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Showing papers by "University of Hawaii at Manoa published in 2012"


Journal ArticleDOI
TL;DR: The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999 as discussed by the authors, which has since supported a wide range of Arc...
Abstract: The International Bathymetric Chart of the Arctic Ocean (IBCAO) released its first gridded bathymetric compilation in 1999. The IBCAO bathymetric portrayals have since supported a wide range of Arc ...

977 citations


Journal ArticleDOI
Stephen Kaptoge1, Emanuele Di Angelantonio1, Lisa Pennells1, Angela M. Wood1, Ian R. White2, Pei Gao1, Matthew G. Walker1, Alexander M. W. Cargill Thompson1, Nadeem Sarwar1, Muriel J. Caslake3, Adam S. Butterworth1, Philippe Amouyel4, Gerd Assmann, Stephan J. L. Bakker5, Elizabeth L M Barr6, Elizabeth Barrett-Connor7, Emelia J. Benjamin8, Cecilia Björkelund9, Hermann Brenner10, Eric J. Brunner11, Robert Clarke12, Jackie A. Cooper11, Peter Cremer13, Mary Cushman14, Gilles R. Dagenais, Ralph B. D'Agostino8, Rachel Dankner, George Davey-Smith15, Dorly J. H. Deeg16, Jacqueline M. Dekker16, Gunnar Engström17, Aaron R. Folsom18, F. Gerry R. Fowkes19, John Gallacher20, J. Michael Gaziano21, Simona Giampaoli22, Richard F. Gillum23, Albert Hofman24, Barbara V. Howard25, Erik Ingelsson26, Hiroyasu Iso27, Torben Jørgensen28, Stefan Kiechl29, Akihiko Kitamura, Yutaka Kiyohara30, Wolfgang Koenig31, Daan Kromhout32, Lewis H. Kuller33, Debbie A Lawlor15, Tom W. Meade34, Aulikki Nissinen35, Børge G. Nordestgaard28, Altan Onat36, Demosthenes B. Panagiotakos37, Bruce M. Psaty38, Beatriz L. Rodriguez39, Annika Rosengren9, Veikko Salomaa35, Jussi Kauhanen40, Jukka T. Salonen41, Jonathan A. Shaffer42, Steven Shea42, Ian Ford3, Coen D.A. Stehouwer43, Timo E. Strandberg44, Robert W. Tipping45, Alberto Tosetto, Sylvia Wassertheil-Smoller46, Patrik Wennberg47, Rudi G. J. Westendorp48, Peter H. Whincup49, Lars Wilhelmsen9, Mark Woodward50, Gordon D.O. Lowe3, Nicholas J. Wareham2, Kay-Tee Khaw1, Naveed Sattar3, Chris J. Packard3, Vilmundur Gudnason51, Paul M. Ridker21, Mark B. Pepys11, Simon G. Thompson1, John Danesh1 
TL;DR: It is estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened.
Abstract: Background There is debate about the value of assessing levels of C-reactive protein (CRP) and other biomarkers of inflammation for the prediction of first cardiovascular events. Methods We analyzed data from 52 prospective studies that included 246,669 participants without a history of cardiovascular disease to investigate the value of adding CRP or fibrinogen levels to conventional risk factors for the prediction of cardiovascular risk. We calculated measures of discrimination and reclassification during follow-up and modeled the clinical implications of initiation of statin therapy after the assessment of CRP or fibrinogen. Results The addition of information on high-density lipoprotein cholesterol to a prognostic model for cardiovascular disease that included age, sex, smoking status, blood pressure, history of diabetes, and total cholesterol level increased the C-index, a measure of risk discrimination, by 0.0050. The further addition to this model of information on CRP or fibrinogen increased the C-index by 0.0039 and 0.0027, respectively (P = 20%) (P = 20% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), additional targeted assessment of CRP or fibrinogen levels in the 13,199 remaining participants at intermediate risk could help prevent approximately 30 additional cardiovascular events over the course of 10 years. Conclusions In a study of people without known cardiovascular disease, we estimated that under current treatment guidelines, assessment of the CRP or fibrinogen level in people at intermediate risk for a cardiovascular event could help prevent one additional event over a period of 10 years for every 400 to 500 people screened. (Funded by the British Heart Foundation and others.)

938 citations



Journal ArticleDOI
02 Mar 2012-Science
TL;DR: This paper reviewed events exhibiting evidence for elevated atmospheric CO2, global warming, and ocean acidification over the past ~300 million years of Earth's history, some with contemporaneous extinction or evolutionary turnover among marine calcifiers.
Abstract: Ocean acidification may have severe consequences for marine ecosystems; however, assessing its future impact is difficult because laboratory experiments and field observations are limited by their reduced ecologic complexity and sample period, respectively. In contrast, the geological record contains long-term evidence for a variety of global environmental perturbations, including ocean acidification plus their associated biotic responses. We review events exhibiting evidence for elevated atmospheric CO2, global warming, and ocean acidification over the past ~300 million years of Earth’s history, some with contemporaneous extinction or evolutionary turnover among marine calcifiers. Although similarities exist, no past event perfectly parallels future projections in terms of disrupting the balance of ocean carbonate chemistry—a consequence of the unprecedented rapidity of CO2 release currently taking place.

