Prevalence of neonatal septicaemia in the University of Port Harcourt Teaching Hospital, Nigeria

Background : Septicaemia is a major cause of morbidity and mortality in the neonatal period. Early detection of neonatal septicaemia is often hampered by its subtle and nonspecific symptoms and signs thus a high index of suspicion is needed.Objectives: To determine the prevalence of neonatal sept ic a emia , ident i fy the predisposing factors, clinical features and causative organisms inthe University of Port Harcourt Teaching Hospital.Methods: Four hundred and six neonates with clinical suspicion of sepsis were recruited into the study over a six months period. Blood culture was used as gold standard for the diagnosis of neonatal septicaemia.Results: One hundred and sixtynine (41.6%) neonates had positive blood culture giving a prevalence rate of neonatal septicaemia as 33.1%. Thepredominant predisposing factors were out-born delivery (68.0%), birth asphyxia (30.2%) and prematurity (21.4%) while the major clinical features of septicaemia were respiratory distress (30.2%), fever (26.6%)and poor suck (22.5%). Klebsiella pneumoniae ( 6 5 . 4 % ), Staphylococcus aureus (15.4%) and Escherichia coli (7.7%) were the commonest organisms isolated in neonates with septicaemia.Conclusion: Prevalence of blood culture-proven septicemia is high, being 33.1%. Klebsiella pneumoniae is the predominant cause of neonatal septicaemia in Port Harcourt.Key Words: Neonatal septicaemia; Prevalence; Port Harcourt

Algorithms for Cut Problems on Trees

We study the {\sc multicut on trees} and the {\sc generalized multiway Cut on trees} problems. For the {\sc multicut on trees} problem, we present a parameterized algorithm that runs in time $O^{*}(\rho^k)$, where $\rho = \sqrt{\sqrt{2} + 1} \approx 1.555$ is the positive root of the polynomial $x^4-2x^2-1$. This improves the current-best algorithm of Chen et al. that runs in time $O^{*}(1.619^k)$. For the {\sc generalized multiway cut on trees} problem, we show that this problem is solvable in polynomial time if the number of terminal sets is fixed; this answers an open question posed in a recent paper by Liu and Zhang. By reducing the {\sc generalized multiway cut on trees} problem to the {\sc multicut on trees} problem, our results give a parameterized algorithm that solves the {\sc generalized multiway cut on trees} problem in time $O^{*}(\rho^k)$, where $\rho = \sqrt{\sqrt{2} + 1} \approx 1.555$ time

Spatial variation in prostate cancer survival in the Northern and Yorkshire region of England using Bayesian relative survival smoothing

Primary Care Trust (PCT) estimates of survival lack robustness as there are small numbers of deaths per year in each area, even when incidence is high. We assess PCT-level spatial variation in prostate cancer survival using Bayesian spatial models of excess mortality. We extracted data on men diagnosed with prostate cancer between 1990 and 1999 from the Northern and Yorkshire Cancer Registry and Information Service database. Models were adjusted for age at diagnosis, period of diagnosis and deprivation. All covariates had a significant association with excess mortality; men from more deprived areas, older age at diagnosis and diagnosed in 1990–1994 had higher excess mortality. The unadjusted relative excess risks (RER) of death by PCT ranged from 0.75 to 1.66. After adjustment, areas of high and low excess mortality were smoothed towards the mean, and the RERs ranged from 0.74 to 1.49. Using Bayesian smoothing techniques to model cancer survival by geographic area offers many advantages over traditional methods; estimates in areas with small populations or low incidence rates are stabilised and shrunk towards local and global risk estimates improving reliability and precision, complex models are easily handled and adjustment for covariates can be made

First observations of separated atmospheric nu_mu and bar{nu-mu} events in the MINOS detector

The complete 5.4 kton MINOS far detector has been taking data since the beginning of August 2003 at a depth of 2070 meters water-equivalent in the Soudan mine, Minnesota. This paper presents the first MINOS observations of nuµ and [overline nu ]µ charged-current atmospheric neutrino interactions based on an exposure of 418 days. The ratio of upward- to downward-going events in the data is compared to the Monte Carlo expectation in the absence of neutrino oscillations, giving Rup/downdata/Rup/downMC=0.62-0.14+0.19(stat.)±0.02(sys.). An extended maximum likelihood analysis of the observed L/E distributions excludes the null hypothesis of no neutrino oscillations at the 98% confidence level. Using the curvature of the observed muons in the 1.3 T MINOS magnetic field nuµ and [overline nu ]µ interactions are separated. The ratio of [overline nu ]µ to nuµ events in the data is compared to the Monte Carlo expectation assuming neutrinos and antineutrinos oscillate in the same manner, giving R[overline nu ][sub mu]/nu[sub mu]data/R[overline nu ][sub mu]/nu[sub mu]MC=0.96-0.27+0.38(stat.)±0.15(sys.), where the errors are the statistical and systematic uncertainties. Although the statistics are limited, this is the first direct observation of atmospheric neutrino interactions separately for nuµ and [overline nu ]µ

