Showing papers by "Queen's University published in 2011"

The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D from the Institute of Medicine: What Clinicians Need to Know

Abstract: This article summarizes the new 2011 report on dietary requirements for calcium and vitamin D from the Institute of Medicine (IOM). An IOM Committee charged with determining the population needs for these nutrients in North America conducted a comprehensive review of the evidence for both skeletal and extraskeletal outcomes. The Committee concluded that available scientific evidence supports a key role of calcium and vitamin D in skeletal health, consistent with a cause-and-effect relationship and providing a sound basis for determination of intake requirements. For extraskeletal outcomes, including cancer, cardiovascular disease, diabetes, and autoimmune disorders, the evidence was inconsistent, inconclusive as to causality, and insufficient to inform nutritional requirements. Randomized clinical trial evidence for extraskeletal outcomes was limited and generally uninformative. Based on bone health, Recommended Dietary Allowances (RDAs; covering requirements of ≥97.5% of the population) for calcium range...

Differences Between Tight and Loose Cultures: A 33-Nation Study

Abstract: With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated multilevel system that comprises distal ecological and historical threats (e.g., high population density, resource scarcity, a history of territorial conflict, and disease and environmental threats), broad versus narrow socialization in societal institutions (e.g., autocracy, media regulations), the strength of everyday recurring situations, and micro-level psychological affordances (e.g., prevention self-guides, high regulatory strength, need for structure). This research advances knowledge that can foster cross-cultural understanding in a world of increasing global interdependence and has implications for modeling cultural change.

Assessment of flow-mediated dilation in humans: a methodological and physiological guideline

Abstract: Endothelial dysfunction is now considered an important early event in the development of atherosclerosis, which precedes gross morphological signs and clinical symptoms. The assessment of flow-mediated dilation (FMD) was introduced almost 20 years ago as a noninvasive approach to examine vasodilator function in vivo. FMD is widely believed to reflect endothelium-dependent and largely nitric oxide-mediated arterial function and has been used as a surrogate marker of vascular health. This noninvasive technique has been used to compare groups of subjects and to evaluate the impact of interventions within individuals. Despite its widespread adoption, there is considerable variability between studies with respect to the protocols applied, methods of analysis, and interpretation of results. Moreover, differences in methodological approaches have important impacts on the response magnitude, can result in spurious data interpretation, and limit the comparability of outcomes between studies. This review results from a collegial discussion between physiologists with the purpose of developing considered guidelines. The contributors represent several distinct research groups that have independently worked to advance the evidence base for improvement of the technical approaches to FMD measurement and analysis. The outcome is a series of recommendations on the basis of review and critical appraisal of recent physiological studies, pertaining to the most appropriate methods to assess FMD in humans.

Shrub expansion in tundra ecosystems: dynamics, impacts and research priorities

Abstract: Recent research using repeat photography, long-term ecological monitoring and dendrochronology has documented shrub expansion in arctic, high-latitude and alpine tundra

Social Entrepreneurship: A Critique and Future Directions

Abstract: Work on social entrepreneurship constitutes a field of study that intersects a number of domains, including entrepreneurial studies, social innovation, and nonprofit management. Scholars are beginning to contribute to the development of this new discipline through efforts that attempt to trace the emergence of social entrepreneurship as well as by comparing it to other organizational activities such as conventional entrepreneurship. However, as a nascent field, social entrepreneurship scholars are in the midst of a number of debates involving definitional and conceptual clarity, boundaries of the field, and a struggle to arrive at a set of relevant and meaningful research questions. This paper examines the promise of social entrepreneurship as a domain of inquiry and suggests a number of research areas and research questions for future study.

Principles of sensorimotor learning.

Abstract: The exploits of Martina Navratilova and Roger Federer represent the pinnacle of motor learning. However, when considering the range and complexity of the processes that are involved in motor learning, even the mere mortals among us exhibit abilities that are impressive. We exercise these abilities when taking up new activities — whether it is snowboarding or ballroom dancing — but also engage in substantial motor learning on a daily basis as we adapt to changes in our environment, manipulate new objects and refine existing skills. Here we review recent research in human motor learning with an emphasis on the computational mechanisms that are involved.

