Microsatellite alteration and immunohistochemical expression profile of chromosome 9p21 in patients with sporadic renal cell carcinoma following surgical resection.

BACKGROUND: Long-term prognostic significance of loss of heterozygosity on chromosome 9p21 for localized renal cell carcinoma following surgery remains unreported. The study assessed the frequency of deletions of different loci of chromosome 9p along with immunohistochemical profile of proteins in surgically resected renal cancer tissue and correlated this with long-term outcomes. METHODS: DNA was extracted from renal tumours and corresponding normal kidney tissues in prospectively collected samples of 108 patients who underwent surgical resection for clinically localized disease between January 2001 and December 2005, providing a minimum of 9 years follow-up for each participant. After checking quality of DNA, amplified by PCR, loss of heterozygosity (LOH) on chromosome 9p was assessed using 6 microsatellite markers in 77 clear cell carcinoma. Only 5 of the markers showed LOH (D9S1814, D9S916, D9S974, D9S942, and D9S171). Protein expression of p15(INK4b), p16(INK4a), p14(ARF), CAIX, and adipose related protein (ADFP) were demonstrated by immunostaining in normal and cancer tissues. Loss of heterozygosity for microsatellite analysis was correlated with tumour characteristics, recurrence free, cancer specific, and overall survival, including significance of immunohistochemical profile of protein expressions. RESULTS: The main deletion was found at loci telomeric to CDKN2A region at D9S916. There was a significant correlation between frequency of LOH stage (p = 0.005) and metastases (p = 0.006) suggesting a higher LOH for advanced and aggressive renal cell carcinoma. Most commonly observed LOH in the 3 markers: D9S916, D9S974, and D9S942 were associated with poor survival, and were statistically significant on multivariate analysis. Immunohistochemical expression of p14, p15, and p16 proteins were either low or absent in cancer tissue compared to normal. CONCLUSIONS: Loss of heterozygosity of p921 chromosome is associated with aggressive tumours, and predicts cancer specific or recurrence free survival on long-term follow-up. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2514-8) contains supplementary material, which is available to authorized users

Les Houches 2011: Physics at TeV Colliders New Physics Working Group Report

We present the activities of the "New Physics" working group for the "Physics at TeV Colliders" workshop (Les Houches, France, 30 May-17 June, 2011). Our report includes new agreements on formats for interfaces between computational tools, new tool developments, important signatures for searches at the LHC, recommendations for presentation of LHC search results, as well as additional phenomenological studies.Comment: 243 pages, report of the Les Houches 2011 New Physics Group; fix three figure

What Will It Take to Eliminate Pediatric HIV? Reaching WHO Target Rates of Mother-to-Child HIV Transmission in Zimbabwe: A Model-Based Analysis

Using a simulation model, Andrea Ciaranello and colleagues find that the latest WHO PMTCT (prevention of mother to child transmission of HIV) guidelines plus better access to PMTCT programs, better retention of women in care, and better adherence to drugs are needed to eliminate pediatric HIV in Zimbabwe

Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development

Screening for inter-hospital differences in cesarean section rates in low-risk deliveries using administrative data: An initiative to improve the quality of care

BACKGROUND: Rising national cesarean section rates (CSRs) and unexplained inter-hospital differences in CSRs, led national and international bodies to select CSR as a quality indicator. Using hospital discharge abstracts, we aimed to document in Belgium (1) inter-hospital differences in CSRs among low risk deliveries, (2) a national upward CSR trend, (3) lack of better neonatal outcomes in hospitals with high CSRs, and (4) possible under-use of CS. METHODS: We defined a population of low risk deliveries (singleton, vertex, full-term, live born, 2499 g). Using multivariable logistic regression techniques, we provided degrees of evidence regarding the observed departure ([relative risk-1]*100) of each hospital (N = 107) from the national CSR and its trend. To determine a benchmark, we defined three CSR groups (high, average and low) and compared them regarding 1 minute Apgar scores and other neonatal endpoints. An anonymous feedback is provided to the hospitals, the College of Physicians (with voluntary disclosure of the outlying hospitals for quality improvement purposes) and to the policy makers. RESULTS: Compared with available information, the completeness and accuracy of the data, regarding the variables selected to determine our study population, showed adequate. Important inter-hospital differences were found. Departures ranged from -65% up to +75%, and 9 "high CSR" and 13 "low CSR" outlying hospitals were identified. We observed a national increasing trend of 1.019 (95%CI [1.015; 1.022]) per semester, adjusted for age groups. In the "high CSR" group 1 minute Apgar scores <4 were over-represented in the subgroup of vaginal deliveries, suggesting CSs not carried out for medical reasons. Under-use of CS was also observed. Given their questionable completeness, except Apgar scores, our neonatal results, showing a significant association of CS with adverse neonatal endpoints, are to be cautiously interpreted. Taking the available evidence into account, the "Average CSR" group seemed to be the best benchmark candidate. CONCLUSION: Rather than firm statements about quality of care, our results are to be considered a useful screening. The inter-hospital differences in CSR, the national CS upward trend, the indications of over-use and under-use, the geographically different obstetric patterns and the admission day-related concentration of deliveries, whether or not by CS, may trigger initiatives aiming at improving quality of care

