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Showing papers by "McGill University published in 2011"


Journal ArticleDOI
TL;DR: The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available.
Abstract: The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.

13,710 citations


Journal ArticleDOI
20 Oct 2011-Nature
TL;DR: It is shown that tremendous progress could be made by halting agricultural expansion, closing ‘yield gaps’ on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste, which could double food production while greatly reducing the environmental impacts of agriculture.
Abstract: Increasing population and consumption are placing unprecedented demands on agriculture and natural resources. Today, approximately a billion people are chronically malnourished while our agricultural systems are concurrently degrading land, water, biodiversity and climate on a global scale. To meet the world's future food security and sustainability needs, food production must grow substantially while, at the same time, agriculture's environmental footprint must shrink dramatically. Here we analyse solutions to this dilemma, showing that tremendous progress could be made by halting agricultural expansion, closing 'yield gaps' on underperforming lands, increasing cropping efficiency, shifting diets and reducing waste. Together, these strategies could double food production while greatly reducing the environmental impacts of agriculture.

5,954 citations


Journal ArticleDOI
TL;DR: Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dACarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma.
Abstract: A B S T R AC T Background Ipilimumab monotherapy (at a dose of 3 mg per kilogram of body weight), as compared with glycoprotein 100, improved overall survival in a phase 3 study involving patients with previously treated metastatic melanoma. We conducted a phase 3 study of ipilimumab (10 mg per kilogram) plus dacarbazine in patients with previously untreated metastatic melanoma. Methods We randomly assigned 502 patients with previously untreated metastatic melanoma, in a 1:1 ratio, to ipilimumab (10 mg per kilogram) plus dacarbazine (850 mg per square meter of body-surface area) or dacarbazine (850 mg per square meter) plus placebo, given at weeks 1, 4, 7, and 10, followed by dacarbazine alone every 3 weeks through week 22. Patients with stable disease or an objective response and no doselimiting toxic effects received ipilimumab or placebo every 12 weeks thereafter as maintenance therapy. The primary end point was overall survival. Results Overall survival was significantly longer in the group receiving ipilimumab plus dacarbazine than in the group receiving dacarbazine plus placebo (11.2 months vs. 9.1 months, with higher survival rates in the ipilimumab–dacarbazine group at 1 year (47.3% vs. 36.3%), 2 years (28.5% vs. 17.9%), and 3 years (20.8% vs. 12.2%) (hazard ratio for death, 0.72; P<0.001). Grade 3 or 4 adverse events occurred in 56.3% of patients treated with ipilimumab plus dacarbazine, as compared with 27.5% treated with dacarbazine and placebo (P<0.001). No drug-related deaths or gastrointestinal perforations occurred in the ipilimumab–dacarbazine group. Conclusions Ipilimumab (at a dose of 10 mg per kilogram) in combination with dacarbazine, as compared with dacarbazine plus placebo, improved overall survival in patients with previously untreated metastatic melanoma. The types of adverse events were consistent with those seen in prior studies of ipilimumab; however, the rates of elevated liver-function values were higher and the rates of gastrointestinal events were lower than expected on the basis of prior studies. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00324155.)

4,069 citations


Journal ArticleDOI
TL;DR: A framework exists on a framework for the definition and classification of cancer cachexia, a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment.
Abstract: Summary To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] 2 ) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages—precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.

3,548 citations


Journal ArticleDOI
TL;DR: This Review assembles the current knowledge on the isolation of microfibrillated cellulose from wood and its application in nanocomposites; the preparation of nanocrystalline cellulose and its use as a reinforcing agent; and the biofabrication of bacterial nanocellulose, as well as its evaluation as a biomaterial for medical implants.
Abstract: Cellulose fibrils with widths in the nanometer range are nature-based materials with unique and potentially useful features. Most importantly, these novel nanocelluloses open up the strongly expanding fields of sustainable materials and nanocomposites, as well as medical and life-science devices, to the natural polymer cellulose. The nanodimensions of the structural elements result in a high surface area and hence the powerful interaction of these celluloses with surrounding species, such as water, organic and polymeric compounds, nanoparticles, and living cells. This Review assembles the current knowledge on the isolation of microfibrillated cellulose from wood and its application in nanocomposites; the preparation of nanocrystalline cellulose and its use as a reinforcing agent; and the biofabrication of bacterial nanocellulose, as well as its evaluation as a biomaterial for medical implants.

