Showing papers by "University of Sydney published in 2014"
Johns Hopkins University1, University of Utah2, University of Rochester3, The Royal Marsden NHS Foundation Trust4, National Institutes of Health5, Stanford University6, Washington University in St. Louis7, Ontario Institute for Cancer Research8, University of Sydney9, St. Jude Medical Center10, University of Toronto11, Mayo Clinic12, American Society of Clinical Oncology13, University of Southern California14, North Carolina State University15, Indiana University16, University of Milan17, University of Michigan18
TL;DR: The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive).
Abstract: Purpose
To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.
2,934 citations
Royal North Shore Hospital1, University of Queensland2, Charité3, University of Melbourne4, University of Sydney5, University of Western Sydney6, University of Lorraine7, University of Adelaide8, Menzies Research Institute9, Monash University10, Deakin University11, Institute for Health Metrics and Evaluation12, Royal Cornwall Hospital13
TL;DR: In this article, the global burden of hip and knee OA was estimated as part of the Global Burden of Disease 2010 study and the burden of OA compared with other conditions.
Abstract: Objective To estimate the global burden of hip and knee osteoarthritis (OA) as part of the Global Burden of Disease 2010 study and to explore how the burden of hip and knee OA compares with other conditions. Methods Systematic reviews were conducted to source age-specific and sex-specific epidemiological data for hip and knee OA prevalence, incidence and mortality risk. The prevalence and incidence of symptomatic, radiographic and self-reported hip or knee OA were included. Three levels of severity were defined to derive disability weights (DWs) and severity distribution (proportion with mild, moderate and severe OA). The prevalence by country and region was multiplied by the severity distribution and the appropriate disability weight to calculate years of life lived with disability (YLDs). As there are no deaths directly attributed to OA, YLDs equate disability-adjusted life years (DALYs). Results Globally, of the 291 conditions, hip and knee OA was ranked as the 11th highest contributor to global disability and 38th highest in DALYs. The global age-standardised prevalence of knee OA was 3.8% (95% uncertainty interval (UI) 3.6% to 4.1%) and hip OA was 0.85% (95% UI 0.74% to 1.02%), with no discernible change from 1990 to 2010. Prevalence was higher in females than males. YLDs for hip and knee OA increased from 10.5 million in 1990 (0.42% of total DALYs) to 17.1 million in 2010 (0.69% of total DALYs). Conclusions Hip and knee OA is one of the leading causes of global disability. Methodological issues within this study make it highly likely that the real burden of OA has been underestimated. With the aging and increasing obesity of the world9s population, health professions need to prepare for a large increase in the demand for health services to treat hip and knee OA.
2,440 citations
University of Minnesota1, State University of New York System2, University of Washington3, Laval University4, Malmö University5, Aarhus University6, Aarhus University Hospital7, VU University Amsterdam8, University of Naples Federico II9, University of Michigan10, University of Zurich11, Johns Hopkins University12, University of Copenhagen13, Katholieke Universiteit Leuven14, University of Kentucky15, University of North Carolina at Chapel Hill16, University of Sydney17, HealthPartners18, University of Minnesota System19, University of Auvergne20
TL;DR: The newly recommended evidence-based new DC/TMD protocol is appropriate for use in both clinical and research settings and includes both a valid screener for detecting any pain-related TMD as well as valid diagnostic criteria for differentiating the most common pain- related TMD.
Abstract: Temporomandibular disorders (TMD) are a significant public health problem affecting approximately 5% to 12% of the population.1 TMD is the second most common musculoskeletal condition (after chronic low back pain) resulting in pain and disability.1 Pain-related TMD can impact the individual's daily activities, psychosocial functioning, and quality of life. Overall, the annual TMD management cost in the USA, not including imaging, has doubled in the last decade to $4 billion.1
Patients often seek consultation with dentists for their TMD, especially for pain-related TMD. Diagnostic criteria for TMD with simple, clear, reliable, and valid operational definitions for the history, examination, and imaging procedures are needed to render physical diagnoses in both clinical and research settings. In addition, biobehavioral assessment of pain-related behavior and psychosocial functioning—an essential part of the diagnostic process—is required and provides the minimal information whereby one can determine whether the patient's pain disorder, especially when chronic, warrants further multidisciplinary assessment. Taken together, a new dual-axis Diagnostic Criteria for TMD (DC/TMD) will provide evidence-based criteria for the clinician to use when assessing patients, and will facilitate communication regarding consultations, referrals, and prognosis.2
The research community benefits from the ability to use well-defined and clinically relevant characteristics associated with the phenotype in order to facilitate more generalizable research. When clinicians and researchers use the same criteria, taxonomy, and nomenclature, then clinical questions and experience can be more easily transferred into relevant research questions, and research findings are more accessible to clinicians to better diagnose and manage their patients. The Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) have been the most widely employed diagnostic protocol for TMD research since its publication in 1992.3 This classification system was based on the biopsychosocial model of pain4 that included an Axis I physical assessment, using reliable and well-operationalized diagnostic criteria, and an Axis II assessment of psychosocial status and pain-related disability. The intent was to simultaneously provide a physical diagnosis and identify other relevant characteristics of the patient that could influence the expression and thus management of their TMD. Indeed, the longer the pain persists, the greater the potential for emergence and amplification of cognitive, psychosocial, and behavioral risk factors, with resultant enhanced pain sensitivity, greater likelihood of additional pain persistence, and reduced probability of success from standard treatments.5
