Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein

N-linked glycosylation of proteins in eukaryotic cells follows a highly conserved pathway. The tetradecasaccharide substrate (Glc3Man9GlcNAc2) is first assembled at the membrane of the endoplasmic reticulum (ER) as a dolichylpyrophosphate (Dol-PP)-linked intermediate, and then transferred to nascent polypeptide chains in the lumen of the ER. The assembly of the oligosaccharide starts on the cytoplasmic side of the ER membrane with the synthesis of a Man5GlcNAc2-PP-Dol intermediate. This lipid-linked intermediate is then translocated across the membrane so that the oligosaccharides face the lumen of the ER, where the biosynthesis of Glc3Man9GlcNAc2-PP-Dol continues to completion. The fully assembled oligosaccharide is transferred to selected asparagine residues of target proteins. The transmembrane movement of lipid-linked Man5GlcNAc2 oligosaccharide is of fundamental importance in this biosynthetic pathway, and similar processes involving phospholipids and glycolipids are essential in all types of cells. The process is predicted to be catalysed by proteins, termed flippases, which to date have remained elusive. Here we provide evidence that yeast RFT1 encodes an evolutionarily conserved protein required for the translocation of Man5GlcNAc2-PP-Dol from the cytoplasmic to the lumenal leaflet of the ER membrane.

Effect of a multifaceted intervention on adherence to hand hygiene among healthcare workers:A cluster-randomized trial

OBJECTIVES. Adherence to hand hygiene among healthcare workers (HCWs) is widely believed to be a key factor in reducing the spread of healthcare-associated infection. The objective of this study was to evaluate the impact of a multifaceted intervention to increase rates of adherence to hand hygiene among HCWs and to assess the effect on the incidence of hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) colonization. DESIGN. Cluster-randomized controlled trial. SETTING. Thirty hospital units in 3 tertiary care hospitals in Hamilton, Ontario, Canada. INTERVENTION. After a 3-month baseline period of data collection, 15 units were randomly assigned to the intervention arm (with performance feedback, small-group teaching seminars, and posters) and 15 units to usual practice. Hand hygiene was observed during randomly selected 15-minute periods on each unit, and the incidence of MRSA colonization was measured using weekly surveillance specimens from June 2007 through May 2008. RESULTS. We found that 3,812 (48.2%) of 7,901 opportunities for hand hygiene in the intervention group resulted in adherence, compared with 3,205 (42.6%) of 7,526 opportunities in the control group (P <.001; independent t test). There was no reduction in the incidence of hospital-acquired MRSA colonization in the intervention group. CONCLUSION. Among HCWs in Ontario tertiary care hospitals, the rate of adherence to hand hygiene had a statistically significant increase of 6% with a multifaceted intervention, but the incidence of MRSA colonization was not reduced.

Complex pattern of genetic structuring in the Atlantic salmon (Salmo salar L.) of the River Foyle system in northwest Ireland: disentangling the evolutionary signal from population stochasticity

Little is known about the microevolutionary processes shaping within river population genetic structure of aquatic organisms characterized by high levels of homing and spawning site fidelity. Using a microsatellite panel, we observed complex and highly significant levels of intrariver population genetic substructure and Isolation-by-Distance, in the Atlantic salmon stock of a large river system. Two evolutionary models have been considered explaining mechanisms promoting genetic substructuring in Atlantic salmon, the member-vagrant and metapopulation models. We show that both models can be simultaneously used to explain patterns and levels of population structuring within the Foyle system. We show that anthropogenic factors have had a large influence on contemporary population structure observed. In an analytical development, we found that the frequently used estimator of genetic differentiation, F-ST, routinely underestimated genetic differentiation by a factor three to four compared to the equivalent statistic Jost's D-est (Jost 2008). These statistics also showed a near-perfect correlation. Despite ongoing discussions regarding the usefulness of "adjusted" F-ST statistics, we argue that these could be useful to identify and quantify qualitative differences between populations, which are important from management and conservation perspectives as an indicator of existence of biologically significant variation among tributary populations or a warning of critical environmental damage.

Pneumonia and lower respiratory infections in nursing home residents:Predictors of hospitalization and mortality

OBJECTIVES: To compare predictors of hospitalization and death in nursing home residents with pneumonia and other lower respiratory infections (LRIs). DESIGN: A nested cohort study. SETTING: Nine nursing homes in southern Ontario. PARTICIPANTS: Three hundred fifty-three nursing home residents with LRIs (enrolled in the control arm of a clinical trial). MEASUREMENTS: Comorbidities, vaccination status, age, health-related quality of life, functional status, and vital statistics were evaluated as potential predictors of hospitalization and mortality at 30 days. RESULTS: Moderate to high disease severity score on a practical severity scale was a strong independent predictor of hospitalization (odds ratio (OR)=7.12, P

Optimizing antibiotics in residents of nursing homes:protocol of a randomized trial.

