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Showing papers by "University of Sydney published in 2010"


Journal ArticleDOI
TL;DR: The most recent developments and emerging concepts in CO(2) separations by solvent absorption, chemical and physical adsorption, and membranes, amongst others, will be discussed, with particular attention on progress in the burgeoning field of metal-organic frameworks.
Abstract: The escalating level of atmospheric carbon dioxide is one of the most pressing environmental concerns of our age. Carbon capture and storage (CCS) from large point sources such as power plants is one option for reducing anthropogenic CO(2) emissions; however, currently the capture alone will increase the energy requirements of a plant by 25-40%. This Review highlights the challenges for capture technologies which have the greatest likelihood of reducing CO(2) emissions to the atmosphere, namely postcombustion (predominantly CO(2)/N(2) separation), precombustion (CO(2)/H(2)) capture, and natural gas sweetening (CO(2)/CH(4)). The key factor which underlies significant advancements lies in improved materials that perform the separations. In this regard, the most recent developments and emerging concepts in CO(2) separations by solvent absorption, chemical and physical adsorption, and membranes, amongst others, will be discussed, with particular attention on progress in the burgeoning field of metal-organic frameworks.

3,388 citations


Journal ArticleDOI
TL;DR: In this article, a meta-analysis of general population cohorts was conducted to assess the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality.

3,087 citations


Journal ArticleDOI
TL;DR: Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas.
Abstract: Cryptococcosis is a global invasive mycosis associated with significant morbidity and mortality. These guidelines for its management have been built on the previous Infectious Diseases Society of America guidelines from 2000 and include new sections. There is a discussion of the management of cryptococcal meningoencephalitis in 3 risk groups: (1) human immunodeficiency virus (HIV)-infected individuals, (2) organ transplant recipients, and (3) non-HIV-infected and nontransplant hosts. There are specific recommendations for other unique risk populations, such as children, pregnant women, persons in resource-limited environments, and those with Cryptococcus gattii infection. Recommendations for management also include other sites of infection, including strategies for pulmonary cryptococcosis. Emphasis has been placed on potential complications in management of cryptococcal infection, including increased intracranial pressure, immune reconstitution inflammatory syndrome (IRIS), drug resistance, and cryptococcomas. Three key management principles have been articulated: (1) induction therapy for meningoencephalitis using fungicidal regimens, such as a polyene and flucytosine, followed by suppressive regimens using fluconazole; (2) importance of early recognition and treatment of increased intracranial pressure and/or IRIS; and (3) the use of lipid formulations of amphotericin B regimens in patients with renal impairment. Cryptococcosis remains a challenging management issue, with little new drug development or recent definitive studies. However, if the diagnosis is made early, if clinicians adhere to the basic principles of these guidelines, and if the underlying disease is controlled, then cryptococcosis can be managed successfully in the vast majority of patients.

2,109 citations


Journal ArticleDOI
Thomas J. Hudson1, Thomas J. Hudson2, Warwick Anderson3, Axel Aretz4  +270 moreInstitutions (92)
15 Apr 2010
TL;DR: Systematic studies of more than 25,000 cancer genomes will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
Abstract: The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

2,041 citations



Journal ArticleDOI
06 Aug 2010-Cell
TL;DR: It is shown that tau, known as axonal protein, has a dendritic function in postsynaptic targeting of the Src kinase Fyn, a substrate of which is the NMDA receptor (NR), which uncouples NR-mediated excitotoxicity and hence mitigates Abeta toxicity.

1,611 citations


Journal ArticleDOI
Georges Aad1, Brad Abbott1, Jalal Abdallah1, A. A. Abdelalim1  +2582 moreInstitutions (23)
TL;DR: The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid, including supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors.
Abstract: The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.