A review of solar photovoltaic levelized cost of electricity

Abstract: As the solar photovoltaic (PV) matures, the economic feasibility of PV projects are increasingly being evaluated using the levelized cost of electricity (LCOE) generation in order to be compared to other electricity generation technologies. Unfortunately, there is lack of clarity of reporting assumptions, justifications and degree of completeness in LCOE calculations, which produces widely varying and contradictory results. This paper reviews the methodology of properly calculating the LCOE for solar PV, correcting the misconceptions made in the assumptions found throughout the literature. Then a template is provided for better reporting of LCOE results for PV needed to influence policy mandates or make invest decisions. A numerical example is provided with variable ranges to test sensitivity, allowing for conclusions to be drawn on the most important variables. Grid parity is considered when the LCOE of solar PV is comparable with grid electrical prices of conventional technologies and is the industry target for cost-effectiveness. Given the state of the art in the technology and favorable financing terms it is clear that PV has already obtained grid parity in specific locations and as installed costs continue to decline, grid electricity prices continue to escalate, and industry experience increases, PV will become an increasingly economically advantageous source of electricity over expanding geographical regions.

The 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D From the Institute of Medicine: What Clinicians Need to Know

Abstract: This report summarizes the findings of the 2011 Institute of Medicine Committee on dietary intake requirements for calcium and vitamin D in North America, and provides updated data from the previous Institute of Medicine report of 1997. The Committee extensively reviewed existing published evidence on dietary and supplemental intake requirements for calcium and vitamin D with respect to both skeletal health and extraskeletal chronic disease outcomes. Calcium and vitamin D intake requirements were examined for several risk indictors of bone and skeletal health as well as extraskeletal outcomes (including cancer, cardiovascular disease, diabetes, and autoimmune disorders, infectious diseases, neuropsychological function, and disorders of pregnancy). Recommended Dietary Allowance (RDA) was defined as the level of intake of calcium or serum 25-hydroxyvitamin D that would meet the requirements of at least 97.5% of the population. The available scientific data supported an important role for calcium and vitamin D in bone and skeletal health outcomes that was consistent with a cause-and-effect relationship. However, data from randomized clinical trials for extraskeletal health outcomes were limited and inconclusive regarding a possible relationship with calcium and vitamin D intake requirements, and no evidence was found for dose-response or other established criteria for cause-and-effect. For bone health outcome, RDAs of calcium ranged from 700 to 1300 mg/d for life-stage groups at ≥1 year of age, and RDAs of vitamin D were 600 IU/d for ages 1 to 70 years and 800 IU/d for ages ≥71 (corresponding to a serum 25-hydroxyvitamin D level of at least 20 ng/mL [50 nmol/L]). There was an assumption of minimal or no sun exposure for estimation of RDA levels because of the wide variation in vitamin D synthesis from ultraviolet light and concern over risk of skin cancer. No consistent evidence was found that dietary or supplemental intake of vitamin D levels above the RDA provides additional benefit for bone health or extraskeletal outcomes; several investigators have found an U-shaped curve for several outcomes related to vitamin D intake, with increased risks at both low and high levels. The findings of this report suggest that prevalence of vitamin D deficiency in North America has been overestimated. The data show that almost all individuals in this population meet their RDA for vitamin D.

A Review of Solar Photovoltaic Levelized Cost of Electricity

Abstract: As the solar photovoltaic (PV) matures, the economic feasibility of PV projects are increasingly being evaluated using the levelized cost of electricity (LCOE) generation in order to be compared to other electricity generation technologies. Unfortunately, there is lack of clarity of reporting assumptions, justifications and degree of completeness in LCOE calculations, which produces widely varying and contradictory results. This paper reviews the methodology of properly calculating the LCOE for solar PV, correcting the misconceptions made in the assumptions found throughout the literature. Then a template is provided for better reporting of LCOE results for PV needed to influence policy mandates or make invest decisions. A numerical example is provided with variable ranges to test sensitivity, allowing for conclusions to be drawn on the most important variables. Grid parity is considered when the LCOE of solar PV is comparable with grid electrical prices of conventional technologies and is the industry target for cost-effectiveness. Given the state of the art in the technology and favorable financing terms it is clear that PV has already obtained grid parity in specific locations and as installed costs continue to decline, grid electricity prices continue to escalate, and industry experience increases, PV will become an increasingly economically advantageous source of electricity over expanding geographical regions.

