Showing papers by "McMaster University published in 2007"

Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults

Abstract: Lionel A. Mandell, Richard G. Wunderink, Antonio Anzueto, John G. Bartlett, G. Douglas Campbell, Nathan C. Dean, Scott F. Dowell, Thomas M. File, Jr. Daniel M. Musher, Michael S. Niederman, Antonio Torres, and Cynthia G. Whitney McMaster University Medical School, Hamilton, Ontario, Canada; Northwestern University Feinberg School of Medicine, Chicago, Illinois; University of Texas Health Science Center and South Texas Veterans Health Care System, San Antonio, and Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas; Johns Hopkins University School of Medicine, Baltimore, Maryland; Division of Pulmonary, Critical Care, and Sleep Medicine, University of Mississippi School of Medicine, Jackson; Division of Pulmonary and Critical Care Medicine, LDS Hospital, and University of Utah, Salt Lake City, Utah; Centers for Disease Control and Prevention, Atlanta, Georgia; Northeastern Ohio Universities College of Medicine, Rootstown, and Summa Health System, Akron, Ohio; State University of New York at Stony Brook, Stony Brook, and Department of Medicine, Winthrop University Hospital, Mineola, New York; and Cap de Servei de Pneumologia i Allergia Respiratoria, Institut Clinic del Torax, Hospital Clinic de Barcelona, Facultat de Medicina, Universitat de Barcelona, Institut d’Investigacions Biomediques August Pi i Sunyer, CIBER CB06/06/0028, Barcelona, Spain.

Optimal Medical Therapy with or without PCI for Stable Coronary Disease

Abstract: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6). Results There were 211 primary events in the PCI group and 202 events in the medicaltherapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P = 0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P = 0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P = 0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P = 0.33). Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657.)

Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma.

Abstract: Background Interferon alfa is widely used for metastatic renal-cell carcinoma but has limited efficacy and tolerability. Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, may benefit patients with this disease. Methods In this multicenter, phase 3 trial, we randomly assigned 626 patients with previously untreated, poor-prognosis metastatic renal-cell carcinoma to receive 25 mg of intravenous temsirolimus weekly, 3 million U of interferon alfa (with an increase to 18 million U) subcutaneously three times weekly, or combination therapy with 15 mg of temsirolimus weekly plus 6 million U of interferon alfa three times weekly. The primary end point was overall survival in comparisons of the temsirolimus group and the combination-therapy group with the interferon group. Results Patients who received temsirolimus alone had longer overall survival (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.58 to 0.92; P=0.008) and progression-free survival (P<0.001) than did patie...

Evolution of genes and genomes on the Drosophila phylogeny.

Abstract: Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

ImageJ for microscopy

Abstract: of short add-on programs to provide additional functionality to the core program. These additional files are either written in Java (the plugins) or in ImageJ’s macro programming language (macros). Once saved to the ImageJ plugins folder, these functions are loaded on start-up and can be accessed via menu commands like any other core function. 400+ PLUGINS

International estimates of infertility prevalence and treatment-seeking: potential need and demand for infertility medical care

Abstract: INTRODUCTION The purpose of the present study was to review existing population surveys on the prevalence of infertility and proportion of couples seeking medical help for fertility problems. METHODS Population surveys, reporting the prevalence of infertility and proportion of couples seeking help in more and less developed countries, were reviewed. RESULTS Estimates on the prevalence of infertility came from 25 population surveys sampling 172 413 women. The 12-month prevalence rate ranged from 3.5% to 16.7% in more developed nations and from 6.9% to 9.3% in less-developed nations, with an estimated overall median prevalence of 9%. In 17 studies sampling 6410 women, the proportion of couples seeking medial care was, on average, 56.1% (range 42–76.3%) in more developed countries and 51.2% (range 27–74.1%) in less developed countries. The proportion of people actually receiving care was substantially less, 22.4%. Based on these estimates and on the current world population, 72.4 million women are currently infertile; of these, 40.5 million are currently seeking infertility medical care. CONCLUSIONS The current evidence indicates a 9% prevalence of infertility (of 12 months) with 56% of couples seeking medical care. These estimates are lower than those typically cited and are remarkably similar between more and less developed countries.