1,514 citations


Journal ArticleDOI
TL;DR: This survey explicitly explores the multidisciplinary foundation that underlies all AC applications by describing how AC researchers have incorporated psychological theories of emotion and how these theories affect research questions, methods, results, and their interpretations.
Abstract: This survey describes recent progress in the field of Affective Computing (AC), with a focus on affect detection. Although many AC researchers have traditionally attempted to remain agnostic to the different emotion theories proposed by psychologists, the affective technologies being developed are rife with theoretical assumptions that impact their effectiveness. Hence, an informed and integrated examination of emotion theories from multiple areas will need to become part of computing practice if truly effective real-world systems are to be achieved. This survey discusses theoretical perspectives that view emotions as expressions, embodiments, outcomes of cognitive appraisal, social constructs, products of neural circuitry, and psychological interpretations of basic feelings. It provides meta-analyses on existing reviews of affect detection systems that focus on traditional affect detection modalities like physiology, face, and voice, and also reviews emerging research on more novel channels such as text, body language, and complex multimodal systems. This survey explicitly explores the multidisciplinary foundation that underlies all AC applications by describing how AC researchers have incorporated psychological theories of emotion and how these theories affect research questions, methods, results, and their interpretations. In this way, models and methods can be compared, and emerging insights from various disciplines can be more expertly integrated.

1,503 citations


Journal ArticleDOI
TL;DR: The neural basis of the integration of learning and motivation in choice and decision-making is still controversial and some recent hypotheses relating to this issue are reviewed.

1,498 citations


Journal ArticleDOI
TL;DR: There is substantial information on low back pain prevalence and estimates of the point prevalence range from 1.0% to 58.1% (mean: 18.1%; median: 15.0%), and 1 year prevalence from 0.8% to 82.5% ( mean: 38.1; median: 37.4%).
Abstract: Low back pain is an extremely common problem that most people experience at some point in their life. While substantial heterogeneity exists among low back pain epidemiological studies limiting the ability to compare and pool data, estimates of the 1 year incidence of a first-ever episode of low back pain range between 6.3% and 15.4%, while estimates of the 1 year incidence of any episode of low back pain range between 1.5% and 36%. In health facility- or clinic-based studies, episode remission at 1 year ranges from 54% to 90%; however, most studies do not indicate whether the episode was continuous between the baseline and follow-up time point(s). Most people who experience activity-limiting low back pain go on to have recurrent episodes. Estimates of recurrence at 1 year range from 24% to 80%. Given the variation in definitions of remission and recurrence, further population-based research is needed to assess the daily patterns of low back pain episodes over 1 year and longer. There is substantial information on low back pain prevalence and estimates of the point prevalence range from 1.0% to 58.1% (mean: 18.1%; median: 15.0%), and 1 year prevalence from 0.8% to 82.5% (mean: 38.1%; median: 37.4%). Due to the heterogeneity of the data, mean estimates need to be interpreted with caution. Many environmental and personal factors influence the onset and course of low back pain. Studies have found the incidence of low back pain is highest in the third decade, and overall prevalence increases with age until the 60-65 year age group and then gradually declines. Other commonly reported risk factors include low educational status, stress, anxiety, depression, job dissatisfaction, low levels of social support in the workplace and whole-body vibration. Low back pain has an enormous impact on individuals, families, communities, governments and businesses throughout the world. The Global Burden of Disease 2005 Study (GBD 2005) is currently making estimates of the global burden of low back pain in relation to impairment and activity limitation. Results will be available in 2011. Further research is needed to help us understand more about the broader outcomes and impacts from low back pain.