The RDC/TMD (1992) was intended to be only a first step toward improved TMD classification, and the authors stated the need for future investigation of the accuracy of the Axis I diagnostic algorithms in terms of reliability and criterion validity—the latter involving the use of credible reference standard diagnoses. Also recommended was further assessment of the clinical utility of the Axis II instruments. The original RDC/TMD Axis I physical diagnoses have content validity based on the critical review by experts of the published diagnostic approach in use at that time and were tested using population-based epidemiologic data.6 Subsequently, a multicenter study showed that, for the most common TMD, the original RDC/TMD diagnoses exhibited sufficient reliability for clinical use.7 While the validity of the individual RDC/TMD diagnoses has been extensively investigated, assessment of the criterion validity for the complete spectrum of RDC/TMD diagnoses had been absent until recently.8
For the original RDC/TMD Axis II instruments, good evidence for their reliability and validity for measuring psychosocial status and pain-related disability already existed when the classification system was published.9–13 Subsequently, a variety of studies have demonstrated the significance and utility of the original RDC/TMD biobehavioral measures in such areas as predicting outcomes of clinical trials, escalation from acute to chronic pain, and experimental laboratory settings.14–20
Other studies have shown that the original RDC/TMD biobehavioral measures are incomplete in terms of prediction of disease course.21–23 The overall utility of the biobehavioral measures in routine clinical settings has, however, yet to be demonstrated, in part because most studies have to date focused on Axis I diagnoses rather than Axis II biobehavioral factors.24
The aims of this article are to present the evidence-based new Axis I and Axis II DC/TMD to be used in both clinical and research settings, as well as present the processes related to their development.
2,283 citations
TL;DR: LBP causes more global disability than any other condition and with the ageing population, there is an urgent need for further research to better understand LBP across different settings.
Abstract: Supported by the Bill and Melinda Gates Foundation (to Dr Hoy and Prof
Vos), the Australian Commonwealth Department of Health and Ageing (to Dr Smith
(University of Sydney, Institute of Bone and Joint Research) and Prof March), the
Australian National Health and Medical Research Council (Postgraduate Scholarship
569772 to Dr Hoy and Practitioner Fellowships 334010 (2005–2009) and 606429
(2010–2014) to Prof Buchbinder, and the Ageing and Alzheimers Research
Foundation (Asst Prof Blyth).
2,085 citations
Duke University1, University of Texas at Austin2, Heidelberg Institute for Theoretical Studies3, Beijing Genomics Institute4, American Museum of Natural History5, Xi'an Jiaotong University6, New Mexico State University7, University of Sydney8, University of California9, Uppsala University10, University of Copenhagen11, Okinawa Institute of Science and Technology12, University of Georgia13, Griffith University14, Catalan Institution for Research and Advanced Studies15, Oak Ridge National Laboratory16, Joint Institute for Nuclear Research17, Aarhus University18, Washington University in St. Louis19, University of California, Santa Cruz20, Cardiff University21, Kunming Institute of Zoology22, China Agricultural University23, Louisiana State University24, Tulane University25, Copenhagen Zoo26, Federal University of Pará27, Oregon Health & Science University28, Technical University of Denmark29, Canterbury Museum30, Curtin University31, Novosibirsk State University32, Smithsonian Institution33, National University of Singapore34, National Museum of Natural History35, Nova Southeastern University36, Occidental College37, University of Edinburgh38, Harvard University39, University of California, San Francisco40, University of Florida41, University of Illinois at Urbana–Champaign42
TL;DR: A genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves recovered a highly resolved tree that confirms previously controversial sister or close relationships and identifies the first divergence in Neoaves, two groups the authors named Passerea and Columbea.
Abstract: To better determine the history of modern birds, we performed a genome-scale phylogenetic analysis of 48 species representing all orders of Neoaves using phylogenomic methods created to handle genome-scale data. We recovered a highly resolved tree that confirms previously controversial sister or close relationships. We identified the first divergence in Neoaves, two groups we named Passerea and Columbea, representing independent lineages of diverse and convergently evolved land and water bird species. Among Passerea, we infer the common ancestor of core landbirds to have been an apex predator and confirm independent gains of vocal learning. Among Columbea, we identify pigeons and flamingoes as belonging to sister clades. Even with whole genomes, some of the earliest branches in Neoaves proved challenging to resolve, which was best explained by massive protein-coding sequence convergence and high levels of incomplete lineage sorting that occurred during a rapid radiation after the Cretaceous-Paleogene mass extinction event about 66 million years ago.