Exploratory factor analysis.

Abstract: Chapter 1: Introductory Factor Analysis Concepts Chapter 2: Requirements for and Decisions in Choosing Exploratory Common Factor Analysis Chapter 3: Requirements and Decisions for Implementing Exploratory Common Factor Analysis Chapter 4: Factor Analysis Assumptions Chapter 5: Implementing and Interpreting Exploratory Factor Analysis Chapter 6: Summary, Conclusions, and Recommendations

The economic burden of obesity worldwide: a systematic review of the direct costs of obesity.

Abstract: In the last decade, the prevalence of obesity has increased significantly in populations worldwide. A less dramatic, but equally important increase has been seen in our knowledge of its effects on health and the burden it places on healthcare systems. This systematic review aims to assess the current published literature on the direct costs associated with obesity. A computerized search of English language articles published between 1990 and June 2009 yielded 32 articles suitable for review. Based on these articles, obesity was estimated to account for between 0.7% and 2.8% of a country's total healthcare expenditures. Furthermore, obese individuals were found to have medical costs that were approximately 30% greater than their normal weight peers. Although variations in inclusion/exclusion criteria, reporting methods and included costs varied widely between the studies, a lack of examination of how and why the excess costs were being accrued appeared to be a commonality between most studies. Accordingly, future studies must better explore how costs accrue among obese populations, in order to best facilitate health and social policy interventions.

Exemestane for Breast-Cancer Prevention in Postmenopausal Women

Abstract: Background Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer. Methods In a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured. Results A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P = 0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P = 0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P = 0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatmentrelated deaths. Minimal quality-of-life differences were observed. Conclusions Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life. (Funded by Pfizer and others; NCIC CTG MAP.3 ClinicalTrials.gov number, NCT00083174.)

Pseudomonas aeruginosa: resistance to the max.

Abstract: Pseudomonas aeruginosa is intrinsically resistant to a variety of antimicrobials and can develop resistance during anti-pseudomonal chemotherapy both of which compromise treatment of infections caused by this organism. Resistance to multiple classes of antimicrobials (multidrug resistance) in particular is increasingly common in P. aeruginosa, with a number of reports of pan-resistant isolates treatable with a single agent, colistin. Acquired resistance in this organism is multifactorial and attributable to chromosomal mutations and the acquisition of resistance genes via horizontal gene transfer. Mutational changes impacting resistance include upregulation of multidrug efflux systems to promote antimicrobial expulsion, derepression of ampC, AmpC alterations that expand the enzyme's substrate specificity (i.e., extended-spectrum AmpC), alterations to outer membrane permeability to limit antimicrobial entry and alterations to antimicrobial targets. Acquired mechanisms contributing to resistance in P. aeruginosa include β-lactamases, notably the extended-spectrum β-lactamases and the carbapenemases that hydrolyze most β-lactams, aminoglycoside-modifying enzymes, and 16S rRNA methylases that provide high-level pan-aminoglycoside resistance. The organism's propensity to grow in vivo as antimicrobial-tolerant biofilms and the occurrence of hypermutator strains that yield antimicrobial resistant mutants at higher frequency also compromise anti-pseudomonal chemotherapy. With limited therapeutic options and increasing resistance will the untreatable P. aeruginosa infection soon be upon us?

Long-term complications of critical care

Abstract: Objectives:As critical care advances and intensive care unit mortality declines, the number of survivors of critical illness is increasing. These survivors frequently experience long-lasting complications of critical care. As a result, it is important to understand these complications and implement

Lipoxygenase and leukotriene pathways: biochemistry, biology, and roles in disease.