1,465 citations


Journal ArticleDOI
TL;DR: Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes, including respiratory, digestive, and skin conditions, and no relationship was found between repeated episodes of severe hypglycemia and vascular outcomes or death.
Abstract: Background Severe hypoglycemia may increase the risk of a poor outcome in patients with type 2 diabetes assigned to an intensive glucose-lowering intervention. We analyzed data from a large study of intensive glucose lowering to explore the relationship between severe hypoglycemia and adverse clinical outcomes. Methods We examined the associations between severe hypoglycemia and the risks of macrovascular or microvascular events and death among 11,140 patients with type 2 diabetes, using Cox proportional-hazards models with adjustment for covariates measured at baseline and after randomization. Results During a median follow-up period of 5 years, 231 patients (2.1%) had at least one severe hypoglycemic episode; 150 had been assigned to intensive glucose control (2.7% of the 5571 patients in that group), and 81 had been assigned to standard glucose control (1.5% of the 5569 patients in that group). The median times from the onset of severe hypoglycemia to the first major macrovascular event, the first major microvascular event, and death were 1.56 years (interquartile range, 0.84 to 2.41), 0.99 years (interquartile range, 0.40 to 2.17), and 1.05 years (interquartile range, 0.34 to 2.41), respectively. During follow-up, severe hypoglycemia was associated with a significant increase in the adjusted risks of major macrovascular events (hazard ratio, 2.88; 95% confidence interval [CI], 2.01 to 4.12), major microvascular events (hazard ratio, 1.81; 95% CI, 1.19 to 2.74), death from a cardiovascular cause (hazard ratio, 2.68; 95% CI, 1.72 to 4.19), and death from any cause (hazard ratio, 2.69; 95% CI, 1.97 to 3.67) (P<0.001 for all comparisons). Similar associations were apparent for a range of nonvascular outcomes, including respiratory, digestive, and skin conditions (P<0.01 for all comparisons). No relationship was found between repeated episodes of severe hypoglycemia and vascular outcomes or death. Conclusions Severe hypoglycemia was strongly associated with increased risks of a range of adverse clinical outcomes. It is possible that severe hypoglycemia contributes to adverse outcomes, but these analyses indicate that hypoglycemia is just as likely to be a marker of vulnerability to such events. (Funded by Servier and the National Health and Medical Research Council of Australia; ClinicalTrials.gov number, NCT00145925.)

Journal ArticleDOI
TL;DR: This Review explores issues by presenting the latest advances in electrochemical, electrical, and optical biosensors that use carbon nanotubes and graphene, and critically compares the performance of the two carbon allotropes in this application.
Abstract: From diagnosis of life-threatening diseases to detection of biological agents in warfare or terrorist attacks, biosensors are becoming a critical part of modern life. Many recent biosensors have incorporated carbon nanotubes as sensing elements, while a growing body of work has begun to do the same with the emergent nanomaterial graphene, which is effectively an unrolled nanotube. With this widespread use of carbon nanomaterials in biosensors, it is timely to assess how this trend is contributing to the science and applications of biosensors. This Review explores these issues by presenting the latest advances in electrochemical, electrical, and optical biosensors that use carbon nanotubes and graphene, and critically compares the performance of the two carbon allotropes in this application. Ultimately, carbon nanomaterials, although still to meet key challenges in fabrication and handling, have a bright future as biosensors.

Journal ArticleDOI
TL;DR: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered.
Abstract: BACKGROUND: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System. OBJECTIVES: To revise these guidelines. METHODS: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion. RECOMMENDATIONS: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

Journal ArticleDOI
TL;DR: All authors to papers in the International Journal of Cardiology must adhere to the following principles: that the corresponding author has the approval of all other listed authors for the submission and publication of all versions of the manuscript.

Journal ArticleDOI
TL;DR: Depression without CVD is associated with reducedHRV, which decreases with increasing depression severity, most apparent with nonlinear measures of HRV, highlighting that antidepressant medications might not have HRV-mediated cardioprotective effects and the need to identify individuals at risk among patients in remission.

Journal ArticleDOI
TL;DR: The various technologies for controlling the porosity and microarchitecture within hydrogels are explored, and successful applications of combining these techniques are demonstrated.
Abstract: Tissue engineering holds great promise for regeneration and repair of diseased tissues, making the development of tissue engineering scaffolds a topic of great interest in biomedical research. Beca...

Journal ArticleDOI
TL;DR: In this paper, the safety and efficacy of dexamethasone intravitreal implant (DEX implant; OZURDEX, Allergan, Inc., Irvine, CA) compared with sham in eyes with vision loss due to macular edema (ME) associated with BRVO or central retinal vein occlusion (CRVO).

