Showing papers by "University of New South Wales published in 2012"
TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
11,809 citations
TL;DR: In this paper, the authors estimated deaths and disability-adjusted life years (DALYs; sum of years lived with disability [YLD] and years of life lost [YLL]) attributable to the independent effects of 67 risk factors and clusters of risk factors for 21 regions in 1990 and 2010.
9,324 citations
TL;DR: Prevalence and severity of health loss were weakly correlated and age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010, but population growth and ageing have increased YLD numbers and crude rates over the past two decades.
7,021 citations
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.
6,861 citations
TL;DR: In this paper, a longitudinal study of 128 patients with Alzheimer's disease was conducted, where the authors used the participant's age at baseline assessment and the parent's age to calculate the estimated years from expected symptom onset (age of the participant minus parent's ages at symptom onset).
Abstract: A B S T R AC T BACKGROUND The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant’s age at baseline assessment and the parent’s age at the onset of symptoms of Alzheimer’s disease to calculate the estimated years from expected symptom onset (age of the participant minus parent’s age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes. RESULTS Concentrations of amyloid-beta (Aβ)42 in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini–Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset. CONCLUSIONS We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease. (Funded by the National Institute on Aging and others; DIAN ClinicalTrials.gov number, NCT00869817.)
2,907 citations
University of New South Wales1, Garvan Institute of Medical Research2, Bankstown Lidcombe Hospital3, University of Queensland4, Baylor College of Medicine5, Ontario Institute for Cancer Research6, University of Newcastle7, Royal North Shore Hospital8, University of Sydney9, Life Technologies10, St. Vincent's Health System11, Royal Prince Alfred Hospital12, Fremantle Hospital13, Royal Adelaide Hospital14, University of Western Australia15, University of California, Los Angeles16, University Health Network17, Mayo Clinic18, University of Toronto19, Johns Hopkins University20, University of Verona21, University of California, San Francisco22, Houston Methodist Hospital23, Cancer Research UK24, Wellcome Trust Sanger Institute25, University of Minnesota26, Netherlands Cancer Institute27
TL;DR: It is found that frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, are also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement ofAxon guidance genes in pancreatic carcinogenesis.
Abstract: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
1,752 citations
University of Amsterdam1, Ghent University2, University of Chicago3, University of Pennsylvania4, Auckland City Hospital5, University of Antwerp6, University of New South Wales7, Katholieke Universiteit Leuven8, St Thomas' Hospital9, University of Nottingham10, University of Zagreb11, Northwestern University12, Medical University of Łódź13, University of Aberdeen14, Innsbruck Medical University15, Medical University of South Carolina16, University of Southampton17, Children's Hospital of Philadelphia18, University of São Paulo19, National University of Singapore20, University of Adelaide21, Flinders University22
TL;DR: The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 as discussed by the authors is the update of similar evidence-based position papers published in 2005 and 2007, it contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinositis, control of disease, and better definitions for rhinosinitis in children.
Abstract: The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.
1,608 citations
TL;DR: Proprioceptive senses, particularly of limb position and movement, deteriorate with age and are associated with an increased risk of falls in the elderly and the more recent information available on proprioception has given a better understanding of the mechanisms underlying these senses.
Abstract: This is a review of the proprioceptive senses generated as a result of our own actions. They include the senses of position and movement of our limbs and trunk, the sense of effort, the sense of force, and the sense of heaviness. Receptors involved in proprioception are located in skin, muscles, and joints. Information about limb position and movement is not generated by individual receptors, but by populations of afferents. Afferent signals generated during a movement are processed to code for endpoint position of a limb. The afferent input is referred to a central body map to determine the location of the limbs in space. Experimental phantom limbs, produced by blocking peripheral nerves, have shown that motor areas in the brain are able to generate conscious sensations of limb displacement and movement in the absence of any sensory input. In the normal limb tendon organs and possibly also muscle spindles contribute to the senses of force and heaviness. Exercise can disturb proprioception, and this has implications for musculoskeletal injuries. Proprioceptive senses, particularly of limb position and movement, deteriorate with age and are associated with an increased risk of falls in the elderly. The more recent information available on proprioception has given a better understanding of the mechanisms underlying these senses as well as providing new insight into a range of clinical conditions.