Mapping autism risk loci using genetic linkage and chromosomal rearrangements

Abstract: Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,181 [corrected] families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.

Outage Capacity Optimization for Free-Space Optical Links With Pointing Errors

Abstract: We investigate the performance and design of free-space optical (FSO) communication links over slow fading channels from an information theory perspective. A statistical model for the optical intensity fluctuation at the receiver due to the combined effects of atmospheric turbulence and pointing errors is derived. Unlike earlier work, our model considers the effect of beam width, detector size, and jitter variance explicitly. Expressions for the outage probability are derived for a variety of atmospheric conditions. For given weather and misalignment conditions, the beam width is optimized to maximize the channel capacity subject to outage. Large gains in achievable rate are realized versus using a nominal beam width. In light fog, by optimizing the beam width, the achievable rate is increased by 80% over the nominal beam width at an outage probability of 10-5. Well-known error control codes are then applied to the channel and shown to realize much of the achievable gains.

The antibiotic resistome: the nexus of chemical and genetic diversity

Abstract: Resistance to antibiotics in microorganisms predates the use of these drugs. This Review examines why antibiotic resistance is inevitable and where it originates from.

Educational outreach visits: effects on professional practice and health care outcomes

Abstract: Background Educational outreach visits (EOVs) have been identified as an intervention that may improve the practice of healthcare professionals. This type of face-to-face visit has been referred to as university-based educational detailing, academic detailing, and educational visiting. Objectives To assess the effects of EOVs on health professional practice or patient outcomes. Search methods For this update, we searched the Cochrane EPOC register to March 2007. In the original review, we searched multiple bibliographic databases including MEDLINE and CINAHL. Selection criteria Randomised trials of EOVs that reported an objective measure of professional performance or healthcare outcomes. An EOV was defined as a personal visit by a trained person to healthcare professionals in their own settings. Data collection and analysis Two reviewers independently extracted data and assessed study quality. We used bubble plots and box plots to visually inspect the data. We conducted both quantitative and qualitative analyses. We used meta-regression to examine potential sources of heterogeneity determined a priori. We hypothesised eight factors to explain variation across effect estimates. In our primary visual and statistical analyses, we included only studies with dichotomous outcomes, with baseline data and with low or moderate risk of bias, in which the intervention included an EOV and was compared to no intervention. Main results We included 69 studies involving more than 15,000 health professionals. Twenty-eight studies (34 comparisons) contributed to the calculation of the median and interquartile range for the main comparison. The median adjusted risk difference (RD) in compliance with desired practice was 5.6% (interquartile range 3.0% to 9.0%). The adjusted RDs were highly consistent for prescribing (median 4.8%, interquartile range 3.0% to 6.5% for 17 comparisons), but varied for other types of professional performance (median 6.0%, interquartile range 3.6% to 16.0% for 17 comparisons). Meta-regression was limited by the large number of potential explanatory factors (eight) with only 31 comparisons, and did not provide any compelling explanations for the observed variation in adjusted RDs. There were 18 comparisons with continuous outcomes, with a median adjusted relative improvement of 21% (interquartile range 11% to 41%). There were eight trials (12 comparisons) in which the intervention included an EOV and was compared to another type of intervention, usually audit and feedback. Interventions that included EOVs appeared to be slightly superior to audit and feedback. Only six studies evaluated different types of visits in head-to-head comparisons. When individual visits were compared to group visits (three trials), the results were mixed. Authors' conclusions EOVs alone or when combined with other interventions have effects on prescribing that are relatively consistent and small, but potentially important. Their effects on other types of professional performance vary from small to modest improvements, and it is not possible from this review to explain that variation.

