant behavioural (diet, exercise, lifestyle) and pharmacological (orlistat) interventions for treating overweight and obesity in children and youth aged 2–18 years if 6-month post-baseline data were provided for BMI, BMI z-score or prevalence of overweight and obesity. In addition, we examined secondary health outcomes such as lipid and glucose levels, blood pressure, quality of life and physical fitness. We included any study reporting harms. We performed meta-analyses when possible, and we examined the features of interventions that showed benefits. Results: Thirty-one studies (29 behavioural, 2 pharmacological and behavioural) were included. Both intervention types showed a significant effect on BMI or BMI z-score in favour of treatment (behavioural: standardized mean difference [SMD] –0.54, 95% confidence interval [CI] –0.73 to –0.36; orlistat plus behavioural: SMD –0.43, 95% CI –0.60 to –0.25). Studies reported no significant difference between groups in the likelihood of reduced prevalence of overweight or overweight and obesity. Pooled estimates for blood pressure and quality of life showed significant benefits in favour of treatment (systolic blood pressure mean difference [MD] –3.42, 95% CI –6.65 to –0.29; diastolic blood pressure MD –3.39, 95% CI –5.17 to –1.60; quality of life MD 2.10, 95% CI 0.60 to 3.60). Gastrointestinal difficulties were more common in youth taking orlistat than in the control group (risk ratio 3.77, 95% CI 2.56 to 5.55). We saw much variability across efficacious interventions. Interpretation: Low- to moderate-quality evidence suggests behavioural treatments are associated with a medium effect in terms of reduced BMI or BMI z-score compared with a small effect shown by combined pharmacological–behavioural interventions. Future research should evaluate active weight maintenance interventions in adolescents with longer follow-up and examine the effectiveness of combined pharmacological and behavioural interventions. Registration: PROSPERO no. CRD42012002754

Background The clinical specialty of obstetrics is under particular scrutiny with increasing litigation costs and unnecessary tests and procedures done in attempts to prevent litigation. We aimed to identify reports evaluating or comparing the effectiveness of medical liability reforms and quality improvement strategies in improving litigation-related outcomes in obstetrics. Methods We conducted a rapid scoping review with a 6-week timeline. MEDLINE, EMBASE, LexisNexis Academic, the Legal Scholarship Network, Justis, LegalTrac, QuickLaw, and HeinOnline were searched for publications in English from 2004 until June 2015. The selection criteria for screening were established a priori and pilot-tested. We included reports comparing or evaluating the impact of obstetrics-related medical liability reforms and quality improvement strategies on cost containment and litigation settlement across all countries. All levels of screening were done by two reviewers independently, and discrepancies were resolved by a third reviewer. In addition, two reviewers independently extracted relevant data using a pre-tested form, and discrepancies were resolved by a third reviewer. The results were summarized descriptively. Results The search resulted in 2729 citations, of which 14 reports met our eligibility criteria. Several initiatives for improving the medical malpractice litigation system were found, including no-fault approaches, patient safety policy initiatives, communication and resolution, caps on compensation and attorney fees, alternative payment system and liabilities, and limitations on litigation. Conclusions Only a few litigation policies in obstetrics were evaluated or compared. Included documents showed that initiatives to reduce medical malpractice litigation could be associated with a decrease in adverse and malpractice events. However, due to heterogeneous settings (e.g., economic structure, healthcare system) and variation in the outcomes reported, the advantages and disadvantages of initiatives may vary. Electronic supplementary material The online version of this article (10.1186/s13643-017-0569-5) contains supplementary material, which is available to authorized users.

BACKGROUND Existing guidelines on screening children less than 5 years of age for developmental delay vary. In this systematic review, we synthesized the literature on the effectiveness and harms of screening for developmental delay in asymptomatic children aged 1-4 years. METHODS We searched MEDLINE, Embase and PsychINFO for relevant articles published to June 16, 2015. We identified studies that included children aged 1-4 years who were not at high risk of developmental delay, screened in a primary care setting. Randomized trials and controlled cohort studies were considered for benefits (cognitive, academic and functional outcomes); no restrictions on study design were imposed for the review of harms. RESULTS Two studies were included. One used the Ages and Stages Questionnaire II for screening and reported significantly more referrals to early intervention in the intervention groups than in the control group (relative risk [RR] 1.95, 95% confidence interval [CI] 1.49-2.54, in the intervention group with office support and RR 1.71, 95% CI 1.30-2.25, in the intervention group without office support). The time to referral was 70% shorter in the intervention group with office support (rate ratio 0.30, 95% CI 0.19-0.48) and 64% shorter in the intervention group without office support (rate ratio 0.36, 95% CI 0.23-0.59), compared with the control group. The other study used the VroegTijdige Onderkenning Ontwikkelingsstoornissen Language Screening instrument to screen children aged 15 months at enrolment for language delay. It reported no differences between groups in academic performance outcomes at age 8 years. INTERPRETATION The evidence on screening for developmental delay in asymptomatic children aged 1-4 years is inconclusive. Further research with longer-term outcomes is needed to inform decisions about screening and screening intervals.

