The phenotype of floating-harbor syndrome:clinical characterization of 52 individuals with mutations in exon 34 of SRCAP

Background\ud Floating-Harbor syndrome (FHS) is a rare condition characterized by short stature, delays in expressive language, and a distinctive facial appearance. Recently, heterozygous truncating mutations in SRCAP were determined to be disease-causing. With the availability of a DNA based confirmatory test, we set forth to define the clinical features of this syndrome.\ud \ud Methods and results\ud Clinical information on fifty-two individuals with SRCAP mutations was collected using standardized questionnaires. Twenty-four males and twenty-eight females were studied with ages ranging from 2 to 52 years. The facial phenotype and expressive language impairments were defining features within the group. Height measurements were typically between minus two and minus four standard deviations, with occipitofrontal circumferences usually within the average range. Thirty-three of the subjects (63%) had at least one major anomaly requiring medical intervention. We did not observe any specific phenotype-genotype correlations.\ud \ud Conclusions\ud This large cohort of individuals with molecularly confirmed FHS has allowed us to better delineate the clinical features of this rare but classic genetic syndrome, thereby facilitating the development of management protocols.The authors would like to thank the families for their cooperation and permission to publish these findings. SdM would like to thank Barto Otten. Funding was provided by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research (CIHR) and the Ontario Genomics Institute (OGI-049), by Genome Québec and Genome British Columbia, and the Manton Center for Orphan Disease Research at Children’s Hospital Boston. KMB is supported by a Clinical Investigatorship Award from the CIHR Institute of Genetics. AD is supported by NIH grant K23HD073351. BBAdV and HGB were financially supported by the AnEUploidy project (LSHG-CT-2006-37627). This work was selected for study by the FORGE Canada Steering Committee, which consists of K. Boycott (University of Ottawa), J. Friedman (University of British Columbia), J. Michaud (University of Montreal), F. Bernier (University of Calgary), M. Brudno (University of Toronto), B. Fernandez (Memorial University), B. Knoppers (McGill University), M. Samuels (Université de Montréal), and S. Scherer (University of Toronto). We thank the Galliera Genetic Bank - “Telethon Genetic Biobank Network” supported by Italian Telethon grants (project no. GTB07001) for providing us with specimens

Lancet

BACKGROUND: In 2015, the second cycle of the CONCORD programme established global surveillance of cancer survival as a metric of the effectiveness of health systems and to inform global policy on cancer control. CONCORD-3 updates the worldwide surveillance of cancer survival to 2014. METHODS: CONCORD-3 includes individual records for 37.5 million patients diagnosed with cancer during the 15-year period 2000-14. Data were provided by 322 population-based cancer registries in 71 countries and territories, 47 of which provided data with 100% population coverage. The study includes 18 cancers or groups of cancers: oesophagus, stomach, colon, rectum, liver, pancreas, lung, breast (women), cervix, ovary, prostate, and melanoma of the skin in adults, and brain tumours, leukaemias, and lymphomas in both adults and children. Standardised quality control procedures were applied; errors were rectified by the registry concerned. We estimated 5-year net survival. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: For most cancers, 5-year net survival remains among the highest in the world in the USA and Canada, in Australia and New Zealand, and in Finland, Iceland, Norway, and Sweden. For many cancers, Denmark is closing the survival gap with the other Nordic countries. Survival trends are generally increasing, even for some of the more lethal cancers: in some countries, survival has increased by up to 5% for cancers of the liver, pancreas, and lung. For women diagnosed during 2010-14, 5-year survival for breast cancer is now 89.5% in Australia and 90.2% in the USA, but international differences remain very wide, with levels as low as 66.1% in India. For gastrointestinal cancers, the highest levels of 5-year survival are seen in southeast Asia: in South Korea for cancers of the stomach (68.9%), colon (71.8%), and rectum (71.1%); in Japan for oesophageal cancer (36.0%); and in Taiwan for liver cancer (27.9%). By contrast, in the same world region, survival is generally lower than elsewhere for melanoma of the skin (59.9% in South Korea, 52.1% in Taiwan, and 49.6% in China), and for both lymphoid malignancies (52.5%, 50.5%, and 38.3%) and myeloid malignancies (45.9%, 33.4%, and 24.8%). For children diagnosed during 2010-14, 5-year survival for acute lymphoblastic leukaemia ranged from 49.8% in Ecuador to 95.2% in Finland. 5-year survival from brain tumours in children is higher than for adults but the global range is very wide (from 28.9% in Brazil to nearly 80% in Sweden and Denmark). INTERPRETATION: The CONCORD programme enables timely comparisons of the overall effectiveness of health systems in providing care for 18 cancers that collectively represent 75% of all cancers diagnosed worldwide every year. It contributes to the evidence base for global policy on cancer control. Since 2017, the Organisation for Economic Co-operation and Development has used findings from the CONCORD programme as the official benchmark of cancer survival, among their indicators of the quality of health care in 48 countries worldwide. Governments must recognise population-based cancer registries as key policy tools that can be used to evaluate both the impact of cancer prevention strategies and the effectiveness of health systems for all patients diagnosed with cancer. FUNDING: American Cancer Society; Centers for Disease Control and Prevention; Swiss Re; Swiss Cancer Research foundation; Swiss Cancer League; Institut National du Cancer; La Ligue Contre le Cancer; Rossy Family Foundation; US National Cancer Institute; and the Susan G Komen Foundation

