MYC regulation of a "poor-prognosis" metastatic cancer cell state.

Gene expression signatures are used in the clinic as prognostic tools to determine the risk of individual patients with localized breast tumors developing distant metastasis. We lack a clear understanding, however, of whether these correlative biomarkers link to a common biological network that regulates metastasis. We find that the c-MYC oncoprotein coordinately regulates the expression of 13 different "poor-outcome" cancer signatures. In addition, functional inactivation of MYC in human breast cancer cells specifically inhibits distant metastasis in vivo and invasive behavior in vitro of these cells. These results suggest that MYC oncogene activity (as marked by "poor-prognosis" signature expression) may be necessary for the translocation of poor-outcome human breast tumors to distant sites.

Environmental effects of Deccan volcanism across the Cretaceous-Tertiary transition in Meghalaya, India

The Urn Sohryngkew section of Meghalaya, NE India, located 800-1000 km from the Deccan volcanic province, is one of the most complete Cretaceous-Tertiary boundary (KTB) transitions worldwide with all defining and supporting criteria present: mass extinction of planktic foraminifera, first appearance of Danian species, delta(13)C shift, Ir anomaly (12 ppb) and KTB red layer. The geochemical signature of the KTB layer indicates not only an extraterrestrial signal (Ni and all Platinum Group Elements (PGEs)) of a second impact that postdates Chicxulub, but also a significant component resulting from condensed sedimentation (P), redox fluctuations (As, Co, Fe, Pb, Zn, and to a lesser extent Ni and Cu) and volcanism. From the late Maastrichtian C29r into the early Danian, a humid climate prevailed (kaolinite: 40-60%, detrital minerals: 50-80%). During the latest Maastrichtian, periodic acid rains (carbonate dissolution; CIA index: 70-80) associated with pulsed Deccan eruptions and strong continental weathering resulted in mesotrophic waters. The resulting super-stressed environmental conditions led to the demise of nearly all planktic foraminiferal species and blooms (>95%) of the disaster opportunist Guembelitria cretacea. These data reveal that detrimental marine conditions prevailed surrounding the Deccan volcanic province during the main phase of eruptions in C29r below the KTB. Ultimately these environmental conditions led to regionally early extinctions followed by global extinctions at the KTB. (C) 2011 Elsevier B.V. All rights reserved.

Species distribution and antifungal susceptibility profile of Candida spp. bloodstream isolates from Latin American hospitals

From March 1999 to March 2000, we conducted a prospective multicenter study of candidemia involving five tertiary care hospitals from four countries in Latin America. Yeast isolates were identified by classical methods and the antifungal susceptibility profile was determined according to the National Committee for Clinical Laboratory Standards microbroth assay method. During a 12 month-period we were able to collect a total of 103 bloodstream isolates of Candida spp. C. albicans was the most frequently isolated species accounting for 42% of all isolates. Non-albicans Candida species strains accounted for 58% of all episodes of candidemia and were mostly represented by C. tropicalis (24.2%) and C. parapsilosis (21.3%). It is noteworthy that we were able to identify two cases of C. lusitaniae from different institutions. In our casuistic, non-albicans Candida species isolates related to candidemic episodes were susceptible to fluconazole. Continuously surveillance programs are needed in order to identify possible changes in the species distribution and antifungal susceptibility patterns of yeasts that may occurs after increasing the use of azoles in Latin American hospitals.

A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations.

To develop a comprehensive overview of copy number aberrations (CNAs) in stage-II/III colorectal cancer (CRC), we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS) samples (n = 269) had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%), 7 (41.8%), 8 q (33.1%) and 13 q (51.0%) and losses on 18 (58.6%), 4 q (26%) and 21 q (21.6%). MSS tumors have significantly more CNAs than microsatellite-instable (MSI) tumors: within the MSI tumors a novel deletion of the tumor suppressor WWOX at 16 q23.1 was identified (p<0.01). Focal aberrations identified by the GISTIC method confirmed amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and deletions of tumor suppressors including TP53, APC, and SMAD4, and gene expression was highly concordant with copy number aberration for these genes. Novel amplicons included putative oncogenes such as WNK1 and HNF4A, which also showed high concordance between copy number and expression. Survival analysis associated a specific patient segment featured by chromosome 20 q gains to an improved overall survival, which might be due to higher expression of genes such as EEF1B2 and PTK6. The CNA clustering also grouped tumors characterized by a poor prognosis BRAF-mutant-like signature derived from mRNA data from this cohort. We further revealed non-random correlation between CNAs among unlinked loci, including positive correlation between 20 q gain and 8 q gain, and 20 q gain and chromosome 18 loss, consistent with co-selection of these CNAs. These results reinforce the non-random nature of somatic CNAs in stage-II/III CRC and highlight loci and genes that may play an important role in driving the development and outcome of this disease.

Disorders of pupillary structure and function.

