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Sökning: WFRF:(Epstein O.)

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1.
  • 2017
  • swepub:Mat__t
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2.
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3.
  • Achberger, Christine, 1968, et al. (författare)
  • State of the Climate in 2011
  • 2012
  • Ingår i: Bulletin of the American Meteorological Society. - 0003-0007. ; 93:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large-scale climate patterns influenced temperature and weather patterns around the globe in 2011. In particular, a moderate-to-strong La Nina at the beginning of the year dissipated during boreal spring but reemerged during fall. The phenomenon contributed to historical droughts in East Africa, the southern United States, and northern Mexico, as well the wettest two-year period (2010-11) on record for Australia, particularly remarkable as this follows a decade-long dry period. Precipitation patterns in South America were also influenced by La Nina. Heavy rain in Rio de Janeiro in January triggered the country's worst floods and landslides in Brazil's history. The 2011 combined average temperature across global land and ocean surfaces was the coolest since 2008, but was also among the 15 warmest years on record and above the 1981-2010 average. The global sea surface temperature cooled by 0.1 degrees C from 2010 to 2011, associated with cooling influences of La Nina. Global integrals of upper ocean heat content for 2011 were higher than for all prior years, demonstrating the Earth's dominant role of the oceans in the Earth's energy budget. In the upper atmosphere, tropical stratospheric temperatures were anomalously warm, while polar temperatures were anomalously cold. This led to large springtime stratospheric ozone reductions in polar latitudes in both hemispheres. Ozone concentrations in the Arctic stratosphere during March were the lowest for that period since satellite records began in 1979. An extensive, deep, and persistent ozone hole over the Antarctic in September indicates that the recovery to pre-1980 conditions is proceeding very slowly. Atmospheric carbon dioxide concentrations increased by 2.10 ppm in 2011, and exceeded 390 ppm for the first time since instrumental records began. Other greenhouse gases also continued to rise in concentration and the combined effect now represents a 30% increase in radiative forcing over a 1990 baseline. Most ozone depleting substances continued to fall. The global net ocean carbon dioxide uptake for the 2010 transition period from El Nino to La Nina, the most recent period for which analyzed data are available, was estimated to be 1.30 Pg C yr(-1), almost 12% below the 29-year long-term average. Relative to the long-term trend, global sea level dropped noticeably in mid-2010 and reached a local minimum in 2011. The drop has been linked to the La Nina conditions that prevailed throughout much of 2010-11. Global sea level increased sharply during the second half of 2011. Global tropical cyclone activity during 2011 was well-below average, with a total of 74 storms compared with the 1981-2010 average of 89. Similar to 2010, the North Atlantic was the only basin that experienced above-normal activity. For the first year since the widespread introduction of the Dvorak intensity-estimation method in the 1980s, only three tropical cyclones reached Category 5 intensity level-all in the Northwest Pacific basin. The Arctic continued to warm at about twice the rate compared with lower latitudes. Below-normal summer snowfall, a decreasing trend in surface albedo, and above-average surface and upper air temperatures resulted in a continued pattern of extreme surface melting, and net snow and ice loss on the Greenland ice sheet. Warmer-than-normal temperatures over the Eurasian Arctic in spring resulted in a new record-low June snow cover extent and spring snow cover duration in this region. In the Canadian Arctic, the mass loss from glaciers and ice caps was the greatest since GRACE measurements began in 2002, continuing a negative trend that began in 1987. New record high temperatures occurred at 20 m below the land surface at all permafrost observatories on the North Slope of Alaska, where measurements began in the late 1970s. Arctic sea ice extent in September 2011 was the second-lowest on record, while the extent of old ice (four and five years) reached a new record minimum that was just 19% of normal. On the opposite pole, austral winter and spring temperatures were more than 3 degrees C above normal over much of the Antarctic continent. However, winter temperatures were below normal in the northern Antarctic Peninsula, which continued the downward trend there during the last 15 years. In summer, an all-time record high temperature of -12.3 degrees C was set at the South Pole station on 25 December, exceeding the previous record by more than a full degree. Antarctic sea ice extent anomalies increased steadily through much of the year, from briefly setting a record low in April, to well above average in December. The latter trend reflects the dispersive effects of low pressure on sea ice and the generally cool conditions around the Antarctic perimeter.