1,624 citations
Institut Gustave Roussy1, University of California, Los Angeles2, Memorial Sloan Kettering Cancer Center3, Harvard University4, University of Sydney5, Westmead Hospital6, Princess Margaret Cancer Centre7, University of Texas MD Anderson Cancer Center8, University of Pennsylvania9, Mayo Clinic10, University of Pittsburgh11, Merck & Co.12, University of California, San Francisco13
TL;DR: The results suggest that pembrolizumab at a dose of 2mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options.
1,569 citations
TL;DR: The purpose of this review is to illustrate how each of these factors interact together to instigate incident OA as well as to outline the need for ongoing epidemiologic studies for the future prevention of both incident and progressive OA.
Abstract: Osteoarthritis (OA) is a leading cause of disability and its incidence is rising due to increasing obesity and an ageing population. Risk factors can be divided into person-level factors, such as age, sex, obesity, genetics, race/ethnicity and diet, and joint-level factors including injury, malalignment and abnormal loading of the joints. The interaction of these risk factors is complex and provides a challenge to the managing physician. The purpose of this review is to illustrate how each of these factors interact together to instigate incident OA as well as to outline the need for ongoing epidemiologic studies for the future prevention of both incident and progressive OA. It is only by understanding the impact of this disease and the modifiable risk factors that we will be able to truly target public health prevention interventions appropriately.
1,504 citations
University of Sydney1, National and Kapodistrian University of Athens2, The Royal Marsden NHS Foundation Trust3, University of Tübingen4, University of Duisburg-Essen5, University of Kiel6, Aix-Marseille University7, University of Paris8, University of Barcelona9, Netherlands Cancer Institute10, Karolinska Institutet11, Heidelberg University12, Mount Vernon Hospital13, Institut Gustave Roussy14, University of California, Los Angeles15, GlaxoSmithKline16, Harvard University17
TL;DR: A combination of dabraenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations.
Abstract: BACKGROUND Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations. METHODS In this phase 3 trial, we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) or dabrafenib and placebo. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted. RESULTS The median progression-free survival was 9.3 months in the dabrafenib–trametinib group and 8.8 months in the dabrafenib-only group (hazard ratio for progression or death in the dabrafenib–trametinib group, 0.75; 95% confidence interval [CI], 0.57 to 0.99; P = 0.03). The overall response rate was 67% in the dabrafenib–trametinib group and 51% in the dabrafenib-only group (P = 0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib–trametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P = 0.02). However, a specified efficacy-stopping boundary (two-sided P = 0.00028) was not crossed. Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenib–trametinib group. The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib–trametinib group than in the dabrafenib-only group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenib–trametinib group. CONCLUSIONS A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. (Funded by GlaxoSmithKline; Clinical Trials.gov number, NCT01584648.)
1,501 citations
TL;DR: In this article, the authors present the implications for cosmic inflation of the Planck measurements of the cosmic microwave background (CMB) anisotropies in both temperature and polarization based on the full Planck survey.
Abstract: We present the implications for cosmic inflation of the Planck measurements of the cosmic microwave background (CMB) anisotropies in both temperature and polarization based on the full Planck survey, which includes more than twice the integration time of the nominal survey used for the 2013 release papers. The Planck full mission temperature data and a first release of polarization data on large angular scales measure the spectral index of curvature perturbations to be ns = 0.968 ± 0.006 and tightly constrain its scale dependence to dns/ dlnk = −0.003 ± 0.007 when combined with the Planck lensing likelihood. When the Planck high-l polarization data are included, the results are consistent and uncertainties are further reduced. The upper bound on the tensor-to-scalar ratio is r0.002< 0.11 (95% CL). This upper limit is consistent with the B-mode polarization constraint r< 0.12 (95% CL) obtained from a joint analysis of the BICEP2/Keck Array and Planck data. These results imply that V(φ) ∝ φ2 and natural inflation are now disfavoured compared to models predicting a smaller tensor-to-scalar ratio, such as R2 inflation. We search for several physically motivated deviations from a simple power-law spectrum of curvature perturbations, including those motivated by a reconstruction of the inflaton potential not relying on the slow-roll approximation. We find that such models are not preferred, either according to a Bayesian model comparison or according to a frequentist simulation-based analysis. Three independent methods reconstructing the primordial power spectrum consistently recover a featureless and smooth over the range of scales 0.008 Mpc-1 ≲ k ≲ 0.1 Mpc-1. At large scales, each method finds deviations from a power law, connected to a deficit at multipoles l ≈ 20−40 in the temperature power spectrum, but at an uncompelling statistical significance owing to the large cosmic variance present at these multipoles. By combining power spectrum and non-Gaussianity bounds, we constrain models with generalized Lagrangians, including Galileon models and axion monodromy models. The Planck data are consistent with adiabatic primordial perturbations, and the estimated values for the parameters of the base Λ cold dark matter (ΛCDM) model are not significantly altered when more general initial conditions are admitted. In correlated mixed adiabatic and isocurvature models, the 95% CL upper bound for the non-adiabatic contribution to the observed CMB temperature variance is | αnon - adi | < 1.9%, 4.0%, and 2.9% for CDM, neutrino density, and neutrino velocity isocurvature modes, respectively. We have tested inflationary models producing an anisotropic modulation of the primordial curvature power spectrum findingthat the dipolar modulation in the CMB temperature field induced by a CDM isocurvature perturbation is not preferred at a statistically significant level. We also establish tight constraints on a possible quadrupolar modulation of the curvature perturbation. These results are consistent with the Planck 2013 analysis based on the nominal mission data and further constrain slow-roll single-field inflationary models, as expected from the increased precision of Planck data using the full set of observations.