La séquence climatique continentale des Echets (alt.: 267 m, Ain, France): état de l'art des études multiproxies menées à bien sur les profils EC1 et EC3 entre la fin du Riss et le Pléniglaciaire würmien.

Cette étude est réalisée dans le cadre d'un groupement de compétences ("Les Echets Working Group") et du Groupement de Laboratoires Géoprospective de l'Andra, avec un financement multinational. A ce jour les principaux résultats sont les suivants. 1- Pendant le tardiglaciaire rissien et le stade de Caluire (Zeifen-Kattegat, H 11 ), des végétations successivement forestières boréales puis steppiques se mettent en place. Les taux de carbone minéral (exogène, loess) restent élevés au début de l'Eémien, alors qu'une chênaie mixte se met en place. C'est aussi le cas pendant les stades et le début des interstades du OIS 5. 2 - Les données biologiques et le rapport S2/S3CO2>4 indiquent que le climat devient plus humide dès l'immixtion de Taxus au sein de la chênaie éémienne. Le retour de la sapinière à la fin de l'Eémien, traduit un ultime réchauffement du climat avant le refroidissement du Mélisey 1 (OIS 5d). 3 - Le St Germain 1 se distingue par sa très forte variabilité climatique: i) au début, événements froids EC1 14a et Montaigu; ii) à la fin, un événement froid (EC1 19a, homologue du C22) et événement tempéré (EC1 19b, homologue du DO 22). 4 - Pendant les stades froids du Mélisey 1 (OIS 5d) et 2 (OIS 5b), les Chironomides indiquent des Tjuil comprises entre 10 et 14°C et un abaissement bathymétrique lacustre. 5 - Au St Germain 2 (OIS 5a), les maximums concordants de Carpinus et de S2/S3CO2>4 indiquent une élévation de l'humidité. 6 - Pendant le Pléniglaciaire würmien, l'évolution concordante et itérative du pollen de la taïga, du COT et du S2/S3CO2>4 pourrait correspondre aux pics thermiques mis en évidence pendant le OIS 3. Le "modèle" chronologique de l'ensemble de la séquence des Echets sera établi à partir des techniques OSL, C14 et Ar/Ar (sur téphras). Les mesures paléomagnétiques montrent que EC1 recèle l'empreinte des "excursions" de Blake (115-120 ka), Laschamps (40 ka) et Mono (32 ka). Les reconstructions climatiques mutiproxies sont en cours, de même que l'édification d'un pont scientifique Continent-Océan-Glace car, plus que d'autres, les séquences continentales proxi-atlantiques françaises, vieilles de 400 ka dans le Massif Central, sont aptes à percevoir la variabilité climatique mise en évidence dans les archives globales et les autres compartiments du "système Terre"