3,452 citations


Journal ArticleDOI
TL;DR: In this paper, the authors identify key areas of uncertainty and specific actions needed to address them and identify the value of mangrove forests, seagrass beds, and salt marshes in sequestering carbon dioxide.
Abstract: Recent research has highlighted the valuable role that coastal and marine ecosystems play in sequestering carbon dioxide (CO(2)). The carbon (C) sequestered in vegetated coastal ecosystems, specifically mangrove forests, seagrass beds, and salt marshes, has been termed blue carbon. Although their global area is one to two orders of magnitude smaller than that of terrestrial forests, the contribution of vegetated coastal habitats per unit area to long-term C sequestration is much greater, in part because of their efficiency in trapping suspended matter and associated organic C during tidal inundation. Despite the value of mangrove forests, seagrass beds, and salt marshes in sequestering C, and the other goods and services they provide, these systems are being lost at critical rates and action is urgently needed to prevent further degradation and loss. Recognition of the C sequestration value of vegetated coastal ecosystems provides a strong argument for their protection and restoration; however, it is necessary to improve scientific understanding of the underlying mechanisms that control C sequestration in these ecosystems. Here, we identify key areas of uncertainty and specific actions needed to address them.

2,313 citations


Journal ArticleDOI
TL;DR: Continuous daily administration of sunitinib at a dose of 37.5 mg improved progression-free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors.
Abstract: The multitargeted tyrosine kinase inhibitor sunitinib has shown activity against pancreatic neuroendocrine tumors in preclinical models and phase 1 and 2 trials.

2,192 citations


Journal ArticleDOI
TL;DR: This paper performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals.
Abstract: We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 - 10'8 and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.

1,705 citations


Journal ArticleDOI
TL;DR: In this article, the components of RFBs with a focus on understanding the underlying physical processes are examined and various transport and kinetic phenomena are discussed along with the most common redox couples.
Abstract: Redox flow batteries (RFBs) are enjoying a renaissance due to their ability to store large amounts of electrical energy relatively cheaply and efficiently. In this review, we examine the components of RFBs with a focus on understanding the underlying physical processes. The various transport and kinetic phenomena are discussed along with the most common redox couples.

1,661 citations


Journal ArticleDOI
TL;DR: Despite the recognized importance of reservoirs and dams, global datasets describing their characteristics and geographical distribution are largely incomplete as mentioned in this paper, which makes it difficult to perform advanced assessments of dams and reservoirs.
Abstract: Despite the recognized importance of reservoirs and dams, global datasets describing their characteristics and geographical distribution are largely incomplete. To enable advanced assessments of th ...

1,493 citations


Journal ArticleDOI
TL;DR: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults.
Abstract: Purpose Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. Methods Thirty-two Task Force members have reevaluated available data on electroclinical presentation, imaging, neuropathological examination of surgical specimens as well as postsurgical outcome. Key findings The ILAE Task Force proposes a three-tiered classification system. FCD Type I refers to isolated lesions, which present either as radial (FCD Type Ia) or tangential (FCD Type Ib) dyslamination of the neocortex, microscopically identified in one or multiple lobes. FCD Type II is an isolated lesion characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). Hence, the major change since a prior classification represents the introduction of FCD Type III, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with epileptogenic lesions acquired in early life (i.e., traumatic injury, ischemic injury or encephalitis). Significance This three-tiered classification system will be an important basis to evaluate imaging, electroclinical features, and postsurgical seizure control as well as to explore underlying molecular pathomechanisms in FCD.

