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  • Publication . Article . Preprint . 2003
    Open Access English
    Authors: 
    Dmitry Jakobson; Nikolai Nadirashvili; Iosif Polterovich;
    Project: NSERC , NSF | Geometry of Eigenvalues, ... (9971932)

    The first eigenvalue of the Laplacian on a surface can be viewed as a functional on the space of Riemannian metrics of a given area. Critical points of this functional are called extremal metrics. The only known extremal metrics are a round sphere, a standard projective plane, a Clifford torus and an equilateral torus. We construct an extremal metric on a Klein bottle. It is a metric of revolution, admitting a minimal isometric embedding into a 4-sphere by the first eigenfunctions. Also, this Klein bottle is a bipolar surface for the Lawson's {3,1}-torus. We conjecture that an extremal metric for the first eigenvalue on a Klein bottle is unique, and hence it provides a sharp upper bound for the first eigenvalue on a Klein bottle of a given area. We present numerical evidence and prove the first results towards this conjecture. 20 pages; minor corrections

  • Restricted
    Authors: 
    Mark S. Ackerman; Marlene Huysman; John M. Carroll; Barry Wellman; Giorgio DeMichelis; Volker Wulf;
    Country: Netherlands

    Communities are social entities whose actors share common needs, interests, or practices: they constitute the basic units of social experience. With regard to communities, social capital captures the structural, relational and cognitive aspects of the relationships among their members. Social capital is defined as a set of properties of a social entity (e.g. norms, level of trust, and intensive social networking) which enables joint activities and cooperation for mutual benefit. It can be understood as the glue which holds communities together. On this panel we will discuss whether and how information technology can strengthen communities by fostering social capital.

  • Open Access English
    Authors: 
    Maria Celeste Fasano; Enrico Glerean; Benjamin P. Gold; Dana Sheng; Mikko Sams; Peter Vuust; Josef P. Rauschecker; Elvira Brattico;

    Human behavior is inherently multimodal and relies on sensorimotor integration. This is evident when pianists exhibit activity in motor and premotor cortices, as part of a dorsal pathway, while listening to a familiar piece of music, or when naïve participants learn to play simple patterns on the piano. Here we investigated the interaction between multimodal learning and dorsal-stream activity over the course of four weeks in ten skilled pianists by adopting a naturalistic data-driven analysis approach. We presented the pianists with audio-only, video-only and audiovisual recordings of a piano sonata during functional magnetic resonance imaging (fMRI) before and after they had learned to play the sonata by heart for a total of four weeks. We followed the learning process and its outcome with questionnaires administered to the pianists, one piano instructor following their training, and seven external expert judges. The similarity of the pianists’ brain activity during stimulus presentations was examined before and after learning by means of inter-subject correlation (ISC) analysis. After learning, an increased ISC was found in the pianists while watching the audiovisual performance, particularly in motor and premotor regions of the dorsal stream. While these brain structures have previously been associated with learning simple audio-motor sequences, our findings are the first to suggest their involvement in learning a complex and demanding audiovisual-motor task. Moreover, the most motivated learners and the best performers of the sonata showed ISC in the dorsal stream and in the reward brain network.

  • Open Access
    Authors: 
    Jimmy A. Irwin; W. Peter Maksym; Gregory R. Sivakoff; Aaron J. Romanowsky; Dacheng Lin; Tyler Speegle; Ian Prado; David T. Mildebrath; Jay Strader; Jifeng Liu; +1 more
    Publisher: Springer Science and Business Media LLC
    Project: NSERC , NSF | Collaborative Research: R... (1515084), NSF | Collaborative Research: R... (1514763), NSF | Black Holes in Globular C... (1308124)

    An X-ray flaring source was found near the galaxy NGC 4697. Two flares were seen, separated by four years. The flux increased by a factor of 90 on a timescale of about one minute. Both flares were very brief. There is no optical counterpart at the position of the flares, but if the source was at the distance of NGC 4697, the luminosities were 10^39 erg/s. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar such flares. We found two flaring sources in globular clusters or ultra-compact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 x 10^40 erg/s, while the other flared five times to 10^40 erg/s. All of the flare rise times were <1 minute, and they then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron star or black hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft gamma repeaters that have repetitive flares of similar luminosities. Published in the Oct 20 2016 issue of Nature

