Decision-Model Estimation of the Age-Specific Disability Weight for Schistosomiasis Japonica: A Systematic Review of the Literature

Schistosomiasis is among the most prevalent parasitic infections worldwide. However, current Global Burden of Disease (GBD) disability-adjusted life year estimates indicate that its population-level impact is negligible. Recent studies suggest that GBD methodologies may significantly underestimate the burden of parasitic diseases, including schistosomiasis. Furthermore, strain-specific disability weights have not been established for schistosomiasis, and the magnitude of human disease burden due to Schistosoma japonicum remains controversial. We used a decision model to quantify an alternative disability weight estimate of the burden of human disease due to S. japonicum. We reviewed S. japonicum morbidity data, and constructed decision trees for all infected persons and two age-specific strata, <15 years (y) and ≥15 y. We conducted stochastic and probabilistic sensitivity analyses for each model. Infection with S. japonicum was associated with an average disability weight of 0.132, with age-specific disability weights of 0.098 (<15 y) and 0.186 (≥15 y). Re-estimated disability weights were seven to 46 times greater than current GBD measures; no simulations produced disability weight estimates lower than 0.009. Nutritional morbidities had the greatest contribution to the S. japonicum disability weight in the <15 y model, whereas major organ pathologies were the most critical variables in the older age group. GBD disability weights for schistosomiasis urgently need to be revised, and species-specific disability weights should be established. Even a marginal increase in current estimates would result in a substantial rise in the estimated global burden of schistosomiasis, and have considerable implications for public health prioritization and resource allocation for schistosomiasis research, monitoring, and control

Genome Wide Meta-analysis Highlights the Role of Genetic Variation in RARRES2 in the Regulation of Circulating Serum Chemerin.

Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p<5.0×10?8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8×10?14, beta = ?0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2 = 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p<0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations

Evaluating Detection and Diagnostic Decision Support Systems for Bioterrorism Response

We evaluated the usefulness of detection systems and diagnostic decision support systems for bioterrorism response. We performed a systematic review by searching relevant databases (e.g., MEDLINE) and Web sites for reports of detection systems and diagnostic decision support systems that could be used during bioterrorism responses. We reviewed over 24,000 citations and identified 55 detection systems and 23 diagnostic decision support systems. Only 35 systems have been evaluated: 4 reported both sensitivity and specificity, 13 were compared to a reference standard, and 31 were evaluated for their timeliness. Most evaluations of detection systems and some evaluations of diagnostic systems for bioterrorism responses are critically deficient. Because false-positive and false-negative rates are unknown for most systems, decision making on the basis of these systems is seriously compromised. We describe a framework for the design of future evaluations of such systems

The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans

Cancer development is often associated with the lack of specific and efficient recognition of tumor cells by the immune system. Natural killer (NK) cells are lymphocytes of the innate immune system that participate in the elimination of tumors. We report the identification of a tumor cell surface molecule that binds NKp30, a human receptor which triggers antitumor NK cell cytotoxicity and cytokine secretion. This previously unannotated gene belongs to the B7 family and, hence, was designated B7-H6. B7-H6 triggers NKp30-mediated activation of human NK cells. B7-H6 was not detected in normal human tissues but was expressed on human tumor cells, emphasizing that the expression of stress-induced self-molecules associated with cell transformation serves as a mode of cell recognition in innate immunity

On Characterizing Adaptive Events Unique to Modern Humans

Ever since the first draft of the human genome was completed in 2001, there has been increased interest in identifying genetic changes that are uniquely human, which could account for our distinct morphological and cognitive capabilities with respect to other apes. Recently, draft sequences of two extinct hominin genomes, a Neanderthal and Denisovan, have been released. These two genomes provide a much greater resolution to identify human-specific genetic differences than the chimpanzee, our closest extant relative. The Neanderthal genome paper presented a list of regions putatively targeted by positive selection around the time of the human–Neanderthal split. We here seek to characterize the evolutionary history of these candidate regions—examining evidence for selective sweeps in modern human populations as well as for accelerated adaptive evolution across apes. Results indicate that 3 of the top 20 candidate regions show evidence of selection in at least one modern human population (P < 5 × 105). Additionally, four genes within the top 20 regions show accelerated amino acid substitutions across multiple apes (P < 0.01), suggesting importance across deeper evolutionary time. These results highlight the importance of evaluating evolutionary processes across both recent and ancient evolutionary timescales and intriguingly suggest a list of candidate genes that may have been uniquely important around the time of the human–Neanderthal split

Simulation modeling for stratified breast cancer screening : a systematic review of cost and quality of life assumptions

BACKGROUND: The economic evaluation of stratified breast cancer screening gains momentum, but produces also very diverse results. Systematic reviews so far focused on modeling techniques and epidemiologic assumptions. However, cost and utility parameters received only little attention. This systematic review assesses simulation models for stratified breast cancer screening based on their cost and utility parameters in each phase of breast cancer screening and care. METHODS: A literature review was conducted to compare economic evaluations with simulation models of personalized breast cancer screening. Study quality was assessed using reporting guidelines. Cost and utility inputs were extracted, standardized and structured using a care delivery framework. Studies were then clustered according to their study aim and parameters were compared within the clusters. RESULTS: Eighteen studies were identified within three study clusters. Reporting quality was very diverse in all three clusters. Only two studies in cluster 1, four studies in cluster 2 and one study in cluster 3 scored high in the quality appraisal. In addition to the quality appraisal, this review assessed if the simulation models were consistent in integrating all relevant phases of care, if utility parameters were consistent and methodological sound and if cost were compatible and consistent in the actual parameters used for screening, diagnostic work up and treatment. Of 18 studies, only three studies did not show signs of potential bias. CONCLUSION: This systematic review shows that a closer look into the cost and utility parameter can help to identify potential bias. Future simulation models should focus on integrating all relevant phases of care, using methodologically sound utility parameters and avoiding inconsistent cost parameters