Journal ArticleDOI
TL;DR: It is found that intense pleasure in response to music can lead to dopamine release in the striatal system, and this results help to explain why music is of such high value across all human societies.
Abstract: Music, an abstract stimulus, can arouse feelings of euphoria and craving, similar to tangible rewards that involve the striatal dopaminergic system. Using the neurochemical specificity of [(11)C]raclopride positron emission tomography scanning, combined with psychophysiological measures of autonomic nervous system activity, we found endogenous dopamine release in the striatum at peak emotional arousal during music listening. To examine the time course of dopamine release, we used functional magnetic resonance imaging with the same stimuli and listeners, and found a functional dissociation: the caudate was more involved during the anticipation and the nucleus accumbens was more involved during the experience of peak emotional responses to music. These results indicate that intense pleasure in response to music can lead to dopamine release in the striatal system. Notably, the anticipation of an abstract reward can result in dopamine release in an anatomical pathway distinct from that associated with the peak pleasure itself. Our results help to explain why music is of such high value across all human societies.

Journal ArticleDOI
08 Sep 2011-Nature
TL;DR: It is shown that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once, and many species are needed to maintain multiple functions at multiple times and places in a changing world.
Abstract: Biodiversity is rapidly declining worldwide, and there is consensus that this can decrease ecosystem functioning and services. It remains unclear, though, whether few or many of the species in an ecosystem are needed to sustain the provisioning of ecosystem services. It has been hypothesized that most species would promote ecosystem services if many times, places, functions and environmental changes were considered; however, no previous study has considered all of these factors together. Here we show that 84% of the 147 grassland plant species studied in 17 biodiversity experiments promoted ecosystem functioning at least once. Different species promoted ecosystem functioning during different years, at different places, for different functions and under different environmental change scenarios. Furthermore, the species needed to provide one function during multiple years were not the same as those needed to provide multiple functions within one year. Our results indicate that even more species will be needed to maintain ecosystem functioning and services than previously suggested by studies that have either (1) considered only the number of species needed to promote one function under one set of environmental conditions, or (2) separately considered the importance of biodiversity for providing ecosystem functioning across multiple years, places, functions or environmental change scenarios. Therefore, although species may appear functionally redundant when one function is considered under one set of environmental conditions, many species are needed to maintain multiple functions at multiple times and places in a changing world.

Journal ArticleDOI
TL;DR: A fibromyalgia survey questionnaire is developed using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010) to allow their use in epidemiologic and clinical studies without the requirement for an examiner.
Abstract: Objective. To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity. Methods. The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician’s estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0–31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA). Results. The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria− patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population. Conclusion. A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.

Journal ArticleDOI
TL;DR: The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens and systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation.
Abstract: The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Journal ArticleDOI
TL;DR: This work discusses the activation of macrophages and microglia following spinal cord injury, and their effects on repair, and suggests that harnessing their anti-inflammatory properties could pave the way for new therapeutic strategies for spinal cord trauma.
Abstract: Macrophages from the peripheral circulation and those derived from resident microglia are among the main effector cells of the inflammatory response that follows spinal cord trauma. There has been considerable debate in the field as to whether the inflammatory response is good or bad for tissue protection and repair. Recent studies on macrophage polarization in non-neural tissues have shed much light on their changing functional states. In the context of this literature, we discuss the activation of macrophages and microglia following spinal cord injury, and their effects on repair. Harnessing their anti-inflammatory properties could pave the way for new therapeutic strategies for spinal cord trauma.

Journal ArticleDOI
TL;DR: Several new questions must now be addressed if this field is going to evolve into a predictive science that can help conserve and manage ecological processes in ecosystems, including questions about how primary producer diversity influences the efficiency of resource use and biomass production in ecosystems.
Abstract: Over the past several decades, a rapidly expanding field of research known as biodiversity and ecosystem functioning has begun to quantify how the world's biological diversity can, as an independent variable, control ecological processes that are both essential for, and fundamental to, the functioning of ecosystems. Research in this area has often been justified on grounds that (1) loss of biological diversity ranks among the most pronounced changes to the global environment and that (2) reductions in diversity, and corresponding changes in species composition, could alter important services that ecosystems provide to humanity (e.g., food production, pest/disease control, water purification). Here we review over two decades of experiments that have examined how species richness of primary producers influences the suite of ecological processes that are controlled by plants and algae in terrestrial, marine, and freshwater ecosystems. Using formal meta-analyses, we assess the balance of evidence for eight fundamental questions and corresponding hypotheses about the functional role of producer diversity in ecosystems. These include questions about how primary producer diversity influences the efficiency of resource use and biomass production in ecosystems, how primary producer diversity influences the transfer and recycling of biomass to other trophic groups in a food web, and the number of species and spatial /temporal scales at which diversity effects are most apparent. After summarizing the balance of evidence and stating our own confidence in the conclusions, we outline several new questions that must now be addressed if this field is going to evolve into a predictive science that can help conserve and manage ecological processes in ecosystems.

