Towards Eliminating Bias in Cluster Analysis of TB Genotyped Data

The relative contributions of transmission and reactivation of latent infection to TB cases observed clinically has been reported in many situations, but always with some uncertainty. Genotyped data from TB organisms obtained from patients have been used as the basis for heuristic distinctions between circulating (clustered strains) and reactivated infections (unclustered strains). Naïve methods previously applied to the analysis of such data are known to provide biased estimates of the proportion of unclustered cases. The hypergeometric distribution, which generates probabilities of observing clusters of a given size as realized clusters of all possible sizes, is analyzed in this paper to yield a formal estimator for genotype cluster sizes. Subtle aspects of numerical stability, bias, and variance are explored. This formal estimator is seen to be stable with respect to the epidemiologically interesting properties of the cluster size distribution (the number of clusters and the number of singletons) though it does not yield satisfactory estimates of the number of clusters of larger sizes. The problem that even complete coverage of genotyping, in a practical sampling frame, will only provide a partial view of the actual transmission network remains to be explored

From Victims of Trafficking to Freedom Fighters: Rethinking Migrant Domestic Workers in the Middle East

Throughout the Middle East migrant women are employed to work in people’s homes. While some experience good working relations with employers, others experience forms of abuse and labour coercion. This chapter evaluates critically different ways that system of unfree labour has been variously described and analysed as a form of ‘contract slavery’, ‘debt bondage’ and ‘trafficking’. It also shows how migrant women who describe themselves as ‘freelancers’ exit their original employer’s home both to escape that relation and in hopes of securing a better situation outside of the regular system of employment. Freelancing is more than simply a form of resistance. Rather, women who work as freelance migrant domestic workers challenge directly that state enforced control over their mobility and are on the vanguard of those migrants who are seeking through their own actions to effect social change

Trade-Off between Toxicity and Signal Detection Orchestrated by Frequency- and Density-Dependent Genes

Behaviors in insects are partly highly efficient Bayesian processes that fulfill exploratory tasks ending with the colonization of new ecological niches. The foraging (for) gene in Drosophila encodes a cGMP-dependent protein kinase (PKG). It has been extensively described as a frequency-dependent gene and its transcripts are differentially expressed between individuals, reflecting the population density context. Some for transcripts, when expressed in a population at high density for many generations, concomitantly trigger strong dispersive behavior associated with foraging activity. Moreover, genotype-by-environment interaction (GEI) analysis has highlighted a dormant role of for in energetic metabolism in a food deprivation context. In our current report, we show that alleles of for encoding different cGMP-dependent kinase isoforms influence the oxidation of aldehyde groups of aromatic molecules emitted by plants via Aldh-III and a phosphorylatable adaptor. The enhanced efficiency of oxidation of aldehyde odorants into carboxyl groups by the action of for lessens their action and toxicity, which should facilitate exploration and guidance in a complex odor environment. Our present data provide evidence that optimal foraging performance requires the fast metabolism of volatile compounds emitted by plants to avoid neurosensory saturation and that the frequency-dependent genes that trigger dispersion influence these processes

T lymphocytes derived from human cord blood provide effective antitumor immunotherapy against a human tumor

Abstract Background Although the graft-versus-tumor (GVT) effect of donor-derived T cells after allogeneic hematopoietic stem cell transplantation has been used as an effective adoptive immunotherapy, the antitumor effects of cord blood (CB) transplantation have not been well studied. Methods We established the animal model by transplantation of CB mononuclear cells and/or tumor cells into NOD/SCID mice. The presence of CB derived T cells in NOD/SCID mice or tumor tissues were determined by flow cytometric and immunohistochemical analysis. The anti-tumor effects of CB derived T cells against tumor was determined by tumor size and weight, and by the cytotoxicity assay and ELISPOT assay of T cells. Results We found dramatic tumor remission following transfer of CB mononuclear cells into NOD/SCID mice with human cervical tumors with a high infiltration of CD3+ T cells in tumors. NOD/SCID mice that receive neonatal CB transplants have reconstituted T cells with significant antitumor effects against human cervical and lung tumors, with a high infiltration of CD3+ T cells showing dramatic induction of apoptotic cell death. We also confirmed that T cells showed tumor specific antigen cytotoxicity in vitro. In adoptive transfer of CD3+ T cells into mice with pre-established tumors, we observed much higher antitumor effects of HPV-specific T cells by ELISPOT assays. Conclusions Our results show that CB derived T lymphocytes will be useful for novel immunotherapeutic candidate cells for therapy of several tumors in clinic.</p

