Tocolytic therapy for preterm delivery: systematic review and network meta-analysis

OBJECTIVE: To determine the most effective tocolytic agent at delaying delivery. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, Medline In-Process, Embase, and CINAHL up to 17 February 2012. STUDY SELECTION: Randomised controlled trials of tocolytic therapy in women at risk of preterm delivery. DATA EXTRACTION: At least two reviewers extracted data on study design, characteristics, number of participants, and outcomes reported (neonatal and maternal). A network meta-analysis was done using a random effects model with drug class effect. Two sensitivity analyses were carried out for the primary outcome; restricted to studies at low risk of bias and restricted to studies excluding women at high risk of preterm delivery (those with multiple gestation and ruptured membranes). RESULTS: Of the 3263 titles initially identified, 95 randomized controlled trials of tocolytic therapy were reviewed. Compared with placebo, the probability of delivery being delayed by 48 hours was highest with prostaglandin inhibitors (odds ratio 5.39, 95% credible interval 2.14 to 12.34) followed by magnesium sulfate (2.76, 1.58 to 4.94), calcium channel blockers (2.71, 1.17 to 5.91), beta mimetics (2.41, 1.27 to 4.55), and the oxytocin receptor blocker atosiban (2.02, 1.10 to 3.80). No class of tocolytic was significantly superior to placebo in reducing neonatal respiratory distress syndrome. Compared with placebo, side effects requiring a change of medication were significantly higher for beta mimetics (22.68, 7.51 to 73.67), magnesium sulfate (8.15, 2.47 to 27.70), and calcium channel blockers (3.80, 1.02 to 16.92). Prostaglandin inhibitors and calcium channel blockers were the tocolytics with the best probability of being ranked in the top three medication classes for the outcomes of 48 hour delay in delivery, respiratory distress syndrome, neonatal mortality, and maternal side effects (all cause). CONCLUSIONS: Prostaglandin inhibitors and calcium channel blockers had the highest probability of delaying delivery and improving neonatal and maternal outcomes

Metaheuristic Based Scheduling Meta-Tasks in Distributed Heterogeneous Computing Systems

Scheduling is a key problem in distributed heterogeneous computing systems in order to benefit from the large computing capacity of such systems and is an NP-complete problem. In this paper, we present a metaheuristic technique, namely the Particle Swarm Optimization (PSO) algorithm, for this problem. PSO is a population-based search algorithm based on the simulation of the social behavior of bird flocking and fish schooling. Particles fly in problem search space to find optimal or near-optimal solutions. The scheduler aims at minimizing makespan, which is the time when finishes the latest task. Experimental studies show that the proposed method is more efficient and surpasses those of reported PSO and GA approaches for this problem

Nurse staffing levels revisited: a consideration of key issues in nurse staffing levels and skill mix research.

AIM: This paper revisits the published evidence relating to how nurse staffing levels impact on patient, nurse and service outcomes and considers the implications of this body of research for nurse managers in their quest to determine optimum nursing numbers. BACKGROUND: Within the context of the recognized global nursing shortage and particular local pressures within international health services, questions of appropriate nurse staffing levels and skill mix are once again becoming increasingly important. It would seem that the determination of optimum nurse staffing levels and skill mix is a central issue in relation to health service governance, service user involvement, as well as in the recruitment, retention and well-being of nursing staff across the service sectors. METHODS: A review of published evidence was carried out, applying key principles of the systematic method, in order to facilitate the identification of current factors and issues in nurse staffing levels research. The review did not seek to address a specific research question. The search covered 10 years from 1998 to 2008 and identified more than 500 relevant papers, giving a wide international perspective. KEY ISSUES: The majority of research in the field relates to the acute service sector and there are considerable similarities in issues that transcend international boundaries. Much of the research focuses on the impact on patients and nurses of 'poor' nurse staffing levels. More recent studies have explored the impact of nurse staffing levels on the service organization itself. However, while there may be an association between models of nurse staffing and outcomes, there is insufficient evidence to establish a causal relationship between these factors. In this context it is perhaps time to reconsider how nursing outcomes are defined and measured. IMPLICATIONS FOR NURSING MANAGEMENT AND CONCLUSION: Nurse managers, commissioners of services and workforce planners need to be cognisant of key issues and analyses in the consideration of nurse staffing levels. Not least of these is the need for a healthy degree of caution regarding the supposed objectivity, scientific basis, or evidence base, for rational calculation of optimum nurse staffing levels

Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and their application in antimicrobial coatings

We report a one-pot synthesis of spherical gold nanoparticles (52-22 nm) and their capping with cefaclor, a second-generation antibiotic, without use of other chemicals. The differently sized gold nanoparticles were fabricated by controlling the rate of reduction of gold ions in aqueous solution by varying the reaction temperature (20-70 C). The primary amine group of cefaclor acted as both the reducing and capping agent for the synthesis of gold nanoparticles leaving the b-lactam ring of cefaclor available for activity against microbes. Antimicrobial testing showed that cefaclor reduced gold nanoparticles have potent antimicrobial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria as compared to cefaclor or gold nanoparticles alone. The minimum inhibition concentrations (MICs) of cefaclor reduced gold nanoparticles were 10m gmL1 and 100m gmL1 for S. aureus and E. coli respectively. The cefaclor reduced gold nanoparticles were further coated onto poly(ethyleneimine) (PEI) modified glass surfaces to obtain antimicrobial coatings suitable for biomedical applications and were tested against E. coli as an exemplar of activity. The antimicrobial coatings were very robust under adverse conditions (pH 3 and 10), inhibited the growth of E. coli on their surfaces, and could be used many times with retained activity. Results from a combined spectroscopic (FTIR) and microscopic study (AFM) suggest that the action of these novel particles is through the combined action of cefaclor inhibiting the synthesis of the peptidoglycan layer and gold nanoparticles generating "holes" in bacterial cell walls thereby increasing the permeability of the cell wall, resulting in the leakage of cell contents and eventually cell death