The effectiveness of treatments for mild cognitive impairment is uncertain. The aim of this review was to evaluate the effectiveness and harms of treatment for mild cognitive impairment in adults 65 years of age and older.We searched MEDLINE, Embase and Cochrane Central (December 2012-December 2014); citations from 2 systematic reviews were considered for inclusion. We included randomized controlled trials involving community-dwelling adults aged 65 years and older with a diagnosis of mild cognitive impairment. Studies reporting on cognition, function, behaviour, global status, mortality and adverse events for treatment with pharmacologic and nonpharmacologic interventions were included.Seventeen studies were included. Cholinesterase inhibitor studies evaluating cognition (Alzheimer's Disease Assessment Scale, cognition subscale) showed no difference between intervention and control groups (mean difference [MD] -0.33, 95% CI -0.73 to 0.06]; one behavioural study showed no significant effect on cognition (Alzheimer's Disease Assessment Scale, cognition subscale) for the intervention group when compared to controls (MD -0.60, (95% CI -1.44 to 0.24), and one study on vitamin E showed no difference between intervention and control groups (MD 0.85, 95% CI -0.32 to 2.02). With the Mini-Mental State Examination, cholinesterase inhibitors showed no difference between intervention and control groups (MD 0.17, 95% CI -0.13 to 0.47); behavioural studies showed a significant difference favouring intervention (MD 1.01, 95% CI 0.25 to 1.77), and studies of dietary supplements and/or vitamins showed no difference between intervention and control groups (MD 0.20, 95% CI -0.04 to 0.43). Pharmacologic studies showed no difference in serious adverse events (risk ratio 0.98, 95% CI 0.86 to 1.10). No serious adverse events were reported for nonpharmacologic interventions.Treatment of mild cognitive impairment with cholinesterase inhibitors showed no benefit when compared with a control group. A small cognitive benefit was observed using behavioural therapies when compared with the control group. However, the clinical significance of this small benefit remains uncertain. The current evidence does not support the use of cholinesterase inhibitors for treating mild cognitive impairment, and future high-quality research using a standardized approach is needed to affirm the finding of a small benefit on cognition that was observed for behavioural interventions.PROSPERO no. CRD42014015431.

e18678Background: The use of neoadjuvant chemotherapy (NAC) has allowed pathologic complete response (pCR) to become a predictive measure for breast cancer recurrence-free survival and overall surv...

Integrated assessment modelling aims to bring together information on emissions, atmospheric transport between sources and exposed areas or populations, criteria for environmental protection, and potential emission control measures and their costs, in order to explore effective abatement strategies. We describe the development of a new UK scale Integrated Assessment Model which can be used to investigate strategies for the attainment of national emission ceilings. The model optimises abatement strategies in relation to acidification, eutrophication, and/or human-exposure to particulate PM10, with reference to the deposition of sulphur and nitrogen (oxidised and reduced), and concentrations of primary and secondary particles. The model combines sector specific emissions, atmospheric transport and deposition, ecosystem specific critical load exceedances, and pollution abatement costs to determine optimised abatement strategies using benefit and, where applicable, recovery functions.

Planning effective strategies to combat air pollution in amajor city such as London requires integration ofinformation on atmospheric concentrations and where theyexceed prescribed air quality standards, detailed data onemissions and potential measures to reduce them includingcosts, and a good understanding of the relativecontributions of different emission sources to pollutantconcentrations plus the remaining background. The UrbanScale Integrated Assessment Model (USIAM) is designed as atool to integrate such information, and to explore andassess a variety of potential strategies for improving airquality. It is based on the same principles as theAbatement Strategies Assessment Model (ASAM) that has beenused in the UN Economic Commission for Europe. To startwith the USIAM model is being developed with respect to theparticulate PM10 only, and in particular the primaryparticulate contribution. The secondary particulate istreated as part of the background superimposed on theprimary particulate concentrations; this may need to betreated more specifically at a later stage, particularlywith respect to nitrate formation over the city. The USIAMmodel therefore sets out to examine a selection of severeepisode conditions as well as long-term annual averageconcentrations, and aims to find strategies that aresuccessful in eliminating exceedance of the prescribedtarget concentrations. By ranking different options forabatement of emissions, for example in terms of cost orease of implementation, the USIAM model can also select andprioritise different potential strategies.

