Showing papers by "University of Melbourne published in 2013"
TL;DR: In this article, the authors present a cloud centric vision for worldwide implementation of Internet of Things (IoT) and present a Cloud implementation using Aneka, which is based on interaction of private and public Clouds, and conclude their IoT vision by expanding on the need for convergence of WSN, the Internet and distributed computing directed at technological research community.
9,593 citations
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) as discussed by the authors was used to estimate the burden of disease attributable to mental and substance use disorders in terms of disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs).
4,753 citations
TL;DR: The re-engineering of navitoclax is reported to create a highly potent, orally bioavailable and BCL-2–selective inhibitor, ABT-199, which inhibits the growth of BCL–dependent tumors in vivo and spares human platelets, indicating that selective pharmacological inhibition of Bcl-2 shows promise for the treatment of B CL-2-dependent hematological cancers.
Abstract: Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting prosurvival proteins was unveiled with the development of navitoclax, a selective inhibitor of both BCL-2 and BCL-2-like 1 (BCL-X(L)), which has shown clinical efficacy in some BCL-2-dependent hematological cancers. However, concomitant on-target thrombocytopenia caused by BCL-X(L) inhibition limits the efficacy achievable with this agent. Here we report the re-engineering of navitoclax to create a highly potent, orally bioavailable and BCL-2-selective inhibitor, ABT-199. This compound inhibits the growth of BCL-2-dependent tumors in vivo and spares human platelets. A single dose of ABT-199 in three patients with refractory chronic lymphocytic leukemia resulted in tumor lysis within 24 h. These data indicate that selective pharmacological inhibition of BCL-2 shows promise for the treatment of BCL-2-dependent hematological cancers.
2,353 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston Medical Center3, University of Zurich4, University of Missouri–Kansas City5, University of Oslo6, International Olympic Committee7, University of Toronto8, University of Michigan9, Vanderbilt University Medical Center10, University of Washington11, University of North Carolina at Chapel Hill12, University of British Columbia13, Burke Rehabilitation Hospital14, Cornell University15, University of Ottawa16, Medical College of Wisconsin17, Monash University18, University of New South Wales19, University of Melbourne20, McMaster University21, University of Medicine and Dentistry of New Jersey22, Princeton University23
TL;DR: The 4th International Conference on Concussion in Sport held in Zurich, November 2012 was attended by Paul McCrory, Willem H Meeuwisse, Mark Aubry, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills and Kathryn Schneider.
2,293 citations
Florey Institute of Neuroscience and Mental Health1, University of Calgary2, Boston University3, University of Missouri–Kansas City4, International Olympic Committee5, University of Michigan6, Veterans Health Administration7, University of North Carolina at Chapel Hill8, University of British Columbia9, Medical College of Wisconsin10, University of Melbourne11, McMaster University12, Rutgers University13
TL;DR: This paper is a revision and update of the recommendations developed following the 1st (Vienna 2001), 2nd (Prague 2004) and 3rd (Zurich 2008) International Consensus Conferences on Concussions in Sport and is based on the deliberations at the 4th International Conference on Concussion in Sport held in Zurich, November 2012.
Abstract: The new 2012 Zurich Consensus statement is designed to build on the principles outlined in the previous documents and to develop further conceptual understanding of this problem using a formal consensus-based approach. A detailed description of the consensus process is outlined at the end of this document under the Background section. This document is developed primarily for use by physicians and healthcare professionals who are involved in the care of injured athletes, whether at the recreational, elite or professional level.
2,269 citations
Institute for Health Metrics and Evaluation1, University of Texas Health Science Center at San Antonio2, Emory University3, Mayo Clinic4, Harvard University5, Boston University6, Michigan State University7, National Institutes of Health8, Cedars-Sinai Medical Center9, Health Effects Institute10, Loyola University Chicago11, University of Washington12, University of California, San Diego13, University of Pennsylvania14, Veterans Health Administration15, Beth Israel Medical Center16, Johns Hopkins University17, Imperial College London18, Carnegie Mellon University19, Howard University20, University of California, San Francisco21, Columbia University22, New York University23, Karolinska Institutet24, George Mason University25, Nova Southeastern University26, University of Miami27, Northwestern University28, Thomas Jefferson University29, China Medical Board30, Pacific Institute31, Duke University32, Brigham and Women's Hospital33, California Environmental Protection Agency34, Centers for Medicare and Medicaid Services35, Brigham Young University36, University of Missouri37, University of California, Los Angeles38, Vanderbilt University39, University of Maryland, College Park40, University of Alabama at Birmingham41, Brandeis University42, University of Tokyo43, The Queen's Medical Center44, Drexel University45, Cincinnati Children's Hospital Medical Center46, National Institute for Occupational Safety and Health47, Brown University48, University of Melbourne49
TL;DR: To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD), systematic analysis of descriptive epidemiology was used.