Altered intercellular communication in lung fibroblast cultures from patients with idiopathic pulmonary fibrosis

RATIONALE: Gap junctions are membrane channels formed by an array of connexins which links adjacent cells realizing an electro- metabolic synapse. Connexin-mediated communication is crucial in the regulation of cell growth, differentiation, and development. The activation and proliferation of phenotypically altered fibroblasts are central events in the pathogenesis of idiopathic pulmonary fibrosis. We sought to evaluate the role of connexin-43, the most abundant gap-junction subunit in the human lung, in the pathogenesis of this condition. METHODS: We investigated the transcription and protein expression of connexin-43 and the gap-junctional intercellular communication (GJIC) in 5 primary lung fibroblast lines derived from normal subjects (NF) and from 3 histologically proven IPF patients (FF). RESULTS: Here we show that connexin-43 mRNA was significantly reduced in FF as demonstrated by standard and quantitative RT-PCR. GJIC was functionally evaluated by means of flow-cytometry. In order to demonstrate that dye spreading was taking place through gap junctions, we used carbenoxolone as a pharmacological gap-junction blocker. Carbenoxolone specifically blocked GJIC in our system in a concentration dependent manner. FF showed a significantly reduced homologous GJIC compared to NF. Similarly, GJIC was significantly impaired in FF when a heterologous NF line was used as dye donor, suggesting a complete defect in GJIC of FF. CONCLUSION: These results suggest a novel alteration in primary lung fibroblasts from IPF patients. The reduced Cx43 expression and the associated alteration in cell-to-cell communication may justify some of the known pathological characteristic of this devastating disease that still represents a challenge to the medical practice

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Surgical strategies for treatment of malignant pancreatic tumors: extended, standard or local surgery?

Tumor related pancreatic surgery has progressed significantly during recent years. Pancreatoduodenectomy (PD) with lymphadenectomy, including vascular resection, still presents the optimal surgical procedure for carcinomas in the head of pancreas. For patients with small or low-grade malignant neoplasms, as well as small pancreatic metastases located in the mid-portion of pancreas, central pancreatectomy (CP) is emerging as a safe and effective option with a low risk of developing de-novo exocrine and/or endocrine insufficiency. Total pancreatectomy (TP) is not as risky as it was years ago and can nowadays safely be performed, but its indication is limited to locally extended tumors that cannot be removed by PD or distal pancreatectomy (DP) with tumor free surgical margins. Consequently, TP has not been adopted as a routine procedure by most surgeons. On the other hand, an aggressive attitude is required in case of advanced distal pancreatic tumors, provided that safe and experienced surgery is available. Due to the development of modern instruments, laparoscopic operations became more and more successful, even in malignant pancreatic diseases. This review summarizes the recent literature on the abovementioned topics

Seroprevalence and Risk Factors Associated to Mycobacterium bovis in Wild Artiodactyl Species from Southern Spain, 2006–2010

The control of bovine tuberculosis (bTB) is at a critical point in the last stage of eradication in livestock. Wildlife species recently have emerged infected with TB in Europe, particularly ungulates in the Iberian Peninsula. Epidemiological information regarding TB in wild ungulates including affected species, prevalence, associated risk factors and appropriate diagnostic methods need to be obtained in these countries