1,401 citations
Nicholas J Kassebaum1, Amelia Bertozzi-Villa1, Megan Coggeshall1, Katya Anne Shackelford1 +349 more•Institutions (179)
TL;DR: Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015, with evidence of continued acceleration in the MMR, and MMR was highest in the oldest age groups in both 1990 and 2013.
1,383 citations
TL;DR: The complex interplay between local immune responses and systemic inflammation, and their influence on clinical outcomes, are examined, and potential anti-inflammatory interventions for patients with cancer are proposed.
Abstract: Inflammation is a recognised hallmark of cancer that substantially contributes to the development and progression of malignancies. In established cancers, there is increasing evidence for the roles that local immune response and systemic inflammation have in progression of tumours and survival of patients with cancer. This knowledge provides an opportunity to target these inflammatory responses to improve patient outcomes. In this Review, we examine the complex interplay between local immune responses and systemic inflammation, and their influence on clinical outcomes, and propose potential anti-inflammatory interventions for patients with cancer.
TL;DR: The current state-of-art of WBANs is surveyed based on the latest standards and publications, and open issues and challenges within each area are explored as a source of inspiration towards future developments inWBANs.
Abstract: Recent developments and technological advancements in wireless communication, MicroElectroMechanical Systems (MEMS) technology and integrated circuits has enabled low-power, intelligent, miniaturized, invasive/non-invasive micro and nano-technology sensor nodes strategically placed in or around the human body to be used in various applications, such as personal health monitoring. This exciting new area of research is called Wireless Body Area Networks (WBANs) and leverages the emerging IEEE 802.15.6 and IEEE 802.15.4j standards, specifically standardized for medical WBANs. The aim of WBANs is to simplify and improve speed, accuracy, and reliability of communication of sensors/actuators within, on, and in the immediate proximity of a human body. The vast scope of challenges associated with WBANs has led to numerous publications. In this paper, we survey the current state-of-art of WBANs based on the latest standards and publications. Open issues and challenges within each area are also explored as a source of inspiration towards future developments in WBANs.
TL;DR: This article comprises the consensus reached to update guidance on the use of PET-CT for staging and response assessment for [18F]fluorodeoxyglucose-avid lymphomas in clinical practice and late-phase trials.
Abstract: PurposeRecent advances in imaging, use of prognostic indices, and molecular profiling techniques have the potential to improve disease characterization and outcomes in lymphoma. International trials are under way to test image-based response–adapted treatment guided by early interim positron emission tomography (PET) –computed tomography (CT). Progress in imaging is influencing trial design and affecting clinical practice. In particular, a five-point scale to grade response using PET-CT, which can be adapted to suit requirements for early- and late-response assessment with good interobserver agreement, is becoming widely used both in practice- and response-adapted trials. A workshop held at the 11th International Conference on Malignant Lymphomas (ICML) in 2011 concluded that revision to current staging and response criteria was timely.MethodsAn imaging working group composed of representatives from major international cooperative groups was asked to review the literature, share knowledge about research i...
University of Sydney1, University of California, Los Angeles2, Netherlands Cancer Institute3, New York University4, University of Groningen5, Women & Children's Hospital of Buffalo6, University of South Florida7, Royal Adelaide Hospital8, California Pacific Medical Center9, Princess Alexandra Hospital10, Roswell Park Cancer Institute11, Tom Baker Cancer Centre12
TL;DR: Biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy, and prolongs disease-free survival and melanoma-specific survival.