Abstract: Importance Understanding the major health problems in the United States and how they are changing over time is critical for informing national health policy. Objectives To measure the burden of diseases, injuries, and leading risk factors in the United States from 1990 to 2010 and to compare these measurements with those of the 34 countries in the Organisation for Economic Co-operation and Development (OECD) countries. Design We used the systematic analysis of descriptive epidemiology of 291 diseases and injuries, 1160 sequelae of these diseases and injuries, and 67 risk factors or clusters of risk factors from 1990 to 2010 for 187 countries developed for the Global Burden of Disease 2010 Study to describe the health status of the United States and to compare US health outcomes with those of 34 OECD countries. Years of life lost due to premature mortality (YLLs) were computed by multiplying the number of deaths at each age by a reference life expectancy at that age. Years lived with disability (YLDs) were calculated by multiplying prevalence (based on systematic reviews) by the disability weight (based on population-based surveys) for each sequela; disability in this study refers to any short- or long-term loss of health. Disability-adjusted life-years (DALYs) were estimated as the sum of YLDs and YLLs. Deaths and DALYs related to risk factors were based on systematic reviews and meta-analyses of exposure data and relative risks for risk-outcome pairs. Healthy life expectancy (HALE) was used to summarize overall population health, accounting for both length of life and levels of ill health experienced at different ages. Results US life expectancy for both sexes combined increased from 75.2 years in 1990 to 78.2 years in 2010; during the same period, HALE increased from 65.8 years to 68.1 years. The diseases and injuries with the largest number of YLLs in 2010 were ischemic heart disease, lung cancer, stroke, chronic obstructive pulmonary disease, and road injury. Age-standardized YLL rates increased for Alzheimer disease, drug use disorders, chronic kidney disease, kidney cancer, and falls. The diseases with the largest number of YLDs in 2010 were low back pain, major depressive disorder, other musculoskeletal disorders, neck pain, and anxiety disorders. As the US population has aged, YLDs have comprised a larger share of DALYs than have YLLs. The leading risk factors related to DALYs were dietary risks, tobacco smoking, high body mass index, high blood pressure, high fasting plasma glucose, physical inactivity, and alcohol use. Among 34 OECD countries between 1990 and 2010, the US rank for the age-standardized death rate changed from 18th to 27th, for the age-standardized YLL rate from 23rd to 28th, for the age-standardized YLD rate from 5th to 6th, for life expectancy at birth from 20th to 27th, and for HALE from 14th to 26th. Conclusions and Relevance From 1990 to 2010, the United States made substantial progress in improving health. Life expectancy at birth and HALE increased, all-cause death rates at all ages decreased, and age-specific rates of years lived with disability remained stable. However, morbidity and chronic disability now account for nearly half of the US health burden, and improvements in population health in the United States have not kept pace with advances in population health in other wealthy nations.
2,159 citations
TL;DR: Empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Abstract: Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
2,058 citations
TL;DR: These projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches the authors' threshold of positivity at 17·0 (95% CI 14·9-19·9) years, hippocampal atrophy at 4·2 (3·6-5·1] years, and memory impairment at 3·3 (2·5-4·5) years before the onset of dementia (clinical dementia rating score 1).
