Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites

Search for the Standard Model Higgs boson decaying into bb¯ produced in association with top quarks decaying hadronically in pp collisions at √s = 8 TeV with the ATLAS detector

A search for Higgs boson production in association with a pair of top quarks (tt¯ H) is performed, where the Higgs boson decays to bb¯, and both top quarks decay hadronically. The data used correspond to an integrated luminosity of 20.3 fb−1 of pp collisions at √s = 8 TeV collected with the ATLAS detector at the Large Hadron Collider. The search selects events with at least six energetic jets and uses a boosted decision tree algorithm to discriminate between signal and Standard Model background. The dominant multijet background is estimated using a dedicated data-driven technique. For a Higgs boson mass of 125 GeV, an upper limit of 6.4 (5.4) times the Standard Model cross section is observed (expected) at 95% confidence level. The best-fit value for the signal strength is μ = 1.6 ± 2.6 times the Standard Model expectation for mH = 125 GeV. Combining all tt¯ H searches carried out by ATLAS at √s = 8 and 7 TeV, an observed (expected) upper limit of 3.1 (1.4) times the Standard Model expectation is obtained at 95% confidence level, with a signal strength μ = 1.7 ± 0.8

CCAT2, a novel noncoding RNA mapping to 8q24, underlies metastatic progression and chromosomal instability in colon cancer

The functional roles of SNPs within the 8q24 gene desert in the cancer phenotype are not yet well understood. Here, we report that CCAT2, a novel long noncoding RNA transcript (lncRNA) encompassing the rs6983267 SNP, is highly overexpressed in microsatellite-stable colorectal cancer and promotes tumor growth, metastasis, and chromosomal instability. We demonstrate that MYC, miR-17-5p, and miR-20a are up-regulated by CCAT2 through TCF7L2-mediated transcriptional regulation. We further identify the physical interaction between CCAT2 and TCF7L2 resulting in an enhancement of WNT signaling activity. We show that CCAT2 is itself a WNT downstream target, which suggests the existence of a feedback loop. Finally, we demonstrate that the SNP status affects CCAT2 expression and the risk allele G produces more CCAT2 transcript. Our results support a new mechanism of MYC and WNT regulation by the novel lncRNA CCAT2 in colorectal cancer pathogenesis, and provide an alternative explanation of the SNP-conferred cancer risk

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Search for the Higgs boson produced in association with a W boson and decaying to four b-quarks via two spin-zero particles in pp collisions at 13 TeV with the ATLAS detector

This paper presents a dedicated search for exotic decays of the Higgs boson to a pair of new spin-zero particles, H → aa, where the particle a decays to b-quarks and has a mass in the range of 20–60 GeV. The search is performed in events where the Higgs boson is produced in association with a W boson, giving rise to a signature of a lepton (electron or muon), missing transverse momentum, and multiple jets from b-quark decays. The analysis is based on the full dataset of pp collisions at √s = 13 TeV recorded in 2015 by the ATLAS detector at the CERN Large Hadron Collider, corresponding to an integrated luminosity of 3.2 fb−1. No significant excess of events above the Standard Model prediction is observed, and a 95% confidence-level upper limit is derived for the product of the production cross section for pp → W H times the branching ratio for the decay H → aa → 4b. The upper limit ranges from 6.2 pb for an a-boson mass ma = 20 GeV to 1.5 pb for ma = 60 GeV

Association between glycemia and mortality in diabetic individuals on renal replacement therapy in the U.K.

OBJECTIVE: In the U.K., one-third of patients receiving treatment with dialysis have diabetes. Guidelines from organizations representing patients with renal disease or diabetes advocate tight glycemic control in patients with end-stage renal disease, despite glucose-lowering trials having excluded these patients. RESEARCH DESIGN AND METHODS: Using national U.K. Renal Registry data, we tested whether glycemia as measured by hemoglobin (Hb) A(1c) (HbA(1c)) level is associated with death in adults with diabetes starting hemodialysis or peritoneal dialysis between 1997 and 2006, and observed for at least 6 months. Of 7,814 patients, we excluded those who had died within 6 months; had received transplants; were lost/recovered; or lacked measures of HbA1c, ethnicity, or Hb. Categorizing HbA1c measured in the first 6 months of starting dialysis as 8.5% was 1.5 (1.2-1.9). The projected difference in median survival time between younger patients with a reference HbA1c value versus >8.5% was 1 year. CONCLUSIONS: In the absence of trials, and confounding notwithstanding, these observational data support improved glycemic control in younger patients prior to and during dialysis