1,280 citations
TL;DR: Mice treated with a moderate dose of resveratrol showed increased mitochondrial biogenesis and function, AMPK activation, and increased NAD(+) levels in skeletal muscle, whereas SIRT1 knockouts displayed none of these benefits, whereas a mouse overexpressing Sirt1 mimicked these effects.
1,278 citations
1,210 citations
TL;DR: The Standardised Major Axis Tests and Routines (SMATR) software provides tools for estimation and inference about allometric lines, currently widely used in ecology and evolution.
Abstract: Summary
1. The Standardised Major Axis Tests and Routines (SMATR) software provides tools for estimation and inference about allometric lines, currently widely used in ecology and evolution.
2. This paper describes some significant improvements to the functionality of the package, now available on R in smatr version 3.
3. New inclusions in the package include sma and ma functions that accept formula input and perform the key inference tasks; multiple comparisons; graphical methods for visualising data and checking (S)MA assumptions; robust (S)MA estimation and inference tools.
TL;DR: The mvabund package for R provides tools for model-based analysis of multivariate abundance data in ecology, which includes methods for visualising data, fitting predictive models, checking model assumptions, as well as testing hypotheses about the community–environment association.
Abstract: Summary
1. The mvabund package for R provides tools for model-based analysis of multivariate abundance data in ecology.
2. This includes methods for visualising data, fitting predictive models, checking model assumptions, as well as testing hypotheses about the community–environment association.
3. This paper briefly introduces the package and demonstrates its functionality by example.
Harvard University1, University of Queensland2, Johns Hopkins University3, ICF International4, Centre for Mental Health5, Boston University6, University of Sydney7, University of Melbourne8, Imperial College London9, University of New South Wales10, University of California, San Diego11, Emory University12, University of Pennsylvania13, Autonomous University of Barcelona14, University of London15, National Institutes of Health16, French Institute of Health and Medical Research17, Medical Research Council18, Auckland University of Technology19, Federal University of São Paulo20, National Institute of Population and Social Security Research21, Howard University22, Flinders University23, Erasmus University Rotterdam24, King's College London25, Karolinska Institutet26, University of California, San Francisco27, All India Institute of Medical Sciences28, Nova Southeastern University29, University of Miami30, Swansea University31, Tehran University of Medical Sciences32, Queen Mary University of London33, Allen Institute for Brain Science34, University of Cape Town35, Columbia University36, Watford General Hospital37, Centro Studi GISED38, University of Oxford39, Deakin University40, University of British Columbia41, University of Toronto42, Box Hill Hospital43, Vanderbilt University44, University of Washington45, Brandeis University46, University of Tokyo47, The Queen's Medical Center48, Norwegian University of Science and Technology49, China Medical Board50, University of Cambridge51, Royal Cornwall Hospital52, Cedars-Sinai Medical Center53, Shanghai Jiao Tong University54
TL;DR: In this paper, a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach.
Karol Estrada1, Unnur Styrkarsdottir, Evangelos Evangelou2, Yi-Hsiang Hsu3 +187 more•Institutions (69)
TL;DR: Light is shed on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility and within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways.
Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
TL;DR: In this paper, a review of magnetoelectric domain walls is presented, focusing on magneto-electrics and multiferroics but making comparisons where possible with magnetic domains and domain walls.
Abstract: Domains in ferroelectrics were considered to be well understood by the middle of the last century: They were generally rectilinear, and their walls were Ising-like. Their simplicity stood in stark contrast to the more complex Bloch walls or N\'eel walls in magnets. Only within the past decade and with the introduction of atomic-resolution studies via transmission electron microscopy, electron holography, and atomic force microscopy with polarization sensitivity has their real complexity been revealed. Additional phenomena appear in recent studies, especially of magnetoelectric materials, where functional properties inside domain walls are being directly measured. In this paper these studies are reviewed, focusing attention on ferroelectrics and multiferroics but making comparisons where possible with magnetic domains and domain walls. An important part of this review will concern device applications, with the spotlight on a new paradigm of ferroic devices where the domain walls, rather than the domains, are the active element. Here magnetic wall microelectronics is already in full swing, owing largely to the work of Cowburn and of Parkin and their colleagues. These devices exploit the high domain wall mobilities in magnets and their resulting high velocities, which can be supersonic, as shown by Kreines' and co-workers 30 years ago. By comparison, nanoelectronic devices employing ferroelectric domain walls often have slower domain wall speeds, but may exploit their smaller size as well as their different functional properties. These include domain wall conductivity (metallic or even superconducting in bulk insulating or semiconducting oxides) and the fact that domain walls can be ferromagnetic while the surrounding domains are not.