WHO 2010 Guidelines for Prevention of Mother-to-Child HIV Transmission in Zimbabwe: Modeling Clinical Outcomes in Infants and Mothers

The Zimbabwean national prevention of mother-to-child HIV transmission (PMTCT) program provided primarily single-dose nevirapine (sdNVP) from 2002-2009 and is currently replacing sdNVP with more effective antiretroviral (ARV) regimens.Published HIV and PMTCT models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). We compared five PMTCT regimens at a fixed level of PMTCT medication uptake: 1) no antenatal ARVs (comparator); 2) sdNVP; 3) WHO 2010 guidelines using "Option A" (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy (ART) for women with advanced disease); 4) WHO "Option B" (ART during pregnancy/breastfeeding without advanced disease; lifelong ART with advanced disease); and 5) "Option B+:" lifelong ART for all pregnant/breastfeeding, HIV-infected women. Pediatric (4-6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected.Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal ARVs) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of sdNVP (13.8 years) or Option B (13.9 years) compared to no antenatal ARVs (14.0 years), Option A (14.0 years), or Option B+ (14.5 years).Replacement of sdNVP with currently recommended regimens for PMTCT (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both pediatric and maternal outcomes

E-NTPDases in human airways: Regulation and relevance for chronic lung diseases

Chronic obstructive lung diseases are characterized by the inability to prevent bacterial infection and a gradual loss of lung function caused by recurrent inflammatory responses. In the past decade, numerous studies have demonstrated the importance of nucleotide-mediated bacterial clearance. Their interaction with P2 receptors on airway epithelia provides a rapid ‘on-and-off’ signal stimulating mucus secretion, cilia beating activity and surface hydration. On the other hand, abnormally high ATP levels resulting from damaged epithelia and bacterial lysis may cause lung edema and exacerbate inflammatory responses. Airway ATP concentrations are regulated by ecto nucleoside triphosphate diphosphohydrolases (E-NTPDases) which are expressed on the mucosal surface and catalyze the sequential dephosphorylation of nucleoside triphosphates to nucleoside monophosphates (ATP → ADP → AMP). The common bacterial product, Pseudomonas aeruginosa lipopolysaccharide (LPS), induces an acute reduction in azide-sensitive E-NTPDase activities, followed by a sustained increase in activity as well as NTPDase 1 and NTPDase 3 expression. Accordingly, chronic lung diseases, including cystic fibrosis (CF) and primary ciliary dyskinesia, are characterized by higher rates of nucleotide elimination, azide-sensitive E-NTPDase activities and expression. This review integrates the biphasic regulation of airway E-NTPDases with the function of purine signaling in lung diseases. During acute insults, a transient reduction in E-NTPDase activities may be beneficial to stimulate ATP-mediated bacterial clearance. In chronic lung diseases, elevating E-NTPDase activities may represent an attempt to prevent P2 receptor desensitization and nucleotide-mediated lung damage

Tree community variation in a tropical continental island according to slope aspect and human interference

ABSTRACT Associating description of unrecorded tropical tree community structure to sampling approaches that can help determine mechanisms behind floristic variation is important to further the comprehension of how plant species coexist at tropical forests. Thus, this study had the goals of (i) evaluating tree community structure on the continental island of Marambaia (23°4’37.09”S; 43°59’2.15”W) and (ii) testing the prediction that there are local scale changes in a tropical tree community structure between slopes facing different geographic orientation and with distinct human interference history. We established 60 (0.6 ha) sampling units in three different slope sites with distinct predominant geographic orientation and human interference. We sampled all woody trees with diameter at breast height (dbh) ≥ 5 cm. We found a total of 1.170 individuals representing 220 species, 120 genera and 50 families. The overall tree community structure and structural descriptors (abundance of individuals, basal area, species richness and diversity) varied extensively between the sites. The evidence presented here supports that local scale topography variations and human interference history can be important factors contributing to the known floristic heterogeneity of the Atlantic Rainforest. Future work on the study area should focus on disentangling effects from distinct causal factors over tree community variation and species occurrence