Lipid a modification systems in gram-negative bacteria

Abstract: The lipid A moiety of lipopolysaccharide forms the outer monolayer of the outer membrane of most gram-negative bacteria. Escherichia coli lipid A is synthesized on the cytoplasmic surface of the inner membrane by a conserved pathway of nine constitutive enzymes. Following attachment of the core oligosaccharide, nascent core-lipid A is flipped to the outer surface of the inner membrane by the ABC transporter MsbA, where the O-antigen polymer is attached. Diverse covalent modifications of the lipid A moiety may occur during its transit from the outer surface of the inner membrane to the outer membrane. Lipid A modification enzymes are reporters for lipopolysaccharide trafficking within the bacterial envelope. Modification systems are variable and often regulated by environmental conditions. Although not required for growth, the modification enzymes modulate virulence of some gram-negative pathogens. Heterologous expression of lipid A modification enzymes may enable the development of new vaccines.

Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17.

Abstract: The C-type lectin dectin-1 binds to yeast and signals through the kinase Syk and the adaptor CARD9 to induce production of interleukin 10 (IL-10) and IL-2 in dendritic cells (DCs). However, whether this pathway promotes full DC activation remains unclear. Here we show that dectin-1-Syk-CARD9 signaling induced DC maturation and the secretion of proinflammatory cytokines, including IL-6, tumor necrosis factor and IL-23, but little IL-12. Dectin-1-activated DCs 'instructed' the differentiation of CD4+ IL-17-producing effector T cells (T(H)-17 cells) in vitro, and a dectin-1 agonist acted as an adjuvant promoting the differentiation of T(H)-17 and T helper type 1 cells in vivo. Infection with Candida albicans induced CARD9-dependent T(H)-17 responses to the organism. Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of T(H)-17 responses to some pathogens.

Primary Prevention of Cardiovascular Diseases in People With Diabetes Mellitus A scientific statement from the American Heart Association and the American Diabetes Association

Abstract: The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: the ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and ADA recommendations differ.

Laparoscopic colectomy for cancer is not inferior to open surgery based on 5-year data from the COST Study Group trial.

Abstract: Purpose: Oncologic concerns from high wound recurrence rates prompted a multi-institutional randomized trial to test the hypothesis that disease-free and overall survival are equivalent, regardless of whether patients receive laparoscopic-assisted or open colectomy. Methods: Eight hundred seventy-two patients with curable colon cancer were randomly assigned to undergo laparoscopic-assisted or open colectomy at 1 of 48 institutions by 1 of 66 credentialed surgeons. Patients were followed for 8 years, with 5-year data on 90% of patients. The primary end point was time to recurrence, tested using a noninferiority trial design. Secondary endpoints included overall survival and disease-free survival. (Kaplan-Meier) Results: As of March 1, 2007, 170 patients have recurred and 252 have died. Patients have been followed a median of 7 years (range 5-10 years). Disease-free 5-year survival (Open 68.4%, Laparoscopic 69.2%, P = 0.94) and overall 5-year survival (Open 74.6%, Laparoscopic 76.4%, P = 0.93) are similar for the 2 groups. Overall recurrence rates were similar for the 2 groups (Open 21.8%, Laparoscopic 19.4%, P = 0.25). These recurrences were distributed similarly between the 2 treatment groups. Sites of first recurrence were distributed similarly between the treatment arms (Open: wound 0.5%, liver 5.8%, lung 4.6%, other 8.4%; Laparoscopic: wound 0.9%, liver 5.5%, lung 4.6%, other 6.1%). Conclusion: Laparoscopic colectomy for curable colon cancer is not inferior to open surgery based on long-term oncologic endpoints from a prospective randomized trial.

Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies

Abstract: Aims The objectives of this study were to determine the association of waist circumference (WC) and waist-to-hip ratio (WHR) with the risk of incident cardiovascular disease (CVD) events and to determine whether the strength of association of WC and WHR with CVD risk is different. Methods and results This meta-regression analysis used a search strategy of keywords and MeSH terms to identify prospective cohort studies and randomized clinical trials of CVD risk and abdominal obesity from the Medline, Embase, and Cochrane databases. Fifteen articles ( n = 258 114 participants, 4355 CVD events) reporting CVD risk by categorical and continuous measures of WC and WHR were included. For a 1 cm increase in WC, the relative risk (RR) of a CVD event increased by 2% (95% CI: 1–3%) overall after adjusting for age, cohort year, or treatment. For a 0.01 U increase in WHR, the RR increased by 5% (95% CI: 4–7%). These results were consistent in men and women. Overall risk estimates comparing the extreme quantiles of each measure suggested that WHR was more strongly associated with CVD than that for WC (WHR: RR = 1.95, 95% CI: 1.55–2.44; WC: RR = 1.63, 95% CI: 1.31–2.04), although this difference was not significant. The strength of association for each measure was similar in men and women. Conclusion WHR and WC are significantly associated with the risk of incident CVD events. These simple measures of abdominal obesity should be incorporated into CVD risk assessments.

Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota

Abstract: Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.

Magneto-optical conductivity in graphene

Abstract: Landau level quantization in graphene reflects the Dirac nature of its quasiparticles and has been found to exhibit an unusual integer quantum Hall effect. In particular, the lowest Landau level can be thought of as shared equally by electrons and holes, and this leads to characteristic behaviour of the magneto-optical conductivity as a function of frequency Ω for various values of the chemical potential μ. Particular attention is paid to the optical spectral weight under various absorption peaks and its redistribution as μ is varied. We also provide results for magnetic field B as well as chemical potential sweeps at selected fixed frequencies, which can be particularly useful for possible measurements in graphene. Both diagonal and Hall conductivities are considered.

Remembering the past and imagining the future: a neural model of spatial memory and imagery

Abstract: The authors model the neural mechanisms underlying spatial cognition, integrating neuronal systems and behavioral data, and address the relationships between long-term memory, short-term memory, and imagery, and between egocentric and allocentric and visual and ideothetic representations. Long-term spatial memory is modeled as attractor dynamics within medial-temporal allocentric representations, and short-term memory is modeled as egocentric parietal representations driven by perception, retrieval, and imagery and modulated by directed attention. Both encoding and retrieval/imagery require translation between egocentric and allocentric representations, which are mediated by posterior parietal and retrosplenial areas and the use of head direction representations in Papez's circuit. Thus, the hippocampus effectively indexes information by real or imagined location, whereas Papez's circuit translates to imagery or from perception according to the direction of view. Modulation of this translation by motor efference allows spatial updating of representations, whereas prefrontal simulated motor efference allows mental exploration. The alternating temporal-parietal flows of information are organized by the theta rhythm. Simulations demonstrate the retrieval and updating of familiar spatial scenes, hemispatial neglect in memory, and the effects on hippocampal place cell firing of lesioned head direction representations and of conflicting visual and ideothetic inputs.

Risk Factors for Early Myocardial Infarction in South Asians Compared With Individuals in Other Countries

Abstract: ContextSouth Asians have high rates of acute myocardial infarction (AMI) at younger ages compared with individuals from other countries but the reasons for this are unclear.ObjectiveTo evaluate the association of risk factors for AMI in native South Asians, especially at younger ages, compared with individuals from other countries.Design, Setting, and ParticipantsStandardized case-control study of 1732 cases with first AMI and 2204 controls matched by age and sex from 15 medical centers in 5 South Asian countries and 10 728 cases and 12 431 controls from other countries. Individuals were recruited to the study between February 1999 and March 2003.Main Outcome MeasureAssociation of risk factors for AMI.ResultsThe mean (SD) age for first AMI was lower in South Asian countries (53.0 [11.4] years) than in other countries (58.8 [12.2] years; P<.001). Protective factors were lower in South Asian controls than in controls from other countries (moderate- or high-intensity exercise, 6.1% vs 21.6%; daily intake of fruits and vegetables, 26.5% vs 45.2%; alcohol consumption ≥once/wk, 10.7% vs 26.9%). However, some harmful factors were more common in native South Asians than in individuals from other countries (elevated apolipoprotein B100 /apolipoprotein A-I ratio, 43.8% vs 31.8%; history of diabetes, 9.5% vs 7.2%). Similar relative associations were found in South Asians compared with individuals from other countries for the risk factors of current and former smoking, apolipoprotein B100 /apolipoprotein A-I ratio for the top vs lowest tertile, waist-to-hip ratio for the top vs lowest tertile, history of hypertension, history of diabetes, psychosocial factors such as depression and stress at work or home, regular moderate- or high-intensity exercise, and daily intake of fruits and vegetables. Alcohol consumption was not found to be a risk factor for AMI in South Asians. The combined odds ratio for all 9 risk factors was similar in South Asians (123.3; 95% confidence interval [CI], 38.7-400.2] and in individuals from other countries (125.7; 95% CI, 88.5-178.4). The similarities in the odds ratios for the risk factors explained a high and similar degree of population attributable risk in both groups (85.8% [95% CI, 78.0%-93.7%] vs 88.2% [95% CI, 86.3%-89.9%], respectively). When stratified by age, South Asians had more risk factors at ages younger than 60 years. After adjusting for all 9 risk factors, the predictive probability of classifying an AMI case as being younger than 40 years was similar in individuals from South Asian countries and those from other countries.ConclusionThe earlier age of AMI in South Asians can be largely explained by higher risk factor levels at younger ages.