BACKGROUND: Antibiotics are frequently prescribed for older adults who reside in long-term care facilities. A substantial proportion of antibiotic use in this setting is inappropriate. Antibiotics are often prescribed for asymptomatic bacteriuria, a condition for which randomized trials of antibiotic therapy indicate no benefit and in fact harm. This proposal describes a randomized trial of diagnostic and therapeutic algorithms to reduce the use of antibiotics in residents of long-term care facilities. METHODS: In this on-going study, 22 nursing homes have been randomized to either use of algorithms (11 nursing homes) or to usual practise (11 nursing homes). The algorithms describe signs and symptoms for which it would be appropriate to send urine cultures or to prescribe antibiotics. The algorithms are introduced by inservicing nursing staff and by conducting one-on-one sessions for physicians using case-scenarios. The primary outcome of the study is courses of antibiotics per 1000 resident days. Secondary outcomes include urine cultures sent and antibiotic courses for urinary indications. Focus groups and semi-structured interviews with key informants will be used to assess the process of implementation and to identify key factors for sustainability.

Effect of a clinical pathway to reduce hospitalizations in nursing home residents with pneumonia:A randomized controlled trial

Context: Nursing home residents with pneumonia are frequently hospitalized. Such transfers may be associated with multiple hazards of hospitalization as well as economic costs. Objective: To assess whether using a clinical pathway for on-site treatment of pneumonia and other lower respiratory tract infections in nursing homes could reduce hospital admissions, related complications, and costs. Design, Setting, and Participants: A cluster randomized controlled trial of 680 residents aged 65 years or older in 22 nursing homes in Hamilton, Ontario, Canada. Nursing homes began enrollment between January 2, 2001, and April 18, 2002, with the last resident follow-up occurring July 4, 2005. Residents were eligible if they met a standardized definition of lower respiratory tract infection. Interventions: Treatment in nursing homes according to a clinical pathway, which included use of oral antimicrobials, portable chest radiographs, oxygen saturation monitoring, rehydration, and close monitoring by a research nurse, or usual care. Main Outcome Measures: Hospital admissions, length of hospital stay, mortality, health-related quality of life, functional status, and cost. Results: Thirty-four (10%) of 327 residents in the clinical pathway group were hospitalized compared with 76 (22%) of 353 residents in the usual care group. Adjusting for clustering of residents in nursing homes, the weighted mean reduction in hospitalizations was 12% (95% confidence interval [CI], 5%-18%; P=.001). The mean number of hospital days per resident was 0.79 in the clinical pathway group vs 1.74 in the usual care group, with a weighted mean difference of 0.95 days per resident (95% CI, 0.34-1.55 days; P=.004). The mortality rate was 8% (24 deaths) in the clinical pathway group vs 9% (32 deaths) in the usual care group, with a weighted mean difference of 2.9% (95% CI, -2.0% to 7.9%; P=.23). There were no significant differences between the groups in health-related quality of life or functional status. The clinical pathway resulted in an overall cost savings of US $1016 per resident (95% CI, $207-$1824) treated. Conclusion: Treating residents of nursing homes with pneumonia and other lower respiratory tract infections with a clinical pathway can result in comparable clinical outcomes, while reducing hospitalizations and health care costs. ©2006 American Medical Association. All rights reserved.

Interobserver Reliability of Radiologists' Interpretations of Mobile Chest Radiographs for Nursing Home-Acquired Pneumonia

Objectives: To determine the interobserver reliability of radiologists' interpretations of mobile chest radiographs for nursing home-acquired pneumonia. Design: A cross-sectional reliability study. Setting: Nursing homes and an acute care hospital. Participants: Four radiologists reviewed 40 mobile chest radiographs obtained from residents of nursing homes who met a clinical definition of lower respiratory tract infections. Measurements: Radiologists were asked to interpret radiographs with respect to the film quality; presence, pattern, and extent of an infiltrate; and the presence of a pleural effusion or adenopathy. Interrater reliability was evaluated using the intraclass correlation coefficient derived from a 2-way random effects model. Results: On average the radiologists reported that 6 of the 40 films were of very good or excellent quality and 16 of the 40 were of fair or poor quality. When the finding of an infiltrate was dichotomized (0 = no; 1 = possible, probable, or definite) all 4 radiologists agreed on 21 of the 37 chest radiographs. The intraclass correlation coefficient for the presence or absence of infiltrates was 0.54 (95% confidence intervals [CI] 0.38 to 0.69). For the 14 radiographs where infiltrates were observed by all radiologists, intraclass correlation coefficients for the presence of pleural effusions was 0.08 (95% CI -0.10 to 0.41), hilar adenopathy 0.54 (95% CI 0.29 to 0.79), and mediastinal adenopathy 0.49 (95% CI 0.21 to 0.76). Conclusion: In conclusion, the interrater agreement among radiologists for mobile chest radiographs in establishing the presence or absence of an infiltrate can be judged to be "fair." Treatment decisions need to include clinical findings and should not be made based on radiographic findings alone. © 2006 American Medical Directors Association.

Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes:Cluster randomised controlled trial

Objective: To assess whether a multifaceted intervention can reduce the number of prescriptions for antimicrobials for suspected urinary tract infections in residents of nursing homes. Design: Cluster randomised controlled trial. Setting: 24 nursing homes in Ontario, Canada, and Idaho, United States. Participants: 12 nursing homes allocated to a multifaceted intervention and 12 allocated to usual care. Outcomes were measured in 4217 residents. Interventions: Diagnostic and treatment algorithm for urinary tract infections implemented at the nursing home level using a multifaceted approach-small group interactive sessions for nurses, videotapes, written material, outreach visits, and one on one interviews with physicians. Main outcome measures: Number of antimicrobials prescribed for suspected urinary tract infections, total use of antimicrobials, admissions to hospital, and deaths. Results: Fewer courses of antimicrobials for suspected urinary tract infections per 1000 resident days were prescribed in the intervention nursing homes than in the usual care homes (1.17 v 1.59 courses; weighted mean difference -0.49, 95% confidence intervals -0.93 to -0.06). Antimicrobials for suspected urinary tract infection represented 28.4% of all courses of drugs prescribed in the intervention nursing homes compared with 38.6% prescribed in the usual care homes (weighted mean difference -9.6%, -16.9% to -2.4%). The difference in total antimicrobial use per 1000 resident days between intervention and usual care groups was not significantly different (3.52 v 3.93; weighed mean difference -0.37, -1.17 to 0.44). No significant difference was found in admissions to hospital or mortality between the study arms. Conclusion: A multifaceted intervention using algorithms can reduce the number of antimicrobial prescriptions for suspected urinary tract infections in residents of nursing homes.

Platinum catalysed hydrosilylation of propargylic alcohols

A facile and user-friendly protocol has been developed for the selective synthesis of E-vinyl silanes derived from propargylic alcohols using a PtCl2/XPhos catalyst system. The reaction is generally high yielding and provides a single regioisomer at the ß-position with E-alkene geometry. The reaction is extremely tolerant of functionality and has a wide scope of reactivity both in terms of alkynes and silanes used. The catalyst loading has been investigated and it is found that good reactivity is observed at extremely low catalyst loadings. This methodology has also been extended to a one-pot hydrosilylation Denmark–Hiyama coupling.

Localized Flux Maxima of Arsenic, Lead, and Iron around Root Apices in Flooded Lowland Rice

In wetland-adapted plants, such as rice, it is typically root apexes, sites of rapid entry for water/nutrients, where radial oxygen losses (ROLs) are highest. Nutrient/toxic metal uptake therefore largely occurs through oxidized zones and pH microgradients. However, the processes controlling the acquisition of trace elements in rice have been difficult to explore experimentally because of a lack of techniques for simultaneously measuring labile trace elements and O2/pH. Here, we use new diffusive gradients in thin films (DGT)/planar optode sandwich sensors deployed in situ on rice roots to demonstrate a new geochemical niche of greatly enhanced As, Pb, and Fe(II) mobilization into solution immediately adjacent to the root tips characterized by O2 enrichment and low pH. Fe(II) mobilization was congruent to that of the peripheral edge of the aerobic root zone, demonstrating that the Fe(II) mobilization maximum only developed in a narrow O2 range as the oxidation front penetrates the reducing soil. The Fe flux to the DGT resin at the root apexes was 3-fold higher than the anaerobic bulk soil and 27 times greater than the aerobic rooting zone. These results provide new evidence for the importance of coupled diffusion and oxidation of Fe in modulating trace metal solubilization, dispersion, and plant uptake.

The statistical significance of randomized controlled trial results is frequently fragile: A case for a Fragility Index

Objectives

A P-value <0.05 is one metric used to evaluate the results of a randomized controlled trial (RCT). We wondered how often statistically significant results in RCTs may be lost with small changes in the numbers of outcomes.

Study Design and Setting

A review of RCTs in high-impact medical journals that reported a statistically significant result for at least one dichotomous or time-to-event outcome in the abstract. In the group with the smallest number of events, we changed the status of patients without an event to an event until the P-value exceeded 0.05. We labeled this number the Fragility Index; smaller numbers indicated a more fragile result.

Results

The 399 eligible trials had a median sample size of 682 patients (range: 15-112,604) and a median of 112 events (range: 8-5,142); 53% reported a P-value <0.01. The median Fragility Index was 8 (range: 0-109); 25% had a Fragility Index of 3 or less. In 53% of trials, the Fragility Index was less than the number of patients lost to follow-up.