  • Publication . Article . Preprint . Other literature type . 2020
    Open Access English
    Authors: 
    Randelle M. Bundy; Alessandro Tagliabue; Nicholas J. Hawco; Peter L. Morton; Benjamin S. Twining; Mariko Hatta; Abigail E. Noble; Mattias R. Cape; Seth G. John; Jay T. Cullen; +1 more
    Project: NSERC , NSF | GEOTRACES Arctic Section:... (1435862), NSF | Collaborative Research: U... (1924554), NSF | Collaborative Research: B... (1436019), NSF | GEOTRACES Arctic Section:... (1439253), NSF | Collaborative Research: G... (1435056), EC | BYONIC (724289), NSF | US GEOTRACES PMT: Cobalt ... (1736599)

    Cobalt (Co) is an important bioactive trace metal that is the metal cofactor in cobalamin (vitamin B12) which can limit or co-limit phytoplankton growth in many regions of the ocean. Total dissolved and labile Co measurements in the Canadian sector of the Arctic Ocean during the U.S. GEOTRACES Arctic expedition (GN01) and the Canadian International Polar Year GEOTRACES expedition (GIPY14) revealed a dynamic biogeochemical cycle for Co in this basin. The major sources of Co in the Arctic were from shelf regions and rivers, with only minimal contributions from other freshwater sources (sea ice, snow) and eolian deposition. The most striking feature was the extremely high concentrations of dissolved Co in the upper 100 m, with concentrations routinely exceeding 800 pmol L−1 over the shelf regions. This plume of high Co persisted throughout the Arctic basin and extended to the North Pole, where sources of Co shifted from primarily shelf-derived to riverine, as freshwater from Arctic rivers was entrained in the Transpolar Drift. Dissolved Co was also strongly organically complexed in the Arctic, ranging from 70 % to 100 % complexed in the surface and deep ocean, respectively. Deep-water concentrations of dissolved Co were remarkably consistent throughout the basin (∼55 pmol L−1), with concentrations reflecting those of deep Atlantic water and deep-ocean scavenging of dissolved Co. A biogeochemical model of Co cycling was used to support the hypothesis that the majority of the high surface Co in the Arctic was emanating from the shelf. The model showed that the high concentrations of Co observed were due to the large shelf area of the Arctic, as well as to dampened scavenging of Co by manganese-oxidizing (Mn-oxidizing) bacteria due to the lower temperatures. The majority of this scavenging appears to have occurred in the upper 200 m, with minimal additional scavenging below this depth. Evidence suggests that both dissolved Co (dCo) and labile Co (LCo) are increasing over time on the Arctic shelf, and these limited temporal results are consistent with other tracers in the Arctic. These elevated surface concentrations of Co likely lead to a net flux of Co out of the Arctic, with implications for downstream biological uptake of Co in the North Atlantic and elevated Co in North Atlantic Deep Water. Understanding the current distributions of Co in the Arctic will be important for constraining changes to Co inputs resulting from regional intensification of freshwater fluxes from ice and permafrost melt in response to ongoing climate change.

  • Publication . Article . Other literature type . 2013
    Open Access
    Authors: 
    Maimoona A. Zariwala; Heon Yung Gee; Małgorzata Kurkowiak; Dalal A. Al-Mutairi; Margaret W. Leigh; Toby W. Hurd; Rim Hjeij; Sharon D. Dell; Moumita Chaki; Gerard W. Dougherty; +48 more
    Publisher: Elsevier BV
    Countries: France, Croatia, Germany
    Project: NIH | Novel genetics, pathobiol... (5R01DK068306-17), NIH | Identifying all Meckel-li... (1RC4DK090917-01), NIH | Genetic Disorder of Mucoc... (5U54HL096458-14), NIH | Pathogenesis of PCD Lung ... (5R01HL071798-04), WT , NIH | Colorado Clinical and Tra... (3UL1TR000154-05S1)

    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.

