Laparoscopic fundoplication compared with medical management for gastro-oesophageal reflux disease : cost effectiveness study

Peer reviewedPublisher PD

Development of cytomegalovirus (CMV) immune recovery uveitis is associated with Th17 cell depletion and poor systemic CMV-specific T cell responses.

Backgroundthe immune reconstitution inflammatory syndromes (IRIS) are a spectrum of inflammatory conditions associated with opportunistic infections and occurring in approximately16% of human immunodeficiency type 1 (HIV-1)-infected patients given antiretroviral therapy. It has been proposed that these conditions are linked by a dysregulated immune system that is prone to exaggerated responses. However, immunologic studies have been limited by the availability of longitudinal samples from patients with IRIS and appropriate matched control subjects. Cytomegalovirus (CMV) immune recovery uveitis (IRU) is an IRIS occurring in up to 38% of patients with CMV retinitis. Although the pathologic immune responses occur in the eye, immune dysregulation that allows for development of pathologic responses is presumably caused by faulty systemic immune cell reconstitution.Methodswe examined CMV-specific T cell responses, regulatory T (T(reg)) cell function and polyclonal T cell responses, including IL-17 production, in 25 patients with CMV IRU and 49 immunorestored control subjects with CMV retinitis who did not develop IRU.Resultspatients with CMV IRU had poor CMV-specific CD4(+) T cell responses, as compared with control subjects, whereas CD8(+) T cell responses were comparable. Patients with CMV IRU were characterized by smaller numbers of circulating Th17 cells. Deficiency in anti-CMV responses was not associated with differences in T(reg) cell function.Conclusionsthe T(reg) cell compartment is intact in patients with CMV IRU, and these patients do not develop exaggerated systemic CMV-specific or polyclonal immune responses. Cases are instead characterized by more profound depletion of Th17 cells and poor antiviral immune responses. CMV IRU may be most likely to develop in persons experiencing the greatest degree of immune dysfunction before initiating highly active antiretroviral therapy

Evaluating the spatial transferability and temporal repeatability of remote sensing-based lake water quality retrieval algorithms at the European scale:a meta-analysis approach

Many studies have shown the considerable potential for the application of remote-sensing-based methods for deriving estimates of lake water quality. However, the reliable application of these methods across time and space is complicated by the diversity of lake types, sensor configuration, and the multitude of different algorithms proposed. This study tested one operational and 46 empirical algorithms sourced from the peer-reviewed literature that have individually shown potential for estimating lake water quality properties in the form of chlorophyll-a (algal biomass) and Secchi disc depth (SDD) (water transparency) in independent studies. Nearly half (19) of the algorithms were unsuitable for use with the remote-sensing data available for this study. The remaining 28 were assessed using the Terra/Aqua satellite archive to identify the best performing algorithms in terms of accuracy and transferability within the period 2001–2004 in four test lakes, namely Vänern, Vättern, Geneva, and Balaton. These lakes represent the broad continuum of large European lake types, varying in terms of eco-region (latitude/longitude and altitude), morphology, mixing regime, and trophic status. All algorithms were tested for each lake separately and combined to assess the degree of their applicability in ecologically different sites. None of the algorithms assessed in this study exhibited promise when all four lakes were combined into a single data set and most algorithms performed poorly even for specific lake types. A chlorophyll-a retrieval algorithm originally developed for eutrophic lakes showed the most promising results (R2 = 0.59) in oligotrophic lakes. Two SDD retrieval algorithms, one originally developed for turbid lakes and the other for lakes with various characteristics, exhibited promising results in relatively less turbid lakes (R2 = 0.62 and 0.76, respectively). The results presented here highlight the complexity associated with remotely sensed lake water quality estimates and the high degree of uncertainty due to various limitations, including the lake water optical properties and the choice of methods

Effect of methamphetamine dependence on inhibitory deficits in a novel human open-field paradigm.