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4.
  • Do, Ron, et al. (författare)
  • Common variants associated with plasma triglycerides and risk for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1345-
  • Tidskriftsartikel (refereegranskat)abstract
    • Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
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5.
  • Patel, Y., et al. (författare)
  • Virtual Ontogeny of Cortical Growth Preceding Mental Illness
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223 .- 1873-2402. ; 92:4, s. 299-313
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life. Methods: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Results: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Conclusions: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
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6.
  • Willer, Cristen J., et al. (författare)
  • Discovery and refinement of loci associated with lipid levels
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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7.
  • Arndt, D. S., et al. (författare)
  • State of the Climate in 2016
  • 2017
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 98:8, s. S1-S280
  • Tidskriftsartikel (refereegranskat)abstract
    • In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.
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8.
  • Arndt, D. S., et al. (författare)
  • STATE OF THE CLIMATE IN 2017
  • 2018
  • Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
  • Forskningsöversikt (refereegranskat)
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10.
  • Alcorn, J, et al. (författare)
  • Basic instrumentation for Hall A at Jefferson Lab
  • 2004
  • Ingår i: Nuclear Instruments & Methods in Physics Research. Section A: Accelerators, Spectrometers, Detectors, and Associated Equipment. - : Elsevier BV. - 0167-5087 .- 0168-9002. ; 522:3, s. 294-346
  • Tidskriftsartikel (refereegranskat)abstract
    • The instrumentation in Hall A at the Thomas Jefferson National Accelerator Facility was designed to study electro-and photo-induced reactions at very high luminosity and good momentum and angular resolution for at least one of the reaction products. The central components of Hall A are two identical high resolution spectrometers, which allow the vertical drift chambers in the focal plane to provide a momentum resolution of better than 2 x 10(-4). A variety of Cherenkov counters, scintillators and lead-glass calorimeters provide excellent particle identification. The facility has been operated successfully at a luminosity well in excess of 10(38) CM-2 s(-1). The research program is aimed at a variety of subjects, including nucleon structure functions, nucleon form factors and properties of the nuclear medium. (C) 2003 Elsevier B.V. All rights reserved.
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14.
  • Puckett, A. J. R., et al. (författare)
  • Final analysis of proton form factor ratio data at Q(2)=4.0, 4.8, and 5.6 GeV2
  • 2012
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Precise measurements of the proton electromagnetic form factor ratio R = mu(p)G(E)(p)/G(M)(p) using the polarization transfer method at Jefferson Lab have revolutionized the understanding of nucleon structure by revealing the strong decrease of R with momentum transfer Q(2) for Q(2) greater than or similar to 1 GeV2, in strong disagreement with previous extractions of R from cross-section measurements. In particular, the polarization transfer results have exposed the limits of applicability of the one-photon-exchange approximation and highlighted the role of quark orbital angular momentum in the nucleon structure. The GEp-II experiment in Jefferson Lab's Hall A measured R at four Q(2) values in the range 3.5 GeV2 <= Q(2) <= 5.6 GeV2. A possible discrepancy between the originally published GEp-II results and more recent measurements at higher Q(2) motivated a new analysis of the GEp-II data. This article presents the final results of the GEp-II experiment, including details of the new analysis, an expanded description of the apparatus, and an overview of theoretical progress since the original publication. The key result of the final analysis is a systematic increase in the results for R, improving the consistency of the polarization transfer data in the high-Q(2) region. This increase is the result of an improved selection of elastic events which largely removes the systematic effect of the inelastic contamination, underestimated by the original analysis.