Individual-Level Cultural Values as Moderators of Perceived Organizational Support–Employee Outcome Relationships in China: Comparing the Effects of Power Distance and Traditionality

Abstract: Drawing on a cross-organizational sample of 163 supervisor-subordinate dyads from mainland China, we examined the moderating effect of power distance and Chinese traditionality on relationships bet...

Human Health Risk Assessment for Aluminium, Aluminium Oxide, and Aluminium Hydroxide

Abstract: Note: This article was originally published with an incorrect version of the Acknowledgments, which appeared on p. 218 of the print version. The correct version of the Acknowledgments appeared on pp. 1–2. The corrected article is available below.

Long-Term Effects of Caffeine Therapy for Apnea of Prematurity

Abstract: Of the 937 infants assigned to caffeine for whom adequate data on the primary outcome were available, 377 (40.2%) died or survived with a neurodevelopmental disability, as compared with 431 of the 932 infants (46.2%) assigned to placebo for whom adequate data on the primary outcome were available (odds ratio adjusted for center, 0.77; 95% confidence interval [CI], 0.64 to 0.93; P = 0.008). Treatment with caffeine as compared with placebo reduced the incidence of cerebral palsy (4.4% vs. 7.3%; adjusted odds ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009) and of cognitive delay (33.8% vs. 38.3%; adjusted odds ratio, 0.81; 95% CI, 0.66 to 0.99; P = 0.04). The rates of death, deafness, and blindness and the mean percentiles for height, weight, and head circumference at follow-up did not differ significantly between the two groups. Conclusions Caffeine therapy for apnea of prematurity improves the rate of survival without neurodevelopmental disability at 18 to 21 months in infants with very low birth weight. (ClinicalTrials.gov number, NCT00182312.)

Manipulating perceived social presence through the web interface and its impact on attitude towards online shopping

Abstract: Electronic commerce typically lacks human warmth and sociability, since it is more impersonal, anonymous and automated than traditional face-to-face commerce. This paper explores how human warmth and sociability can be integrated through the web interface to positively impact consumer attitudes towards online shopping. An empirical study was undertaken to investigate the impact of various levels of socially rich text and picture design elements on the perception of online social presence and its subsequent effect on antecedents of attitudes towards websites. Higher levels of perceived social presence are shown to positively impact the perceived usefulness, trust and enjoyment of shopping websites, leading to more favourable consumer attitudes. Implications of these finding for practitioners and future research are outlined.

