Outcome of the ‘Drip-and-Ship’ Paradigm among Patients with Acute Ischemic Stroke: Results of a Statewide Study

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Alternative tissue fixation for combined histopathological and molecular analysis in a clinically representative setting

Formalin is the principal tissue fixative used worldwide for clinical and research purposes. Despite optimal preservation of morphology, its preservation of DNA and RNA is poor. As clinical diagnostics increasingly incorporates molecular-based analysis, the requirement for maintaining nucleic acid quality is of increasing importance. Here we assess an alternative non-formalin-based tissue fixation method, PAXgene Tissue system, with the aim of better preserving nucleic acids, while maintaining the quality of the tissue to be used for vital existing diagnostic techniques. In this study, these criteria are assessed in a clinically representative setting. In total, 203 paired PAXgene Tissue and formalin-fixed samples were obtained. Blind-scored haematoxylin and eosin (H&E) sections showed comparable and acceptable staining. Immunohistochemistry (IHC) staining was suboptimal using existing protocols but improved with minor method adjustment and optimisation. Quality of DNA and RNA was significantly improved by PAXgene tissue fixation [RIN 2.8 versus 3.8 (p < 0.01), DIN 5.68 versus 6.77 (p < 0.001)], which translated into improved performance on qPCR assay. These results demonstrate the potential of PAXgene Tissue to be used routinely in place of formalin, maintaining adequate histological staining and significantly improving the preservation of biological molecules in the genomic era

Coffee consumption and prostate cancer risk: further evidence for inverse relationship

<p>Abstract</p> <p>Background</p> <p>Higher consumption of coffee intake has recently been linked with reduced risk of aggressive prostate cancer (PC) incidence, although meta-analysis of other studies that examine the association between coffee consumption and overall PC risk remains inconclusive. Only one recent study investigated the association between coffee intake and grade-specific incidence of PC, further evidence is required to understand the aetiology of aggressive PCs. Therefore, we conducted a prospective study to examine the relationship between coffee intake and overall as well as grade-specific PC risk.</p> <p>Methods</p> <p>We conducted a prospective cohort study of 6017 men who were enrolled in the Collaborative cohort study in the UK between 1970 and 1973 and followed up to 31st December 2007. Cox Proportional Hazards Models were used to evaluate the association between coffee consumption and overall, as well as Gleason grade-specific, PC incidence.</p> <p>Results</p> <p>Higher coffee consumption was inversely associated with risk of high grade but not with overall risk of PC. Men consuming 3 or more cups of coffee per day experienced 55% lower risk of high Gleason grade disease compared with non-coffee drinkers in analysis adjusted for age and social class (HR 0.45, 95% CI 0.23-0.90, p value for trend 0.01). This association changed a little after additional adjustment for Body Mass Index, smoking, cholesterol level, systolic blood pressure, tea intake and alcohol consumption.</p> <p>Conclusion</p> <p>Coffee consumption reduces the risk of aggressive PC but not the overall risk.</p

GW150914: First search for the electromagnetic counterpart of a gravitational-wave event by the TOROS collaboration

We present the results of the optical follow-up conducted by the TOROS collaboration of the first gravitational-wave event GW150914. We conducted unfiltered CCD observations (0.35-1 micron) with the 1.5-m telescope at Bosque Alegre starting ~2.5 days after the alarm. Given our limited field of view (~100 square arcmin), we targeted 14 nearby galaxies that were observable from the site and were located within the area of higher localization probability. We analyzed the observations using two independent implementations of difference-imaging algorithms, followed by a Random-Forest-based algorithm to discriminate between real and bogus transients. We did not find any bona fide transient event in the surveyed area down to a 5-sigma limiting magnitude of r=21.7 mag (AB). Our result is consistent with the LIGO detection of a binary black hole merger, for which no electromagnetic counterparts are expected, and with the expected rates of other astrophysical transients.Comment: ApJ Letters, in pres

Supermassive Black Hole Binaries: The Search Continues

Gravitationally bound supermassive black hole binaries (SBHBs) are thought to be a natural product of galactic mergers and growth of the large scale structure in the universe. They however remain observationally elusive, thus raising a question about characteristic observational signatures associated with these systems. In this conference proceeding I discuss current theoretical understanding and latest advances and prospects in observational searches for SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