Abstract: Background Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase 3 trial. Methods We evaluated outcomes in 2001 patients with primary cutaneous melanomas randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observation group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). Results No significant treatment-related difference in the 10-year melanoma-specific survival rate was seen in the overall study population (20.8% with and 79.2% without nodal metastases). Mean (±SE) 10-year disease-free survival rates were significantly improved in the biopsy group, as compared with the observation group, among patients with intermediate-thickness melanomas, defined as 1.20 to 3.50 mm (71.3±1.8% vs. 64.7±2.3%; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as >3.50 mm (50.7±4.0% vs...
University of Tokyo1, University of Wisconsin-Madison2, University of Toronto3, University of Kentucky4, University of Texas at Austin5, University of Washington6, University of St Andrews7, University of Portsmouth8, European Southern Observatory9, University of Nottingham10, National Autonomous University of Mexico11, University of Pittsburgh12, University of Cambridge13, New Mexico State University14, Carnegie Institution for Science15, University of Sydney16, New York University17, University of Utah18, University of Oxford19, University of California, Santa Cruz20, Max Planck Society21, École normale supérieure de Lyon22, Claude Bernard University Lyon 123, Texas Christian University24, University of Iowa25, Princeton University26, Case Western Reserve University27, University of La Laguna28, Chinese Academy of Sciences29, Academia Sinica30, University of Manchester31, Macquarie University32, Australian Astronomical Observatory33, Yale University34, Lawrence Berkeley National Laboratory35, University of Potsdam36, University of Victoria37, University of Groningen38
TL;DR: MaNGA (Mapping Nearby Galaxies at Apache Point Observatory) as mentioned in this paper employs dithered observations with 17 fiber-bundle integral field units that vary in diameter from 12'' (19 fibers) to 32'' (127 fibers).
Abstract: We present an overview of a new integral field spectroscopic survey called MaNGA (Mapping Nearby Galaxies at Apache Point Observatory), one of three core programs in the fourth-generation Sloan Digital Sky Survey (SDSS-IV) that began on 2014 July 1. MaNGA will investigate the internal kinematic structure and composition of gas and stars in an unprecedented sample of 10,000 nearby galaxies. We summarize essential characteristics of the instrument and survey design in the context of MaNGA's key science goals and present prototype observations to demonstrate MaNGA's scientific potential. MaNGA employs dithered observations with 17 fiber-bundle integral field units that vary in diameter from 12'' (19 fibers) to 32'' (127 fibers). Two dual-channel spectrographs provide simultaneous wavelength coverage over 3600-10300 A at R ~ 2000. With a typical integration time of 3 hr, MaNGA reaches a target r-band signal-to-noise ratio of 4-8 (A–1 per 2'' fiber) at 23 AB mag arcsec–2, which is typical for the outskirts of MaNGA galaxies. Targets are selected with M * 109 M ☉ using SDSS-I redshifts and i-band luminosity to achieve uniform radial coverage in terms of the effective radius, an approximately flat distribution in stellar mass, and a sample spanning a wide range of environments. Analysis of our prototype observations demonstrates MaNGA's ability to probe gas ionization, shed light on recent star formation and quenching, enable dynamical modeling, decompose constituent components, and map the composition of stellar populations. MaNGA's spatially resolved spectra will enable an unprecedented study of the astrophysics of nearby galaxies in the coming 6 yr.
TL;DR: An extinct spreading ridge in the Gulf of Mexico, a major propagating rift in the South Atlantic Ocean, abyssal hill fabric on slow-spreading ridges, and thousands of previously uncharted seamounts are found.
Abstract: Gravity models are powerful tools for mapping tectonic structures, especially in the deep ocean basins where the topography remains unmapped by ships or is buried by thick sediment. We combined new radar altimeter measurements from satellites CryoSat-2 and Jason-1 with existing data to construct a global marine gravity model that is two times more accurate than previous models. We found an extinct spreading ridge in the Gulf of Mexico, a major propagating rift in the South Atlantic Ocean, abyssal hill fabric on slow-spreading ridges, and thousands of previously uncharted seamounts. These discoveries allow us to understand regional tectonic processes and highlight the importance of satellite-derived gravity models as one of the primary tools for the investigation of remote ocean basins.
TL;DR: The PLATO 2.0 mission as discussed by the authors has been selected for ESA's M3 launch opportunity (2022/24) to provide accurate key planet parameters (radius, mass, density and age) in statistical numbers.