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15.
  • Walker, Donald A., et al. (författare)
  • Cumulative Effects of Rapid Land-Cover and Land-Use Changes on the Yamal Peninsula, Russia
  • 2011
  • Ingår i: Eurasian Arctic Land Cover and Land Use in a Changing Climate. - New York : Springer Netherlands. - 9789048191178 - 9789048191185 ; , s. 207-236
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • The Yamal Peninsula in northwest Siberia is undergoing some of the most rapid land-cover and land-use changes in the Arctic due to a combination of gas development, reindeer herding, and climate change. Unusual geological conditions (nutrient-poor sands, massive ground ice and extensive landslides) exacerbate the impacts. These changes will likely increase markedly as transportation corridors are built to transport the gas to market. Understanding the nature, extent, causes and consequences (i.e., the cumulative effects) of the past and ongoing rapid changes on the Yamal is important for effective, long-term decision-making and planning. The cumulative effects to vegetation are the focus of this chapter because the plants are a critical component of the Yamal landscape that support the indigenous Nenets people and their reindeer and also protect the underlying ice-rich permafrost from melting. We are using a combination of ground-based studies (a transect of live locations across the Yamal), remote-sensing studies, and analyses of Nenets land-use activities to develop vegetation-change models that can be used to help anticipate future states of the tundra and how those changes might affect traditional reindeer herding practices and the thermal state of the permafrost. This chapter provides an overview of the approach, some early results, and recommendations for expanding the concept of cumulative-effects analysis to include examining the simultaneous and interactive effects of multiple drivers of change.
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16.
  • Wijesooriya, K, et al. (författare)
  • Polarization measurements in high-energy deuteron photodisintegration
  • 2001
  • Ingår i: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 86:14, s. 2975-2979
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of the recoil proton polarization for the d(γ⃗,p⃗)n reaction at θc.m. = 90° for photon energies up to 2.4 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. The induced polarization py vanishes above 1 GeV, contrary to meson-baryon model expectations, in which resonances lead to large polarizations. However, the polarization transfer Cx does not vanish above 1 GeV, inconsistent with hadron helicity conservation. Thus, we show that the scaling behavior observed in the d(γ,p)ncross sections is not a result of perturbative QCD. These data should provide important tests of new nonperturbative calculations in the intermediate energy regime.
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17.
  • Wijesooriya, K, et al. (författare)
  • Polarization measurements in neutral pion photoproduction
  • 2002
  • Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 66:3
  • Tidskriftsartikel (refereegranskat)abstract
    • We present measurements of the recoil proton polarization for the H-1((γ) over right arrow,(p) over right arrow)pi(0) reaction for theta(c.m.)(pi) = 60degrees-135degrees and for photon energies up to 4.1 GeV. These are the first data in this reaction for polarization transfer with circularly polarized photons. Various theoretical models are compared with the results. No evidence for hadron helicity conservation is observed. Models that employ factorization are not favored. It appears from the strong angular dependence of the induced polarization at photon energies of 2.5 and 3.1 GeV that a relatively high spin resonance or background amplitude might exist in this energy region.
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18.
  • Bongiorni, Maria G, et al. (författare)
  • 2018 EHRA expert consensus statement on lead extraction : recommendations on definitions, endpoints, research trial design, and data collection requirements for clinical scientific studies and registries: endorsed by APHRS/HRS/LAHRS
  • 2018
  • Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 20:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The number of cardiac implantable electronic device (CIED) implantations has increased over recent years as a result of population growth, increasing life expectancy, adoption of guidelines, and better access to healthcare. Transvenous lead extraction (TLE), as a part of an overall lead management strategy, has also been increasing, not only as a consequence of this growth, but also because of increasing rates of infection, lead failure, awareness of indications for lead management, and development of extraction tools. Clinical research is essential for understanding efficacy and risks of TLE, which has important implications regarding decision-making and therapeutic strategies in patients who are candidates for this procedure. Data on TLE have mainly come from retrospective series, with variable reporting of endpoints. Recently, the ELECTRa registry conducted by the European Heart Rhythm Association (EHRA), has reported the largest prospective experience on lead extraction published to date in 3555 patients recruited from 19 European countries. There remain unresolved issues, which is a strong incentive for conducting further specifically-designed clinical trials to answer important questions in this area. In addition to clinical studies, national registries are potentially useful for evaluating epidemiology of TLE as well as for quality control and understanding resource implications. Standardization of definitions and reporting of parameters are paramount in order to analyse, compare, and pool data for scientific purposes. Expert consensus statements on lead extraction have been published by the Heart Rhythm Society (HRS) in 2009 and 2017, and by EHRA in 2012. Experience from the ELECTRa registry has been valuable for identifying challenges faced with conducting scientific studies in this field, and provides a framework for future endeavours.This writing group has been commissioned by EHRA to provide recommendations for designing scientific studies, reports and registries relating to lead extraction.
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21.
  • Fischerova, D., et al. (författare)
  • Terms, definitions and measurements to describe sonographic features of lymph nodes : consensus opinion from the Vulvar International Tumor Analysis (VITA) group
  • 2021
  • Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 57:6, s. 861-879
  • Tidskriftsartikel (refereegranskat)abstract
    • In centers with access to high-end ultrasound machines and expert sonologists, ultrasound is used to detect metastases in regional lymph nodes from melanoma, breast cancer and vulvar cancer. There is, as yet, no international consensus on ultrasound assessment of lymph nodes in any disease or medical condition. The lack of standardized ultrasound nomenclature to describe lymph nodes makes it difficult to compare results from different ultrasound studies and to find reliable ultrasound features for distinguishing non-infiltrated lymph nodes from lymph nodes infiltrated by cancer or lymphoma cells. The Vulvar International Tumor Analysis (VITA) collaborative group consists of gynecologists, gynecologic oncologists and radiologists with expertise in gynecologic cancer, particularly in the ultrasound staging and treatment of vulvar cancer. The work herein is a consensus opinion on terms, definitions and measurements which may be used to describe inguinal lymph nodes on grayscale and color/power Doppler ultrasound. The proposed nomenclature need not be limited to the description of inguinal lymph nodes as part of vulvar cancer staging; it can be used to describe peripheral lymph nodes in general, as well as non-peripheral (i.e. parietal or visceral) lymph nodes if these can be visualized clearly. The association between the ultrasound features described here and histopathological diagnosis has not yet been established. VITA terms and definitions lay the foundations for prospective studies aiming to identify ultrasound features typical of metastases and other pathology in lymph nodes and studies to elucidate the role of ultrasound in staging of vulvar and other malignancies.
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23.
  • Gayou, O, et al. (författare)
  • Measurement of G(Ep)/G(Mp) in (e)over-right-arrowp -> e(p)over-right-arrow to Q(2)=5.6 GeV2
  • 2002
  • Ingår i: Physical Review Letters. - 1079-7114. ; 88:9
  • Tidskriftsartikel (refereegranskat)abstract
    • The ratio of the electric and magnetic form factors of the proton G(Ep)/G(Mp), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic (e) over right arrowp --> e (p) over right arrow reaction. The new data presented span the range 3.5 < Q(2) < 5.6 GeV2 and are well described by a linear Q(2) fit. Also, the ratio rootQ(2) F-2p/F-1p reaches a constant value above Q(2) = 2 GeV2.
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24.
  • Kitagawa, M, et al. (författare)
  • Dual blockade of the lipid kinase PIP4Ks and mitotic pathways leads to cancer-selective lethality
  • 2017
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 2200-
  • Tidskriftsartikel (refereegranskat)abstract
    • Achieving robust cancer-specific lethality is the ultimate clinical goal. Here, we identify a compound with dual-inhibitory properties, named a131, that selectively kills cancer cells, while protecting normal cells. Through an unbiased CETSA screen, we identify the PIP4K lipid kinases as the target of a131. Ablation of the PIP4Ks generates a phenocopy of the pharmacological effects of PIP4K inhibition by a131. Notably, PIP4Ks inhibition by a131 causes reversible growth arrest in normal cells by transcriptionally upregulating PIK3IP1, a suppressor of the PI3K/Akt/mTOR pathway. Strikingly, Ras activation overrides a131-induced PIK3IP1 upregulation and activates the PI3K/Akt/mTOR pathway. Consequently, Ras-transformed cells override a131-induced growth arrest and enter mitosis where a131’s ability to de-cluster supernumerary centrosomes in cancer cells eliminates Ras-activated cells through mitotic catastrophe. Our discovery of drugs with a dual-inhibitory mechanism provides a unique pharmacological strategy against cancer and evidence of cross-activation between the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways via a Ras˧PIK3IP1˧PI3K signaling network.
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27.
  • Lipinski, Michael J., et al. (författare)
  • A Systematic Review and Collaborative Meta-Analysis to Determine the Incremental Value of Copeptin for Rapid Rule-Out of Acute Myocardial Infarction
  • 2014
  • Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 113:9, s. 1581-1591
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients. Study investigators were contacted, and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination. There were a total of 9,244 patients from the 14 included studies. Mean age was 62 years; 64% were men; and 18.4% were ultimately diagnosed with AMI. Patients with AMI had a higher presentation copeptin level than those without AMI (22.8 vs 8.3 pmol/L, respectively, p <0.001). Although troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686 [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97 [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, p <0.001) compared with troponin alone. Elevation in copeptin carried a similar risk of all-cause mortality to an elevation in troponin (odds ratio 5.84 vs 6.74, respectively, p = 0.67). In conclusion, copeptin not only identifies patients at risk of all-cause mortality, but its addition to troponin improved the sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone. Thus, copeptin may help identify patients who may be safely discharged early from the emergency department.
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29.
  • Rvachev, MM, et al. (författare)
  • Quasielastic He-3(e,e(')p)H-2 reaction at Q(2)=1.5 GeV2 for recoil momenta up to 1 GeV/c
  • 2005
  • Ingår i: Physical Review Letters. - 1079-7114. ; 94:19
  • Tidskriftsartikel (refereegranskat)abstract
    • We have studied the quasielastic He-3(e,e(')p)H-2 reaction in perpendicular coplanar kinematics, with the energy and the momentum transferred by the electron fixed at 840 MeV and 1502 MeV/c, respectively. The He-3(e,e(')p)H-2 cross section was measured for missing momenta up to 1000 MeV/c, while the A(TL) asymmetry was extracted for missing momenta up to 660 MeV/c. For missing momenta up to 150 MeV/c, the cross section is described by variational calculations using modern He-3 wave functions. For missing momenta from 150 to 750 MeV/c, strong final-state interaction effects are observed. Near 1000 MeV/c, the experimental cross section is more than an order of magnitude larger than predicted by available theories. The A(TL) asymmetry displays characteristic features of broken factorization with a structure that is similar to that generated by available models.
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30.
  • Schulte, EC, et al. (författare)
  • High energy angular distribution measurements of the exclusive deuteron photodisintegration reaction
  • 2002
  • Ingår i: Physical Review C (Nuclear Physics). - : American Physical Society. - 0556-2813 .- 1089-490X. ; 66:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The first complete measurements of the angular distributions of the two-body deuteron photodisintegration differential cross section at photon energies above 1.6 GeV were performed at the Thomas Jefferson National Accelerator Facility. The results show a persistent forward-backward asymmetry up to E-gamma=2.4 GeV, the highest-energy measured in this experiment. The Hard Rescattering and the Quark-Gluon string models are in fair agreement with the results.
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31.
  • Spada, C., et al. (författare)
  • Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
  • 2012
  • Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 1438-8812 .- 0013-726X. ; 44:5, s. 527-535
  • Tidskriftsartikel (refereegranskat)abstract
    • PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.
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32.
  • Spada, C., et al. (författare)
  • Kolonkapselendoskopie: Leitlinie der Europäischen Gesellschaft für Gastrointestinale Endoskopie
  • 2012
  • Ingår i: Endoskopie Heute. - : Georg Thieme Verlag KG. - 0933-811X .- 1439-2577. ; 25:2, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and workup of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.
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33.
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34.
  • Strauch, S, et al. (författare)
  • Polarization transfer in the He-4((e)over-right-arrow,e '(p)over-right-arrow)H-3 reaction up to Q(2)=2.6 (GeV/c)(2)
  • 2003
  • Ingår i: Physical Review Letters. - 1079-7114. ; 91:5: 052301
  • Tidskriftsartikel (refereegranskat)abstract
    • We have measured the proton recoil polarization in the He-4((e) over right arrow ,e(')(p) over right arrow)H-4 reaction at Q(2)=0.5, 1.0, 1.6, and 2.6 (GeV/c)(2). The measured ratio of polarization transfer coefficients differs from a fully relativistic calculation, favoring the inclusion of a medium modification of the proton form factors predicted by a quark-meson coupling model. In addition, the measured induced polarizations agree reasonably well with the fully relativistic calculation indicating that the treatment of final-state interactions is under control.
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35.
  • Waeijen-Smit, Kiki, et al. (författare)
  • Global mortality and readmission rates following COPD exacerbation-related hospitalisation : a meta-analysis of 65 945 individual patients
  • 2024
  • Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations < 12 months prior to the index event. Conclusions This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.
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36.
  • Walker, M. D., et al. (författare)
  • Plant community responses to experimental warming across the tundra biome
  • 2006
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:5, s. 1342-1346
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent observations of changes in some tundra ecosystems appear to be responses to a warming climate. Several experimental studies have shown that tundra plants and ecosystems can respond strongly to environmental change, including warming; however, most studies were limited to a single location and were of short duration and based on a variety of experimental designs. In addition, comparisons among studies are difficult because a variety of techniques have been used to achieve experimental warming and different measurements have been used to assess responses. We used metaanalysis on plant community measurements from standardized warming experiments at 11 locations across the tundra biome involved in the International Tundra Experiment. The passive warming treatment increased plant-level air temperature by 1-3 degrees C, which is in the range of predicted and observed warming for tundra regions. Responses were rapid and detected in whole plant communities after only two growing seasons. Overall, warming increased height and cover of deciduous shrubs and graminoids, decreased cover of mosses and lichens, and decreased species diversity and evenness. These results predict that warming will cause a decline in biodiversity across a wide variety of tundra, at least in the short term. They also provide rigorous experimental evidence that recently observed increases in shrub cover in many tundra regions are in response to climate warming. These changes have important implications for processes and interactions within tundra ecosystems and between tundra and the atmosphere.
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37.
  • Wong, K.Y., et al. (författare)
  • Electronic state of nitrogen containing polypyridine at the interfaces with model sulfonic acid containing polymer and molecule
  • 2003
  • Konferensbidrag (refereegranskat)abstract
    • We present results of an X-ray photoelectron spectroscopy (XPS) study of the interfaces between polypyridine (PPy) and model sulfonic acid containing polymer and molecule. We show that the N 1s level splits reflecting protonation of a substantial fraction of the PPy N sites. Density functional theory (DFT) is employed to compare excitation energies, bond angles, highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), and density of states of oligomers of pyridine and protonated pyridine. These results are in accord with the proposed origin of the red shift of the emitted light under forward bias in color-variable alternating-current light emitting (SCALE) devices.
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