Journal ArticleDOI
TL;DR: Test hypotheses about the influence of wind and depositional regime on spatial patterns of micro- and macro-plastic debris within the Tamar Estuary, UK show habitats that are downwind acting as potential sinks for the accumulation of debris.
Abstract: The human population generates vast quantities of waste material. Macro (>1 mm) and microscopic (<1 mm) fragments of plastic debris represent a substantial contamination problem. Here, we test hypotheses about the influence of wind and depositional regime on spatial patterns of micro- and macro-plastic debris within the Tamar Estuary, UK. Debris was identified to the type of polymer using Fourier-transform infrared spectroscopy (FT-IR) and categorized according to density. In terms of abundance, microplastic accounted for 65% of debris recorded and mainly comprised polyvinylchloride, polyester, and polyamide. Generally, there were greater quantities of plastic at downwind sites. For macroplastic, there were clear patterns of distribution for less dense items, while for microplastic debris, clear patterns were for denser material. Small particles of sediment and plastic are both likely to settle slowly from the water-column and are likely to be transported by the flow of water and be deposited in areas whe...

Journal ArticleDOI
TL;DR: The study provides summary data on the prevalence of RVO and suggests that approximately 16 million people may have this condition and research on preventive and treatment strategies for this sight-threatening eye disease is needed.

Journal ArticleDOI
30 Apr 2010-Science
TL;DR: A synthesis of grass evolutionary biology with grassland ecosystem science will further knowledge of the evolution of traits that promote dominance in grassland systems and will provide a new context in which to evaluate the relative importance of C4 photosynthesis in transforming ecosystems across large regions of Earth.
Abstract: The evolution of grasses using C4 photosynthesis and their sudden rise to ecological dominance 3 to 8 million years ago is among the most dramatic examples of biome assembly in the geological record. A growing body of work suggests that the patterns and drivers of C4 grassland expansion were considerably more complex than originally assumed. Previous research has benefited substantially from dialog between geologists and ecologists, but current research must now integrate fully with phylogenetics. A synthesis of grass evolutionary biology with grassland ecosystem science will further our knowledge of the evolution of traits that promote dominance in grassland systems and will provide a new context in which to evaluate the relative importance of C4 photosynthesis in transforming ecosystems across large regions of Earth.

Journal ArticleDOI
TL;DR: A system of nosology was introduced that grouped the FTLD subtypes into broad categories, based on the molecular defect that is most characteristic, according to current evidence, and provided a concise and consistent terminology that has now been widely adopted in the literature.
Abstract: Nomenclature and nosology for neuropathologic subtypes of frontotemporal lobar degeneration : an update

Journal ArticleDOI
TL;DR: In this article, the authors used X-ray diffraction analysis to identify the presence of whewellite in E. saligna biochars produced at 400°C and 550°C with activation.
Abstract: Biochar properties can be significantly influenced by feedstock source and pyrolysis conditions; this warrants detailed characterisation of biochars for their application to improve soil fertility and sequester carbon. We characterised 11 biochars, made from 5 feedstocks [Eucalyptus saligna wood (at 400°C and 550°C both with and without steam activation); E. saligna leaves (at 400°C and 550°C with activation); papermill sludge (at 550°C with activation); poultry litter and cow manure (each at 400°C without activation and at 550°C with activation)] using standard or modified soil chemical procedures. Biochar pH values varied from near neutral to highly alkaline. In general, wood biochars had higher total C, lower ash content, lower total N, P, K, S, Ca, Mg, Al, Na, and Cu contents, and lower potential cation exchange capacity (CEC) and exchangeable cations than the manure-based biochars, and the leaf biochars were generally in-between. Papermill sludge biochar had the highest total and exchangeable Ca, CaCO3 equivalence, total Cu, and potential CEC, and the lowest total and exchangeable K. Water-soluble salts were higher in the manure-based biochars, followed by leaf, papermill sludge, and wood biochars. Total As, Cd, Pb, and polycyclic aromatic hydrocarbons in the biochars were either very low or below detection limits. In general, increase in pyrolysis temperature increased the ash content, pH, and surface basicity and decreased surface acidity. The activation treatment had a little effect on most of the biochar properties. X-ray diffraction analysis showed the presence of whewellite in E. saligna biochars produced at 400°C, and the whewellite was converted to calcite in biochars formed at 550°C. Papermill sludge biochar contained the largest amount of calcite. Water-soluble salts and calcite interfered with surface charge measurements and should be removed before the surface charge measurements of biochar. The biochars used in the study ranged from C-rich to nutrient-rich to lime-rich soil amendment, and these properties could be optimised through feedstock formulation and pyrolysis temperature for tailored soil application.