KIM-1 as a blood-based marker for early detection of kidney cancer: a prospective nested case-control study

Purpose: Renal cell carcinoma (RCC) has the potential for cure with surgery when diagnosed at an early stage. Kidney injury molecule-1 (KIM-1) has been shown to be elevated in the plasma of RCC patients. We aimed to test whether plasma KIM-1 could represent a means of detecting RCC prior to clinical diagnosis. Experimental Design: KIM-1 concentrations were measured in pre-diagnostic plasma from 190 RCC cases and 190 controls nested within a population-based prospective cohort study. Cases had entered the cohort up to five years before diagnosis, and controls were matched on cases for date of birth, date at blood donation, sex, and country. We applied conditional logistic regression and flexible parametric survival models to evaluate the association between plasma KIM-1 concentrations and RCC risk and survival. Results: The incidence rate ratio (IRR) of RCC for a doubling in KIM-1 concentration was 1.71 (95% confidence interval [CI]: 1.44-2.03, p-value = 4.1x10-23), corresponding to an IRR of 63.3 (95% CI: 16.2-246.9) comparing the 80th to the 20th percentile of the KIM-1 distribution in this sample. Compared with a risk model including known risk factors of RCC (age, sex, country, body mass index and tobacco smoking status), a risk model additionally including KIM-1 substantially improved discrimination between cases and controls (area under the receiver operating characteristic curve of 0.8 compared to 0.7). High plasma KIM-1 concentrations were also associated with poorer survival (p=0.0053). Conclusions: Plasma KIM-1 concentrations could predict RCC incidence up to 5 years prior to diagnosis and were associated with poorer survival

A new molecular breast cancer subclass defined from a large scale real-time quantitative RT-PCR study

BACKGROUND: Current histo-pathological prognostic factors are not very helpful in predicting the clinical outcome of breast cancer due to the disease's heterogeneity. Molecular profiling using a large panel of genes could help to classify breast tumours and to define signatures which are predictive of their clinical behaviour. METHODS: To this aim, quantitative RT-PCR amplification was used to study the RNA expression levels of 47 genes in 199 primary breast tumours and 6 normal breast tissues. Genes were selected on the basis of their potential implication in hormonal sensitivity of breast tumours. Normalized RT-PCR data were analysed in an unsupervised manner by pairwise hierarchical clustering, and the statistical relevance of the defined subclasses was assessed by Chi2 analysis. The robustness of the selected subgroups was evaluated by classifying an external and independent set of tumours using these Chi2-defined molecular signatures. RESULTS: Hierarchical clustering of gene expression data allowed us to define a series of tumour subgroups that were either reminiscent of previously reported classifications, or represented putative new subtypes. The Chi2 analysis of these subgroups allowed us to define specific molecular signatures for some of them whose reliability was further demonstrated by using the validation data set. A new breast cancer subclass, called subgroup 7, that we defined in that way, was particularly interesting as it gathered tumours with specific bioclinical features including a low rate of recurrence during a 5 year follow-up. CONCLUSION: The analysis of the expression of 47 genes in 199 primary breast tumours allowed classifying them into a series of molecular subgroups. The subgroup 7, which has been highlighted by our study, was remarkable as it gathered tumours with specific bioclinical features including a low rate of recurrence. Although this finding should be confirmed by using a larger tumour cohort, it suggests that gene expression profiling using a minimal set of genes may allow the discovery of new subclasses of breast cancer that are characterized by specific molecular signatures and exhibit specific bioclinical features

Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Background:&nbsp;Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods:&nbsp;Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results:&nbsp;Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake&thinsp;=&thinsp;1.05, 95% CI 1.03&ndash;1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment&thinsp;=&thinsp;1.05, 95% CI 1.03&ndash;1.06 and 1.04, 95% CI 1.02&ndash;1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment&thinsp;=&thinsp;0.96, 95% CI 0.94&ndash;0.98; 0.96, 95% CI 0.94&ndash;0.99; and 0.96, 95% CI 0.95&ndash;0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions:&nbsp;Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.</p

Genetic Variation in the HSD17B1 Gene and Risk of Prostate Cancer

Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17β-hydroxysteroid dehydrogenase 1, an enzyme that converts dihydroepiandrosterone to the testosterone precursor Δ5-androsterone-3β,17β-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites