Search for Large Extra Dimensions in Dielectron and Diphoton Production

We report a search for effects of large extra spatial dimensions in ppbar collisions at a center-of-mass energy of 1.8 TeV with the DZero detector, using events containing a pair of electrons or photons. The data are in good agreement with the expected background and do not exhibit evidence for large extra dimensions. We set the most restrictive lower limits to date, at the 95% confidence level, on the effective Planck scale between 1.0 TeV and 1.4 TeV for several formalisms and numbers of extra dimensions.Comment: 6 pages, 2 figures, submitted to Phys. Rev. Let

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

Murine hematopoietic stem cell activity is derived from pre-circulation embryos but not yolk sacs.

The embryonic site of definitive hematopoietic stem cell (dHSC) origination has been debated for decades. Although an intra-embryonic origin is well supported, the yolk sac (YS) contribution to adult hematopoiesis remains controversial. The same developmental origin makes it difficult to identify specific markers that discern between an intraembryonic versus YS-origin using a lineage trace approach. Additionally, the highly migratory nature of blood cells and the inability of pre-circulatory embryonic cells (i.e., 5-7 somite pairs (sp)) to robustly engraft in transplantation, even after culture, has precluded scientists from properly answering these questions. Here we report robust, multi-lineage and serially transplantable dHSC activity from cultured 2-7sp murine embryonic explants (Em-Ex). dHSC are undetectable in 2-7sp YS explants. Additionally, the engraftment from Em-Ex is confined to an emerging CD31+CD45+c-Kit+CD41- population. In sum, our work supports a model in which the embryo, not the YS, is the major source of lifelong definitive hematopoiesis

Diversity of Matriptase Expression Level and Function in Breast Cancer

Overexpression of matriptase has been reported in a variety of human cancers and is sufficient to trigger tumor formation in mice, but the importance of matriptase in breast cancer remains unclear. We analysed matriptase expression in 16 human breast cancer cell lines and in 107 primary breast tumors. The data revealed considerable diversity in the expression level of this protein indicating that the significance of matriptase may vary from case to case. Matriptase protein expression was correlated with HER2 expression and highest expression was seen in HER2-positive cell lines, indicating a potential role in this subgroup. Stable overexpression of matriptase in two breast cancer cell lines had different consequences. In MDA-MB-231 human breast carcinoma cells the only noted consequence of matriptase overexpression was modestly impaired growth in vivo. In contrast, overexpression of matriptase in 4T1 mouse breast carcinoma cells resulted in visible changes in morphology, actin staining and cell to cell contacts. This correlated with downregulation of the cell-cell adhesion molecule E-cadherin. These results suggest that the functions of matriptase in breast cancer are likely to be variable and cell context dependent

An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus

DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses

Blocking and its response to climate change

Purpose of review: Atmospheric blocking events represent some of the most high-impact weather patterns in the mid-latitudes, yet they have often been a cause for concern in future climate projections. There has been low confidence in predicted future changes in blocking, despite relatively good agreement between climate models on a decline in blocking. This is due to the lack of a comprehensive theory of blocking and a pervasive underestimation of blocking occurrence by models. This paper reviews the state of knowledge regarding blocking under climate change, with the aim of providing an overview for those working in related fields. Recent Findings: Several avenues have been identified by which blocking can be improved in numerical models, though a fully reliable simulation remains elusive (at least, beyond a few days lead time). Models are therefore starting to provide some useful information on how blocking and its impacts may change in the future, although deeper understanding of the processes at play will be needed to increase confidence in model projections. There are still major uncertainties regarding the processes most important to the onset, maintenance and decay of blocking and advances in our understanding of atmospheric dynamics, for example in the role of diabatic processes, continue to inform the modelling and prediction efforts. Summary: The term ‘blocking’ covers a diverse array of synoptic patterns, and hence a bewildering range of indices has been developed to identify events. Results are hence not considered fully trustworthy until they have been found using several different methods. Examples of such robust results are the underestimation of blocking by models, and an overall decline in future occurrence, albeit with a complex regional and seasonal variation. In contrast, hemispheric trends in blocking over the recent historical period are not supported by different methods, and natural variability will likely dominate regional variations over the next few decades

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

BEL/Pao retrotransposons in metazoan genomes

Background Long terminal repeat (LTR) retrotransposons are a widespread kind of transposable element present in eukaryotic genomes. They are a major factor in genome evolution due to their ability to create large scale mutations and genome rearrangements. Compared to other transposable elements, little attention has been paid to elements belonging to the metazoan BEL/Pao subclass of LTR retrotransposons. No comprehensive characterization of these elements is available so far. The aim of this study was to describe all BEL/Pao elements in a set of 62 sequenced metazoan genomes, and to analyze their phylogenetic relationship. Results We identified a total of 7,861 BEL/Pao elements in 53 of our 62 study genomes. We identified BEL/Pao elements in 20 genomes where such elements had not been found so far. Our analysis shows that BEL/Pao elements are the second-most abundant class of LTR retrotransposons in the genomes we study, more abundant than Ty1/Copia elements, and second only to Ty3/Gypsy elements. They occur in multiple phyla, including basal metazoan phyla, suggesting that BEL/Pao elements arose early in animal evolution. We confirm findings from previous studies that BEL/Pao elements do not occur in mammals. The elements we found can be grouped into more than 1725 families, 1623 of which are new, previously unknown families. These families fall into seven superfamilies, only five of which have been characterized so far. One new superfamily is a major subdivision of the Pao superfamily which we propose to call Dan, because it is restricted to the genome of the zebrafish Danio rerio. The other new superfamily comprises 83 elements and is restricted to lower aquatic eumetazoans. We propose to call this superfamily Flow. BEL/Pao elements do not show any signs of recent horizontal gene transfer between distantly related species. Conclusions In sum, our analysis identifies thousands of new BEL/Pao elements and provides new insights into their distribution, abundance, and evolution