Background Low fruit and vegetable (FV) consumption is one of the top 10 global risk factors for mortality, and is related to increased risk for cancer, cardiovascular disease and diabetes. Many environmental, sociodemographic and personal factors affect FV consumption. The purpose of this review is to examine the effects of interventions delivered in the home, school and other nutritional environments designed to increase FV availability for five to 18-year olds. Methods The search included: 19 electronic bibliographic databases; grey literature databases; reference lists of key articles; targeted Internet searching of key organization websites; hand searching of key journals and conference proceedings; and consultation with experts for additional references. Articles were included if: in English, French and Spanish; from high-, middle-, and low-income countries; delivered to anyone who could bring about change in FV environment for 5 to 18 year olds; with randomized and non-randomized study designs that provided before-after comparisons, with or without a control group. Primary outcomes of interest were measures of FV availability. Results The search strategy retrieved nearly 23,000 citations and resulted in 23 unique studies. Interventions were primarily policy interventions at the regional or state level, a number of curriculum type interventions in schools and community groups and a garden intervention. The majority of studies were done in high-income countries. The diversity of interventions, populations, outcomes and outcome measurements precluded meta-analysis. The most promising strategies for improving the FV environment for children are through local school food service policies. Access to FV was successfully improved in four of the six studies that evaluated school-based policies, with the other two studies finding no effect. Broader state or federally mandated policies or educational programs for food service providers and decision makers had mixed or small impact. Similarly family interventions had no or small impact on home accessibility, with smaller impact on consumption. Conclusions The studies have high risk of bias but more rigorous studies are difficult to impossible to conduct in naturalistic settings and in policy implementation and evaluation. However, there are promising strategies to improve the FV environment, particularly through school food service policies.

The paper reviews published studies focused on disparities in receipt of cancer treatments and supportive care services in countries where cancer care is free at the point of access. We map these studies in terms of the equity stratifiers they examined, the countries in which they took place, and the care settings and cancer populations they investigated. Based on this map, we reflect on patterns of scholarly attention to equity and disparity in cancer care. We then consider conceptual challenges and opportunities in the field, including how treatment disparities are defined, how equity stratifiers are defined and conceptualized and how disparities are explained, with special attention to the challenge of psychosocial explanations.

Transport first became a significant source of air pollution after the problems of sooty smog from coal combustion had largely been solved in western European and North American cities. Since then, emissions from road, air, rail and water transport have been partly responsible for acid deposition, stratospheric ozone depletion and climate change. Most recently, road traffic exhaust emissions have been the cause of much concern about the effects of urban air quality on human health and tropospheric ozone production. This article considers the variety of transport impacts on the atmospheric environment by reviewing three examples: urban road traffic and human health, aircraft emissions and global atmospheric change, and the contribution of sulphur emissions from ships to acid deposition. Each example has associated with it a different level of uncertainty, such that a variety of policy responses to the problems are appropriate, from adaptation through precautionary emissions abatement to cost-benefit analysis and optimised abatement. There is some evidence that the current concern for road transport contribution to urban air pollution is justified, but aircraft emissions should also give cause for concern given that air traffic is projected to continue to increase. Emissions from road traffic are being reduced substantially by the introduction of technology especially three-way catalysts and also, most recently, by local traffic reduction measures especially in western European cities. In developing countries and Eastern Europe, however, there remains the possibility of great increase in car ownership and use, and it remains to be seen whether these countries will adopt measures now to prevent transport-related air pollution problems becoming severe later in the 21st Century. (C) 2001 Elsevier Science Ltd. All rights reserved.

The integrated assessment model, Abatement Strategies Assessment Model (ASAM) is described and applied to the reduction of sulphur dioxide emissions in order to ameliorate European acidification in a cost-effective manner. The use of critical loads to map the spatial variation of environmental sensitivity is a key factor underpinning this approach. Since these critical loads are not in practice attainable, intermediate target loads are required. ASAM is used in this paper to show that the use of the ‘gap-closure’ approach, to define target loads, and in particular the 60% gap-closure target used as a basis for the Oslo protocol, is particularly appropriate. The unique feature of ASAM it its step-wise approach to optimisation which allows examination of an abatement strategy aiming at a particular environmental target at any required overall European expenditure level, even if the target is not attained at this point. This is key to ASAM’s ability to compare the cost-effectiveness of strategies based upon different target-loads. Similarly, ASAM has been used to demonstrate the influence of the use of current reduction plans as a starting point for optimisation in countries which plan substantial emissions reductions. ASAM is also used to show that abatement strategies are robust to large uncertainties in abatement cost estimates in individual countries. Finally, the role played by individual countries in a typical model strategy is investigated by comparing the ecosystem areas brought under protection by expenditure in each country. This work was undertaken in the context of the United Nations Economic Commission for Europe’s (UNECE) preparations for a second sulphur protocol.