Abstract: PLATO 2.0 has recently been selected for ESA’s M3 launch opportunity (2022/24). Providing accurate key planet parameters (radius, mass, density and age) in statistical numbers, it addresses fundamental questions such as: How do planetary systems form and evolve? Are there other systems with planets like ours, including potentially habitable planets? The PLATO 2.0 instrument consists of 34 small aperture telescopes (32 with 25 s readout cadence and 2 with 2.5 s candence) providing a wide field-of-view (2232 deg 2) and a large photometric magnitude range (4–16 mag). It focusses on bright (4–11 mag) stars in wide fields to detect and characterize planets down to Earth-size by photometric transits, whose masses can then be determined by ground-based radial-velocity follow-up measurements. Asteroseismology will be performed for these bright stars to obtain highly accurate stellar parameters, including masses and ages. The combination of bright targets and asteroseismology results in high accuracy for the bulk planet parameters: 2 %, 4–10 % and 10 % for planet radii, masses and ages, respectively. The planned baseline observing strategy includes two long pointings (2–3 years) to detect and bulk characterize planets reaching into the habitable zone (HZ) of solar-like stars and an additional step-and-stare phase to cover in total about 50 % of the sky. PLATO 2.0 will observe up to 1,000,000 stars and detect and characterize hundreds of small planets, and thousands of planets in the Neptune to gas giant regime out to the HZ. It will therefore provide the first large-scale catalogue of bulk characterized planets with accurate radii, masses, mean densities and ages. This catalogue will include terrestrial planets at intermediate orbital distances, where surface temperatures are moderate. Coverage of this parameter range with statistical numbers of bulk characterized planets is unique to PLATO 2.0. The PLATO 2.0 catalogue allows us to e.g.: - complete our knowledge of planet diversity for low-mass objects, - correlate the planet mean density-orbital distance distribution with predictions from planet formation theories,- constrain the influence of planet migration and scattering on the architecture of multiple systems, and - specify how planet and system parameters change with host star characteristics, such as type, metallicity and age. The catalogue will allow us to study planets and planetary systems at different evolutionary phases. It will further provide a census for small, low-mass planets. This will serve to identify objects which retained their primordial hydrogen atmosphere and in general the typical characteristics of planets in such low-mass, low-density range. Planets detected by PLATO 2.0 will orbit bright stars and many of them will be targets for future atmosphere spectroscopy exploring their atmosphere. Furthermore, the mission has the potential to detect exomoons, planetary rings, binary and Trojan planets. The planetary science possible with PLATO 2.0 is complemented by its impact on stellar and galactic science via asteroseismology as well as light curves of all kinds of variable stars, together with observations of stellar clusters of different ages. This will allow us to improve stellar models and study stellar activity. A large number of well-known ages from red giant stars will probe the structure and evolution of our Galaxy. Asteroseismic ages of bright stars for different phases of stellar evolution allow calibrating stellar age-rotation relationships. Together with the results of ESA’s Gaia mission, the results of PLATO 2.0 will provide a huge legacy to planetary, stellar and galactic science.
SUNY Downstate Medical Center1, McGill University2, University of Connecticut3, Cornell University4, Umeå University5, Wayne State University6, University of Iowa7, University of Miami8, University of Pennsylvania9, Mayo Clinic10, University of Sydney11, University of Buenos Aires12, University of Chicago13, Shanghai Jiao Tong University14, North-West University15, University of Rochester16, University of Glasgow17, Virginia Commonwealth University18, University of Melbourne19
TL;DR: Clinical Practice Guidelines for the Management of Hypertension in the Community as mentioned in this paper A Statement by the American Society of hypertension and the International Society of Hyperpharmension (ISH).
Abstract: Clinical Practice Guidelines for the Management of Hypertension in the Community A Statement by the American Society of Hypertension and the International Society of Hypertension
01 Dec 2014
TL;DR: A statistical propagation model is proposed for predicting the air-to-ground path loss between a low altitude platform and a terrestrial terminal based on the urban environment properties, and is dependent on the elevation angle between the terminal and the platform.
Abstract: The reliable prediction of coverage footprint resulting from an airborne wireless radio base station, is at utmost importance, when it comes to the new emerging applications of air-to-ground wireless services. These applications include the rapid recovery of damaged terrestrial wireless infrastructure due to a natural disaster, as well as the fulfillment of sudden wireless traffic overload in certain spots due to massive movement of crowds. In this paper, we propose a statistical propagation model for predicting the air-to-ground path loss between a low altitude platform and a terrestrial terminal. The prediction is based on the urban environment properties, and is dependent on the elevation angle between the terminal and the platform. The model shows that air-to-ground path loss is following two main propagation groups, characterized by two different path loss profiles. In this paper we illustrate the methodology of which the model was deduced, as well as we present the different path loss profiles including the occurrence probability of each.
Christopher J L Murray1, Katrina F Ortblad1, Caterina Guinovart1, Stephen S Lim1 +367 more•Institutions (179)
TL;DR: The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
TL;DR: In this paper, the authors estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions.