Journal ArticleDOI
TL;DR: This study provides the first evidence that oxytocin nasal spray improves emotion recognition in young people diagnosed with autism spectrum disorders.

Journal ArticleDOI
TL;DR: Although dissection of the mechanism or mechanisms of ALT has been challenging, recent advances have led to the identification of several genes that are required for ALT and the elucidation of the biological significance of some phenotypic markers of ALTs, which has enabled development of a rapid assay ofALT activity levels and the construction of molecular models of ALt.
Abstract: Unlimited cellular proliferation depends on counteracting the telomere attrition that accompanies DNA replication. In human cancers this usually occurs through upregulation of telomerase activity, but in 10-15% of cancers - including some with particularly poor outcome - it is achieved through a mechanism known as alternative lengthening of telomeres (ALT). ALT, which is dependent on homologous recombination, is therefore an important target for cancer therapy. Although dissection of the mechanism or mechanisms of ALT has been challenging, recent advances have led to the identification of several genes that are required for ALT and the elucidation of the biological significance of some phenotypic markers of ALT. This has enabled development of a rapid assay of ALT activity levels and the construction of molecular models of ALT.

Journal ArticleDOI
TL;DR: Fibrates can reduce the risk of major cardiovascular events predominantly by prevention of coronary events, and might have a role in individuals at high risk of cardiovascular events and in those with combined dyslipidaemia.

Journal ArticleDOI
TL;DR: 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound, and clinical dosimetry applications of polymer gel Dosimetry are presented.
Abstract: Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented.

Journal ArticleDOI
TL;DR: In this article, the authors provide a critical overview of the major ecological effects of increasing infrastructure to marine habitats, identify future research directions for advancing our understanding of marine urban ecosystems and highlight how alternative management options might mitigate their impacts.
Abstract: Summary 1. Coastal landscapes are being transformed as a consequence of the increasing demand for urban infrastructure to sustain commercial, residential and tourist activities. A variety of man-made structures, such as breakwaters, jetties and seawalls have thus become ubiquitous features of intertidal and shallow subtidal habitats. This transformation will accelerate in response to the exponential growth of human populations and to global changes, such as sea-level rise and increased frequency of extreme meteorological events (e.g. storms). Here, we provide a critical overview of the major ecological effects of increasing infrastructure to marine habitats, we identify future research directions for advancing our understanding of marine urban ecosystems and we highlight how alternative management options might mitigate their impacts. 2. Urban infrastructure supports different epibiota and associated assemblages and does not function as surrogate of natural rocky habitats. Its introduction in the intertidal zone or in near-shore waters can cause fragmentation and loss of natural habitats. Furthermore, the provision of novel habitat (hard substrata) along sedimentary shores can alter local and regional biodiversity by modifying natural patterns of dispersal of species, or by facilitating the establishment and spread of exotic species. 3. Attempts to use ecological criteria to solve problems of urban infrastructure are promising. Incorporating natural elements of habitat (e.g. wetland vegetation; seagrass) into shoreline stabilization can reduce ecological impacts, without impinging on its efficacy in halting erosion. Likewise, improving the ecological value of artificial structures by adding features of habitat that are generally missing from such structures (e.g. rock-pools) can contribute to mitigation of the detrimental effects of urbanization on biodiversity. Management of anthropogenic disturbances (e.g. maintenance works; harvesting) to artificial habitat is, however, necessary if such attempts are to be successful. 4. Synthesis and applications. Increasing our understanding of the ecological functioning of marine habitats created by urban infrastructure and incorporating ecological criteria into coastal engineering are crucial for preserving biodiversity in the face of the growth of human populations in coastal areas and of forecasted global changes. Achieving this goal will need strong collaboration between engineers, managers and ecologists.