King Juan Carlos University1, University of Vermont2, Pablo de Olavide University3, Technical University of Madrid4, Northern Arizona University5, University of La Serena6, Instituto Potosino de Investigación Científica y Tecnológica7, Universidad Simón Rodríguez8, Ben-Gurion University of the Negev9, State University of Feira de Santana10, Universidad Técnica Particular de Loja11, University of Sfax12, University of New South Wales13, Central University of Venezuela14, National University of San Juan15, University of the Bío Bío16, Virginia Tech College of Natural Resources and Environment17, Ohio State University18, National Agrarian University19, National University of La Pampa20, University of New England (Australia)21, Office of Environment and Heritage22, Spanish National Research Council23, Northeast Normal University24, Agricultural Research Organization, Volcani Center25
TL;DR: A global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth’s land surface and support over 38% of the human population, suggests that the preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in dryland.
Abstract: Experiments suggest that biodiversity enhances the ability of ecosystems to maintain multiple functions, such as carbon storage, productivity, and the buildup of nutrient pools (multifunctionality). However, the relationship between biodiversity and multifunctionality has never been assessed globally in natural ecosystems. We report here on a global empirical study relating plant species richness and abiotic factors to multifunctionality in drylands, which collectively cover 41% of Earth’s land surface and support over 38% of the human population. Multifunctionality was positively and significantly related to species richness. The best-fitting models accounted for over 55% of the variation in multifunctionality and always included species richness as a predictor variable. Our results suggest that the preservation of plant biodiversity is crucial to buffer negative effects of climate change and desertification in drylands.
TL;DR: A systematic overview of the state of the art in energy and resource efficiency increasing methods and techniques in the domain of discrete part manufacturing, with attention for the effectiveness of the available options is provided in this paper.
Abstract: A B S T R A C T This paper aims to provide a systematic overview of the state of the art in energy and resource efficiency increasing methods and techniques in the domain of discrete part manufacturing, with attention for the effectiveness of the available options. For this purpose a structured approach, distinguishing different system scale levels, is applied: starting from a unit process focus, respectively the multi-machine, factory, multi-facility and supply chain levels are covered. Determined by the research contributions reported in literature, the de facto focus of the paper is mainly on energy related aspects of manufacturing. Significant opportunities for systematic efficiency improving measures are identified and summarized in this area. 2012 CIRP.
TL;DR: In this paper, the authors consider what is being implicitly assumed about the mean-variance relationship in distance-based analyses and what the effect is of any misspecification of the mean -variances relationship.
Abstract: Summary
1. A critical property of count data is its mean–variance relationship, yet this is rarely considered in multivariate analysis in ecology.
2. This study considers what is being implicitly assumed about the mean–variance relationship in distance-based analyses – multivariate analyses based on a matrix of pairwise distances – and what the effect is of any misspecification of the mean–variance relationship.
3. It is shown that distance-based analyses make implicit assumptions that are typically out-of-step with what is observed in real data, which has major consequences.
4. Potential consequences of this mean–variance misspecification are: confounding location and dispersion effects in ordinations; misleading results when trying to identify taxa in which an effect is expressed; failure to detect a multivariate effect unless it is expressed in high-variance taxa.
5. Data transformation does not solve the problem.
6. A solution is to use generalised linear models and their recent multivariate generalisations, which is shown here to have desirable properties.
University of New South Wales1, National Health Service2, MedStar Washington Hospital Center3, Wake Forest University4, Claude Bernard University Lyon 15, Institut Gustave Roussy6, Mercy Medical Center (Baltimore, Maryland)7, St George's Hospital8, University of Barcelona9, Ghent University10, University of Würzburg11, University of Regensburg12, University of Texas MD Anderson Cancer Center13
TL;DR: The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years with Optimal cytoreduction achieves the best outcomes.
Abstract: Purpose Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. Patients and Methods A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International. Results Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), p...
TL;DR: In this paper, the authors search PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, intraepithelial neoplasia (AIN), and anal cancer in MSM.