RationaleMethamphetamine (MA) is an addictive psychostimulant associated with neurocognitive impairment, including inhibitory deficits characterized by a reduced ability to control responses to stimuli. While various domains of inhibition such as exaggerated novelty seeking and perseveration have been assessed in rodents by quantifying activity in open-field tests, similar models have not been utilized in human substance abusers. We recently developed a cross-species translational human open-field paradigm, the human behavior pattern monitor (hBPM), consisting of an unfamiliar room containing novel and engaging objects. Previous work demonstrated that manic bipolar subjects exhibit a disinhibited pattern of behavior in the hBPM characterized by increased object interactions.ObjectivesIn the current study, we examined the effect of MA dependence on inhibitory deficits using this paradigm. hBPM activity and object interactions were quantified in 16 abstinent MA-dependent individuals and 18 matched drug-free comparison subjects. The Wisconsin card sorting task (WCST) and the positive and negative syndrome scale (PANSS) were administered to assess executive function and psychopathology.ResultsMA-dependent participants exhibited a significant increase in total object interactions, time spent with objects, and perseverative object interactions relative to comparison subjects. Greater object interaction was associated with impaired performance on the WCST, higher PANSS scores, and more frequent MA use in the past year.ConclusionsAbstinent MA-dependent individuals exhibited impaired inhibition in the hBPM, displaying increased interaction with novel stimuli. Utilization of this measure may enable assessment of inhibitory deficits relevant to drug-seeking behavior and facilitate development of intervention methods to reduce high-risk conduct in this population

A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis.

BackgroundRheumatoid arthritis (RA) can be divided into two major subsets based on the presence or absence of antibodies to citrullinated peptide antigens (ACPA). Until now, data from genome-wide association studies (GWAS) have only been published from ACPA-positive subsets of RA or from studies that have not separated the two subsets. The aim of the current study is to provide and compare GWAS data for both subsets.Methods and resultsGWAS using the Illumina 300K chip was performed for 774 ACPA-negative patients with RA, 1147 ACPA-positive patients with RA and 1079 controls from the Swedish population-based case-control study EIRA. Imputation was performed which allowed comparisons using 1,723,056 single nucleotide polymorphisms (SNPs). No SNP achieved genome-wide significance (2.9 × 10⁻⁸) in the comparison between ACPA-negative RA and controls. A case-case association study was then performed between ACPA-negative and ACPA-positive RA groups. The major difference in this analysis was in the HLA region where 768 HLA SNPs passed the threshold for genome-wide significance whereas additional contrasting SNPs did not reach genome-wide significance. However, one SNP close to the RPS12P4 locus in chromosome 2 reached a p value of 2 × 10⁶ and this locus can thus be considered as a tentative candidate locus for ACPA-negative RA.ConclusionsACPA-positive and ACPA-negative RA display significant risk allele frequency differences which are mainly confined to the HLA region. The data provide further support for distinct genetic aetiologies of RA subsets and emphasise the need to consider them separately in genetic as well as functional studies of this disease

Ex vivo cytokine mRNA levels correlate with changing clinical status of ethiopian TB patients and their contacts over time.

There is an increasing body of evidence which suggests that IL-4 plays a role in the pathogenesis of TB, but a general consensus on its role remains elusive. We have previously published data from a cohort of Ethiopian TB patients, their contacts, and community controls suggesting that enhanced IL-4 production is associated with infection with M. tuberculosis, rather than overt disease and that long-term protection in infected community controls is associated with co-production of the IL-4 antagonist IL-4d2, alongside elevated IL-4. Here, for the first time, we compare data on expression of IFN-gamma, IL-4 and IL-4delta2 over time in TB patients and their household contacts. During the follow-up period, the TB patients completed therapy and ceased to display TB-like symptoms. This correlated with a decrease in the relative amount of IL-4 expressed. Over the same period, the clinical status of some of their contacts also changed, with a number developing TB-like symptoms or clinically apparent TB. IL-4 expression was disproportionately increased in this group. The findings support the hypothesis that elevated IL-4 production is generally associated with infection, but that TB disease is associated with a relatively increased expression of IL-4 compared to IFN-gamma and IL-4delta2. However, the data also suggest that there are no clear-cut differences between groups: the immune response over time appears to include changes in the expression of IFN-gamma, IL-4 and IL-4delta2, and it is the relative, not absolute levels of cytokine expression that are characteristic of clinical status

Does sticky blood predict a sticky end? Associations of blood viscosity, haematocrit and fibrinogen with mortality in the West of Scotland