  • Open Access English
    Authors: 
    Leclère, Brice; Buckeridge, David L.; Boëlle, Pierre-Yves; Astagneau, Pascal; Lepelletier, Didier;
    Publisher: HAL CCSD
    Country: France

    International audience; ObjectivesSeveral automated algorithms for epidemiological surveillance in hospitals have been proposed. However, the usefulness of these methods to detect nosocomial outbreaks remains unclear. The goal of this review was to describe outbreak detection algorithms that have been tested within hospitals, consider how they were evaluated, and synthesize their results.MethodsWe developed a search query using keywords associated with hospital outbreak detection and searched the MEDLINE database. To ensure the highest sensitivity, no limitations were initially imposed on publication languages and dates, although we subsequently excluded studies published before 2000. Every study that described a method to detect outbreaks within hospitals was included, without any exclusion based on study design. Additional studies were identified through citations in retrieved studies.ResultsTwenty-nine studies were included. The detection algorithms were grouped into 5 categories: simple thresholds (n = 6), statistical process control (n = 12), scan statistics (n = 6), traditional statistical models (n = 6), and data mining methods (n = 4). The evaluation of the algorithms was often solely descriptive (n = 15), but more complex epidemiological criteria were also investigated (n = 10). The performance measures varied widely between studies: e.g., the sensitivity of an algorithm in a real world setting could vary between 17 and 100%.ConclusionEven if outbreak detection algorithms are useful complementary tools for traditional surveillance, the heterogeneity in results among published studies does not support quantitative synthesis of their performance. A standardized framework should be followed when evaluating outbreak detection methods to allow comparison of algorithms across studies and synthesis of results.

  • Open Access
    Authors: 
    Montserrat Garcia-Closas; Fergus J. Couch; Kyriaki Michailidou; Marjanka K. Schmidt; Mark N. Brook; Nick Orr; Suhn K. Rhie; Elio Riboli; Heather Spencer Feigelson; Loic Le Marchand; +207 more
    Publisher: Springer Nature
    Countries: Netherlands, Ireland, United Kingdom, United Kingdom
    Project: CIHR , NIH | Characterizing Genetic Su... (5U01CA098233-06), NIH | Discovery Expansion and R... (5U19CA148065-04), NIH | Breast &prostate cancer &... (1U01CA098216-01), NIH | Breast &Prostate Cancer &... (1U01CA098758-01), WT , EC | COGS (223175), NIH | Characterizing Genetic Su... (5U01CA098710-06), NIH | Genetic epidemiology of c... (3R01CA122340-03S1)

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P&gt; 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  • Open Access
    Authors: 
    SEYED MOHAMMAD REZA HASHEMIAN; Hernan Aguirre-Bermeo; John Laffey; Arnaud FOLLIN; Shreedhar Kulkarni; Gustavo A. Plotnikow; Giuseppe Foti; Philip Hopkins; Michael Lanspa; Philippe Michel; +55 more
    Countries: United Kingdom, Belgium, Germany, Italy, Italy, Netherlands

    IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS: The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES: Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02010073.

  • Closed Access English
    Authors: 
    Axel S. Merseburger; Daniel Castellano; Thomas Powles; Yohann Loriot; Margitta Retz; Jens Voortman; Robert Huddart; Craig Gedye; Michiel S. van der Heijden; Howard Gurney; +5 more
    Country: Netherlands

    PURPOSE: Atezolizumab is an established treatment option for pretreated urothelial carcinoma, demonstrating efficacy in phase II/III trials. The SAUL study enrolled a broader patient population to determine safety and efficacy in underrepresented subgroups. MATERIALS AND METHODS: Patients with metastatic urinary tract carcinoma received atezolizumab 1,200 mg every 3 weeks until disease progression, unacceptable toxicity, loss of clinical benefit, or patient/physician decision. The primary endpoint was safety. Efficacy was a secondary endpoint. Analyses by programmed cell death ligand-1 (PD-L1) status, age, Eastern Cooperative Oncology Group performance status (ECOG PS) and renal impairment were prespecified; post hoc analyses explored outcomes by tumor location. RESULTS: A total of 1,004 patients were enrolled. Subgroup analyses in patients with older age, renal impairment, or upper tract urothelial carcinoma showed safety and efficacy similar to those in patients without these characteristics. Patients with ECOG PS 2 had clinical features typically associated with aggressive disease; median overall survival was 2.3 months versus 10.0 months in patients with ECOG PS0/1. Patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells tended to have better outcomes than those with <5% PD-L1 expression, although conclusions on the relative efficacy of atezolizumab cannot be drawn from this single-arm study. CONCLUSIONS: The understudied populations included in the SAUL study had similar outcomes to those in more selected populations included in phase II/III trials of atezolizumab, except for those with ECOG PS 2. Age ≥80 years and/or creatinine clearance <30 ml/minute does not preclude administration of atezolizumab; however, treatment risk versus benefit must be carefully assessed in patients with ECOG PS 2.

