Evaluating contribution of the cellular and humoral immune responses to the control of shedding of \u3cem\u3eMycobacterium avium\u3c/em\u3e spp. \u3cem\u3eparatuberculosis\u3c/em\u3e in cattle

Mycobacterium avium spp. paratuberculosis (MAP) causes a persistent infection and chronic inflammation of the gut in ruminants leading to bacterial shedding in feces in many infected animals. Although there are often strong MAP-specific immune responses in infected animals, immunological correlates of protection against progression to disease remain poorly defined. Analysis of cross-sectional data has suggested that the cellular immune response observed early in infection is effective at containing bacterial growth and shedding, in contrast to humoral immune responses. In this study, 20 MAP-infected calves were followed for nearly 5 years during which MAP shedding, antigen-specific cellular (LPT) and humoral (ELISA) immune responses were measured. We found that MAP-specific cellular immune response developed slowly, with the peak of the immune response occurring one year post infection. MAP-specific humoral immunity expanded only in a subset of animals. Only in a subset of animals there was a statistically significant negative correlation between the amount of MAP shedding and magnitude of the MAP-specific cellular immune response. Direct fitting of simple mechanistic mathematical models to the shedding data suggested that MAP-specific immune responses contributed significantly to the kinetics of MAP shedding in most animals. However, whereas the MAP-specific cellular immune response was predicted to suppress shedding in some animals, in other animals it was predicted to increase shedding. In contrast, MAP-specific humoral response was always predicted to increase shedding. Our results illustrate the use of mathematical methods to understand relationships between mycobacteria and immunity in vivo but also highlight problems with establishing cause-effect links from observational data

Vascular rings: A rare cause of common respiratory symptoms

Upper airway symptoms or dysphagia may be caused by vascular anomalies, forming a ring around the trachea, oesophagus or both. To analyse the clinical presentation, use of various diagnostic techniques, treatment and follow-up we carried out a retrospective study of 38 children who had been diagnosed with a vascular ting between 1981 and 1996. We found 74% of the vascular tings to be symptomatic, with inspiratory stridor and wheezing as the main complaints. The delay between the onset of symptoms and diagnosis of a vascular ting in patients without associated anomalies ranged from 1 to 84 mo. Associated anomalies were found in 53% of cases and 80% of these anomalies consisted of associated cardiovascular malformations. Oesophagography proved to be a valuable diagnostic technique when a vascular ting was suspected. Echocardiography appeared to be of little value for the diagnosis of a vascular ring, but was essential to exclude associated cardiovascular malformations. Although angiography has always been considered to be the gold standard in the determination of the exact anatomy of vascular tings, increasing evidence is available that CT scan or MRI may replace this role. Mortality was related to co-existent tracheal deformities in 5/6 cases. Of the remaining, preoperatively symptomatic patients, relief of symptoms was achieved immediately after surgery in 43% and within 4y after surgery in 57%. Prolonged and recurrent respiratory complaints or dysphagia in infancy or childhood should alert the paediatrician to the possibility of a vascular ring

Calibrating the Performance of SNP Arrays for Whole-Genome Association Studies

To facilitate whole-genome association studies (WGAS), several high-density SNP genotyping arrays have been developed. Genetic coverage and statistical power are the primary benchmark metrics in evaluating the performance of SNP arrays. Ideally, such evaluations would be done on a SNP set and a cohort of individuals that are both independently sampled from the original SNPs and individuals used in developing the arrays. Without utilization of an independent test set, previous estimates of genetic coverage and statistical power may be subject to an overfitting bias. Additionally, the SNP arrays' statistical power in WGAS has not been systematically assessed on real traits. One robust setting for doing so is to evaluate statistical power on thousands of traits measured from a single set of individuals. In this study, 359 newly sampled Americans of European descent were genotyped using both Affymetrix 500K (Affx500K) and Illumina 650Y (Ilmn650K) SNP arrays. From these data, we were able to obtain estimates of genetic coverage, which are robust to overfitting, by constructing an independent test set from among these genotypes and individuals. Furthermore, we collected liver tissue RNA from the participants and profiled these samples on a comprehensive gene expression microarray. The RNA levels were used as a large-scale set of quantitative traits to calibrate the relative statistical power of the commercial arrays. Our genetic coverage estimates are lower than previous reports, providing evidence that previous estimates may be inflated due to overfitting. The Ilmn650K platform showed reasonable power (50% or greater) to detect SNPs associated with quantitative traits when the signal-to-noise ratio (SNR) is greater than or equal to 0.5 and the causal SNP's minor allele frequency (MAF) is greater than or equal to 20% (N = 359). In testing each of the more than 40,000 gene expression traits for association to each of the SNPs on the Ilmn650K and Affx500K arrays, we found that the Ilmn650K yielded 15% times more discoveries than the Affx500K at the same false discovery rate (FDR) level