Effects of Float Nursing on Patient Care and Safety

https://scholarlycommons.baptisthealth.net/cohort-5-ebp-showcase/1011/thumbnail.jp

Terrestrial and limnic response to rapid climate variability between 20-60 kyr BP – the Les Echets sequence

The last glacial period was characterized by centennial-millennial scale climatic instabilities, which involved rapid changes in oceanographic conditions and in atmospheric temperature over different continental regions of the Northern Hemisphere. These Dansgaard-Oeschger cycles, which are most pronounced between 20-60 kyr BP, are a prominent feature in ice core and marine records, but have only rarely been documented from terrestrial records. Several hypotheses have been brought forward to explain the observed fluctuations, but understanding the relationship between different mechanisms is hampered by large dating uncertainties and insufficient sampling resolution to perform detailed correlations between different archives. One of the few European terrestrial sequences, with adequate sedimentation rates to record this rapid climate variability is the site Les Echets (45°54'N; 4°56'E) in south-central France. The strategic location of the site, south of the large ice sheets, at some distance from the North Atlantic and north of the Mediterranean region, fills an important gap in determining the spatial vari¬ability and environmental impact of these fluctuations. New sediment cores were obtained at Les Echets in autumn 2001 and are currently analysed for a variety of different climatic and environmental proxies (tephra, mineral magnetics, grain-size, LOI, carbonates, C/N ratio, δ13C, δ15N, δ18O, biogenic silica, biomarkers, pollen, macrofossils, charcoal, chironomids, diatoms, ostracods). High-resolution sampling (<50 yrs) and detailed age control (AMS 14C, OSL) provides the necessary framework for assessing rapid environmental changes and allows creating an independent time scale. The proxy data sets analysed so far give clear evidence that the limnic and terrestrial environment underwent dramatic changes, which resemble the high-frequency climate oscillations seen in ice cores and marine sediments

Genetic Susceptibility to Hepatic Sinusoidal Obstruction Syndrome in Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation

Sinusoidal obstruction syndrome (SOS) is a well-recognized and potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT). SOS arises from endothelial cell damage and hepatocellular injury mostly due to the transplantation conditioning regimens but also to other patient, disease, and treatment-related factors. Understanding risk factors associated with the development of SOS is critical for early initiation of treatment or prophylaxis. The knowledge about genetic contribution is limited; few studies investigated so far selected a set of genes. To get more comprehensive insight in the genetic component, we performed an exome-wide association study using genetic variants derived from whole-exome sequencing. The analyses were performed in a discovery cohort composed of 87 pediatric patients undergoing HSCT following a busulfan-containing conditioning regimen. Eight lead single-nucleotide polymorphisms (SNPs) were identified after correction for multiple testing and subsequently analyzed in a validation cohort (n = 182). Three SNPs were successfully replicated, including rs17146905 (P = .001), rs16931326 (P = .04), and rs2289971 (P = .03), located respectively in the UGT2B10, BHLHE22, and KIAA1715 genes. UGT2B10 and KIAA1715 were retained in a multivariable model while controlling for nongenetic covariates and previously identified risk variants in the GSTA1 promoter. The modulation of associations by conditioning regimens was noted; KIAA1715 was dependent on the intensity of the conditioning regimen, whereas the effect of UGT2B10 was equally applicable to all of them. Combined effect of associated loci was also observed (P = .00006) with a genotype-related SOS risk of 9.8. To our knowledge, this is the first study addressing the genetic component of SOS at an exome-wide level and identifying novel genetic variations conferring a higher risk of SOS, which might be useful for personalized prevention and treatment strategies