Abstract: Summary Background Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes. Methods We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis. Findings 53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9–37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6–17·6), and clearance occurred in 14·6% (10·2–21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8–35·4) with incidences of 8·5% (6·9–10·4) and 15·4% (11·8–19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2–60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8–15·4). Incidence of HPV-16 was 11·8% (9·2–14·9) and 5·8% (1·9–13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7–29·3), with incidence of 3·3% (2·2–4·7) and 6·0% (4·2–8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0–11·5; based on two estimates). There were no published estimates of high-grade AIN regression. Interpretation Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM. Funding Australian Government Department of Health and Ageing.
Flanders Marine Institute1, University of New South Wales2, Australian Museum3, University of Southern Mississippi4, National Oceanography Centre, Southampton5, University of Hasselt6, WorldFish7, American Museum of Natural History8, San Diego State University9, Museum Victoria10, Natural History Museum11, Dowling College12, University of Hamburg13, James Cook University14, University of Johannesburg15, National Museum of Natural History16, National Taiwan Ocean University17, Scripps Institution of Oceanography18, National Oceanic and Atmospheric Administration19, University of Queensland20, University of Sassari21, Université libre de Bruxelles22, Vrije Universiteit Brussel23, Queensland Museum24, University of California, Merced25, Ghent University26, Naturalis27, Howard University28, University of Gothenburg29, California Academy of Sciences30, Florida Museum of Natural History31, Centre for Environment, Fisheries and Aquaculture Science32, Osaka University33, University of Santiago de Compostela34, University of Alaska Anchorage35, University of Málaga36, National Institute of Water and Atmospheric Research37, National University of Ireland, Galway38, University of Alaska Fairbanks39, Spanish National Research Council40, CABI41, University of Siegen42, Massey University43, University of Copenhagen44, Naturhistorisches Museum45, University of Washington46, Museum für Naturkunde47, Woods Hole Oceanographic Institution48, Western Washington University49, University of Bergen50, Nova Southeastern University51, Shirshov Institute of Oceanology52, National University of Singapore53, Shimane University54, Agnes Scott College55, University of the Ryukyus56, University of California, Davis57, Federal University of Paraná58, University of the Basque Country59, University of Veterinary Medicine Hanover60, Royal Belgian Institute of Natural Sciences61, Tel Aviv University62, Swedish Museum of Natural History63, Joint Nature Conservation Committee64, The Evergreen State College65, Estonian University of Life Sciences66, University of Maine67, Virginia Commonwealth University68, Trinity College, Dublin69, University of Auckland70
TL;DR: The first register of the marine species of the world is compiled and it is estimated that between one-third and two-thirds of marine species may be undescribed, and previous estimates of there being well over one million marine species appear highly unlikely.
TL;DR: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death, and the association exhibits a dose-response relationship and is strongest for death from distributive shock.
Abstract: Background: Whether hypoglycemia leads to death in critically ill patients is unclear.
Methods: We examined the associations between moderate and severe hypoglycemia (blood glucose, 41 to 70 mg per deciliter [2.3 to 3.9 mmol per liter] and ≤40 mg per deciliter [2.2 mmol per liter], respectively) and death among 6026 critically ill patients in intensive care units (ICUs). Patients were randomly assigned to intensive or conventional glucose control. We used Cox regression analysis with adjustment for treatment assignment and for baseline and postrandomization covariates.
Results: Follow-up data were available for 6026 patients: 2714 (45.0%) had moderate hypoglycemia, 2237 of whom (82.4%) were in the intensive-control group (i.e., 74.2% of the 3013 patients in the group), and 223 patients (3.7%) had severe hypoglycemia, 208 of whom (93.3%) were in the intensive-control group (i.e., 6.9% of the patients in this group). Of the 3089 patients who did not have hypoglycemia, 726 (23.5%) died, as compared with 774 of the 2714 with moderate hypoglycemia (28.5%) and 79 of the 223 with severe hypoglycemia (35.4%). The adjusted hazard ratios for death among patients with moderate or severe hypoglycemia, as compared with those without hypoglycemia, were 1.41 (95% confidence interval [CI], 1.21 to 1.62; P 1 day vs. 1 day, P=0.01), those who died from distributive (vasodilated) shock (P<0.001), and those who had severe hypoglycemia in the absence of insulin treatment (hazard ratio, 3.84; 95% CI, 2.37 to 6.23; P<0.001).