Journal ArticleDOI
TL;DR: In this paper, the authors reported the creation of Greenberger-Horne-Zeilinger states with up to 14 qubits by investigating the coherence of up to 8 ions over time and observed a decay proportional to the square of the number of qubits.
Abstract: We report the creation of Greenberger-Horne-Zeilinger states with up to 14 qubits. By investigating the coherence of up to 8 ions over time, we observe a decay proportional to the square of the number of qubits. The observed decay agrees with a theoretical model which assumes a system affected by correlated, Gaussian phase noise. This model holds for the majority of current experimental systems developed towards quantum computation and quantum metrology.

Journal ArticleDOI
TL;DR: Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion, but findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.
Abstract: Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.

Journal ArticleDOI
TL;DR: The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.
Abstract: Iron is an essential but potentially hazardous biometal. Mammalian cells require sufficient amounts of iron to satisfy metabolic needs or to accomplish specialized functions. Iron is delivered to tissues by circulating transferrin, a transporter that captures iron released into the plasma mainly from intestinal enterocytes or reticuloendothelial macrophages. The binding of iron-laden transferrin to the cell-surface transferrin receptor 1 results in endocytosis and uptake of the metal cargo. Internalized iron is transported to mitochondria for the synthesis of haem or iron–sulfur clusters, which are integral parts of several metalloproteins, and excess iron is stored and detoxified in cytosolic ferritin. Iron metabolism is controlled at different levels and by diverse mechanisms. The present review summarizes basic concepts of iron transport, use and storage and focuses on the IRE (iron-responsive element)/IRP (iron-regulatory protein) system, a well known post-transcriptional regulatory circuit that not only maintains iron homoeostasis in various cell types, but also contributes to systemic iron balance.

Book
01 Jan 2011
TL;DR: This book examines various aspects of the evaluation process with an emphasis on classification algorithms, describing several techniques for classifier performance assessment, error estimation and resampling, obtaining statistical significance as well as selecting appropriate domains for evaluation.
Abstract: The field of machine learning has matured to the point where many sophisticated learning approaches can be applied to practical applications. Thus it is of critical importance that researchers have the proper tools to evaluate learning approaches and understand the underlying issues. This book examines various aspects of the evaluation process with an emphasis on classification algorithms. The authors describe several techniques for classifier performance assessment, error estimation and resampling, obtaining statistical significance as well as selecting appropriate domains for evaluation. They also present a unified evaluation framework and highlight how different components of evaluation are both significantly interrelated and interdependent. The techniques presented in the book are illustrated using R and WEKA facilitating better practical insight as well as implementation.Aimed at researchers in the theory and applications of machine learning, this book offers a solid basis for conducting performance evaluations of algorithms in practical settings.

Journal ArticleDOI
18 Nov 2011-Science
TL;DR: The experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells, and inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.
Abstract: Bacteria become highly tolerant to antibiotics when nutrients are limited. The inactivity of antibiotic targets caused by starvation-induced growth arrest is thought to be a key mechanism producing tolerance. Here we show that the antibiotic tolerance of nutrient-limited and biofilm Pseudomonas aeruginosa is mediated by active responses to starvation, rather than by the passive effects of growth arrest. The protective mechanism is controlled by the starvation-signaling stringent response (SR), and our experiments link SR-mediated tolerance to reduced levels of oxidant stress in bacterial cells. Furthermore, inactivating this protective mechanism sensitized biofilms by several orders of magnitude to four different classes of antibiotics and markedly enhanced the efficacy of antibiotic treatment in experimental infections.