Abstract: Summary Background Similar to most chronic diseases, Alzheimer's disease (AD) develops slowly from a preclinical phase into a fully expressed clinical syndrome. We aimed to use longitudinal data to calculate the rates of amyloid β (Aβ) deposition, cerebral atrophy, and cognitive decline. Methods In this prospective cohort study, healthy controls, patients with mild cognitive impairment (MCI), and patients with AD were assessed at enrolment and every 18 months. At every visit, participants underwent neuropsychological examination, MRI, and a carbon-11-labelled Pittsburgh compound B ( 11 C-PiB) PET scan. We included participants with three or more 11 C-PiB PET follow-up assessments. Aβ burden was expressed as 11 C-PiB standardised uptake value ratio (SUVR) with the cerebellar cortex as reference region. An SUVR of 1·5 was used to discriminate high from low Aβ burdens. The slope of the regression plots over 3–5 years was used to estimate rates of change for Aβ deposition, MRI volumetrics, and cognition. We included those participants with a positive rate of Aβ deposition to calculate the trajectory of each variable over time. Findings 200 participants (145 healthy controls, 36 participants with MCI, and 19 participants with AD) were assessed at enrolment and every 18 months for a mean follow-up of 3·8 (95% CI CI 3·6–3·9) years. At baseline, significantly higher Aβ burdens were noted in patients with AD (2·27, SD 0·43) and those with MCI (1·94, 0·64) than in healthy controls (1·38, 0·39). At follow-up, 163 (82%) of the 200 participants showed positive rates of Aβ accumulation. Aβ deposition was estimated to take 19·2 (95% CI 16·8–22·5) years in an almost linear fashion—with a mean increase of 0·043 (95% CI 0·037–0·049) SUVR per year—to go from the threshold of 11 C-PiB positivity (1·5 SUVR) to the levels observed in AD. It was estimated to take 12·0 (95% CI 10·1–14·9) years from the levels observed in healthy controls with low Aβ deposition (1·2 [SD 0·1] SUVR) to the threshold of 11 C-PiB positivity. As AD progressed, the rate of Aβ deposition slowed towards a plateau. Our projections suggest a prolonged preclinical phase of AD in which Aβ deposition reaches our threshold of positivity at 17·0 (95% CI 14·9–19·9) years, hippocampal atrophy at 4·2 (3·6–5·1) years, and memory impairment at 3·3 (2·5–4·5) years before the onset of dementia (clinical dementia rating score 1). Interpretation Aβ deposition is slow and protracted, likely to extend for more than two decades. Such predictions of the rate of preclinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aimed at modifying the course of this illness. Funding Science and Industry Endowment Fund (Australia), The Commonwealth Scientific and Industrial Research Organisation (Australia), The National Health and Medical Research Council of Australia Program and Project Grants, the Austin Hospital Medical Research Foundation, Victorian State Government, The Alzheimer's Drug Discovery Foundation, and the Alzheimer's Association.
1,733 citations
University of Cincinnati1, Medical University of South Carolina2, Allen Institute for Brain Science3, University of Pittsburgh4, University of Melbourne5, University of Toronto6, Autonomous University of Barcelona7, Mayo Clinic8, Riverside Methodist Hospital9, Oregon Health & Science University10, Medical College of Wisconsin11, Utrecht University12, University of Paris13, University of Basel14, Royal Prince Alfred Hospital15, National Institutes of Health16
TL;DR: The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenoust-PA alone.
Abstract: BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator (t-PA) for patients with moderate-to-severe acute ischemic stroke, but whether a combined approach is more effective than intravenous t-PA alone is uncertain. METHODS We randomly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone, in a 2:1 ratio. The primary outcome measure was a modified Rankin scale score of 2 or less (indicating functional independence) at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). RESULTS The study was stopped early because of futility after 656 participants had undergone randomization (434 patients to endovascular therapy and 222 to intravenous t-PA alone). The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment (40.8% with endovascular therapy and 38.7% with intravenous t-PA; absolute adjusted difference, 1.5 percentage points; 95% confidence interval [CI], −6.1 to 9.1, with adjustment for the National Institutes of Health Stroke Scale [NIHSS] score [8–19, indicating moderately severe stroke, or ≥20, indicating severe stroke]), nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher (6.8 percentage points; 95% CI, −4.4 to 18.1) and those with a score of 19 or lower (−1.0 percentage point; 95% CI, −10.8 to 8.8). Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days (19.1% and 21.6%, respectively; P = 0.52) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA (6.2% and 5.9%, respectively; P = 0.83). CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA, as compared with intravenous t-PA alone. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT00359424.)
1,702 citations
University of Melbourne1, Australian Department of Health and Ageing2, Monash University3, International Agency for Research on Cancer4, Cancer Council Victoria5, Australian Radiation Protection and Nuclear Safety Agency6, Australian Institute of Health and Welfare7, University of Canberra8, Clinical Trial Service Unit9, Royal Children's Hospital10
TL;DR: The increased incidence of cancer after CT scan exposure in this cohort was mostly due to irradiation, and future CT scans should be limited to situations where there is a definite clinical indication, with every scan optimised to provide a diagnostic CT image at the lowest possible radiation dose.