Neurologists are frequently consulted because of a pupillary abnormality. An unequal size of the pupils, an unusual shape, white colored pupils, or a poorly reactive pupil are common reasons for referral. A directed history and careful observation of the iris and pupil movements can bear out ocular pathology such as congenital or structural anomalies as the cause of abnormal pupils. Thereafter, it is important to evaluate the neurologic causes of anisocoria and poor pupil function. The first part of this article emphasizes pupillary abnormalities frequently encountered in infants and children and discusses some of the more common acquired iris structural defects. The second part focuses on evaluation of lesions in the neural pathways that result in pupillary dysfunction, with particular attention to those conditions having neurologic, systemic, or visual implications.

Modular analysis of gene expression data with R.

SUMMARY: Large sets of data, such as expression profiles from many samples, require analytic tools to reduce their complexity. The Iterative Signature Algorithm (ISA) is a biclustering algorithm. It was designed to decompose a large set of data into so-called 'modules'. In the context of gene expression data, these modules consist of subsets of genes that exhibit a coherent expression profile only over a subset of microarray experiments. Genes and arrays may be attributed to multiple modules and the level of required coherence can be varied resulting in different 'resolutions' of the modular mapping. In this short note, we introduce two BioConductor software packages written in GNU R: The isa2 package includes an optimized implementation of the ISA and the eisa package provides a convenient interface to run the ISA, visualize its output and put the biclusters into biological context. Potential users of these packages are all R and BioConductor users dealing with tabular (e.g. gene expression) data. AVAILABILITY: http://www.unil.ch/cbg/ISA CONTACT: sven.bergmann@unil.ch

Cook It!

We have two Deaf members who are fully trained to deliver the COOK IT programme to other Deaf members. We have developed a signed COOK IT DVD for Deaf people to view.  It covers the information from the COOK IT programme and is signed in British Sign Language. Big Lottery Fund, Santander, Henry Smith Charity, Lloyds Foundation, Children in Need Initiative Type Nutrition Education and Training Programmes Location Derry/Londonderry Target Groups People with physical sensory and intellectual disability Funding Big Lottery Fund, Santander, Henry Smith Charity, Lloyds Foundation, Children in Need Partner Agencies Action on Hearing Loss Arts & Leisure Derry Healthy Cities Limavady Council North West Regional College Public Health Agency Signature Western Health and Social Care Trust

Decoupled post-glacial history in mutualistic plant-insect interactions: insights from the yellow loosestrife (Lysimachia vulgaris) and its associated oil-collecting bees (Macropis europaea and M-fulvipes)

AimWe take a comparative phylogeographical approach to assess whether three species involved in a specialized oil-rewarding pollination system (i.e. Lysimachia vulgaris and two oil-collecting bees within the genus Macropis) show congruent phylogeographical trajectories during post-glacial colonization processes. Our working hypothesis is that within specialized mutualistic interactions, where each species relies on the co-occurrence of the other for survival and/or reproduction, partners are expected to show congruent evolutionary trajectories, because they are likely to have followed parallel migration routes and to have shared glacial refugia. LocationWestern Palaearctic. MethodsOur analysis relies on the extensive sampling of 104 Western Palaearctic populations (totalling 434, 159 and 74 specimens of Lysimachiavulgaris, Macropiseuropaea and Macropisfulvipes, respectively), genotyped with amplified fragment length polymorphism. Based on this, we evaluated the regional genetic diversity (Shannon diversity and allele rarity index) and genetic structure (assessed using structure, population networks, isolation-by-distance and spatial autocorrelation metrics) of each species. Finally, we compared the general phylogeographical patterns obtained. ResultsContrary to our expectations, the analyses revealed phylogeographical signals suggesting that the investigated organisms demonstrate independent post-glacial trajectories as well as distinct contemporaneous demographic parameters, despite their mutualistic interaction. Main conclusionsThe mutualistic partners investigated here are likely to be experiencing distinct and independent evolutionary dynamics because of their contrasting life-history traits (e.g. dispersal abilities), as well as distinct hubs and migration routes. Such conditions would prevent and/or erase any signature of co-structuring of lineages in space and time. As a result, the lack of phylogeographical congruence driven by differences in life-history traits might have arisen irrespective of the three species having shared similar Pleistocene glacial refugia.

The prediction of cardiovascular events is improved by combination of Framingham risk score and subclinical atherosclerosis imaging

Purpose: In primary prevention of cardiovascular disease (CVD), it is accepted that the intensity of risk factor treatment should be guided by the magnitude of absolute risk. Risk factors tools like Framingham risk score (FHS) or noninvasive atherosclerosis imaging tests are available to detect high risk subjects. However, these methods are imperfect and may misclassify a large number of individuals. The purpose of this prospective study was to evaluate whether the prediction of future cardiovascular events (CVE) can be improved when subclinical imaging atherosclerosis (SCATS) is combined with the FRS in asymptomatic subjects. Methods: Overall, 1038 asymptomatic subjects (413 women, 625 men, mean age 49.1±12.8 years) were assessed for their cardiovascular risk using the FRS. B-mode ultrasonography on carotid and femoral arteries was performed by two investigators to detect atherosclerotic plaques (focal thickening of intima-media > 1.2 mm) and to measure carotid intima-media thickness (C-IMT). The severity of SCATS was expressed by an ATS-burden Score (ABS) reflecting the number of the arterial sites with >1 plaques (range 0-4). CVE were defined as fatal or non fatal acute coronary syndrome, stroke, or angioplasty for peripheral artery disease. Results: during a mean follow-up of 4.9±3.1 years, 61 CVE were recorded. Event rates the rate of CVE increased significantly from 2.7% to 39.1% according to the ABS (p<0.001) and from 4% to 24.6% according to the quartiles of C-IMT. Similarly, FRS predicted CVE (p<0.001). When computing the angiographic markers of SCATS in addition of FRS, we observed an improvement of net reclassification rate of 16.6% (p< 0.04) for ABS as compared to 5.5% (p = 0.26) for C-IMT. Conclusion: these results indicate that the detection of subjects requiring more attention to prevent CVE can be significantly improved when using both FRS and SCATS imaging.