838 citations


Journal ArticleDOI
TL;DR: In this paper, the association between self-reported endometriosis and risk of ovarian cancer was found to be a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear.
Abstract: Summary Background Endometriosis is a risk factor for epithelial ovarian cancer; however, whether this risk extends to all invasive histological subtypes or borderline tumours is not clear. We undertook an international collaborative study to assess the association between endometriosis and histological subtypes of ovarian cancer. Methods Data from 13 ovarian cancer case–control studies, which were part of the Ovarian Cancer Association Consortium, were pooled and logistic regression analyses were undertaken to assess the association between self-reported endometriosis and risk of ovarian cancer. Analyses of invasive cases were done with respect to histological subtypes, grade, and stage, and analyses of borderline tumours by histological subtype. Age, ethnic origin, study site, parity, and duration of oral contraceptive use were included in all analytical models. Findings 13 226 controls and 7911 women with invasive ovarian cancer were included in this analysis. 818 and 738, respectively, reported a history of endometriosis. 1907 women with borderline ovarian cancer were also included in the analysis, and 168 of these reported a history of endometriosis. Self-reported endometriosis was associated with a significantly increased risk of clear-cell (136 [20·2%] of 674 cases vs 818 [6·2%] of 13 226 controls, odds ratio 3·05, 95% CI 2·43–3·84, p Interpretation Clinicians should be aware of the increased risk of specific subtypes of ovarian cancer in women with endometriosis. Future efforts should focus on understanding the mechanisms that might lead to malignant transformation of endometriosis so as to help identify subsets of women at increased risk of ovarian cancer. Funding Ovarian Cancer Research Fund, National Institutes of Health, California Cancer Research Program, California Department of Health Services, Lon V Smith Foundation, European Community's Seventh Framework Programme, German Federal Ministry of Education and Research of Germany, Programme of Clinical Biomedical Research, German Cancer Research Centre, Eve Appeal, Oak Foundation, UK National Institute of Health Research, National Health and Medical Research Council of Australia, US Army Medical Research and Materiel Command, Cancer Council Tasmania, Cancer Foundation of Western Australia, Mermaid 1, Danish Cancer Society, and Roswell Park Alliance Foundation.

726 citations


Journal ArticleDOI
TL;DR: Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes and a randomised controlled trial of endov vascular treatment for patients with the target mismatch profile is warranted.
Abstract: Summary Background Whether endovascular stroke treatment improves clinical outcomes is unclear because of the paucity of data from randomised placebo-controlled trials. We aimed to establish whether MRI can be used to identify patients who are most likely to benefit from endovascular reperfusion. Methods In this prospective cohort study we consecutively enrolled patients scheduled to have endovascular treatment within 12 h of onset of stroke at eight centres in the USA and one in Austria. Aided by an automated image analysis computer program, investigators interpreted a baseline MRI scan taken before treatment to establish whether the patient had an MRI profile (target mismatch) that suggested salvageable tissue was present. Reperfusion was assessed on an early follow-up MRI scan (within 12 h of the revascularisation procedure) and defined as a more than 50% reduction in the volume of the lesion from baseline on perfusion-weighted MRI. The primary outcome was favourable clinical response, defined as an improvement of 8 or more on the National Institutes of Health Stroke Scale between baseline and day 30 or a score of 0–1 at day 30. The secondary clinical endpoint was good functional outcome, defined as a modified Rankin scale score of 2 or less at day 90. Analyses were adjusted for imbalances in baseline predictors of outcome. Investigators assessing outcomes were masked to baseline data. Findings 138 patients were enrolled. 110 patients had catheter angiography and of these 104 had an MRI profile and 99 could be assessed for reperfusion. 46 of 78 (59%) patients with target mismatch and 12 of 21 (57%) patients without target mismatch had reperfusion after endovascular treatment. The adjusted odds ratio (OR) for favourable clinical response associated with reperfusion was 8·8 (95% CI 2·7–29·0) in the target mismatch group and 0·2 (0·0–1·6) in the no target mismatch group (p=0·003 for difference between ORs). Reperfusion was associated with increased good functional outcome at 90 days (OR 4·0, 95% CI 1·3–12·2) in the target mismatch group, but not in the no target mismatch group (1·9, 0·2–18·7). Interpretation Target mismatch patients who had early reperfusion after endovascular stroke treatment had more favourable clinical outcomes. No association between reperfusion and favourable outcomes was present in patients without target mismatch. Our data suggest that a randomised controlled trial of endovascular treatment for patients with the target mismatch profile is warranted. Funding National Institute for Neurological Disorders and Stroke.