Abstract: Objectives To estimate the global burden of rheumatoid arthritis (RA), as part of the Global Burden of Disease 2010 study of 291 conditions and how the burden of RA compares with other conditions. Methods The optimum case definition of RA for the study was the American College of Rheumatology 1987 criteria. A series of systematic reviews were conducted to gather age-sex-specific epidemiological data for RA prevalence, incidence and mortality. Cause-specific mortality data were also included. Data were entered into DisMod-MR, a tool to pool available data, making use of study-level covariates to adjust for country, region and super-region random effects to estimate prevalence for every country and over time. The epidemiological data, in addition to disability weights, were used to calculate years of life lived with disability (YLDs). YLDs were added to the years of life lost due to premature mortality to estimate the overall burden (disability-adjusted life years (DALYs)) for RA for the years 1990, 2005 and 2010. Results The global prevalence of RA was 0.24% (95% CI 0.23% to 0.25%), with no discernible change from 1990 to 2010. DALYs increased from 3.3 million (M) (95% CI 2.6 M to 4.1 M) in 1990 to 4.8 M (95% CI 3.7 M to 6.1 M) in 2010. This increase was due to a growth in population and increase in aging. Globally, of the 291 conditions studied, RA was ranked as the 42nd highest contributor to global disability, just below malaria and just above iodine deficiency (measured in YLDs). Conclusions RA continues to cause modest global disability, with severe consequences in the individuals affected.
TL;DR: In this article, the authors identify the core resistance pathways and the extent of tumor heterogeneity during disease progression and show that mitogenactivated protein kinase reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification, and alternative splicing being most common.
Abstract: BRAF inhibitors elicit rapid antitumor responses in the majority of patients with BRAF(V600)-mutant melanoma, but acquired drug resistance is almost universal. We sought to identify the core resistance pathways and the extent of tumor heterogeneity during disease progression. We show that mitogen-activated protein kinase reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification, and alternative splicing being most common. We also detected PI3K-PTEN-AKT-upregulating genetic alterations among 22% of progressive melanomas. Distinct molecular lesions in both core drug escape pathways were commonly detected concurrently in the same tumor or among multiple tumors from the same patient. Beyond harboring extensively heterogeneous resistance mechanisms, melanoma regrowth emerging from BRAF inhibitor selection displayed branched evolution marked by altered mutational spectra/signatures and increased fitness. Thus, melanoma genomic heterogeneity contributes significantly to BRAF inhibitor treatment failure, implying upfront, cotargeting of two core pathways as an essential strategy for durable responses.
TL;DR: Concepts and algorithms related to clustering, a concise survey of existing (clustering) algorithms as well as a comparison, both from a theoretical and an empirical perspective are introduced.
Abstract: Clustering algorithms have emerged as an alternative powerful meta-learning tool to accurately analyze the massive volume of data generated by modern applications. In particular, their main goal is to categorize data into clusters such that objects are grouped in the same cluster when they are similar according to specific metrics. There is a vast body of knowledge in the area of clustering and there has been attempts to analyze and categorize them for a larger number of applications. However, one of the major issues in using clustering algorithms for big data that causes confusion amongst practitioners is the lack of consensus in the definition of their properties as well as a lack of formal categorization. With the intention of alleviating these problems, this paper introduces concepts and algorithms related to clustering, a concise survey of existing (clustering) algorithms as well as providing a comparison, both from a theoretical and an empirical perspective. From a theoretical perspective, we developed a categorizing framework based on the main properties pointed out in previous studies. Empirically, we conducted extensive experiments where we compared the most representative algorithm from each of the categories using a large number of real (big) data sets. The effectiveness of the candidate clustering algorithms is measured through a number of internal and external validity metrics, stability, runtime, and scalability tests. In addition, we highlighted the set of clustering algorithms that are the best performing for big data.
Salk Institute for Biological Studies1, Cold Spring Harbor Laboratory2, University of California, San Francisco3, Leidos4, University of California, Los Angeles5, Tohoku University6, University of New South Wales7, Garvan Institute of Medical Research8, University of Sydney9, Westmead Hospital10, Hospital of the University of Pennsylvania11, University of Pennsylvania12, Howard Hughes Medical Institute13
TL;DR: It is shown that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone.
Johns Hopkins University1, University of Calgary2, The George Institute for Global Health3, University of Sydney4, Royal Prince Alfred Hospital5, University of Salerno6, Geisinger Medical Center7, Saarland University8, Tufts Medical Center9, University of Minnesota10, University of California, San Diego11, University of Tennessee Health Science Center12, Veterans Health Administration13, University of Aberdeen14, Tohoku University15, Shiga University of Medical Science16, Teikyo University17, Tel Aviv University18, Virginia Commonwealth University19, National Health Research Institutes20, China Medical University (Taiwan)21, University Medical Center Groningen22, University of Paris-Sud23
TL;DR: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in Estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
Abstract: IMPORTANCE: The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of −57% or greater) is a late event.OBJECTIVE: To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated.DATA SOURCES AND STUDY SELECTION: Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data.DATA EXTRACTION AND SYNTHESIS: Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012.MAIN OUTCOMES AND MEASURES: End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR.RESULTS: The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of −57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of −30%. However, changes of −30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of −57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of −57%, was 83% (95% CI, 71%-93%) for estimated GFR change of −40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of −30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern.CONCLUSIONS AND RELEVANCE: Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.