Bingo segur

En aquest TFC es proposa un protocol de CMS aplicat a un Joc de Bingo, en que les entrades són nombres generats pels jugadors i el resultat cercat és un nombre aleatori per al joc.

Efficacy And Safety Of Baerveldt Aqueous Shunts In Glaucoma Secondary To Anterior Segment Irradiation, For Uveal Melanoma

Purpose: Elevated IOP is commonly associated with iris and ciliary body melanoma. Traditional management requires the majority of eyes to undergo enucleation. The authors describe the first series of Baerveldt aqueous shunts in eyes with uveal melanoma, treated by total anterior segment irradiation.Methods: 25 consecutive patients with unilateral iris melanoma were prospectively recruited after obtaining informed consent. All patients underwent anterior segment proton beam irradiation, corneal limbal autografts and Baerveldt tube implantation at Jules Gonin Eye Hospital, Lausanne. Postoperative examinations were performed on day 1, weeks 1,3,6,9 and months 3,6,12 and annually thereafter. Success was defined as: IOP </=18mmHg (definition A); IOP </= 21mmHg and 20% reduction in IOP (definition B). All complications were recorded.Results: Mean age was 53; mean follow up, 10.3 months; mean interval to treatment following irradiation, 2.4 years; mean pre-op IOP was 29.9 mmHg; mean post-op IOP 14.1 mmHg; mean pre-op medications 3.0; post-op medications 1.3. Success rates were, definition A: 95%; definition B: 90%. Only11% had minor complications and there were no sight-threatening complications. Aggressive ocular hypertension was observed in the several eyes prior to shunt implantation. Two eyes were enucleated for non-glaucoma related sequelae.Conclusions: Baerveldt aqueous shunts are safe and efficacious following total anterior segment irradiation for uveal melanoma. The novel interdisciplinary approach improved ocular retention rates, offering a promising alternative to current management algorithms.

Biomarkers of human gastrointestinal tract regions.

Dysregulation of intestinal epithelial cell performance is associated with an array of pathologies whose onset mechanisms are incompletely understood. While whole-genomics approaches have been valuable for studying the molecular basis of several intestinal diseases, a thorough analysis of gene expression along the healthy gastrointestinal tract is still lacking. The aim of this study was to map gene expression in gastrointestinal regions of healthy human adults and to implement a procedure for microarray data analysis that would allow its use as a reference when screening for pathological deviations. We analyzed the gene expression signature of antrum, duodenum, jejunum, ileum, and transverse colon biopsies using a biostatistical method based on a multivariate and univariate approach to identify region-selective genes. One hundred sixty-six genes were found responsible for distinguishing the five regions considered. Nineteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion and six novel genes. Moreover, by crossing these genes with those retrieved from an existing data set of gene expression in the intestine of ulcerative colitis and Crohn's disease patients, we identified genes that might be biomarkers of Crohn's and/or ulcerative colitis in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. This study furnishes the first map of gene expression along the healthy human gastrointestinal tract. Furthermore, the approach implemented here, and validated by retrieving known gene profiles, allowed the identification of promising new leads in both healthy and disease states.

Signatura digital

Aquest projecte tracta la Signatura Digital des del punt de vista d'un Enginyer de Software que ha d'iniciar un projecte que doni serveis de Signatura Digital a un projecte més ampli d'Administració Electrònica. El projecte contempla: els conceptes bàsics de la Signatura Digital, les particularitats de la Signatura Digital, les funcionalitats i serveis que pot proporcionar a una plataforma de tramitació electrònica, els requeriments de Signatura Electrònica per l'AE, la selecció d'un proveïdor de serveis de Signatura que cobreixi els nostres requeriments i els de l'AE, les funcionalitats del proveïdor CATCert (plataforma PSIS); i a través d'aquests estudis, la realització de l'anàlisi, disseny i construcció d'un mòdul que pugui subministrar autenticació, identificació i signatura digital a una plataforma d'AE.

Memòria TFC : gestió de Factures electròniques

El projecte que s'ha desenvolupat és la gestió de factures amb firma electrònica, on la finalitat és integrar una aplicació completament funcional a la suit d'ofimàtica Microsoft Office, amb certs requisits com la firma amb certificat digital, la qual cosa fa que les factures sigui vàlides per Hisenda.