Langetermijnresultaten van continent katheteriseerbare urostoma’s bij volwassenen met niet-neurogene of neurogene blaasontledigingsstoornissen

The objective was to evaluate the long-term results after the construction of a continent catheterizable urinary conduit in adults. We retrospectively reviewed the charts of 41 adults who received a continent catheterizable urinary conduit and extracted indications and complications (29/41 women, average age 32, median follow-up durations 52 months, 48% ≥1 reoperation). Patients who were still using the conduit during this research (n = 32) were sent a questionnaire about their impression of improvement, continence and catheterization problems. 24 patients completed the questionnaire and on average reported a ‘much better’ situation. In conclusion, the construction of a continent catheterizable urinary conduit in adults is associated with a high complication and reoperation rate. Nevertheless, patients perceive improvement compared to before the construction of the stoma

BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer.Measures of genetic risk (report of family history, segregation) were assessed for 68 BRCA1 c.5096G>A p.Arg1699Gln (R1699Q) families recruited through family cancer clinics, comparing results with 34 families carrying the previously classified pathogenic BRCA1 c.5095C>T p.Arg1699Trp (R1699W) mutation at the same residue, and to 243 breast cancer families with no BRCA1 pathogenic mutation (BRCA-X).Comparison of BRCA1 carrier prediction scores of probands using the BOADICEA risk prediction tool revealed that BRCA1 c.5096G>A p.Arg1699Gln variant carriers had family histories that were less 'BRCA1-like' than BRCA1 c.5095C>T p.Arg1699Trp mutation carriers (pA p.Arg1699Gln had reduced penetrance compared with the average truncating BRCA1 mutation penetrance (p=0.0002), with estimated cumulative risks to age 70 of breast or ovarian cancer of 24%.Our results provide substantial evidence that the BRCA1 c.5096G>A p.Arg1699Gln (R1699Q) variant, demonstrating ambiguous functional deficiency across multiple assays, is associated with intermediate risk of breast and ovarian cancer, highlighting challenges for risk modelling and clinical management of patients of this and other potential moderate-risk variants

Long-term results of continent catheterizable urinary channels in adults with non-neurogenic or neurogenic lower urinary tract dysfunction

Objectives: To evaluate the long-term results after the construction of a Continent Catheterizable Urinary Conduit (CCUC) in adults. Methods: This study retrospectively reviewed the charts of 41 adults from two tertiary centers who received a CCUC. The demographics, underlying diseases, indications for a CCUC and outcomes such as the reoperation rate and the occurrence of complications were extracted. The patient reported outcome was measured with the Patient Global Impression of Improvement (PGI-I) scale and four additional questions about continence, leakage and stomal problems. Results: Twenty-nine patients were women. The median age at surgery was 32 years, with a median follow-up of 52 months. Twenty-six patients had a neurogenic bladder. The reoperation rate was 48.8%, with a median of 10.5 months after constructing the CCUC. Superficial stomal stenosis was the most common registered complication (20 times) and stoma revision was the most often performed reoperation (12 times). Twenty-four patients completed the PGI-I; the mean improvement rating was 2 (=much better). Conclusion: The construction of a CCUC in adults is associated with a high complication and reoperation rate. The high reoperation rate is in accordance with the sparse literature. Despite this, patients reported 'much better' on the PGI-I

Tundra in the rain:differential vegetation responses to three years of experimentally doubled summer precipitation in Siberian shrub and Swedish bog tundra

Precipitation amounts and patterns at high latitude sites have been predicted to change as a result of global climatic changes. We addressed vegetation responses to three years of experimentally increased summer precipitation in two previously unaddressed tundra types: Betula nana-dominated shrub tundra (northeast Siberia) and a dry Sphagnum fuscum-dominated bog (northern Sweden). Positive responses to approximately doubled ambient precipitation (an increase of 200 mm year(−1)) were observed at the Siberian site, for B. nana (30 % larger length increments), Salix pulchra (leaf size and length increments) and Arctagrostis latifolia (leaf size and specific leaf area), but none were observed at the Swedish site. Total biomass production did not increase at either of the study sites. This study corroborates studies in other tundra vegetation types and shows that despite regional differences at the plant level, total tundra plant productivity is, at least at the short or medium term, largely irresponsive to experimentally increased summer precipitation

Genotype-phenotype relationships as prognosticators in Rett syndrome should be handled with care in clinical practice

Rett syndrome (RTT; OMIM 312750) is an X-linked dominant neurodevelopmental disorder leading to cognitive and motor impairment, epilepsy, and autonomic dysfunction in females. Since the discovery that RTT is caused by mutations in MECP2, large retrospective genotype-phenotype correlation studies have been performed. A number of general genotype-phenotype relationships were confirmed and specific disorder profiles were described. Nevertheless, conflicting results are still under discussion, partly due to the variability in classification of mutations, assessment tools, and structure of the data sets. The aim of this study was to investigate relationships between genotype and specific clinical data collected by the same experienced physician in a well-documented RTT cohort, and evaluate its prognostic value in counseling young parents with a newly diagnosed RTT girl regarding her future outcome. The Maastricht-Leuven Rett Syndrome Database is a register of 137 molecularly confirmed clinical RTT cases, containing both molecular and clinical data on examination and follow up by the same experienced physician. Although the general genotype-phenotype relationships were confirmed, the clinical severity was still found to be very variable. We therefore recommend caution in using genotype-phenotype data in the prognosis of outcome for children in Rett syndrome. Early diagnosis, early intervention, and preventive management are imperative for better outcomes and better quality of daily life for RTT females and their families. © 2011 Wiley Periodicals, Inc.status: publishe

Winters are changing: Snow effects on Arctic and alpine tundra ecosystems

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions, and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes, and biogeochemical cycling. We also compare studies of natural snow gradients with snow experimental manipulation studies to assess time scale difference of these approaches. The number of tundra snow studies has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. Specifically, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by snow addition and snow removal manipulations (average 7.9 days advance and 5.5 days delay, respectively) were substantially lower than the temporal variation over natural spatial gradients within a given year (mean range 56 days) or among years (mean range 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates

Winters are changing: snow effects on Arctic and alpine tundra ecosystems

Snow is an important driver of ecosystem processes in cold biomes. Snow accumulation determines ground temperature, light conditions and moisture availability during winter. It also affects the growing season’s start and end, and plant access to moisture and nutrients. Here, we review the current knowledge of the snow cover’s role for vegetation, plant-animal interactions, permafrost conditions, microbial processes and biogeochemical cycling. We also compare studies of natural snow gradients with snow manipulation studies, altering snow depth and duration, to assess time scale difference of these approaches. The number of studies on snow in tundra ecosystems has increased considerably in recent years, yet we still lack a comprehensive overview of how altered snow conditions will affect these ecosystems. In specific, we found a mismatch in the timing of snowmelt when comparing studies of natural snow gradients with snow manipulations. We found that snowmelt timing achieved by manipulative studies (average 7.9 days advance, 5.5 days delay) were substantially lower than those observed over spatial gradients (mean range of 56 days) or due to interannual variation (mean range of 32 days). Differences between snow study approaches need to be accounted for when projecting snow dynamics and their impact on ecosystems in future climates

Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes: An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group

Purpose To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes. Methods Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy. Results Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations. Conclusion Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies. (C) 2018 by American Society of Clinical Oncolog