There is increasing evidence that blood viscosity and its major determinants (haematocrit, plasma viscosity and fibrinogen) are associated with an increased risk of incident cardiovascular events; however, their associations with mortality are not established. We therefore studied the associations of these variables with cardiovascular events and total mortality in 1238 men and women aged 25-64 years, followed for 13 years in the first North Glasgow MONICA (MONItoring CArdiovascular disease) survey and West of Scotland centres in the Scottish Heart Health Study. After adjustment for age and sex, increasing whole blood viscosity, plasma viscosity, haematocrit and fibrinogen (analysed by both von Clauss and heat precipitation assays) were significantly associated with mortality. Only the association for fibrinogen (von Clauss assay) remained significant after adjustment for major cardiovascular risk factors. We conclude that clottable fibrinogen may be independently associated with mortality. However, the significance of this association, and the extent to which viscosity is associated with mortality, remain to be established in larger studies and meta-analyses

Report of the ESRC Expert Advisory Group on International Development October 2014

Very real transformations are now occurring in the nature and extent of poverty, in the processes leading to impoverishment, inequality and injustice, and in the policy space and practices that can address these. The purpose of this report is to identify for ESRC the new challenges that these unfolding realities pose for social science researchers in the field of international development.This will (a) inform emerging ESRC research strategy more broadly and (b) inform the development of joint funding arrangements between ESRC and funding partners. In our increasingly interconnected world, the emerging research priorities in international development that we document inevitably dovetail closely with emergent social science agendas more generally.There is not one discipline for ‘the developing world’ and many for ‘the developed’. Development studies research and teaching centres do bring new tools, frameworks, methods and experience to grapple with these future development pressures and problems, but all social science disciplines are expanding their boundaries to think more globally rather than territorially – and in ways that the emergence of international development studies as a field has been encouraging. Re-emphasising the opportunities for research in international development to draw on and feed into wider methodological, theoretical and substantive research repertoires echoes a core principle of the post-2015 Sustainable Development Agenda which is to be ‘integrated, holistic and universal, applying to all countries and all people’ and which thus eschews specific geographical foci. It echoes, too, the proposed Sustainable Development Goals which, beyond the principles of ending extreme poverty, seek to integrate social, economic, and environmental sustainability and inclusive growth within “a common understanding of our shared humanity, based on mutual respect and mutual benefit.”The ‘Third World’ and its euphemisms are fast becoming history. International development studies research does not secure its identity in a focus on a particular sub-set of countries or methods. International development research is, however, characterised by a problem-focused approach which this report is built around. But whilst much research in international development studies is unashamedly impact-led and supports a ‘what works’ agenda that speaks directly to wider policy concerns, this report prioritises, too, increased attention to the rapid transformations in global environments, economy, societies, cultures, politics and technologies that now reshape poverty and so reshape ‘what works’ as well as ‘for whom, when and why’.These changes are happening so fast and are so massive that for research to have maximum impact in informing the alleviation of mid-21st century poverty and inequality, it will need to be couched within new conceptualisations and new theorisations that capture these future realities. In particular, given the rising inequalities associated with current economic growth and new geographies of poverty that do not easily fall into particular countries,‘worlds,’ or points of the compass, it is our contention that ‘international development’ research needs not only to dwell on a broader range of countries and regions, but also to capture changing global orders producing and addressing poverty. In particular, embracing research on ‘middle income countries’ (MICs) is now important for understanding not only the predicament of the poor within, but also the drivers of steeply rising inequalities there which are of significance to the poor in countries with middle income aspirations. It will help, too, in understanding the nature of the multi-polar international order in which this will happen. In addition, BRICS and other MICs are sources of enormous social policy innovation that other countries stand to learn from; yet are often not well analysed. This report outlines challenges for a wide range of research, from that focused on refining specific interventions (education, health etc.) to the much broader analytical challenges that will necessitate conceptual breakthroughs and new analytical paradigms. Given the availability of more operational funding for the former, we suggest that there is a clear opportunity (and need) for ESRC to focus more (though not exclusively) on the broader questions and conceptual challenges. There are many ways to relate the cross cutting issues that we identify. Rather than develop a matrix, we set out key challenges and opportunities for research in relation to eight key trends: 1. Increasing inequalities in a connected world 2. Massive, differentiated urbanisation 3. Climate change and pushing against planetary limits 4. Emerging sensitivity to shocks, and their securitisation 5. Increasing political multipolarity 6. Emerging challenges to nation states in delivering development: social and physical infrastructure 7. New cultural shaping of poverty 8. Digital development, Big Data and the technological revolution We also highlight more methodological challenges: - Levering change: learning, incentives and beyond - Governing ‘international development’: measurement and beyon