TL;DR: This work reviews current footprints and relates those to maximum sustainable levels, highlighting the need for future work on combining footprints, assessing trade-offs between them, improving computational techniques, estimating maximum sustainable footprint levels, and benchmarking efficiency of resource use.
Abstract: Within the context of Earth’s limited natural resources and assimilation capacity, the current environmental footprint of humankind is not sustainable. Assessing land, water, energy, material, and other footprints along supply chains is paramount in understanding the sustainability, efficiency, and equity of resource use from the perspective of producers, consumers, and government. We review current footprints and relate those to maximum sustainable levels, highlighting the need for future work on combining footprints, assessing trade-offs between them, improving computational techniques, estimating maximum sustainable footprint levels, and benchmarking efficiency of resource use. Ultimately, major transformative changes in the global economy are necessary to reduce humanity’s environmental footprint to sustainable levels
TL;DR: The Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum, suggesting that longevity can be extended in ad Libitum-fed animals by manipulating the ratio of macronutrients.
TL;DR: This Perspectives article focuses on the burden of OA for the individual, the health-care system and society, to draw attention to the magnitude of the current problem with some reference to projected figures.
Abstract: Osteoarthritis (OA) is a highly prevalent, disabling disease, with a commensurate tremendous individual and socioeconomic burden. This Perspectives article focuses on the burden of OA for the individual, the health-care system and society, to draw attention to the magnitude of the current problem with some reference to projected figures. We have an urgent opportunity to make fundamental changes to the way we care for individuals with OA that will have an effect upon the direct and indirect costs of this disease. By focusing on the burden of this prevalent, disabling, and costly disease, we hope to highlight the opportunity for shifts in health-care policy towards prevention and chronic-disease management.
TL;DR: A three dimensional micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photocrosslinkable hydrogel constructs with useful applications in tissue engineering and organs on a chip is reported.
Abstract: Vascularization remains a critical challenge in tissue engineering. The development of vascular networks within densely populated and metabolically functional tissues facilitate transport of nutrients and removal of waste products, thus preserving cellular viability over a long period of time. Despite tremendous progress in fabricating complex tissue constructs in the past few years, approaches for controlled vascularization within hydrogel based engineered tissue constructs have remained limited. Here, we report a three dimensional (3D) micromolding technique utilizing bioprinted agarose template fibers to fabricate microchannel networks with various architectural features within photocrosslinkable hydrogel constructs. Using the proposed approach, we were able to successfully embed functional and perfusable microchannels inside methacrylated gelatin (GelMA), star poly(ethylene glycol-co-lactide) acrylate (SPELA), poly(ethylene glycol) dimethacrylate (PEGDMA) and poly(ethylene glycol) diacrylate (PEGDA) hydrogels at different concentrations. In particular, GelMA hydrogels were used as a model to demonstrate the functionality of the fabricated vascular networks in improving mass transport, cellular viability and differentiation within the cell-laden tissue constructs. In addition, successful formation of endothelial monolayers within the fabricated channels was confirmed. Overall, our proposed strategy represents an effective technique for vascularization of hydrogel constructs with useful applications in tissue engineering and organs on a chip.
University of New South Wales1, Georgia Institute of Technology2, Spanish National Research Council3, University of South Alabama4, University of Technology, Sydney5, New South Wales Department of Primary Industries6, University of Sydney7, University of Western Australia8, Macquarie University9, University of Queensland10, Kōchi University11, Marine Biological Association of the United Kingdom12, Oregon State University13
TL;DR: It is argued that this phase shift is facilitated by poleward-flowing boundary currents that are creating ocean warming hotspots around the globe, enabling the range expansion of tropical species and increasing their grazing rates in temperate areas.
Abstract: Climate-driven changes in biotic interactions can profoundly alter ecological communities, particularly when they impact foundation species. In marine systems, changes in herbivory and the consequent loss of dominant habitat forming species can result in dramatic community phase shifts, such as from coral to macroalgal dominance when tropical fish herbivory decreases, and from algal forests to ‘barrens’ when temperate urchin grazing increases. Here, we propose a novel phase-shift away from macroalgal dominance caused by tropical herbivores extending their range into temperate regions. We argue that this phase shift is facilitated by poleward-flowing boundary currents that are creating ocean warming hotspots around the globe, enabling the range expansion of tropical species and increasing their grazing rates in temperate areas. Overgrazing of temperate macroalgae by tropical herbivorous fishes has already occurred in Japan and the Mediterranean. Emerging evidence suggests similar phenomena are occurring in other temperate regions, with increasing occurrence of tropical fishes on temperate reefs.