713 citations


Journal ArticleDOI
16 Mar 2012-Science
TL;DR: It is shown that when analog climates are compared between regions, fewer than 15% of species have more than 10% of their invaded distribution outside their native climatic niche, revealing that substantial niche shifts are rare in terrestrial plant invaders.
Abstract: The assumption that climatic niche requirements of invasive species are conserved between their native and invaded ranges is key to predicting the risk of invasion. However, this assumption has been challenged recently by evidence of niche shifts in some species. Here, we report the first large-scale test of niche conservatism for 50 terrestrial plant invaders between Eurasia, North America, and Australia. We show that when analog climates are compared between regions, fewer than 15% of species have more than 10% of their invaded distribution outside their native climatic niche. These findings reveal that substantial niche shifts are rare in terrestrial plant invaders, providing support for an appropriate use of ecological niche models for the prediction of both biological invasions and responses to climate change.

692 citations


Journal ArticleDOI
TL;DR: Particular emphasis is given to how Se and selenoproteins are linked to redox signaling, oxidative burst, calcium flux, and the subsequent effector functions of immune cells, as well as the benefits and potential adverse effects of intervention with Se supplementation for various inflammatory or immune disorders.
Abstract: Dietary selenium (]Se), mainly through its incorporation into selenoproteins, plays an important role in inflammation and immunity. Adequate levels of Se are important for initiating immunity, but they are also involved in regulating excessive immune responses and chronic inflammation. Evidence has emerged regarding roles for individual selenoproteins in regulating inflammation and immunity, and this has provided important insight into mechanisms by which Se influences these processes. Se deficiency has long been recognized to negatively impact immune cells during activation, differentiation, and proliferation. This is related to increased oxidative stress, but additional functions such as protein folding and calcium flux may also be impaired in immune cells under Se deficient conditions. Supplementing diets with above-adequate levels of Se can also impinge on immune cell function, with some types of inflammation and immunity particularly affected and sexually dimorphic effects of Se levels in so...

612 citations


Journal ArticleDOI
TL;DR: In this paper, a mechanistic model that can enable battery diagnosis and prognosis is presented, which can simulate various "what-if" scenarios of battery degradation modes via a synthetic approach based on specific electrode behavior with proper adjustment of the loading ratio and the extent of degradation in and between the two electrodes.

580 citations


Journal ArticleDOI
08 Jun 2012-Science
TL;DR: The arrival of the parasitic Varroa mite into the Hawaiian honey bee population allowed us to investigate changes in the prevalence, load, and strain diversity of honey bee viruses.
Abstract: Emerging diseases are among the greatest threats to honey bees. Unfortunately, where and when an emerging disease will appear are almost impossible to predict. The arrival of the parasitic Varroa mite into the Hawaiian honey bee population allowed us to investigate changes in the prevalence, load, and strain diversity of honey bee viruses. The mite increased the prevalence of a single viral species, deformed wing virus (DWV), from ~10 to 100% within honey bee populations, which was accompanied by a millionfold increase in viral titer and a massive reduction in DWV diversity, leading to the predominance of a single DWV strain. Therefore, the global spread of Varroa has selected DWV variants that have emerged to allow it to become one of the most widely distributed and contagious insect viruses on the planet.

549 citations


Journal ArticleDOI
TL;DR: Clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) is detected using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies to identify common deleted regions with genes previously associated with hematological cancers.
Abstract: We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).

Journal ArticleDOI
Kevin B. Jacobs1, Kevin B. Jacobs2, Meredith Yeager1, Meredith Yeager2  +205 moreInstitutions (52)
TL;DR: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, this paper observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples.
Abstract: In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.