Abstract: Objective To assess the cancer risk in children and adolescents following exposure to low dose ionising radiation from diagnostic computed tomography (CT) scans. Design Population based, cohort, data linkage study in Australia. Cohort members 10.9 million people identified from Australian Medicare records, aged 0-19 years on 1 January 1985 or born between 1 January 1985 and 31 December 2005; all exposures to CT scans funded by Medicare during 1985-2005 were identified for this cohort. Cancers diagnosed in cohort members up to 31 December 2007 were obtained through linkage to national cancer records. Main outcome Cancer incidence rates in individuals exposed to a CT scan more than one year before any cancer diagnosis, compared with cancer incidence rates in unexposed individuals. Results 60 674 cancers were recorded, including 3150 in 680 211 people exposed to a CT scan at least one year before any cancer diagnosis. The mean duration of follow-up after exposure was 9.5 years. Overall cancer incidence was 24% greater for exposed than for unexposed people, after accounting for age, sex, and year of birth (incidence rate ratio (IRR) 1.24 (95% confidence interval 1.20 to 1.29); P Conclusions The increased incidence of cancer after CT scan exposure in this cohort was mostly due to irradiation. Because the cancer excess was still continuing at the end of follow-up, the eventual lifetime risk from CT scans cannot yet be determined. Radiation doses from contemporary CT scans are likely to be lower than those in 1985-2005, but some increase in cancer risk is still likely from current scans. Future CT scans should be limited to situations where there is a definite clinical indication, with every scan optimised to provide a diagnostic CT image at the lowest possible radiation dose.
1,655 citations
TL;DR: The nitrogen-vacancy (NV) colour centre in diamond is an important physical system for emergent quantum technologies, including quantum metrology, information processing and communications, as well as for various nanotechnologies such as biological and sub-diffraction limit imaging, and for tests of entanglement in quantum mechanics as mentioned in this paper.
Abstract: The nitrogen-vacancy (NV) colour centre in diamond is an important physical system for emergent quantum technologies, including quantum metrology, information processing and communications, as well as for various nanotechnologies, such as biological and sub-diffraction limit imaging, and for tests of entanglement in quantum mechanics. Given this array of existing and potential applications and the almost 50 years of NV research, one would expect that the physics of the centre is well understood, however, the study of the NV centre has proved challenging, with many early assertions now believed false and many remaining issues yet to be resolved. This review represents the first time that the key empirical and ab initio results have been extracted from the extensive NV literature and assembled into one consistent picture of the current understanding of the centre. As a result, the key unresolved issues concerning the NV centre are identified and the possible avenues for their resolution are examined.
TL;DR: A comprehensive assessment of disease burden in China, how it changed between 1990 and 2010, and how China's health burden compares with other nations is done to guide policy responses to the changing disease spectrum in China.
TL;DR: The nitrogen-vacancy (NV) colour centre in diamond is an important physical system for emergent quantum technologies, including quantum metrology, information processing and communications, as well as for various nanotechnologies such as biological and sub-diffraction limit imaging, and for tests of entanglement in quantum mechanics as mentioned in this paper.
TL;DR: Aqueous deposition is performed on a range of planar as well as inorganic, organic, and biological particle templates, demonstrating an extremely rapid technique for producing structurally diverse, thin films and capsules that can disassemble.
Abstract: The development of facile and versatile strategies for thin-film and particle engineering is of immense scientific interest. However, few methods can conformally coat substrates of different composition, size, shape, and structure. We report the one-step coating of various interfaces using coordination complexes of natural polyphenols and Fe(III) ions. Film formation is initiated by the adsorption of the polyphenol and directed by pH-dependent, multivalent coordination bonding. Aqueous deposition is performed on a range of planar as well as inorganic, organic, and biological particle templates, demonstrating an extremely rapid technique for producing structurally diverse, thin films and capsules that can disassemble. The ease, low cost, and scalability of the assembly process, combined with pH responsiveness and negligible cytotoxicity, makes these films potential candidates for biomedical and environmental applications.
TL;DR: The burden that disease places on societies around the world is complex and changing as communicable diseases are replaced by noncommunicable diseases, and the current burden is summarized.