Conclusions: In critically ill patients, intensive glucose control leads to moderate and severe hypoglycemia, both of which are associated with an increased risk of death. The association exhibits a dose-response relationship and is strongest for death from distributive shock. However, these data cannot prove a causal relationship. (Funded by the Australian National Health and Medical Research Council and others; NICE-SUGAR ClinicalTrials.gov number, NCT00220987.).
TL;DR: This work presents atomic-scale images and electronic characteristics of these atomically precise devices and the impact of strong vertical and lateral confinement on electron transport and discusses the opportunities ahead for atomic- scale quantum computing architectures.
Abstract: The ability to control matter at the atomic scale and build devices with atomic precision is central to nanotechnology. The scanning tunnelling microscope can manipulate individual atoms and molecules on surfaces, but the manipulation of silicon to make atomic-scale logic circuits has been hampered by the covalent nature of its bonds. Resist-based strategies have allowed the formation of atomic-scale structures on silicon surfaces, but the fabrication of working devices-such as transistors with extremely short gate lengths, spin-based quantum computers and solitary dopant optoelectronic devices-requires the ability to position individual atoms in a silicon crystal with atomic precision. Here, we use a combination of scanning tunnelling microscopy and hydrogen-resist lithography to demonstrate a single-atom transistor in which an individual phosphorus dopant atom has been deterministically placed within an epitaxial silicon device architecture with a spatial accuracy of one lattice site. The transistor operates at liquid helium temperatures, and millikelvin electron transport measurements confirm the presence of discrete quantum levels in the energy spectrum of the phosphorus atom. We find a charging energy that is close to the bulk value, previously only observed by optical spectroscopy.
TL;DR: Prediction of biochar stability was improved by a combination of volatile matter and H:C ratios corrected for inorganic C, and agronomic utility of biochars is not an absolute value, as it needs to meet local soil constraints.
TL;DR: This work demonstrates the coherent manipulation of an individual electron spin qubit bound to a phosphorus donor atom in natural silicon, measured electrically via single-shot read-out.
Abstract: A single atom is the prototypical quantum system, and a natural candidate for a quantum bit, or qubit--the elementary unit of a quantum computer. Atoms have been successfully used to store and process quantum information in electromagnetic traps, as well as in diamond through the use of the nitrogen-vacancy-centre point defect. Solid-state electrical devices possess great potential to scale up such demonstrations from few-qubit control to larger-scale quantum processors. Coherent control of spin qubits has been achieved in lithographically defined double quantum dots in both GaAs (refs 3-5) and Si (ref. 6). However, it is a formidable challenge to combine the electrical measurement capabilities of engineered nanostructures with the benefits inherent in atomic spin qubits. Here we demonstrate the coherent manipulation of an individual electron spin qubit bound to a phosphorus donor atom in natural silicon, measured electrically via single-shot read-out. We use electron spin resonance to drive Rabi oscillations, and a Hahn echo pulse sequence reveals a spin coherence time exceeding 200 µs. This time should be even longer in isotopically enriched (28)Si samples. Combined with a device architecture that is compatible with modern integrated circuit technology, the electron spin of a single phosphorus atom in silicon should be an excellent platform on which to build a scalable quantum computer.
09 Feb 2012
TL;DR: This review summarizes the current opinions in metagenomics, and provides practical guidance and advice on sample processing, sequencing technology, assembly, binning, annotation, experimental design, statistical analysis, data storage, and data sharing.
Abstract: Metagenomics applies a suite of genomic technologies and bioinformatics tools to directly access the genetic content of entire communities of organisms. The field of metagenomics has been responsible for substantial advances in microbial ecology, evolution, and diversity over the past 5 to 10 years, and many research laboratories are actively engaged in it now. With the growing numbers of activities also comes a plethora of methodological knowledge and expertise that should guide future developments in the field. This review summarizes the current opinions in metagenomics, and provides practical guidance and advice on sample processing, sequencing technology, assembly, binning, annotation, experimental design, statistical analysis, data storage, and data sharing. As more metagenomic datasets are generated, the availability of standardized procedures and shared data storage and analysis becomes increasingly important to ensure that output of individual projects can be assessed and compared.