Journal ArticleDOI
TL;DR: The authors developed and applied a methodology to track and characterize adaptation action; they applied these methods to the peer-reviewed, English-language literature and found that climate change is rarely the sole or primary motivator for adaptation action.
Abstract: Human systems will have to adapt to climate change. Understanding of the magnitude of the adaptation challenge at a global scale, however, is incomplete, constrained by a limited understanding of if and how adaptation is taking place. Here we develop and apply a methodology to track and characterize adaptation action; we apply these methods to the peer-reviewed, English-language literature. Our results challenge a number of common assumptions about adaptation while supporting others: (1) Considerable research on adaptation has been conducted yet the majority of studies report on vulnerability assessments and natural systems (or intentions to act), not adaptation actions. (2) Climate change is rarely the sole or primary motivator for adaptation action. (3) Extreme events are important adaptation stimuli across regions. (4) Proactive adaptation is the most commonly reported adaptive response, particularly in developed nations. (5) Adaptation action is more frequently reported in developed nations, with middle income countries underrepresented and low-income regions dominated by reports from a small number of countries. (6) There is limited reporting on adaptations being developed to take advantage of climate change or focusing on women, elderly, or children.

Journal ArticleDOI
TL;DR: The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniaZid alone in preventing tuberculosis and had a higher treatment-completion rate.
Abstract: In the modified intention-to-treat analysis, tuberculosis developed in 7 of 3986 subjects in the combination-therapy group (cumulative rate, 0.19%) and in 15 of 3745 subjects in the isoniazid-only group (cumulative rate, 0.43%), for a difference of 0.24 percentage points. Rates of treatment completion were 82.1% in the combination-therapy group and 69.0% in the isoniazid-only group (P<0.001). Rates of permanent drug discontinuation owing to an adverse event were 4.9% in the combination-therapy group and 3.7% in the isoniazid-only group (P = 0.009). Rates of investigator-assessed drug-related hepatotoxicity were 0.4% and 2.7%, respectively (P<0.001). Conclusions The use of rifapentine plus isoniazid for 3 months was as effective as 9 months of isoniazid alone in preventing tuberculosis and had a higher treatment-completion rate. Long-term safety monitoring will be important. (Funded by the Centers for Disease Control and Prevention; PREVENT TB ClinicalTrials.gov number, NCT00023452.)

Book ChapterDOI
01 Jan 2011
TL;DR: In this paper, the inverse matrix of A is defined as the inverse transformation from y ∈ En to x ∈ Em, whereas the matrix A represents a transformation from x to y, and the solution vector x in the equation y = Ax is determined uniquely as x = A -1 y.
Abstract: Let A be a square matrix of order n. If it is nonsingular, then Ker(A) = {0} and, as mentioned earlier, the solution vector x in the equation y = Ax is determined uniquely as x = A -1 y. Here, A -1 is called the inverse (matrix) of A defining the inverse transformation from y ∈ En to x ∈ Em, whereas the matrix A represents a transformation from x to y. When A is n by m, Ax = y has a solution if and only if y ∈ Sp(A). Even then, if Ker(A) ≠ {A}, there are many solutions to the equation Ax = A due to the existence of x 0 (≠ 0) such that Ax 0 = 0, so that A(x+x 0) = y. If y ∉ Sp(A), there is no solution vector to the equation Ax = y.