Under the Convention on Transboundary Air Pollution the UN Economic Commission for Europe has produced a series of international agreements to reduce emissions of pollutants contributing to acidification, eutrophication and formation of tropospheric ozone. This includes the Second Sulphur Protocol signed in Oslo in 1994, which took into account maps of critical loads as those levels of annual deposition which are deemed sustainable without adverse effects. This paper describes scientific and technical work undertaken in the course of development of this protocol, and how the approach might be extended in future as attention turns to new protocols on NO x and VOCs.

European emissions of reduced nitrogen, arising principally from agriculture, are comparable with those of oxidised nitrogen from mobile and stationary combustion sources. It is therefore important to include ammonia emissions in working towards a new protocol on nitrogen under the programme of the UN Economic Commission for Europe on the control of transboundary air pollution. However the nature of the sources and the subsequent atmospheric transport and chemistry are very different from other acidifying pollutants. This paper describes work in hand under the MARACCAS project to compare agricultural activities in different European countries and to assess the applicability and efficacy of potential abatement measures. The aim is to derive abatement costs for each country relating successive emission reductions to the costs of achieving them, to be used by the UN ECE Task Force on Integrated Assessment Modelling (TFIAM) — in particular with our Abatement Strategies Assessment Model, ASAM. The paper will also address the large uncertainties involved in integrated assessment modelling with respect to ammonia, and suggest how these may be allowed for in deriving cost-effective abatement strategies.

Transport first became a significant source of air pollution after the problems of sooty smog from coal combustion had largely been solved in western European and North American cities. Since then, emissions from road, air, rail and water transport have been partly responsible for acid deposition, stratospheric ozone depletion and climate change. Most recently, road traffic exhaust emissions have been the cause of much concern about the effects of urban air quality on human health and tropospheric ozone production. This article considers the variety of transport impacts on the atmospheric environment by reviewing three examples: urban road traffic and human health, aircraft emissions and global atmospheric change, and the contribution of sulphur emissions from ships to acid deposition. Each example has associated with it a different level of uncertainty, such that a variety of policy responses to the problems are appropriate, from adaptation through precautionary emissions abatement to cost-benefit analysis and optimised abatement. There is some evidence that the current concern for road transport contribution to urban air quality is justified, but aircraft emissions should also give cause for concern given that air traffic is projected to continue to increase. Emissions from road traffic are being reduced substantially by the introduction of technology especially three-way catalysts and also, most recently, by local traffic reduction measures especially in western European cities. In developing countries and Eastern Europe, however, there remains the possibility of great increase in car ownership and use, and it remains to be seen whether these countries will adopt measures now to prevent transport-related air pollution problems becoming severe later in the 21 st Century.

Advances in technological and medical understanding in the past half century have brought substantial improvement in health. It is ironic that, at a time when potential returns from medical interventions are higher than ever before, the satisfaction levels of both doctors1 and the public2 seem particularly low. In this article we examine the external forces that are driving change and creating huge tensions within medicine; and, looking to the future, we broaden our discussion and ask what medicine really is and how its various components will fit into a broader concept of the organization of healthcare.

Background The systematic review on which this paper is based provided evidence for the Canadian Task Force on Preventive Health Care to update their guideline regarding screening for cervical cancer. In this article we highlight three questions covered in the full review that pertain to the effectiveness of screening for reducing cervical cancer mortality and incidence as well as optimal timing and frequency of screening. Methods We searched MEDLINE, Embase and Cochrane Central from 1995 to 2012 for relevant randomized controlled trials and observational studies with comparison groups. Eligible studies included women aged 15 to 70 years who were screened using conventional cytology, liquid-based cytology or human papillomavirus DNA tests. Relevance screening, data extraction, risk of bias analyses and quality assessments were performed in duplicate. We conducted a meta-analysis using a random-effects model on the one body of evidence that could be pooled. Results From the 15,145 screened citations, 27 papers (24 studies) were included; five older studies located in a United States Preventive Services Task Force review were also included. A randomized controlled trial in India showed even a single lifetime screening test significantly decreased the risk of mortality from and incidence of advanced cervical cancer compared to no screening (mortality: risk ratio 0.65, 95% confidence interval 0.47, 0.90; incidence: relative risk 0.56, 95% confidence interval 0.42, 0.75). Cytology screening was shown to be beneficial in a cohort study that found testing significantly reduced the risk of being diagnosed with invasive cervical cancer compared to no screening (risk ratio 0.38; 95% confidence interval 0.23, 0.63). Pooled evidence from a dozen case–control studies also indicated a significant protective effect of cytology screening (odds ratio 0.35; 95% confidence interval 0.30, 0.41). This review found no conclusive evidence for establishing optimal ages to start and stop cervical screening, or to determine how often to screen; however the available data suggests substantial protective effects for screening women 30 years and older and for intervals of up to five years. Conclusions The available evidence supports the conclusion that cervical screening does offer protective benefits and is associated with a reduction in the incidence of invasive cervical cancer and cervical cancer mortality.