search
Include:
The following results are related to Canada. Are you interested to view more results? Visit OpenAIRE - Explore.
454,475 Research products, page 1 of 45,448
  • Publication . Article . Preprint . 2003
    Open Access English
    Authors: 
    Dmitry Jakobson; Nikolai Nadirashvili; Iosif Polterovich;
    Project: NSERC , NSF | Geometry of Eigenvalues, ... (9971932)

    The first eigenvalue of the Laplacian on a surface can be viewed as a functional on the space of Riemannian metrics of a given area. Critical points of this functional are called extremal metrics. The only known extremal metrics are a round sphere, a standard projective plane, a Clifford torus and an equilateral torus. We construct an extremal metric on a Klein bottle. It is a metric of revolution, admitting a minimal isometric embedding into a 4-sphere by the first eigenfunctions. Also, this Klein bottle is a bipolar surface for the Lawson's {3,1}-torus. We conjecture that an extremal metric for the first eigenvalue on a Klein bottle is unique, and hence it provides a sharp upper bound for the first eigenvalue on a Klein bottle of a given area. We present numerical evidence and prove the first results towards this conjecture. 20 pages; minor corrections

  • Restricted
    Authors: 
    Mark S. Ackerman; Marlene Huysman; John M. Carroll; Barry Wellman; Giorgio DeMichelis; Volker Wulf;
    Country: Netherlands

    Communities are social entities whose actors share common needs, interests, or practices: they constitute the basic units of social experience. With regard to communities, social capital captures the structural, relational and cognitive aspects of the relationships among their members. Social capital is defined as a set of properties of a social entity (e.g. norms, level of trust, and intensive social networking) which enables joint activities and cooperation for mutual benefit. It can be understood as the glue which holds communities together. On this panel we will discuss whether and how information technology can strengthen communities by fostering social capital.

  • Open Access English
    Authors: 
    Maria Celeste Fasano; Enrico Glerean; Benjamin P. Gold; Dana Sheng; Mikko Sams; Peter Vuust; Josef P. Rauschecker; Elvira Brattico;

    Human behavior is inherently multimodal and relies on sensorimotor integration. This is evident when pianists exhibit activity in motor and premotor cortices, as part of a dorsal pathway, while listening to a familiar piece of music, or when naïve participants learn to play simple patterns on the piano. Here we investigated the interaction between multimodal learning and dorsal-stream activity over the course of four weeks in ten skilled pianists by adopting a naturalistic data-driven analysis approach. We presented the pianists with audio-only, video-only and audiovisual recordings of a piano sonata during functional magnetic resonance imaging (fMRI) before and after they had learned to play the sonata by heart for a total of four weeks. We followed the learning process and its outcome with questionnaires administered to the pianists, one piano instructor following their training, and seven external expert judges. The similarity of the pianists’ brain activity during stimulus presentations was examined before and after learning by means of inter-subject correlation (ISC) analysis. After learning, an increased ISC was found in the pianists while watching the audiovisual performance, particularly in motor and premotor regions of the dorsal stream. While these brain structures have previously been associated with learning simple audio-motor sequences, our findings are the first to suggest their involvement in learning a complex and demanding audiovisual-motor task. Moreover, the most motivated learners and the best performers of the sonata showed ISC in the dorsal stream and in the reward brain network.

  • Open Access
    Authors: 
    Jimmy A. Irwin; W. Peter Maksym; Gregory R. Sivakoff; Aaron J. Romanowsky; Dacheng Lin; Tyler Speegle; Ian Prado; David T. Mildebrath; Jay Strader; Jifeng Liu; +1 more
    Publisher: Springer Science and Business Media LLC
    Project: NSERC , NSF | Collaborative Research: R... (1515084), NSF | Collaborative Research: R... (1514763), NSF | Black Holes in Globular C... (1308124)