European guideline on IgG4-related digestive disease – UEG and SGF evidence-based recommendations

The overall objective of these guidelines is to provide evidence-based recommendations for the diagnosis and management of immunoglobulin G4 (IgG4)-related digestive disease in adults and children. IgG4-related digestive disease can be diagnosed only with a comprehensive work-up that includes histology, organ morphology at imaging, serology, search for other organ involvement, and response to glucocorticoid treatment. Indications for treatment are symptomatic patients with obstructive jaundice, abdominal pain, posterior pancreatic pain, and involvement of extra-pancreatic digestive organs, including IgG4-related cholangitis. Treatment with glucocorticoids should be weight-based and initiated at a dose of 0.6–0.8 mg/kg body weight/day orally (typical starting dose 30-40 mg/day prednisone equivalent) for 1 month to induce remission and then be tapered within two additional months. Response to initial treatment should be assessed at week 2–4 with clinical, biochemical and morphological markers. Maintenance treatment with glucocorticoids should be considered in multi-organ disease or history of relapse. If there is no change in disease activity and burden within 3 months, the diagnosis should be reconsidered. If the disease relapsed during the 3 months of treatment, immunosuppressive drugs should be added

Decrease in thyroid adenoma associated (THADA) expression is a marker of dedifferentiation of thyroid tissue

<p>Abstract</p> <p>Background</p> <p><it>Thyroid adenoma associated (THADA) </it>has been identified as the target gene affected by chromosome 2p21 translocations in thyroid adenomas, but the role of THADA in the thyroid is still elusive. The aim of this study was to quantify <it>THADA </it>gene expression in normal tissues and in thyroid hyper- and neoplasias, using real-time PCR.</p> <p>Methods</p> <p>For the analysis <it>THADA </it>and 18S rRNA gene expression assays were performed on 34 normal tissue samples, including thyroid, salivary gland, heart, endometrium, myometrium, lung, blood, and adipose tissue as well as on 85 thyroid hyper- and neoplasias, including three adenomas with a 2p21 translocation. In addition, <it>NIS </it>(<it>sodium-iodide symporter</it>) gene expression was measured on 34 of the pathological thyroid samples.</p> <p>Results</p> <p>Results illustrated that <it>THADA </it>expression in normal thyroid tissue was significantly higher (<it>p </it>< 0.0001, exact Wilcoxon test) than in the other tissues. Significant differences were also found between non-malignant pathological thyroid samples (goiters and adenomas) and malignant tumors (<it>p </it>< 0.001, Wilcoxon test, t approximation), anaplastic carcinomas (ATCs) and all other samples and also between ATCs and all other malignant tumors (<it>p </it>< 0.05, Wilcoxon test, t approximation). Furthermore, in thyroid tumors <it>THADA </it>mRNA expression was found to be inversely correlated with <it>HMGA2 </it>mRNA. <it>HMGA2 </it>expression was recently identified as a marker revealing malignant transformation of thyroid follicular tumors. A correlation between <it>THADA </it>and <it>NIS </it>has also been found in thyroid normal tissue and malignant tumors.</p> <p>Conclusions</p> <p>The results suggest <it>THADA </it>being a marker of dedifferentiation of thyroid tissue.</p

A Common CNR1 (Cannabinoid Receptor 1) Haplotype Attenuates the Decrease in HDL Cholesterol That Typically Accompanies Weight Gain

We have previously shown that genetic variability in CNR1 is associated with low HDL dyslipidemia in a multigenerational obesity study cohort of Northern European descent (209 families, median  = 10 individuals per pedigree). In order to assess the impact of CNR1 variability on the development of dyslipidemia in the community, we genotyped this locus in all subjects with class III obesity (body mass index >40 kg/m2) participating in a population-based biobank of similar ancestry. Twenty-two haplotype tagging SNPs, capturing the entire CNR1 gene locus plus 15 kb upstream and 5 kb downstream, were genotyped and tested for association with clinical lipid data. This biobank contains data from 645 morbidly obese study subjects. In these subjects, a common CNR1 haplotype (H3, frequency 21.1%) is associated with fasting TG and HDL cholesterol levels (p = 0.031 for logTG; p = 0.038 for HDL-C; p = 0.00376 for log[TG/HDL-C]). The strength of this relationship increases when the data are adjusted for age, gender, body mass index, diet and physical activity. Mean TG levels were 160±70, 155±70, and 120±60 mg/dL for subjects with 0, 1, and 2 copies of the H3 haplotype. Mean HDL-C levels were 45±10, 47±10, and 48±9 mg/dL, respectively. The H3 CNR1 haplotype appears to exert a protective effect against development of obesity-related dyslipidemia