Abstract: 4. Biosynthesis of Leukotrienes 5869 4.1. Discovery of the Leukotriene Pathway and a Common Unstable Intermediate 5869 4.2. Conversion of Arachidonic Acid into Leukotriene A4 (LTA4) Is a Two-Step Concerted Reaction Catalyzed by a Single Lipoxygenase 5869 4.3. Structural Elucidation of Slow-Reacting Substance of Anaphylaxis, A Mixture of Leukotrienes 5870 5. Enzymes and Proteins in Leukotriene Biosynthesis 5870 5.1. Cytosolic Phospholipase A2α (cPLA2α) 5870 5.1.1. Molecular Properties and Regulation of cPLA2α 5870 5.1.2. Crystal Structure and Catalytic Mechanism of cPLA2α 5871 5.2. 5-Lipoxygenase (5-LO) 5871 5.2.1. Cellular Expression of 5-LO 5871 5.2.2. Regulation of 5-LO Gene (ALOX5) Transcription 5872 5.2.3. Naturally Occurring Mutations in the Gene Promoter of 5-LO 5872 5.2.4. Allosteric and Post-translational Regulation of 5-LO 5872 5.2.5. Structure function relationships in 5-LO 5872 5.2.6. Crystal Structure of 5-LO 5872 5.3. 5-Lipoxygenase-Activating Protein (FLAP) 5873 5.3.1. FLAP Is Critical for Cellular 5-LO Activity 5873 5.3.2. Effects of FLAP on Leukotriene Production 5873 5.3.3. FLAP Gene (ALOX5AP) and Regulation of Expression 5874 5.3.4. Crystal Structure of FLAP 5874 5.4. LTA4 Hydrolase 5874 5.4.1. LTA4 Hydrolase Is a Substrate-Selective and Suicide-Inactivated Epoxide Hydrolase 5874 5.4.2. LTA4 Hydrolase Is Bifunctional and Belongs to the M1 Family of Zinc Metallopeptidases 5874 5.4.3. LTA4 Hydrolase Cleaves the Chemotactic Pro-Gly-Pro, a Role for the Aminopeptidase Activity during Resolution of Inflammation 5875 5.4.4. Crystal Structure of LTA4 Hydrolase 5875 5.4.5. Mechanism of the Epoxide Hydrolase Reaction 5876 5.4.6. Mechanism of the Aminopeptidase Activity 5876 5.4.7. Two Catalytic Activities Exerted via Specific but Overlapping Active Sites 5877 5.5. LTC4 Synthase 5877 5.5.1. Molecular Properties of LTC4 Synthase 5877 5.5.2. LTC4 Synthase Is a Member of the MAPEG Superfamily of IntegralMembraneProteins 5877 5.5.3. Gene Structure and Regulation of LTC4 Synthase Expression 5877 5.5.4. Crystal Structure of LTC4 Synthase 5877 5.5.5. Catalytic Mechanism of LTC4 Synthase 5878 6. Intracellular Protein Trafficking and Compartmentalization of Leukotriene Biosynthesis 5878 6.1. Translocation of cPLA2α 5878 6.2. Translocation of 5-LO and Association with FLAP on the Nuclear Envelope 5879 6.2.1. 5-LO in the Nucleoplasm 5879 6.2.2. Organization of a Leukotriene Biosynthetic Complex in the Nuclear Membrane 5879 6.3. Leukotriene Biosynthesis in Lipid Bodies and Actions on Extracellular Granules 5879

CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group.

Abstract: Summary Background The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma. Extended follow-up was needed to establish long-term effects. Methods In the randomised open-label MInT study, patients from 18 countries (aged 18–60 years with none or one risk factor according to the age-adjusted International Prognostic Index [IPI], stage II–IV disease or stage I disease with bulk) were randomly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab. Bulky and extranodal sites received additional radiotherapy. Randomisation was done centrally with a computer-based tool and was stratified by centre, bulky disease, age-adjusted IPI, and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component. Patients and investigators were not masked to treatment allocation. The primary endpoint was event-free survival. Analyses were by intention to treat. This observational study is a follow-up of the MInT trial, which was stopped in 2003, and is registered at ClinicalTrials.gov, number NCT00400907. Findings The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab. After a median follow-up of 72 months (range 0·03–119), 6-year event-free survival was 55·8% (95% CI 50·4–60·9; 166 events) for patients assigned to chemotherapy alone and 74·3% (69·3–78·6; 98 events) for those assigned to chemotherapy plus rituximab (difference between groups 18·5%, 11·5–25·4, log-rank p vs 71·0% [65·1–76·1], log-rank p=0·005). 18 (4·4%, 95% CI 2·6–6·9) second malignancies occurred in the chemotherapy-alone group and 16 (3·9%, 2·2–6·2) in the chemotherapy and rituximab group (Fisher's exact p=0·730). Interpretation Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma. The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone. Funding Hoffmann–La Roche.