Journal ArticleDOI
Daniele S. M. Alves1, Nima Arkani-Hamed, S. Arora2, Yang Bai1, Matthew Baumgart3, Joshua Berger4, Matthew R. Buckley5, Bart Butler1, Spencer Chang6, Spencer Chang7, Hsin-Chia Cheng7, Clifford Cheung8, R. Sekhar Chivukula9, Won Sang Cho10, R. Cotta1, Mariarosaria D'Alfonso11, Sonia El Hedri1, Rouven Essig12, Jared A. Evans7, Liam Fitzpatrick13, Patrick J. Fox5, Roberto Franceschini14, Ayres Freitas15, James S. Gainer16, James S. Gainer17, Yuri Gershtein2, R. N.C. Gray2, Thomas Gregoire18, Ben Gripaios19, J.F. Gunion7, Tao Han20, Andy Haas1, P. Hansson1, JoAnne L. Hewett1, Dmitry Hits2, Jay Hubisz21, Eder Izaguirre1, Jared Kaplan1, Emanuel Katz13, Can Kilic2, Hyung Do Kim22, Ryuichiro Kitano23, Sue Ann Koay11, Pyungwon Ko24, David Krohn25, Eric Kuflik26, Ian M. Lewis20, Mariangela Lisanti27, Tao Liu11, Zhen Liu20, Ran Lu26, Markus A. Luty7, Patrick Meade12, David E. Morrissey28, Stephen Mrenna5, Mihoko M. Nojiri, Takemichi Okui29, Sanjay Padhi30, Michele Papucci31, Michael Park2, Myeonghun Park32, Maxim Perelstein4, Michael E. Peskin1, Daniel J. Phalen7, Keith Rehermann33, Vikram Rentala34, Vikram Rentala35, Tuhin S. Roy36, Joshua T. Ruderman27, Veronica Sanz37, Martin Schmaltz13, S. Schnetzer2, Philip Schuster38, Pedro Schwaller39, Pedro Schwaller40, Pedro Schwaller17, Matthew D. Schwartz25, Ariel Schwartzman1, Jing Shao21, J. Shelton41, David Shih2, Jing Shu10, Daniel Silverstein1, Elizabeth H. Simmons9, Sunil Somalwar2, Michael Spannowsky6, Christian Spethmann13, Matthew J. Strassler2, Shufang Su35, Shufang Su34, Tim M. P. Tait34, Brooks Thomas42, Scott Thomas2, Natalia Toro38, Tomer Volansky8, Jay G. Wacker1, Wolfgang Waltenberger43, Itay Yavin44, Felix Yu34, Yue Zhao2, Kathryn M. Zurek26 
TL;DR: A collection of simplified models relevant to the design of new-physics searches at the Large Hadron Collider (LHC) and the characterization of their results is presented in this paper.
Abstract: This document proposes a collection of simplified models relevant to the design of new-physics searches at the Large Hadron Collider (LHC) and the characterization of their results. Both ATLAS and CMS have already presented some results in terms of simplified models, and we encourage them to continue and expand this effort, which supplements both signature-based results and benchmark model interpretations. A simplified model is defined by an effective Lagrangian describing the interactions of a small number of new particles. Simplified models can equally well be described by a small number of masses and cross-sections. These parameters are directly related to collider physics observables, making simplified models a particularly effective framework for evaluating searches and a useful starting point for characterizing positive signals of new physics. This document serves as an official summary of the results from the 'Topologies for Early LHC Searches' workshop, held at SLAC in September of 2010, the purpose of which was to develop a set of representative models that can be used to cover all relevant phase space in experimental searches. Particular emphasis is placed on searches relevant for the first similar to 50-500 pb(-1) of data and those motivated by supersymmetric models. This note largely summarizes material posted at http://lhcnewphysics.org/, which includes simplified model definitions, Monte Carlo material, and supporting contacts within the theory community. We also comment on future developments that may be useful as more data is gathered and analyzed by the experiments.

Journal ArticleDOI
10 May 2012-Nature
TL;DR: A luminous ultraviolet–optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696 is reported and it is determined that the disrupted star was a helium-rich stellar core, modulo a factor dependent on the mass and radius of the star disrupted.
Abstract: The flare of radiation from the tidal disruption and accretion of a star can be used as a marker for supermassive black holes that otherwise lie dormant and undetected in the centres of distant galaxies. Previous candidate flares have had declining light curves in good agreement with expectations, but with poor constraints on the time of disruption and the type of star disrupted, because the rising emission was not observed. Recently, two ‘relativistic’ candidate tidal disruption events were discovered, each of whose extreme X-ray luminosity and synchrotron radio emission were interpreted as the onset of emission from a relativistic jet. Here we report a luminous ultraviolet–optical flare from the nuclear region of an inactive galaxy at a redshift of 0.1696. The observed continuum is cooler than expected for a simple accreting debris disk, but the well-sampled rise and decay of the light curve follow the predicted mass accretion rate and can be modelled to determine the time of disruption to an accuracy of two days. The black hole has a mass of about two million solar masses, modulo a factor dependent on the mass and radius of the star disrupted. On the basis of the spectroscopic signature of ionized helium from the unbound debris, we determine that the disrupted star was a helium-rich stellar core.

Book
29 Mar 2012
TL;DR: Supersymmetric models of particle physics predict new superpartner matter states for each particle in the Standard Model These superpartners will have wide ranging implications, from cosmology to observations at high energy accelerators, such as CERN's LHC as mentioned in this paper.
Abstract: Supersymmetric models of particle physics predict new superpartner matter states for each particle in the Standard Model These superpartners will have wide ranging implications, from cosmology to observations at high energy accelerators, such as CERN's LHC In this 2006 text, the authors develop the basic concepts of supersymmetry and show how it can be incorporated into a theoretical framework for describing unified theories of elementary particles They develop the technical tools of supersymmetry using four-component spinor notation familiar to high energy experimentalists and phenomenologists The text takes the reader from an abstract formalism to a straightforward recipe for writing supersymmetric gauge theories of particle physics, and ultimately to the calculations necessary for practical applications at colliders and in cosmology This is a comprehensive, practical and accessible introduction to supersymmetry for experimental and phenomenological particle physicists and graduate students Exercises and worked examples that clarify the material are interspersed throughout

