Identifying causes of Western Pacific ITCZ drift in ECMWF System 4 hindcasts

The development of systematic biases in climate models used in operational seasonal forecasting adversely affects the quality of forecasts they produce. In this study, we examine the initial evolution of systematic biases in the ECMWF System 4 forecast model, and isolate aspects of the model simulations that lead to the development of these biases. We focus on the tendency of the simulated intertropical convergence zone in the western equatorial Pacific to drift northwards by between 0.5° and 3° of latitude depending on season. Comparing observations with both fully coupled atmosphere–ocean hindcasts and atmosphere-only hindcasts (driven by observed sea-surface temperatures), we show that the northward drift is caused by a cooling of the sea-surface temperature on the Equator. The cooling is associated with anomalous easterly wind stress and excessive evaporation during the first twenty days of hindcast, both of which occur whether air-sea interactions are permitted or not. The easterly wind bias develops immediately after initialisation throughout the lower troposphere; a westerly bias develops in the upper troposphere after about ten days of hindcast. At this point, the baroclinic structure of the wind bias suggests coupling with errors in convective heating, although the initial wind bias is barotropic in structure and appears to have an alternative origin

Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience

<p>Abstract</p> <p>Background</p> <p>To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.</p> <p>Methods</p> <p>Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation.</p> <p>Results</p> <p>Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse.</p> <p>Conclusion</p> <p>When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.</p

Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains

The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positioning. The interactions with extranucleosomal DNA and the requirement of a minimal length of extranucleosomal DNA by ISWI mediate the spacing of nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain), whose binding to extranucleosomal DNA ~19 bp from the edge of nucleosomes is required for efficiently pushing DNA into nucleosomes and maintaining the unidirectional movement of nucleosomes, as reported here. Loss of SLIDE binding does not perturb ATPase domain binding to the SHL2 site of nucleosomes or its initial movement of DNA inside of nucleosomes. ISW2 has therefore two distinct roles in mobilizing nucleosomes, with the ATPase domain translocating and moving DNA inside nucleosomes, and the SLIDE domain facilitating the entry of linker DNA into nucleosomes

A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids

Experimental in vitro models that capture pathophysiological characteristics of human tumours are essential for basic and translational cancer biology. Here, we describe a fully synthetic hydrogel extracellular matrix designed to elicit key phenotypic traits of the pancreatic environment in culture. To enable the growth of normal and cancerous pancreatic organoids from genetically engineered murine models and human patients, essential adhesive cues were empirically defined and replicated in the hydrogel scaffold, revealing a functional role of laminin–integrin α3/α6 signalling in establishment and survival of pancreatic organoids. Altered tissue stiffness—a hallmark of pancreatic cancer—was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro

Candidiasis, Bacterial Vaginosis, Trichomoniasis and Other Vaginal Conditions Affecting the Vulva

info:eu-repo/semantics/publishedVersio

A critical review and development of a conceptual model of exclusion from social relations for older people

Social exclusion is complex and dynamic, and it leads to the non-realization of social, economic, political or cultural rights or participation within a society. This critical review takes stock of the literature on exclusion of social relations. Social relations are defined as comprising social resources, social connections and social networks. An evidence review group undertook a critical review which integrates, interprets and synthesizes information across studies to develop a conceptual model of exclusion from social relations. The resulting model is a subjective interpretation of the literature and is intended to be the starting point for further evaluations. The conceptual model identifies individual risks for exclusion from social relations (personal attributes, biological and neurological risk, retirement, socio-economic status, exclusion from material resources and migration). It incorporates the evaluation of social relations, and the influence of psychosocial resources and socioemotional processes, sociocultural, social-structural, environmental and policy contextual influences on exclusion from social relations. It includes distal outcomes of exclusion from social relations, that is, individual well-being, health and functioning, social opportunities and social cohesion. The dynamic relationships between elements of the model are also reported. We conclude that the model provides a subjective interpretation of the data and an excellent starting point for further phases of conceptual development and systematic evaluation(s). Future research needs to consider the use of sophisticated analytical tools and an interdisciplinary approach in order to understand the underlying biological and ecopsychosocial associations that contribute to individual and dynamic differences in the experience of exclusion from social relation