Abstract: The burden that disease places on societies around the world is complex and changing as communicable diseases are replaced by noncommunicable diseases. This article summarizes these changes and the current burden.
TL;DR: The evidence for the Hippo pathway as a cancer signalling network is appraised, and potential mechanisms by which Hippo pathways activity is altered in cancer and emerging therapeutic strategies are discussed.
Abstract: The Hippo pathway controls organ size in diverse species, whereas pathway deregulation can induce tumours in model organisms and occurs in a broad range of human carcinomas, including lung, colorectal, ovarian and liver cancer. Despite this, somatic or germline mutations in Hippo pathway genes are uncommon, with only the upstream pathway gene neurofibromin 2 (NF2) recognized as a bona fide tumour suppressor gene. In this Review, we appraise the evidence for the Hippo pathway as a cancer signalling network, and discuss cancer-relevant biological functions, potential mechanisms by which Hippo pathway activity is altered in cancer and emerging therapeutic strategies.
TL;DR: A new program, PHI, with the ability to calculate the magnetic properties of large spin systems and complex orbitally degenerate systems, such as clusters of d‐block and f‐block ions, is presented.
Abstract: A new program, PHI, with the ability to calculate the magnetic properties of large spin systems and complex orbitally degenerate systems, such as clusters of d-block and f-block ions, is presented. The program can intuitively fit experimental data from multiple sources, such as magnetic and spectroscopic data, simultaneously. PHI is extensively parallelized and can operate under the symmetric multiprocessing, single process multiple data, or GPU paradigms using a threaded, MPI or GPU model, respectively. For a given problem PHI is been shown to be almost 12 times faster than the well-known program MAGPACK, limited only by available hardware.
TL;DR: It is proposed that species distribution modellers should get involved in real decision-making processes that will benefit from their technical input and have the potential to better bridge theory and practice, and contribute to improve both scientific knowledge and conservation outcomes.
Abstract: Species distribution models (SDMs) are increasingly proposed to support conservation decision making. However, evidence of SDMs supporting solutions for on-ground conservation problems is still scarce in the scientific literature. Here, we show that successful examples exist but are still largely hidden in the grey literature, and thus less accessible for analysis and learning. Furthermore, the decision framework within which SDMs are used is rarely made explicit. Using case studies from biological invasions, identification of critical habitats, reserve selection and translocation of endangered species, we propose that SDMs may be tailored to suit a range of decision-making contexts when used within a structured and transparent decision-making process. To construct appropriate SDMs to more effectively guide conservation actions, modellers need to better understand the decision process, and decision makers need to provide feedback to modellers regarding the actual use of SDMs to support conservation decisions. This could be facilitated by individuals or institutions playing the role of 'translators' between modellers and decision makers. We encourage species distribution modellers to get involved in real decision-making processes that will benefit from their technical input; this strategy has the potential to better bridge theory and practice, and contribute to improve both scientific knowledge and conservation outcomes.
Anglia Ruskin University1, Norwegian Institute of Public Health2, University of London3, Carnegie Mellon University4, Heidelberg University5, L V Prasad Eye Institute6, Nova Southeastern University7, University of KwaZulu-Natal8, Brien Holden Vision Institute9, Flinders University10, University of Melbourne11
TL;DR: The differences and temporal changes found in causes of blindness and MSVI have implications for planning and resource allocation in eye care.
University of British Columbia1, University of Toronto2, McGill University3, Dalhousie University4, University of Calgary5, University of Western Ontario6, Queen's University7, McMaster University8, University of São Paulo9, University of Pittsburgh10, Seoul National University11, University of Melbourne12, Deakin University13
TL;DR: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009, and this third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunctionWith the previous publications.
Abstract: The Canadian Network for Mood and Anxiety Treatments published guidelines for the management of bipolar disorder in 2005, with updates in 2007 and 2009. This third update, in conjunction with the International Society for Bipolar Disorders, reviews new evidence and is designed to be used in conjunction with the previous publications.The recommendations for the management of acute mania remain largely unchanged. Lithium, valproate, and several atypical antipsychotic agents continue to be first-line treatments for acute mania. Monotherapy with asenapine, paliperidone extended release (ER), and divalproex ER, as well as adjunctive asenapine, have been added as first-line options.For the management of bipolar depression, lithium, lamotrigine, and quetiapine monotherapy, as well as olanzapine plus selective serotonin reuptake inhibitor (SSRI), and lithium or divalproex plus SSRI/bupropion remain first-line options. Lurasidone monotherapy and the combination of lurasidone or lamotrigine plus lithium or divalproex have been added as a second-line options. Ziprasidone alone or as adjunctive therapy, and adjunctive levetiracetam have been added as not-recommended options for the treatment of bipolar depression. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone long-acting injection, and adjunctive ziprasidone continue to be first-line options for maintenance treatment of bipolar disorder. Asenapine alone or as adjunctive therapy have been added as third-line options.