Journal ArticleDOI
TL;DR: In this paper, the authors used non-redundant aperture masking interferometry at three epochs to reveal a faint and relatively blue point source (, K' -L' = 0.98 ± 0.22), flanked by approximately co-orbital emission that is red and resolved into at least two sources (K' −L' − L' = 2.6 ± 1.3;, K'
Abstract: Young and directly imaged exoplanets offer critical tests of planet-formation models that are not matched by radial velocity surveys of mature stars. These targets have been extremely elusive to date, with no exoplanets younger than 10-20 Myr and only a handful of direct-imaged exoplanets at all ages. We report the direct-imaging discovery of a likely (proto)planet around the young (~2 Myr) solar analog LkCa 15, located inside a known gap in the protoplanetary disk (a transitional disk). Our observations use non-redundant aperture masking interferometry at three epochs to reveal a faint and relatively blue point source (, K' – L' = 0.98 ± 0.22), flanked by approximately co-orbital emission that is red and resolved into at least two sources (, K' – L' = 2.7 ± 0.3; , K' – L' = 1.94 ± 0.16). We propose that the most likely geometry consists of a newly formed (proto)planet that is surrounded by dusty material. The nominal estimated mass is ~6 M Jup according to the 1 Myr hot-start models. However, we argue based on its luminosity, color, and the presence of circumplanetary material that the planet has likely been caught at its epoch of assembly, and hence this mass is an upper limit due to its extreme youth and flux contributed by accretion. The projected separations (71.9 ± 1.6 mas, 100.7 ± 1.9 mas, and 88.2 ± 1.8 mas) and deprojected orbital radii (16, 21, and 19 AU) correspond to the center of the disk gap, but are too close to the primary star for a circular orbit to account for the observed inner edge of the outer disk, so an alternative explanation (i.e., additional planets or an eccentric orbit) is likely required. This discovery is the first direct evidence that at least some transitional disks do indeed host newly formed (or forming) exoplanetary systems, and the observed properties provide crucial insight into the gas giant formation process.

Journal ArticleDOI
17 Oct 2012-JAMA
TL;DR: Universal tumor MMR testing among CRC probands had a greater sensitivity for the identification of Lynch syndrome compared with multiple alternative strategies, although the increase in the diagnostic yield was modest.
Abstract: Context Lynch syndrome is the most common form of hereditary colorectal cancer (CRC) and is caused by germline mutations in DNA mismatch repair (MMR) genes. Identification of gene carriers currently relies on germline analysis in patients with MMR-deficient tumors, but criteria to select individuals in whom tumor MMR testing should be performed are unclear. Objective To establish a highly sensitive and efficient strategy for the identification of MMR gene mutation carriers among CRC probands. Design, Setting, and Patients Pooled-data analysis of 4 large cohorts of newly diagnosed CRC probands recruited between 1994 and 2010 (n = 10 206) from the Colon Cancer Family Registry, the EPICOLON project, the Ohio State University, and the University of Helsinki examining personal, tumor-related, and family characteristics, as well as microsatellite instability, tumor MMR immunostaining, and germline MMR mutational status data. Main Outcome Measures Performance characteristics of selected strategies (Bethesda guidelines, Jerusalem recommendations, and those derived from a bivariate/multivariate analysis of variables associated with Lynch syndrome) were compared with tumor MMR testing of all CRC patients (universal screening). Results Of 10 206 informative, unrelated CRC probands, 312 (3.1%) were MMR gene mutation carriers. In the population-based cohorts (n = 3671 probands), the universal screening approach (sensitivity, 100%; 95% CI, 99.3%-100%; specificity, 93.0%; 95% CI, 92.0%-93.7%; diagnostic yield, 2.2%; 95% CI, 1.7%-2.7%) was superior to the use of Bethesda guidelines (sensitivity, 87.8%; 95% CI, 78.9%-93.2%; specificity, 97.5%; 95% CI, 96.9%-98.0%; diagnostic yield, 2.0%; 95% CI, 1.5%-2.4%; P Conclusion Universal tumor MMR testing among CRC probands had a greater sensitivity for the identification of Lynch syndrome compared with multiple alternative strategies, although the increase in the diagnostic yield was modest.

Journal ArticleDOI
TL;DR: A major effort by the paleoclimate research community to characterize changes through the development of well-dated, high-resolution records of the deep and intermediate ocean as well as surface climate indicates that the superposition of two modes explains much of the variability in regional and global climate during the last deglaciation.
Abstract: Deciphering the evolution of global climate from the end of the Last Glacial Maximum approximately 19 ka to the early Holocene 11 ka presents an outstanding opportunity for understanding the transient response of Earth’s climate system to external and internal forcings. During this interval of global warming, the decay of ice sheets caused global mean sea level to rise by approximately 80 m; terrestrial and marine ecosystems experienced large disturbances and range shifts; perturbations to the carbon cycle resulted in a net release of the greenhouse gases CO2 and CH4 to the atmosphere; and changes in atmosphere and ocean circulation affected the global distribution and fluxes of water and heat. Here we summarize a major effort by the paleoclimate research community to characterize these changes through the development of well-dated, high-resolution records of the deep and intermediate ocean as well as surface climate. Our synthesis indicates that the superposition of two modes explains much of the variability in regional and global climate during the last deglaciation, with a strong association between the first mode and variations in greenhouse gases, and between the second mode and variations in the Atlantic meridional overturning circulation.