    An X-ray flaring source was found near the galaxy NGC 4697. Two flares were seen, separated by four years. The flux increased by a factor of 90 on a timescale of about one minute. Both flares were very brief. There is no optical counterpart at the position of the flares, but if the source was at the distance of NGC 4697, the luminosities were 10^39 erg/s. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar such flares. We found two flaring sources in globular clusters or ultra-compact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 x 10^40 erg/s, while the other flared five times to 10^40 erg/s. All of the flare rise times were <1 minute, and they then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron star or black hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft gamma repeaters that have repetitive flares of similar luminosities. Published in the Oct 20 2016 issue of Nature

  • Publication . Article . Preprint . Other literature type . 2020
    Open Access English
    Authors: 
    Randelle M. Bundy; Alessandro Tagliabue; Nicholas J. Hawco; Peter L. Morton; Benjamin S. Twining; Mariko Hatta; Abigail E. Noble; Mattias R. Cape; Seth G. John; Jay T. Cullen; +1 more
    Project: NSERC , NSF | GEOTRACES Arctic Section:... (1435862), NSF | Collaborative Research: U... (1924554), NSF | Collaborative Research: B... (1436019), NSF | GEOTRACES Arctic Section:... (1439253), NSF | Collaborative Research: G... (1435056), EC | BYONIC (724289), NSF | US GEOTRACES PMT: Cobalt ... (1736599)

    Cobalt (Co) is an important bioactive trace metal that is the metal cofactor in cobalamin (vitamin B12) which can limit or co-limit phytoplankton growth in many regions of the ocean. Total dissolved and labile Co measurements in the Canadian sector of the Arctic Ocean during the U.S. GEOTRACES Arctic expedition (GN01) and the Canadian International Polar Year GEOTRACES expedition (GIPY14) revealed a dynamic biogeochemical cycle for Co in this basin. The major sources of Co in the Arctic were from shelf regions and rivers, with only minimal contributions from other freshwater sources (sea ice, snow) and eolian deposition. The most striking feature was the extremely high concentrations of dissolved Co in the upper 100 m, with concentrations routinely exceeding 800 pmol L−1 over the shelf regions. This plume of high Co persisted throughout the Arctic basin and extended to the North Pole, where sources of Co shifted from primarily shelf-derived to riverine, as freshwater from Arctic rivers was entrained in the Transpolar Drift. Dissolved Co was also strongly organically complexed in the Arctic, ranging from 70 % to 100 % complexed in the surface and deep ocean, respectively. Deep-water concentrations of dissolved Co were remarkably consistent throughout the basin (∼55 pmol L−1), with concentrations reflecting those of deep Atlantic water and deep-ocean scavenging of dissolved Co. A biogeochemical model of Co cycling was used to support the hypothesis that the majority of the high surface Co in the Arctic was emanating from the shelf. The model showed that the high concentrations of Co observed were due to the large shelf area of the Arctic, as well as to dampened scavenging of Co by manganese-oxidizing (Mn-oxidizing) bacteria due to the lower temperatures. The majority of this scavenging appears to have occurred in the upper 200 m, with minimal additional scavenging below this depth. Evidence suggests that both dissolved Co (dCo) and labile Co (LCo) are increasing over time on the Arctic shelf, and these limited temporal results are consistent with other tracers in the Arctic. These elevated surface concentrations of Co likely lead to a net flux of Co out of the Arctic, with implications for downstream biological uptake of Co in the North Atlantic and elevated Co in North Atlantic Deep Water. Understanding the current distributions of Co in the Arctic will be important for constraining changes to Co inputs resulting from regional intensification of freshwater fluxes from ice and permafrost melt in response to ongoing climate change.

  • Publication . Article . Other literature type . 2013
    Open Access
    Authors: 
    Maimoona A. Zariwala; Heon Yung Gee; Małgorzata Kurkowiak; Dalal A. Al-Mutairi; Margaret W. Leigh; Toby W. Hurd; Rim Hjeij; Sharon D. Dell; Moumita Chaki; Gerard W. Dougherty; +48 more
    Publisher: Elsevier BV
    Countries: France, Croatia, Germany
    Project: NIH | Novel genetics, pathobiol... (5R01DK068306-17), NIH | Identifying all Meckel-li... (1RC4DK090917-01), NIH | Genetic Disorder of Mucoc... (5U54HL096458-14), NIH | Pathogenesis of PCD Lung ... (5R01HL071798-04), WT , NIH | Colorado Clinical and Tra... (3UL1TR000154-05S1)