UNC2025, a MERTK Small-Molecule Inhibitor, Is Therapeutically Effective Alone and in Combination with Methotrexate in Leukemia Models

MERTK tyrosine kinase is ectopically expressed in 30–50% of acute lymphoblastic leukemias (ALL) and over 80% of acute myeloid leukemias (AML) and is a potential therapeutic target. Here, we evaluated the utility of UNC2025, a MERTK tyrosine kinase inhibitor, for treatment of acute leukemia

Early childhood epilepsies:epidemiology, classification, aetiology, and socio-economic determinants

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216–263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251–357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139–233), χ2 odds ratio = 1.7 (95% CI 1.3–2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations

The angular clustering of infrared-selected obscured and unobscured quasars

This article has been accepted for publication in Monthly Notices of the Royal Astronomical Society. ©: 2014 The Author(s). Published by Oxford University Press on behalf of the Royal Astronomical Society. All rights reserved.Recent studies of luminous infrared-selected active galactic nuclei (AGN) suggest that the reddest, most obscured objects display a higher angular clustering amplitude, and thus reside in higher mass darkmatter haloes. This is a direct contradiction to the prediction of the simplest unification-by-orientation models of AGN and quasars. However, clustering measurements depend strongly on the 'mask' that removes low-quality data and describes the sky and selection function.We find that applying a robust, conservative mask to WISE-selected quasars yields a weaker but still significant difference in the bias between obscured and unobscured quasars. These findings are consistent with results from previous Spitzer surveys, and removes any scale dependence of the bias. For obscured quasars with =0.99, we measure a bias of bq = 2.67 ± 0.16, corresponding to a halo mass of log(Mh/M⊙h-1) = 13.3 ± 0.1, while for unobscured sources with = 1.04 we find bq = 2.04 ± 0.17 with a halo mass log(Mh/M⊙h-1) = 12.8 ± 0.1. This improved measurement indicates that WISE-selected obscured quasars reside in haloes only a few times more massive than the haloes of their unobscured counterparts, a reduction in the factor of ∼10 larger halo mass as has been previously reported using WISE-selected samples. Additionally, an abundance matching analysis yields lifetimes for both obscured and unobscured quasar phases on the order of a few 100 Myr (∼1 per cent of the Hubble time) - however, the obscured phase lasts roughly twice as long, in tension with many model predictions.Peer reviewe

Efficacy of a Mer and Flt3 tyrosine kinase small molecule inhibitor, UNC1666, in acute myeloid leukemia

Mer and Flt3 receptor tyrosine kinases have been implicated as therapeutic targets in acute myeloid leukemia (AML). In this manuscript we describe UNC1666, a novel ATP-competitive small molecule tyrosine kinase inhibitor, which potently diminishes Mer and Flt3 phosphorylation in AML. Treatment with UNC1666 mediated biochemical and functional effects in AML cell lines expressing Mer or Flt3 internal tandem duplication (ITD), including decreased phosphorylation of Mer, Flt3 and downstream effectors Stat, Akt and Erk, induction of apoptosis in up to 98% of cells, and reduction of colony formation by greater than 90%, compared to treatment with vehicle. These effects were dose-dependent, with inhibition of downstream signaling and functional effects correlating with the degree of Mer or Flt3 kinase inhibition. Treatment of primary AML patient samples expressing Mer and/or Flt3-ITD with UNC1666 also inhibited Mer and Flt3 intracellular signaling, induced apoptosis, and inhibited colony formation. In summary, UNC1666 is a novel potent small molecule tyrosine kinase inhibitor that decreases oncogenic signaling and myeloblast survival, thereby validating dual Mer/Flt3 inhibition as an attractive treatment strategy for AML

The Merging of Two Dynasties—Identification of an African Cotton Leaf Curl Disease-Associated Begomovirus with Cotton in Pakistan

Cotton leaf curl disease (CLCuD) is a severe disease of cotton that occurs in Africa and Pakistan/northwestern India. The disease is caused by begomoviruses in association with specific betasatellites that differ between Africa and Asia. During survey of symptomatic cotton in Sindh (southern Pakistan) Cotton leaf curl Gezira virus (CLCuGV), the begomovirus associated with CLCuD in Africa, was identified. However, the cognate African betasatellite (Cotton leaf curl Gezira betasatellite) was not found. Instead, two Asian betasatellites, the CLCuD-associated Cotton leaf curl Multan betasatellite (CLCuMB) and Chilli leaf curl betasatellite (ChLCB) were identified. Inoculation of the experimental plant species Nicotiana benthamiana showed that CLCuGV was competent to maintain both CLCuMB and ChLCB. Interestingly, the enations typical of CLCuD were only induced by CLCuGV in the presence of CLCuMB. Also in infections involving both CLCuMB and ChLCB the enations typical of CLCuMB were less evident. This is the first time an African begomovirus has been identified on the Indian sub-continent, highlight the growing threat of begomoviruses and particularly the threat of CLCuD causing viruses to cotton cultivation in the rest of the world