Journal ArticleDOI
21 Sep 2012-Science
TL;DR: The detection of Kepler-47 establishes that close binary stars can host complete planetary systems, and reveals two small planets orbiting a pair of two low-mass stars.
Abstract: We report the detection of Kepler-47, a system consisting of two planets orbiting around an eclipsing pair of stars. The inner and outer planets have radii 3.0 and 4.6 times that of Earth, respectively. The binary star consists of a Sun-like star and a companion roughly one-third its size, orbiting each other every 7.45 days. With an orbital period of 49.5 days, 18 transits of the inner planet have been observed, allowing a detailed characterization of its orbit and those of the stars. The outer planet’s orbital period is 303.2 days, and although the planet is not Earth-like, it resides within the classical "habitable zone," where liquid water could exist on an Earth-like planet. With its two known planets, Kepler-47 establishes that close binary stars can host complete planetary systems.

Journal ArticleDOI
19 Apr 2012-Blood
TL;DR: It is suggested that NK-cell responses may be negatively regulated when NK cells encounter target cells expressing cognate ligands of Tim-3, which is a maturation marker on NK cells.

Journal ArticleDOI
TL;DR: Subanalyses revealed that limited English proficient Latinos, Vietnamese, and Whites had equal or greater odds of poor health compared with low health literate/limited English proficient respondents.
Abstract: This study estimated health status by low health literacy and limited English proficiency alone and in combination for Latino, Chinese, Korean, Vietnamese, and White respondents in a population-based sample: 48,427 adults from the 2007 California Health Interview Survey, including 3,715 with limited English proficiency. Multivariate logistic models examined self-reported health by health literacy and English proficiency in the full sample and in racial/ethnic subgroups. Overall, 44.9% with limited English proficiency reported low health literacy, versus 13.8% of English speakers. Among the limited English proficient, Chinese respondents had the highest prevalence of low health literacy (68.3%), followed by Latinos (45.3%), Koreans (35.6%), Vietnamese (29.7%), and Whites (18.8%). In the full sample, respondents with both limited English proficiency/low health literacy reported the highest prevalence of poor health (45.1%), followed by limited English proficiency–only (41.1%), low health literacy–only (22.2...

Journal ArticleDOI
TL;DR: This article showed that regional monsoons are coordinated not only by external solar forcing but also by internal feedback processes such as El Nino-Southern Oscillation (ENSO), which is a defining feature of the annual variation of Earth's climate system.
Abstract: The global monsoon (GM) is a defining feature of the annual variation of Earth’s climate system. Quantifying and understanding the present-day monsoon precipitation change are crucial for prediction of its future and reflection of its past. Here we show that regional monsoons are coordinated not only by external solar forcing but also by internal feedback processes such as El Nino-Southern Oscillation (ENSO). From one monsoon year (May to the next April) to the next, most continental monsoon regions, separated by vast areas of arid trade winds and deserts, vary in a cohesive manner driven by ENSO. The ENSO has tighter regulation on the northern hemisphere summer monsoon (NHSM) than on the southern hemisphere summer monsoon (SHSM). More notably, the GM precipitation (GMP) has intensified over the past three decades mainly due to the significant upward trend in NHSM. The intensification of the GMP originates primarily from an enhanced east–west thermal contrast in the Pacific Ocean, which is coupled with a rising pressure in the subtropical eastern Pacific and decreasing pressure over the Indo-Pacific warm pool. While this mechanism tends to amplify both the NHSM and SHSM, the stronger (weaker) warming trend in the NH (SH) creates a hemispheric thermal contrast, which favors intensification of the NHSM but weakens the SHSM. The enhanced Pacific zonal thermal contrast is largely a result of natural variability, whilst the enhanced hemispherical thermal contrast is likely due to anthropogenic forcing. We found that the enhanced global summer monsoon not only amplifies the annual cycle of tropical climate but also promotes directly a “wet-gets-wetter” trend pattern and indirectly a “dry-gets-drier” trend pattern through coupling with deserts and trade winds. The mechanisms recognized in this study suggest a way forward for understanding past and future changes of the GM in terms of its driven mechanisms.