Journal ArticleDOI
TL;DR: In this article, the authors discuss the needs and benefits for a system that would monitor and predict the Earth's terrestrial water, energy, and biogeochemical cycles, and they call upon the international hydrologic community and the hydrological science support infrastructure to endorse the effort.
Abstract: Monitoring Earth's terrestrial water conditions is critically important to many hydrological applications such as global food production; assessing water resources sustainability; and flood, drought, and climate change prediction. These needs have motivated the development of pilot monitoring and prediction systems for terrestrial hydrologic and vegetative states, but to date only at the rather coarse spatial resolutions (∼10–100 km) over continental to global domains. Adequately addressing critical water cycle science questions and applications requires systems that are implemented globally at much higher resolutions, on the order of 1 km, resolutions referred to as hyperresolution in the context of global land surface models. This opinion paper sets forth the needs and benefits for a system that would monitor and predict the Earth's terrestrial water, energy, and biogeochemical cycles. We discuss six major challenges in developing a system: improved representation of surface-subsurface interactions due to fine-scale topography and vegetation; improved representation of land-atmospheric interactions and resulting spatial information on soil moisture and evapotranspiration; inclusion of water quality as part of the biogeochemical cycle; representation of human impacts from water management; utilizing massively parallel computer systems and recent computational advances in solving hyperresolution models that will have up to 109 unknowns; and developing the required in situ and remote sensing global data sets. We deem the development of a global hyperresolution model for monitoring the terrestrial water, energy, and biogeochemical cycles a “grand challenge” to the community, and we call upon the international hydrologic community and the hydrological science support infrastructure to endorse the effort.

Journal ArticleDOI
TL;DR: In this article, the authors developed a database of experimental data of steel components and the use of this database for quantification of important parameters that affect the cyclic moment-rotation relationship at plastic hinge regions in beams.
Abstract: Reliable collapse assessment of structural systems under earthquake loading requires analytical models that are able to capture component deterioration in strength and stiffness. For calibration and validation of these models, a large set of experimental data is needed. This paper discusses the development of a database of experimental data of steel components and the use of this database for quantification of important parameters that affect the cyclic moment-rotation relationship at plastic hinge regions in beams. On the basis of information deduced from the steel component database, empirical relationships for modeling of precapping plastic rotation, postcapping rotation, and cyclic deterioration for beams with reduced beam section (RBS) and other-than-RBS beams are proposed. Quantitative information is also provided for modeling of the effective yield strength, postyield strength ratio, residual strength, and ductile tearing of steel components subjected to cyclic loading.

Journal ArticleDOI
05 Oct 2011-Nature
TL;DR: Excess phosphorus is polluting the environment while, ironically, mineable resources of this essential nutrient are limited, and recycling programmes are urgently needed.
Abstract: Excess phosphorus is polluting our environment while, ironically, mineable resources of this essential nutrient are limited. James Elser and Elena Bennett argue that recycling programmes are urgently needed.

Journal ArticleDOI
TL;DR: Resolving agronomic P imbalances may be possible with more efficient use of P fertilizers and more effective recycling of manure P, to increase global agricultural productivity while maintaining or improving freshwater quality.
Abstract: Increased phosphorus (P) fertilizer use and livestock production has fundamentally altered the global P cycle. We calculated spatially explicit P balances for cropland soils at 0.5° resolution based on the principal agronomic P inputs and outputs associated with production of 123 crops globally for the year 2000. Although agronomic inputs of P fertilizer (14.2 Tg of P·y−1) and manure (9.6 Tg of P·y−1) collectively exceeded P removal by harvested crops (12.3 Tg of P·y−1) at the global scale, P deficits covered almost 30% of the global cropland area. There was massive variation in the magnitudes of these P imbalances across most regions, particularly Europe and South America. High P fertilizer application relative to crop P use resulted in a greater proportion of the intense P surpluses (>13 kg of P·ha−1·y−1) globally than manure P application. High P fertilizer application was also typically associated with areas of relatively low P-use efficiency. Although manure was an important driver of P surpluses in some locations with high livestock densities, P deficits were common in areas producing forage crops used as livestock feed. Resolving agronomic P imbalances may be possible with more efficient use of P fertilizers and more effective recycling of manure P. Such reforms are needed to increase global agricultural productivity while maintaining or improving freshwater quality.

Journal ArticleDOI
TL;DR: The similarly pronounced effects of B-cell depletion with both ocrelizumab doses on MRI and relapse-related outcomes support a role for B-cells in disease pathogenesis and warrant further assessment in large, long-term trials.