Journal ArticleDOI
TL;DR: A genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls identified 10 gene sets that were all associated with PD.
Abstract: Parkinson’s disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson’s disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson’s disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson’s disease identifies PGC-1α as a potential therapeutic target for early intervention.

Journal ArticleDOI
TL;DR: The number of patients with type 2 diabetes is increasing rapidly in both developed and developing countries around the world and it is projected that by 2025 there will be 380 million people with type 1 diabetes and 418 millionPeople with impaired glucose tolerance.
Abstract: The number of patients with type 2 diabetes is increasing rapidly in both developed and developing countries around the world. The emerging pandemic is driven by the combined effects of population ageing, rising levels of obesity and inactivity, and greater longevity among patients with diabetes that is attributable to improved management. The vascular complications of type 2 diabetes account for the majority of the social and economic burden among patients and society more broadly. This review summarizes the burden of type 2 diabetes, impaired glucose tolerance, and their vascular complications. It is projected that by 2025 there will be 380 million people with type 2 diabetes and 418 million people with impaired glucose tolerance. Diabetes is a major global cause of premature mortality that is widely underestimated, because only a minority of persons with diabetes dies from a cause uniquely related to the condition. Approximately one half of patients with type 2 diabetes die prematurely of a cardiovascular cause and approximately 10% die of renal failure. Global excess mortality attributable to diabetes in adults was estimated to be 3.8 million deaths.

Journal ArticleDOI
TL;DR: In this article, the authors examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease and found no significant difference between the groups in the frequency of adverse events, infections, or complications of dialysis.
Abstract: BACKGROUND In clinical practice, there is considerable variation in the timing of the initiation of maintenance dialysis for patients with stage V chronic kidney disease, with a worldwide trend toward early initiation. In this study, conducted at 32 centers in Australia and New Zealand, we examined whether the timing of the initiation of maintenance dialysis influenced survival among patients with chronic kidney disease. METHODS We randomly assigned patients 18 years of age or older with progressive chronic kidney disease and an estimated glomerular filtration rate (GFR) between 10.0 and 15.0 ml per minute per 1.73 m 2 of body-surface area (calculated with the use of the Cockcroft–Gault equation) to planned initiation of dialysis when the estimated GFR was 10.0 to 14.0 ml per minute (early start) or when the estimated GFR was 5.0 to 7.0 ml per minute (late start). The primary outcome was death from any cause. RESULTS Between July 2000 and November 2008, a total of 828 adults (mean age, 60.4 years; 542 men and 286 women; 355 with diabetes) underwent randomization, with a median time to the initiation of dialysis of 1.80 months (95% confidence interval [CI], 1.60 to 2.23) in the early-start group and 7.40 months (95% CI, 6.23 to 8.27) in the late-start group. A total of 75.9% of the patients in the late-start group initiated dialysis when the estimated GFR was above the target of 7.0 ml per minute, owing to the development of symptoms. During a median follow-up period of 3.59 years, 152 of 404 patients in the early-start group (37.6%) and 155 of 424 in the late-start group (36.6%) died (hazard ratio with early initiation, 1.04; 95% CI, 0.83 to 1.30; P = 0.75). There was no significant difference between the groups in the frequency of adverse events (cardiovascular events, infections, or complications of dialysis). CONCLUSIONS In this study, planned early initiation of dialysis in patients with stage V chronic kidney disease was not associated with an improvement in survival or clinical outcomes. (Funded by the National Health and Medical Research Council of Australia and others; Australian New Zealand Clinical Trials Registry number, 12609000266268.)