Journal ArticleDOI
29 Feb 2012-PLOS ONE
TL;DR: The gradients reported here represent a trajectory of degradation that can be used to assess the health of any similar habitat in the Mediterranean, and to evaluate the efficacy of marine protected areas.
Abstract: Historical exploitation of the Mediterranean Sea and the absence of rigorous baselines makes it difficult to evaluate the current health of the marine ecosystems and the efficacy of conservation actions at the ecosystem level. Here we establish the first current baseline and gradient of ecosystem structure of nearshore rocky reefs at the Mediterranean scale. We conducted underwater surveys in 14 marine protected areas and 18 open access sites across the Mediterranean, and across a 31-fold range of fish biomass (from 3.8 to 118 g m 22 ). Our data showed remarkable variation in the structure of rocky reef ecosystems. Multivariate analysis showed three alternative community states: (1) large fish biomass and reefs dominated by non-canopy algae, (2) lower fish biomass but abundant native algal canopies and suspension feeders, and (3) low fish biomass and extensive barrens, with areas covered by turf algae. Our results suggest that the healthiest shallow rocky reef ecosystems in the Mediterranean have both large fish and algal biomass. Protection level and primary production were the only variables significantly correlated to community biomass structure. Fish biomass was significantly larger in well-enforced no-take marine reserves, but there were no significant differences between multi-use marine protected areas (which allow some fishing) and open access areas at the regional scale. The gradients reported here represent a trajectory of degradation that can be used to assess the health of any similar habitat in the Mediterranean, and to evaluate the efficacy of marine protected areas.

Journal ArticleDOI
01 Oct 2012-Cytokine
TL;DR: The roles of MCP-1 in the development of obesity, diabetes, cardiovascular diseases, insulitis, diabetic nephropathy, and diabetic retinopathy are reviewed.

Journal ArticleDOI
TL;DR: It is estimated that about 50–80% of pleural MM in men and 20–30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings, and about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos.
Abstract: Malignant mesothelioma (MM) is a neoplasm arising from mesothelial cells lining the pleural, peritoneal, and pericardial cavities. Over 20 million people in the US are at risk of developing MM due to asbestos exposure. MM mortality rates are estimated to increase by 5-10% per year in most industrialized countries until about 2020. The incidence of MM in men has continued to rise during the past 50 years, while the incidence in women appears largely unchanged. It is estimated that about 50-80% of pleural MM in men and 20-30% in women developed in individuals whose history indicates asbestos exposure(s) above that expected from most background settings. While rare for women, about 30% of peritoneal mesothelioma in men has been associated with exposure to asbestos. Erionite is a potent carcinogenic mineral fiber capable of causing both pleural and peritoneal MM. Since erionite is considerably less widespread than asbestos, the number of MM cases associated with erionite exposure is smaller. Asbestos induces DNA alterations mostly by inducing mesothelial cells and reactive macrophages to secrete mutagenic oxygen and nitrogen species. In addition, asbestos carcinogenesis is linked to the chronic inflammatory process caused by the deposition of a sufficient number of asbestos fibers and the consequent release of pro-inflammatory molecules, especially HMGB-1, the master switch that starts the inflammatory process, and TNF-alpha by macrophages and mesothelial cells. Genetic predisposition, radiation exposure and viral infection are co-factors that can alone or together with asbestos and erionite cause MM.

Journal ArticleDOI
30 Aug 2012-Nature
TL;DR: A carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean is presented and large superimposed fluctuations in carbonate compensation depth are found during the middle and late Eocene.
Abstract: Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5 kilometres during the early Cenozoic (approximately 55 million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.

Journal ArticleDOI
06 Dec 2012-Nature
TL;DR: The presence of a rotationally supported disk is confirmed, and significantly more mass may be added to its planet-forming region as well as to the protostar itself in the future.
Abstract: In the earliest stage of star formation, protostars accrete mass from their surrounding envelopes through circumstellar disks; observations of the protostar L1527 IRS find a large, rotating proto-planetary disk from which the protostellar mass is measured to be 0.19 solar masses, with a protostar-to-envelope mass ratio of about 0.2. This paper reports the use of submillimetre interferometry to obtain the first detection of a large Keplerian disk around a protostar in the earliest phase of evolution, the class 0 phase. Hitherto the smallest observed protostar-to-envelope mass ratio was about 2.1. The newly discovered protostar, L1527 IRS, has a mass of approximately 0.2 solar masses and a protostar-to-envelope mass ratio of about 0.2. L1527 already has a proto-planetary disk of at least seven Jupiter masses, similar to presumed planet-forming disks, so it appears to have all the elements of a solar system in the making. In their earliest stages, protostars accrete mass from their surrounding envelopes through circumstellar disks. Until now, the smallest observed protostar-to-envelope mass ratio was about 2.1 (ref. 1). The protostar L1527 IRS is thought to be in the earliest stages of star formation2. Its envelope contains about one solar mass of material within a radius of about 0.05 parsecs (refs 3, 4), and earlier observations suggested the presence of an edge-on disk5. Here we report observations of dust continuum emission and 13CO (rotational quantum number J = 2 → 1) line emission from the disk around L1527 IRS, from which we determine a protostellar mass of 0.19 ± 0.04 solar masses and a protostar-to-envelope mass ratio of about 0.2. We conclude that most of the luminosity is generated through the accretion process, with an accretion rate of about 6.6 × 10−7 solar masses per year. If it has been accreting at that rate through much of its life, its age is approximately 300,000 years, although theory suggests larger accretion rates earlier6, so it may be younger. The presence of a rotationally supported disk is confirmed, and significantly more mass may be added to its planet-forming region as well as to the protostar itself in the future.