Conclusion

The statistically significant results of many RCTs hinge on small numbers of events. The Fragility Index complements the P-value and helps identify less robust results. 

A Stubbornly Large Mass of Cold Dust in the Ejecta of Supernova 1987A

We present new Herschel photometric and spectroscopic observations of Supernova 1987A, carried out in 2012. Our dedicated photometric measurements provide new 70 mu m data and improved imaging quality at 100 and 160 mu m compared to previous observations in 2010. Our Herschel spectra show only weak CO line emission, and provide an upper limit for the 63 mu m [O-I] line flux, eliminating the possibility that line contaminations distort the previously estimated dustmass. The far-infrared spectral energy distribution (SED) is well fitted by thermal emission from cold dust. The newly measured 70 mu m flux constrains the dust temperature, limiting it to nearly a single temperature. The far-infrared emission can be fitted by 0.5 +/- 0.1M(circle dot) of amorphous carbon, about a factor of two larger than the current nucleosynthetic mass prediction for carbon. The observation of SiO molecules at early and late phases suggests that silicates may also have formed and we could fit the SED with a combination of 0.3M(circle dot) of amorphous carbon and 0.5M(circle dot) of silicates, totalling 0.8M(circle dot) of dust. Our analysis thus supports the presence of a large dust reservoir in the ejecta of SN 1987A. The inferred dust mass suggests that supernovae can be an important source of dust in the interstellar medium, from local to high-redshift galaxies.

Aspects of dietary carbohydrate intake are not related to risk of colorectal polyps in the Tennessee Colorectal Polyp Study

Purpose: High digestible carbohydrate intakes can induce hyperglycemia and hyperinsulinemia and collectively have been implicated in colorectal tumor development. Our aim was to explore the association between aspects of dietary carbohydrate intake and risk of colorectal adenomas and hyperplastic polyps in a large case–control study.

Methods: Colorectal polyp cases (n = 1,315 adenomas only, n = 566 hyperplastic polyps only and n = 394 both) and controls (n = 3,184) undergoing colonoscopy were recruited between 2003 and 2010 in Nashville, Tennessee, USA. Dietary intakes were estimated by a 108-item food frequency questionnaire. Unconditional logistic regression analysis was applied to determine odds ratios (OR) and corresponding 95 % confidence intervals (CI) for colorectal polyps according to dietary carbohydrate intakes, after adjustment for potential confounders.

Results: No significant associations were detected for risk of colorectal adenomas when comparing the highest versus lowest quartiles of intake for total sugars (OR 1.03; 95 % CI 0.84–1.26), starch (OR 1.01; 95 % CI 0.81–1.26), total or available carbohydrate intakes. Similar null associations were observed between dietary carbohydrate intakes and risk of hyperplastic polyps, or concurrent adenomas and hyperplastic polyps.

Conclusion: In this US population, digestible carbohydrate intakes were not associated with risk of colorectal polyps, suggesting that dietary carbohydrate does not have an etiological role in the early stages of colorectal carcinogenesis.

Commission 15: Physical Studies of Comets and Minor Planets

This report of the business meeting of Commission 15 at the 2009 IAU GA is based on notes provided by Walter Huebner, past president, and on the minutes taken by Daniel Boice, secretary of Commission 15 in the triennium 2006 to 2009, with additional notes from the current secretary, Daniel Hestroffer. The business meeting was split into two sessions, the first held on 5 August and the second held on 11 August. This report presents the minutes of the two Commission 15 business-meeting sessions held during General Assembly XXVII.

Hui and Walter's latent-class model extended to estimate diagnostic test properties from surveillance data: a latent model for latent data

Diagnostic test sensitivity and specificity are probabilistic estimates with far reaching implications for disease control, management and genetic studies. In the absence of 'gold standard' tests, traditional Bayesian latent class models may be used to assess diagnostic test accuracies through the comparison of two or more tests performed on the same groups of individuals. The aim of this study was to extend such models to estimate diagnostic test parameters and true cohort-specific prevalence, using disease surveillance data. The traditional Hui-Walter latent class methodology was extended to allow for features seen in such data, including (i) unrecorded data (i.e. data for a second test available only on a subset of the sampled population) and (ii) cohort-specific sensitivities and specificities. The model was applied with and without the modelling of conditional dependence between tests. The utility of the extended model was demonstrated through application to bovine tuberculosis surveillance data from Northern and the Republic of Ireland. Simulation coupled with re-sampling techniques, demonstrated that the extended model has good predictive power to estimate the diagnostic parameters and true herd-level prevalence from surveillance data. Our methodology can aid in the interpretation of disease surveillance data, and the results can potentially refine disease control strategies.