AMPHIBIAN RESPONSE TO A LARGE-SCALE HABITAT RESTORATION IN THE PRAIRIE POTHOLE REGION

Over the next half-century, scientists anticipate that nearly one third of the currently recognized 7,450 amphibian species will become extinct. Many organizations have responded to the challenge of conserving amphibian biodiversity, some indirectly. Under the auspices of the Iowa Great Lakes Management Plan, the United States Fish and Wildlife Service, Department of Natural Resources, and their partners have been implementing habitat restoration efforts designed to protect water quality, provide recreational opportunities, and benefit wildlife at the regional level. With this program, over 130 wetlands have been created in the past 30 years on recently purchased public lands—one of the largest wetland restoration projects conducted in the Prairie Pothole Region of the Great Plains. While amphibians were not the main target of these restorations, we show that in response, 121 new breeding populations of native Northern Leopard Frogs (Lithobates pipiens; n = 80) and Eastern Tiger Salamanders (Ambystoma tigrinum; n = 41) have been established; in addition, we found 19 populations of non-native American Bullfrogs (L. catesbeianus). Using the program PRESENCE, we show that leopard frog occupancy was greatest in newer (<18 years old), intermediate-sized wetlands, and that tiger salamander occupancy was greatest in small wetlands without fish and larval bullfrogs. These data imply that because native amphibians responded positively to these newly established wetlands, habitat availability has likely been a factor in limiting population numbers. Further, these data suggest the presence of fishes and introduced bullfrogs interferes with the ability of tiger salamanders to colonize restored wetlands

Developing questionnaires for educational research: AMEE Guide No. 87

In this AMEE Guide, we consider the design and development of self-administered surveys, commonly called questionnaires. Questionnaires are widely employed in medical education research. Unfortunately, the processes used to develop such questionnaires vary in quality and lack consistent, rigorous standards. Consequently, the quality of the questionnaires used in medical education research is highly variable. To address this problem, this AMEE Guide presents a systematic, seven-step process for designing high-quality questionnaires, with particular emphasis on developing survey scales. These seven steps do not address all aspects of survey design, nor do they represent the only way to develop a high-quality questionnaire. Instead, these steps synthesize multiple survey design techniques and organize them into a cohesive process for questionnaire developers of all levels. Addressing each of these steps systematically will improve the probabilities that survey designers will accurately measure what they intend to measure

On the presentation of the LHC Higgs Results

We put forth conclusions and suggestions regarding the presentation of the LHC Higgs results that may help to maximize their impact and their utility to the whole High Energy Physics community.Comment: Conclusions from the workshops "Likelihoods for the LHC Searches", 21-23 January 2013 at CERN, "Implications of the 125 GeV Higgs Boson", 18-22 March 2013 at LPSC Grenoble, and from the 2013 Les Houches "Physics at TeV Colliders" workshop. 16 pages, 3 figures. Version 2: Comment added on the first publication of signal strength likelihoods in digital form by ATLA

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

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

Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

AbstractBackgroundCandidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated.ObjectiveTo validate published ccRCC prognostic biomarkers in an independent patient cohort and to assess intratumour heterogeneity (ITH) of the most promising markers to guide biomarker optimisation.Design, setting, and participantsCancer-specific survival (CSS) for each of 28 identified genetic or transcriptomic biomarkers was assessed in 350 ccRCC patients. ITH was interrogated in a multiregion biopsy data set of 10 ccRCCs.Outcome measurements and statistical analysisBiomarker association with CSS was analysed by univariate and multivariate analyses.Results and limitationsA total of 17 of 28 biomarkers (TP53 mutations; amplifications of chromosomes 8q, 12, 20q11.21q13.32, and 20 and deletions of 4p, 9p, 9p21.3p24.1, and 22q; low EDNRB and TSPAN7 expression and six gene expression signatures) were validated as predictors of poor CSS in univariate analysis. Tumour stage and the ccB expression signature were the only independent predictors in multivariate analysis. ITH of the ccB signature was identified in 8 of 10 tumours. Several genetic alterations that were significant in univariate analysis were enriched, and chromosomal instability indices were increased in samples expressing the ccB signature. The study may be underpowered to validate low-prevalence biomarkers.ConclusionsThe ccB signature was the only independent prognostic biomarker. Enrichment of multiple poor prognosis genetic alterations in ccB samples indicated that several events may be required to establish this aggressive phenotype, catalysed in some tumours by chromosomal instability. Multiregion assessment may improve the precision of this biomarker.Patient summaryWe evaluated the ability of published biomarkers to predict the survival of patients with clear cell kidney cancer in an independent patient cohort. Only one molecular test adds prognostic information to routine clinical assessments. This marker showed good and poor prognosis results within most individual cancers. Future biomarkers need to consider variation within tumours to improve accuracy

Mechanism of KMT5B haploinsufficiency in neurodevelopment in humans and mice

Pathogenic variants in KMT5B, a lysine methyltransferase, are associated with global developmental delay, macrocephaly, autism, and congenital anomalies (OMIM# 617788). Given the relatively recent discovery of this disorder, it has not been fully characterized. Deep phenotyping of the largest (n = 43) patient cohort to date identified that hypotonia and congenital heart defects are prominent features that were previously not associated with this syndrome. Both missense variants and putative loss-of-function variants resulted in slow growth in patient-derived cell lines. KMT5B homozygous knockout mice were smaller in size than their wild-type littermates but did not have significantly smaller brains, suggesting relative macrocephaly, also noted as a prominent clinical feature. RNA sequencing of patient lymphoblasts and Kmt5b haploinsufficient mouse brains identified differentially expressed pathways associated with nervous system development and function including axon guidance signaling. Overall, we identified additional pathogenic variants and clinical features in KMT5B-related neurodevelopmental disorder and provide insights into the molecular mechanisms of the disorder using multiple model systems

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