Identifying critically ill patients who benefit the most from nutrition therapy: the development and initial validation of a novel risk assessment tool

Abstract: To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU). A prospective, observational study of patients expected to stay > 24 hours. We collected data for key variables considered for inclusion in the score which included: age, baseline APACHE II, baseline SOFA score, number of comorbidities, days from hospital admission to ICU admission, Body Mass Index (BMI) < 20, estimated % oral intake in the week prior, weight loss in the last 3 months and serum interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) levels. Approximate quintiles of each variable were assigned points based on the strength of their association with 28 day mortality. A total of 597 patients were enrolled in this study. Based on the statistical significance in the multivariable model, the final score used all candidate variables except BMI, CRP, PCT, estimated percentage oral intake and weight loss. As the score increased, so did mortality rate and duration of mechanical ventilation. Logistic regression demonstrated that nutritional adequacy modifies the association between the score and 28 day mortality (p = 0.01). This scoring algorithm may be helpful in identifying critically ill patients most likely to benefit from aggressive nutrition therapy.

Results from a Low-Energy Analysis of the CDMS II Germanium Data

Abstract: We report results from a reanalysis of data from the Cryogenic Dark Matter Search (CDMS II) experiment at the Soudan Underground Laboratory. Data taken between October 2006 and September 2008 using eight germanium detectors are reanalyzed with a lowered, 2 keV recoil-energy threshold, to give increased sensitivity to interactions from Weakly Interacting Massive Particles (WIMPs) with masses below {approx}10 GeV/c{sup 2}. This analysis provides stronger constraints than previous CDMS II results for WIMP masses below 9 GeV/c{sup 2} and excludes parameter space associated with possible low-mass WIMP signals from the DAMA/LIBRA and CoGeNT experiments.

On plantations, prisons, and a black sense of place

Abstract: The complexities of black geographies—shaped by histories of colonialism, transatlantic slavery, contemporary practices of racism, and resistances to white supremacy—shed light on how slave and post-slave struggles in the Americas form a unique sense of place. Rather than simply identifying black suffering and naming racism (and opposition to it) as the sole conceptual schemas through which to ‘understand’ or ‘know’ blackness or race, it is emphasized that a black sense of place, black histories, and communities are not only integral to production of space, but also that the analytical interconnectedness of race, practices of domination, and geography undoubtedly put pressure on how we presently study and assess racial violence.

Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis.

Abstract: Context Adjuvant chemotherapy (AC) improves survival among patients with resected colorectal cancer. However, the optimal timing from surgery to initiation of AC is unknown. Objective To determine the relationship between time to AC and survival outcomes via a systematic review and meta-analysis. Data Sources MEDLINE (1975 through January 2011), EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched to identify studies that described the relationship between time to AC and survival. Study Selection Studies were only included if the relevant prognostic factors were adequately described and either comparative groups were balanced or results adjusted for these prognostic factors. Data Extraction Hazard ratios (HRs) for overall survival and disease-free survival from each study were converted to a regression coefficient (β) and standard error corresponding to a continuous representation per 4 weeks of time to AC. The adjusted β from individual studies were combined using a fixed-effects model. Inverse variance (1/SE 2 ) was used to weight individual studies. Publication bias was investigated using the trim and fill approach. Results We identified 10 eligible studies involving 15 410 patients (7 published articles, 3 abstracts). Nine of the studies were cohort or population based and 1 was a secondary analysis from a randomized trial of chemotherapy. Six studies reported time to AC as a binary variable and 4 as 3 or more categories. Meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both overall survival (HR, 1.14; 95% confidence interval [CI], 1.10-1.17) and disease-free survival (HR, 1.14; 95% CI, 1.10-1.18). There was no significant heterogeneity among included studies. Results remained significant after adjustment for potential publication bias and when the analysis was repeated to exclude studies of largest weight. Conclusion In a meta-analysis of the available literature on time to AC, longer time to AC was associated with worse survival among patients with resected colorectal cancer.