TL;DR: This paper assess the eff ectiveness of self-regulation, public-private partnerships, and public regulation models of interaction with unhealthy commodity industries and conclude that unhealthy commodity industry should have no role in the formation of national or international NCD policy.
Duke University1, University of Melbourne2, Université de Montréal3, Royal College of Surgeons in Ireland4, University of Pennsylvania5, University of Washington6, Emory University7, Cincinnati Children's Hospital Medical Center8, Royal Children's Hospital9, Imperial College London10, New York University11, University of California, San Francisco12, University of Liverpool13, Royal Melbourne Hospital14, Columbia University15, Harvard University16, Vanderbilt University17, Cleveland Clinic18, Yeshiva University19, Mayo Clinic20, University of Pittsburgh21, University of Minnesota22, University of Virginia23, Saint Barnabas Medical Center24, University of Michigan25, Kaiser Permanente26, University of Chicago27, University of Texas Health Science Center at Houston28, Johns Hopkins University29, Children's Hospital Oakland Research Institute30, Boston Children's Hospital31, Oregon Health & Science University32, Cornell University33, United States Department of Veterans Affairs34, Washington University in St. Louis35
TL;DR: In this paper, a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms and Lennox-Gastaut syndrome (n = 115) was performed.
Abstract: Epileptic encephalopathies are a devastating group of severe childhood epilepsy disorders for which the cause is often unknown. Here we report a screen for de novo mutations in patients with two classical epileptic encephalopathies: infantile spasms (n = 149) and Lennox-Gastaut syndrome (n = 115). We sequenced the exomes of 264 probands, and their parents, and confirmed 329 de novo mutations. A likelihood analysis showed a significant excess of de novo mutations in the ∼4,000 genes that are the most intolerant to functional genetic variation in the human population (P = 2.9 × 10(-3)). Among these are GABRB3, with de novo mutations in four patients, and ALG13, with the same de novo mutation in two patients; both genes show clear statistical evidence of association with epileptic encephalopathy. Given the relevant site-specific mutation rates, the probabilities of these outcomes occurring by chance are P = 4.1 × 10(-10) and P = 7.8 × 10(-12), respectively. Other genes with de novo mutations in this cohort include CACNA1A, CHD2, FLNA, GABRA1, GRIN1, GRIN2B, HNRNPU, IQSEC2, MTOR and NEDD4L. Finally, we show that the de novo mutations observed are enriched in specific gene sets including genes regulated by the fragile X protein (P < 10(-8)), as has been reported previously for autism spectrum disorders.
TL;DR: The first few pages of the first issue of Network Science, the new journal created because network science is exploding, share their own vision of the emerging science of networks.
Abstract: This is the beginning of Network Science. The journal has been created because network science is exploding. As is typical for a field in formation, the discussions about its scope, contents, and foundations are intense. On these first few pages of the first issue of our new journal, we would like to share our own vision of the emerging science of networks.
Ashley Beecham1, Nikolaos A. Patsopoulos2, Nikolaos A. Patsopoulos3, Dionysia K. Xifara4 +203 more•Institutions (73)
TL;DR: This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
Abstract: Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 10 × 10(-4)) In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 50 × 10(-8)), 3 of which we found after conditioning on previously identified variants Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals
Curtin University1, Massachusetts Institute of Technology2, Arizona State University3, University of Washington4, University of Western Australia5, Monash University6, Harvard University7, Commonwealth Scientific and Industrial Research Organisation8, Raman Research Institute9, Victoria University of Wellington10, University of Wisconsin–Milwaukee11, National Centre for Radio Astrophysics12, National Radio Astronomy Observatory13, University of Melbourne14
TL;DR: The Murchison Widefield Array (MWA) as discussed by the authors is one of three Square Kilometre Array Precursor telescopes and is located at the MUR-astronomy Observatory in Western Australia, a location chosen for its extremely low levels of radio frequency interference.