TL;DR: Barber et al. as mentioned in this paper found that female and male directors differ systematically in their core values and risk attitudes, but in ways that differ from gender differences in the general population.
Abstract: A large literature documents that women are different from men in their choices and preferences, but little is known about gender differences in the boardroom. If women must be like men to break the glass ceiling, we might expect gender differences to disappear among directors. Using a large survey of directors, we show that female and male directors differ systematically in their core values and risk attitudes, but in ways that differ from gender differences in the general population. These results are robust to controlling for differences in observable characteristics. Consistent with findings for the population, female directors are more benevolent and universally concerned but less power oriented than male directors. However, in contrast to findings for the population, they are less tradition and security oriented than their male counterparts. They are also more risk loving than male directors. Thus, having a woman on the board need not lead to more risk-averse decision making.
This paper was accepted by Brad Barber, Teck Ho, and Terrance Odean, special issue editors.
TL;DR: Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis.
Abstract: Medulloblastoma is a malignant childhood brain tumour comprising four discrete subgroups. Here, to identify mutations that drive medulloblastoma, we sequenced the entire genomes of 37 tumours and matched normal blood. One-hundred and thirty-six genes harbouring somatic mutations in this discovery set were sequenced in an additional 56 medulloblastomas. Recurrent mutations were detected in 41 genes not yet implicated in medulloblastoma; several target distinct components of the epigenetic machinery in different disease subgroups, such as regulators of H3K27 and H3K4 trimethylation in subgroups 3 and 4 (for example, KDM6A and ZMYM3), and CTNNB1-associated chromatin re-modellers in WNT-subgroup tumours (for example, SMARCA4 and CREBBP). Modelling of mutations in mouse lower rhombic lip progenitors that generate WNT-subgroup tumours identified genes that maintain this cell lineage (DDX3X), as well as mutated genes that initiate (CDH1) or cooperate (PIK3CA) in tumorigenesis. These data provide important new insights into the pathogenesis of medulloblastoma subgroups and highlight targets for therapeutic development.
TL;DR: Recent progress in this emerging field is reviewed and it is suggested that the merging of detailed molecular mechanisms with ecological theory will significantly advance understanding of biofilm biology and ecology.
Abstract: In most environments, bacteria reside primarily in biofilms, which are social consortia of cells that are embedded in an extracellular matrix and undergo developmental programmes resulting in a predictable biofilm 'life cycle'. Recent research on many different bacterial species has now shown that the final stage in this life cycle includes the production and release of differentiated dispersal cells. The formation of these cells and their eventual dispersal is initiated through diverse and remarkably sophisticated mechanisms, suggesting that there are strong evolutionary pressures for dispersal from an otherwise largely sessile biofilm. The evolutionary aspect of biofilm dispersal is now being explored through the integration of molecular microbiology with eukaryotic ecological and evolutionary theory, which provides a broad conceptual framework for the diversity of specific mechanisms underlying biofilm dispersal. Here, we review recent progress in this emerging field and suggest that the merging of detailed molecular mechanisms with ecological theory will significantly advance our understanding of biofilm biology and ecology.
TL;DR: Although the rate of mortality from SAB is declining, it remains high, and questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin.
Abstract: Staphylococcus aureus bacteremia (SAB) is an important infection with an incidence rate ranging from 20 to 50 cases/100,000 population per year. Between 10% and 30% of these patients will die from SAB. Comparatively, this accounts for a greater number of deaths than for AIDS, tuberculosis, and viral hepatitis combined. Multiple factors influence outcomes for SAB patients. The most consistent predictor of mortality is age, with older patients being twice as likely to die. Except for the presence of comorbidities, the impacts of other host factors, including gender, ethnicity, socioeconomic status, and immune status, are unclear. Pathogen-host interactions, especially the presence of shock and the source of SAB, are strong predictors of outcomes. Although antibiotic resistance may be associated with increased mortality, questions remain as to whether this reflects pathogen-specific factors or poorer responses to antibiotic therapy, namely, vancomycin. Optimal management relies on starting appropriate antibiotics in a timely fashion, resulting in improved outcomes for certain patient subgroups. The roles of surgery and infectious disease consultations require further study. Although the rate of mortality from SAB is declining, it remains high. Future international collaborative studies are required to tease out the relative contributions of various factors to mortality, which would enable the optimization of SAB management and patient outcomes.