Intrapleural use of tissue plasminogen activator and DNase in pleural infection

Abstract: A B S T R AC T Background More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial. Methods We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. Results The mean (±SD) change in pleural opacity was greater in the t-PA–DNase group than in the placebo group (−29.5±23.3% vs. −17.2±19.6%; difference, −7.9%; 95% confidence interval [CI], −13.4 to −2.4; P = 0.005); the change observed with t-PA alone and with DNase alone (−17.2±24.3 and −14.7±16.4%, respectively) was not significantly differ ent from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA–DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA–DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, −6.7 days; 95% CI, −12.0 to −1.9; P = 0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. Conclusions Intrapleural t-PA–DNase therapy improved fluid drainage in patients with pleural in fection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.)

Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis

Abstract: Critical illness polyneuropathy (CIP) and myopathy (CIM) are complications of critical illness that present with muscle weakness and failure to wean from the ventilator. In addition to prolonging mechanical ventilation and hospitalisation, CIP and CIM increase hospital mortality in patients who are critically ill and cause chronic disability in survivors of critical illness. Structural changes associated with CIP and CIM include axonal nerve degeneration, muscle myosin loss, and muscle necrosis. Functional changes can cause electrical inexcitability of nerves and muscles with reversible muscle weakness. Microvascular changes and cytopathic hypoxia might disrupt energy supply and use. An acquired sodium channelopathy causing reduced muscle membrane and nerve excitability is a possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy investigations. Control of hyperglycaemia might reduce the severity of these complications of critical illness, and early rehabilitation in the intensive care unit might improve the functional recovery and independence of patients.

Metabolic adaptations of phosphate-starved plants.

Abstract: Orthophosphate (Pi) is an essential macronutrient that plays a central role in virtually all major metabolic processes in plants, particularly photosynthesis and respiration. Many metabolites are Pi monoesters, whereas the phosphoanhydride bonds of compounds such as ATP function to transfer energy

Childhood attention-deficit/hyperactivity Disorder and Future Substance Use Disorders: Comparative Meta-Analyses

Abstract: Objective In recent years cohort studies have examined childhood attention-deficit/hyperactivity disorder (ADHD) as a risk factor for substance use disorders (SUDs) in adolescence and young adulthood. The long-term risk is estimated for development of alcohol, cannabis, combined alcohol and psychoactive SUDs, combined SUDs (nonalcohol), and nicotine use disorders in children with ADHD. Method MEDLINE, CINHAL, PsycINFO, and EMBASE were searched through October 2009; reference lists of included studies were hand-searched. Prospective cohort studies were included if they compared children with ADHD to children without, identified cases using standardized criteria by mean age of 12 years, followed participants until adolescence (nicotine use) or young adulthood (psychoactive substance use disorder, with and without alcohol, alcohol use disorder, cannabis use disorder), and reported SUD outcomes. Two independent reviewers examined articles and extracted and cross-checked data. Effects were summarized as pooled odds ratios (ORs) in a random effects model. Results Thirteen studies were included. Only two of five meta-analyses, for alcohol use disorder (N = 3,184) and for nicotine use (N = 2,067), estimated ORs showing stability when evaluated by sensitivity analyses. Childhood ADHD was associated with alcohol use disorder by young adulthood (OR = 1.35, 95% confidence interval=1.11-1.64) and with nicotine use by middle adolescence (OR = 2.36, 95% confidence interval=1.71-3.27). The association with drug use disorder, nonalcohol (N = 593), was highly influenced by a single study. Conclusions Childhood ADHD is associated with alcohol and drug use disorders in adulthood and with nicotine use in adolescence.