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

AIMS/HYPOTHESIS: Vasopressin plays a role in osmoregulation, glucose homeostasis and inflammation. Therefore, plasma copeptin, the stable C-terminal portion of the precursor of vasopressin, has strong potential as a biomarker for the cardiometabolic syndrome and diabetes. Previous results were contradictory, which may be explained by differences between men and women in responsiveness of the vasopressin system. The aim of this study was to evaluate the usefulness of copeptin for prediction of future type 2 diabetes in men and women separately. METHODS: From the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, 4,063 women and 3,909 men without diabetes at baseline were included. A total of 208 women and 288 men developed diabetes during a median follow-up of 7.7 years. RESULTS: In multivariable-adjusted models, we observed a stronger association of copeptin with risk of future diabetes in women (OR 1.49 [95% CI 1.24, 1.79]) than in men (OR 1.01 [95% CI 0.85, 1.19]) (p (interaction) < 0.01). The addition of copeptin to the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) clinical model improved the discriminative value (C-statistic,+0.007, p = 0.02) and reclassification (integrated discrimination improvement [IDI] = 0.004, p < 0.01) in women. However, we observed no improvement in men. The additive value of copeptin in women was maintained when other independent predictors, such as glucose, high sensitivity C-reactive protein (hs-CRP) and 24 h urinary albumin excretion (UAE), were included in the model. CONCLUSIONS/INTERPRETATION: The association of plasma copeptin with the risk of developing diabetes was stronger in women than in men. Plasma copeptin alone, and along with existing biomarkers (glucose, hs-CRP and UAE), significantly improved the risk prediction for diabetes in women

Commodification and ‘the commons’: the politics of privatising public water in Greece and Portugal during the Eurozone Crisis

In response to the Eurozone crisis, austerity and restructuring has been imposed on the European Union’s (EU) peripheral member states in order to receive financial bailout loans. In addition to cuts in funding of essential public services, cuts in public sector employment and further liberalisation of labour markets, this has also included pressure towards the privatisation of state assets. And yet, workers have not simply accepted these restructuring pressures. They have organised and fought back against austerity and enforced privatisation. Based on a historical materialist perspective and following a strategy of incorporated comparison, in this paper we will comparatively assess the struggles against enforced water privatisation in Greece and Portugal set against the background of the structuring conditions surrounding the Eurozone crisis

Sporormiella as a tool for detecting the presence of large herbivores in the Neotropics

The reliability of using the abundance of Sporormiella spores as a proxy for the presence and abundance of megaherbivores was tested in southern Brazil. Mud-water interface samples from nine lakes, in which cattle-use was categorized as high, medium, or low, were assayed for Sporormiella representation. The sampling design allowed an analysis of both the influence of the number of animals using the shoreline and the distance of the sampling site from the nearest shoreline. Sporormiella was found to be a reliable proxy for the presence of large livestock. The concentration and abundance of spores declined from the edge of the lake toward the center, with the strongest response being in sites with high livestock use. Consistent with prior studies in temperate regions, we find that Sporormiella spores are a useful proxy to study the extinction of Pleistocene megafauna or the arrival of European livestock in Neotropical landscapes

Integrated approach to prevent functional decline in hospitalized elderly: the Prevention and Reactivation Care Program (PReCaP)

<p>Abstract</p> <p>Background</p> <p>Hospital related functional decline in older patients is an underestimated problem. Thirty-five procent of 70-year old patients experience functional decline during hospital admission in comparison with pre-illness baseline. This percentage increases considerably with age.</p> <p>Methods/design</p> <p>To address this issue, the Vlietland Ziekenhuis in The Netherlands has implemented an innovative program (PReCaP), aimed at reducing hospital related functional decline among elderly patients by offering interventions that are multidisciplinary, integrated and goal-oriented at the physical, social, and psychological domains of functional decline.</p> <p>Discussion</p> <p>This paper presents a detailed description of the intervention, which incorporates five distinctive elements: (1) Early identification of elderly patients with a high risk of functional decline, and if necessary followed by the start of the reactivation treatment within 48 h after hospital admission; (2) Intensive follow-up treatment for a selected patient group at the Prevention and Reactivation Centre (PRC); (3) Availability of multidisciplinary geriatric expertise; (4) Provision of support and consultation of relevant professionals to informal caregivers; (5) Intensive follow-up throughout the entire chain of care by a casemanager with geriatric expertise. Outcome and process evaluations are ongoing and results will be published in a series of future papers.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2317">NTR2317</a></p

Power analysis for genome-wide association studies

Abstract Background Genome-wide association studies are a promising new tool for deciphering the genetics of complex diseases. To choose the proper sample size and genotyping platform for such studies, power calculations that take into account genetic model, tag SNP selection, and the population of interest are required. Results The power of genome-wide association studies can be computed using a set of tag SNPs and a large number of genotyped SNPs in a representative population, such as available through the HapMap project. As expected, power increases with increasing sample size and effect size. Power also depends on the tag SNPs selected. In some cases, more power is obtained by genotyping more individuals at fewer SNPs than fewer individuals at more SNPs. Conclusion Genome-wide association studies should be designed thoughtfully, with the choice of genotyping platform and sample size being determined from careful power calculations.</p