    Defects of motile cilia cause primary ciliary dyskinesia (PCD), characterized by recurrent respiratory infections and male infertility. Using whole-exome resequencing and high-throughput mutation analysis, we identified recessive biallelic mutations in ZMYND10 in 14 families and mutations in the recently identified LRRC6 in 13 families. We show that ZMYND10 and LRRC6 interact and that certain ZMYND10 and LRRC6 mutations abrogate the interaction between the LRRC6 CS domain and the ZMYND10 C-terminal domain. Additionally, ZMYND10 and LRRC6 colocalize with the centriole markers SAS6 and PCM1. Mutations in ZMYND10 result in the absence of the axonemal protein components DNAH5 and DNALI1 from respiratory cilia. Animal models support the association between ZMYND10 and human PCD, given that zmynd10 knockdown in zebrafish caused ciliary paralysis leading to cystic kidneys and otolith defects and that knockdown in Xenopus interfered with ciliogenesis. Our findings suggest that a cytoplasmic protein complex containing ZMYND10 and LRRC6 is necessary for motile ciliary function. © 2013 The American Society of Human Genetics.

  • Open Access English
    Authors: 
    Leclère, Brice; Buckeridge, David L.; Boëlle, Pierre-Yves; Astagneau, Pascal; Lepelletier, Didier;
    Publisher: HAL CCSD
    Country: France

    International audience; ObjectivesSeveral automated algorithms for epidemiological surveillance in hospitals have been proposed. However, the usefulness of these methods to detect nosocomial outbreaks remains unclear. The goal of this review was to describe outbreak detection algorithms that have been tested within hospitals, consider how they were evaluated, and synthesize their results.MethodsWe developed a search query using keywords associated with hospital outbreak detection and searched the MEDLINE database. To ensure the highest sensitivity, no limitations were initially imposed on publication languages and dates, although we subsequently excluded studies published before 2000. Every study that described a method to detect outbreaks within hospitals was included, without any exclusion based on study design. Additional studies were identified through citations in retrieved studies.ResultsTwenty-nine studies were included. The detection algorithms were grouped into 5 categories: simple thresholds (n = 6), statistical process control (n = 12), scan statistics (n = 6), traditional statistical models (n = 6), and data mining methods (n = 4). The evaluation of the algorithms was often solely descriptive (n = 15), but more complex epidemiological criteria were also investigated (n = 10). The performance measures varied widely between studies: e.g., the sensitivity of an algorithm in a real world setting could vary between 17 and 100%.ConclusionEven if outbreak detection algorithms are useful complementary tools for traditional surveillance, the heterogeneity in results among published studies does not support quantitative synthesis of their performance. A standardized framework should be followed when evaluating outbreak detection methods to allow comparison of algorithms across studies and synthesis of results.

  • Open Access
    Authors: 
    Montserrat Garcia-Closas; Fergus J. Couch; Kyriaki Michailidou; Marjanka K. Schmidt; Mark N. Brook; Nick Orr; Suhn K. Rhie; Elio Riboli; Heather Spencer Feigelson; Loic Le Marchand; +207 more
    Publisher: Springer Nature
    Countries: Netherlands, Ireland, United Kingdom, United Kingdom
    Project: CIHR , NIH | Characterizing Genetic Su... (5U01CA098233-06), NIH | Discovery Expansion and R... (5U19CA148065-04), NIH | Breast &prostate cancer &... (1U01CA098216-01), NIH | Breast &Prostate Cancer &... (1U01CA098758-01), WT , EC | COGS (223175), NIH | Characterizing Genetic Su... (5U01CA098710-06), NIH | Genetic epidemiology of c... (3R01CA122340-03S1)

    Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a metaanalysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P= 2.1 x 10(-12) and LGR6, P = 1.4 x 10(-8)), 2p24.1 (P = 4.6 x 10(-8)) and 16q12.2 (FTO, P = 4.0 x 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P&gt; 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.