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TL;DR: In this paper, a new version of the high-resolution 20-and 60-km-mesh Meteorological Research Institute (MRI) atmospheric general circulation models (MRI-AGCM version 3.2) has been developed and used to investigate potential future changes in tropical cyclone (TC) activity.
Abstract: New versions of the high-resolution 20- and 60-km-mesh Meteorological Research Institute (MRI) atmospheric general circulation models (MRI-AGCM version 3.2) have been developed and used to investigate potential future changes in tropical cyclone (TC) activity. Compared with the previous version (version 3.1), version 3.2 yields a more realistic simulation of the present-day (1979–2003) global distribution of TCs. Moreover, the 20-km-mesh model version 3.2 is able to simulate extremely intense TCs (categories 4 and 5), which is the first time a global climate model has been able to simulate such extremely intense TCs through a multidecadal simulation. Future (2075–99) projections under the Intergovernmental Panel on Climate Change (IPCC) A1B scenario are conducted using versions 3.1 and 3.2, showing consistent decreases in the number of TCs globally and in both hemispheres as climate warms. Although projected future changes in basin-scale TC numbers show some differences between the two versions, t...

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TL;DR: It was confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increase risk of cancer for their noncarrier relatives.
Abstract: Purpose To determine whether cancer risks for carriers and noncarriers from families with a mismatch repair (MMR) gene mutation are increased above the risks of the general population. Patients and Methods We prospectively followed a cohort of 446 unaffected carriers of an MMR gene mutation (MLH1, n 161; MSH2 ,n 222; MSH6 ,n 47; and PMS2 ,n 16) and 1,029 their unaffected relatives who did not carry a mutation every 5 years at recruitment centers of the Colon Cancer Family Registry. For comparison of cancer risk with the general population, we estimated country-, age-, and sex-specific standardized incidence ratios (SIRs) of cancer for carriers and noncarriers. Results Over a median follow-up of 5 years, mutation carriers had an increased risk of colorectal cancer (CRC; SIR, 20.48; 95% CI, 11.71 to 33.27; P .001), endometrial cancer (SIR, 30.62; 95% CI, 11.24 to 66.64; P .001), ovarian cancer (SIR, 18.81; 95% CI, 3.88 to 54.95; P .001), renal cancer (SIR, 11.22; 95% CI, 2.31 to 32.79; P .001), pancreatic cancer (SIR, 10.68; 95% CI, 2.68 to 47.70; P .001), gastric cancer (SIR, 9.78; 95% CI, 1.18 to 35.30; P .009), urinary bladder cancer (SIR, 9.51; 95% CI, 1.15 to 34.37; P .009), and female breast cancer (SIR, 3.95; 95% CI, 1.59 to 8.13; P .001). We found no evidence of their noncarrier relatives having an increased risk of any cancer, including CRC (SIR, 1.02; 95% CI, 0.33 to 2.39; P .97). Conclusion We confirmed that carriers of an MMR gene mutation were at increased risk of a wide variety of cancers, including some cancers not previously recognized as being a result of MMR mutations, and found no evidence of an increased risk of cancer for their noncarrier relatives. J Clin Oncol 30:958-964. © 2012 by American Society of Clinical Oncology

Journal ArticleDOI
15 Nov 2012-Nature
TL;DR: It is found that SST warming patterns are the main cause of the weakened Walker circulation over the past six decades, and model experiments show that the observed slowdown in the Walker circulation is presumably driven by oceanic rather than atmospheric processes.
Abstract: Global mean sea surface temperature (SST) has risen steadily over the past century, but the overall pattern contains extensive and often uncertain spatial variations, with potentially important effects on regional precipitation. Observations suggest a slowdown of the zonal atmospheric overturning circulation above the tropical Pacific Ocean (the Walker circulation) over the twentieth century. Although this change has been attributed to a muted hydrological cycle forced by global warming, the effect of SST warming patterns has not been explored and quantified. Here we perform experiments using an atmospheric model, and find that SST warming patterns are the main cause of the weakened Walker circulation over the past six decades (1950-2009). The SST trend reconstructed from bucket-sampled SST and night-time marine surface air temperature features a reduced zonal gradient in the tropical Indo-Pacific Ocean, a change consistent with subsurface temperature observations. Model experiments with this trend pattern robustly simulate the observed changes, including the Walker circulation slowdown and the eastward shift of atmospheric convection from the Indonesian maritime continent to the central tropical Pacific. Our results cannot establish whether the observed changes are due to natural variability or anthropogenic global warming, but they do show that the observed slowdown in the Walker circulation is presumably driven by oceanic rather than atmospheric processes.