Anidulafungin versus Fluconazole for Invasive Candidiasis

Abstract: Eighty-nine percent of the 245 patients in the primary analysis had candidemia only. Candida albicans was isolated in 62% of the 245 patients. In vitro fluconazole resistance was infrequent. Most of the patients (97%) did not have neutropenia. At the end of intravenous therapy, treatment was successful in 75.6% of patients treated with anidulafungin, as compared with 60.2% of those treated with fluconazole (difference, 15.4 percentage points; 95% confidence interval [CI], 3.9 to 27.0). The results were similar for other efficacy end points. The statistical analyses failed to show a “center effect”; when data from the site enrolling the largest number of patients were removed, success rates at the end of intravenous therapy were 73.2% in the anidulafungin group and 61.1% in the fluconazole group (difference, 12.1 percentage points; 95% CI, −1.1 to 25.3). The frequency and types of adverse events were similar in the two groups. The rate of death from all causes was 31% in the fluconazole group and 23% in the anidulafungin group (P = 0.13). CONCLUSIONS Anidulafungin was shown to be noninferior to fluconazole in the treatment of invasive candidiasis. (ClinicalTrials.gov number, NCT00056368).

Evaluation and treatment of chagas disease in the United States : A systematic review

Abstract: ContextBecause of population migration from endemic areas and newly instituted blood bank screening, US clinicians are likely to see an increasing number of patients with suspected or confirmed chronic Trypanosoma cruzi infection (Chagas disease).ObjectiveTo examine the evidence base and provide practical recommendations for evaluation, counseling, and etiologic treatment of patients with chronic T cruzi infection.Evidence AcquisitionLiterature review conducted based on a systematic MEDLINE search for all available years through 2007; review of additional articles, reports, and book chapters; and input from experts in the field.Evidence SynthesisThe patient newly diagnosed with Chagas disease should undergo a medical history, physical examination, and resting 12-lead electrocardiogram (ECG) with a 30-second lead II rhythm strip. If this evaluation is normal, no further testing is indicated; history, physical examination, and ECG should be repeated annually. If findings suggest Chagas heart disease, a comprehensive cardiac evaluation, including 24-hour ambulatory ECG monitoring, echocardiography, and exercise testing, is recommended. If gastrointestinal tract symptoms are present, barium contrast studies should be performed. Antitrypanosomal treatment is recommended for all cases of acute and congenital Chagas disease, reactivated infection, and chronic T cruzi infection in individuals 18 years or younger. In adults aged 19 to 50 years without advanced heart disease, etiologic treatment may slow development and progression of cardiomyopathy and should generally be offered; treatment is considered optional for those older than 50 years. Individualized treatment decisions for adults should balance the potential benefit, prolonged course, and frequent adverse effects of the drugs. Strong consideration should be given to treatment of previously untreated patients with human immunodeficiency virus infection or those expecting to undergo organ transplantation.ConclusionsChagas disease presents an increasing challenge for clinicians in the United States. Despite gaps in the evidence base, current knowledge is sufficient to make practical recommendations to guide appropriate evaluation, management, and etiologic treatment of Chagas disease.

Forming disc galaxies in ΛCDM simulations

Abstract: We used fully cosmological, high-resolution N-body + smooth particle hydrodynamic (SPH) simulations to follow the formation of disc galaxies with rotational velocities between 135 and 270km s -1 in a A cold dark matter (CDM) universe. The simulations include gas cooling, star formation, the effects of a uniform ultraviolet (UV) background and a physically motivated description of feedback from supernovae (SNe). The host dark matter haloes have a spin and last major merger redshift typical of galaxy-sized haloes as measured in recent large-scale N-body simulations. The simulated galaxies form rotationally supported discs with realistic exponential scalelengths and fall on both the / band and baryonic Tully-Fisher relations. An extended stellar disc forms inside the Milky Way (MW)-sized halo immediately after the last major merger. The combination of UV background and SN feedback drastically reduces the number of visible satellites orbiting inside a MW-sized halo, bringing it in fair agreement with observations. Our simulations predict that the average age of a primary galaxy's stellar population decreases with mass, because feedback delays star formation in less massive galaxies. Galaxies have stellar masses and current star formation rates as a function of total mass that are in good agreement with observational data. We discuss how both high mass and force resolution and a realistic description of star formation and feedback are important ingredients to match the observed properties of galaxies.