Abstract: The Murchison Widefield Array (MWA) is one of three Square Kilometre Array Precursor telescopes and is located at the Murchison Radio-astronomy Observatory in the Murchison Shire of the mid-west of Western Australia, a location chosen for its extremely low levels of radio frequency interference. The MWA operates at low radio frequencies, 80-300 MHz, with a processed bandwidth of 30.72 MHz for both linear polarisations, and consists of 128 aperture arrays (known as tiles) distributed over a ∼3-km diameter area. Novel hybrid hardware/software correlation and a real-time imaging and calibration systems comprise the MWA signal processing backend. In this paper, the as-built MWA is described both at a system and sub-system level, the expected performance of the array is presented, and the science goals of the instrument are summarised. © 2013 Astronomical Society of Australia.
TL;DR: In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability, and an ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive loweringof blood pressure.
Abstract: Background Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known. Methods We randomly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure (with a target systolic level of <140 mm Hg within 1 hour) or guideline-recommended treatment (with a target systolic level of <180 mm Hg) with the use of agents of the physician’s choosing. The primary outcome was death or major disability, which was defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90 days. A prespecified ordinal analysis of the modified Rankin score was also performed. The rate of serious adverse events was compared between the two groups. Results Among the 2794 participants for whom the primary outcome could be determined, 719 of 1382 participants (52.0%) receiving intensive treatment, as compared with 785 of 1412 (55.6%) receiving guideline-recommended treatment, had a primary outcome event (odds ratio with intensive treatment, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The ordinal analysis showed significantly lower modi fied Rankin scores with intensive treatment (odds ratio for greater disability, 0.87; 95% CI, 0.77 to 1.00; P = 0.04). Mortality was 11.9% in the group receiving intensive treatment and 12.0% in the group receiving guideline-recommended treatment. Nonfatal serious adverse events occurred in 23.3% and 23.6% of the patients in the two groups, respectively. Conclusions In patients with intracerebral hemorrhage, intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability. An ordinal analysis of modified Rankin scores indi cated improved functional outcomes with intensive lowering of blood pressure. (Funded by the National Health and Medical Research Council of Australia; INTERACT2 ClinicalTrials.gov number, NCT00716079.)
Abstract: Plants that accumulate metal and metalloid trace elements to extraordinarily high concentrations in their living biomass have inspired much research worldwide during the last decades. Hyperaccumulators have been recorded and experimentally confirmed for elements such as nickel, zinc, cadmium, manganese, arsenic and selenium. However, to date, hyperaccumulation of lead, copper, cobalt, chromium and thallium remain largely unconfirmed. Recent uses of the term in relation to rare-earth elements require critical evaluation. Since the mid-1970s the term ‘hyperaccumulator’ has been used millions of times by thousands of people, with varying degrees of precision, aptness and understanding that have not always corresponded with the views of the originators of the terminology and of the present authors. There is therefore a need to clarify the circumstances in which the term ‘hyperaccumulator’ is appropriate and to set out the conditions that should be met when the terms are used. We outline here the main considerations for establishing metal or metalloid hyperaccumulation status of plants, (re)define some of the terminology and note potential pitfalls. Unambiguous communication will require the international scientific community to adopt standard terminology and methods for confirming the reliability of analytical data in relation to metal and metalloid hyperaccumulators.
TL;DR: This article provides a comprehensive review on the elastomeric biomaterials used in tissue engineering, with emphasis on the most important candidates to date.
TL;DR: A meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, and identified 29,807 SNPs for further genotyping suggests that more than 1,000 additional loci are involved in breast cancer susceptibility.
Abstract: Breast cancer is the most common cancer among women Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC) The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)) Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility
Columbia University1, Katholieke Universiteit Leuven2, Johns Hopkins University3, University of Cambridge4, University of California, San Francisco5, Monash University6, University of Erlangen-Nuremberg7, McGill University8, Indiana University – Purdue University Indianapolis9, Harvard University10, University of California, Berkeley11, University of Michigan12, Australian Catholic University13, Leiden University14, Maine Medical Center15, University of Melbourne16, University of Oxford17, Washington University in St. Louis18, Shriners Hospitals for Children19, Icahn School of Medicine at Mount Sinai20
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