  • Open Access
    Authors: 
    SEYED MOHAMMAD REZA HASHEMIAN; Hernan Aguirre-Bermeo; John Laffey; Arnaud FOLLIN; Shreedhar Kulkarni; Gustavo A. Plotnikow; Giuseppe Foti; Philip Hopkins; Michael Lanspa; Philippe Michel; +55 more
    Countries: United Kingdom, Belgium, Germany, Italy, Italy, Netherlands

    IMPORTANCE: Limited information exists about the epidemiology, recognition, management, and outcomes of patients with the acute respiratory distress syndrome (ARDS). OBJECTIVES: To evaluate intensive care unit (ICU) incidence and outcome of ARDS and to assess clinician recognition, ventilation management, and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition. DESIGN, SETTING, AND PARTICIPANTS: The Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) was an international, multicenter, prospective cohort study of patients undergoing invasive or noninvasive ventilation, conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents. EXPOSURES: Acute respiratory distress syndrome. MAIN OUTCOMES AND MEASURES: The primary outcome was ICU incidence of ARDS. Secondary outcomes included assessment of clinician recognition of ARDS, the application of ventilatory management, the use of adjunctive interventions in routine clinical practice, and clinical outcomes from ARDS. RESULTS: Of 29,144 patients admitted to participating ICUs, 3022 (10.4%) fulfilled ARDS criteria. Of these, 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with invasive mechanical ventilation. The period prevalence of mild ARDS was 30.0% (95% CI, 28.2%-31.9%); of moderate ARDS, 46.6% (95% CI, 44.5%-48.6%); and of severe ARDS, 23.4% (95% CI, 21.7%-25.2%). ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4% (95% CI, 10.0%-10.7%) of ICU admissions and 23.4% of patients requiring mechanical ventilation. Clinical recognition of ARDS ranged from 51.3% (95% CI, 47.5%-55.0%) in mild to 78.5% (95% CI, 74.8%-81.8%) in severe ARDS. Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight. Plateau pressure was measured in 40.1% (95% CI, 38.2-42.1), whereas 82.6% (95% CI, 81.0%-84.1%) received a positive end-expository pressure (PEEP) of less than 12 cm H2O. Prone positioning was used in 16.3% (95% CI, 13.7%-19.2%) of patients with severe ARDS. Clinician recognition of ARDS was associated with higher PEEP, greater use of neuromuscular blockade, and prone positioning. Hospital mortality was 34.9% (95% CI, 31.4%-38.5%) for those with mild, 40.3% (95% CI, 37.4%-43.3%) for those with moderate, and 46.1% (95% CI, 41.9%-50.4%) for those with severe ARDS. CONCLUSIONS AND RELEVANCE: Among ICUs in 50 countries, the period prevalence of ARDS was 10.4% of ICU admissions. This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate. These findings indicate the potential for improvement in the management of patients with ARDS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02010073.

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    Authors: 
    Axel S. Merseburger; Daniel Castellano; Thomas Powles; Yohann Loriot; Margitta Retz; Jens Voortman; Robert Huddart; Craig Gedye; Michiel S. van der Heijden; Howard Gurney; +5 more
    Country: Netherlands

    PURPOSE: Atezolizumab is an established treatment option for pretreated urothelial carcinoma, demonstrating efficacy in phase II/III trials. The SAUL study enrolled a broader patient population to determine safety and efficacy in underrepresented subgroups. MATERIALS AND METHODS: Patients with metastatic urinary tract carcinoma received atezolizumab 1,200 mg every 3 weeks until disease progression, unacceptable toxicity, loss of clinical benefit, or patient/physician decision. The primary endpoint was safety. Efficacy was a secondary endpoint. Analyses by programmed cell death ligand-1 (PD-L1) status, age, Eastern Cooperative Oncology Group performance status (ECOG PS) and renal impairment were prespecified; post hoc analyses explored outcomes by tumor location. RESULTS: A total of 1,004 patients were enrolled. Subgroup analyses in patients with older age, renal impairment, or upper tract urothelial carcinoma showed safety and efficacy similar to those in patients without these characteristics. Patients with ECOG PS 2 had clinical features typically associated with aggressive disease; median overall survival was 2.3 months versus 10.0 months in patients with ECOG PS0/1. Patients with PD-L1 expression on ≥5% of tumor-infiltrating immune cells tended to have better outcomes than those with <5% PD-L1 expression, although conclusions on the relative efficacy of atezolizumab cannot be drawn from this single-arm study. CONCLUSIONS: The understudied populations included in the SAUL study had similar outcomes to those in more selected populations included in phase II/III trials of atezolizumab, except for those with ECOG PS 2. Age ≥80 years and/or creatinine clearance <30 ml/minute does not preclude administration of atezolizumab; however, treatment risk versus benefit must be carefully assessed in patients with ECOG PS 2.