ARHGEF7 (BETA-PIX) Acts as Guanine Nucleotide Exchange Factor for Leucine-Rich Repeat Kinase 2

Background: Mutations within the leucine-rich repeat kinase 2 (LRRK2) gene are a common cause of familial and sporadic Parkinson’s disease. The multidomain protein LRRK2 exhibits overall low GTPase and kinase activity in vitro. Methodology/Principal Findings: Here, we show that the rho guanine nucleotide exchange factor ARHGEF7 and the small GTPase CDC42 are interacting with LRRK2 in vitro and in vivo. GTPase activity of full-length LRRK2 increases in the presence of recombinant ARHGEF7. Interestingly, LRRK2 phosphorylates ARHGEF7 in vitro at previously unknown phosphorylation sites. We provide evidence that ARHGEF7 might act as a guanine nucleotide exchange factor for LRRK2 and that R1441C mutant LRRK2 with reduced GTP hydrolysis activity also shows reduced binding to ARHGEF7. Conclusions/Significance: Downstream effects of phosphorylation of ARHGEF7 through LRRK2 could be (i) a feedback control mechanism for LRRK2 activity as well as (ii) an impact of LRRK2 on actin cytoskeleton regulation. A newly identified familial mutation N1437S, localized within the GTPase domain of LRRK2, further underlines the importance of the GTPas

What are the factors driving antimicrobial resistance? Perspectives from a public event in London, England.

BACKGROUND: Antimicrobial resistance is driven by multiple factors. Resolving the threat to human and animal health presented by drug-resistant infections remains a societal challenge that demands close collaboration between scientists and citizens. We compared current public views about key contributing factors to antimicrobial resistance with those expressed by experts. METHODS: Overarching factors contributing to antimicrobial resistance were identified following a review of literature. The factors were then described in plain language and attached to ballot boxes at a public engagement event organised by a university. Responses to each factor were counted at the end of the event. RESULTS: Four hundred five responses were received from 3750 visitors (11 % response rate). Nearly half of responses (192/405, 47 · 4 %) considered the misuse/overuse of antibiotics in humans as the main determinant of antimicrobial resistance. The misuse of antibiotics in animal health obtained 16 · 3 % (66/405) responses. However, the lack of quick tests to diagnose infections received 10/405 votes (2 · 47 %), and the lack of effective vaccines received one vote (0 · 25 %). CONCLUSIONS: The majority of responses ascribed the emergence of drug-resistant infections to the misuse of antibiotics in human and animals. Suboptimal dosing, availability of diagnostics and environmental contamination were considered less influential on the development of antimicrobial resistance. The growing recognition of broader multifaceted drivers of drug resistance by experts is not yet echoed in the public mind

Characteristics and outcomes of patients with advanced non-small-cell lung cancer who declined to participate in randomised clinical chemotherapy trials

There are inadequate data on the outcomes of patients who declined to participate in randomised clinical trials as compared with those of participants. We retrospectively reviewed the patient characteristics and treatment outcomes of both participants and non-participants in the two randomised trials for chemotherapy-naive advanced non-small-cell lung cancer. Trial 1 compared four platinum-based combination regimens. Trial 2 compared two sequences of carboplatin plus paclitaxel and gefitinib therapies. Nineteen of 119 (16%) and 153 (37%) patients declined to participate in Trials 1 and 2, respectively. Among the background patient characteristics, the only variable associated with trial participation or declining was the patients' attending physicians (P<0.001). Important differences were not observed in the clinical outcomes between participants and non-participants, for whom the response rates were 30.6 vs 34.2% and the median survival times were 489 vs 461 days, respectively. The hazard ratio for overall survival, adjusted for other confounding variables, was 0.965 (95% confidence interval: 0.73–1.28). In conclusion, there was no evidence to suggest any difference in the characteristics and clinical outcomes between participants and non-participants. Trial designs and the doctor–patient relationship may have an impact on the patient accrual to randomised trials

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

The Role of Histone H4 Biotinylation in the Structure of Nucleosomes

Background: Post-translational modifications of histones play important roles in regulating nucleosome structure and gene transcription. It has been shown that biotinylation of histone H4 at lysine-12 in histone H4 (K12Bio-H4) is associated with repression of a number of genes. We hypothesized that biotinylation modifies the physical structure of nucleosomes, and that biotin-induced conformational changes contribute to gene silencing associated with histone biotinylation. Methodology/Principal Findings: To test this hypothesis we used atomic force microscopy to directly analyze structures of nucleosomes formed with biotin-modified and non-modified H4. The analysis of the AFM images revealed a 13% increase in the length of DNA wrapped around the histone core in nucleosomes with biotinylated H4. This statistically significant (p,0.001) difference between native and biotinylated nucleosomes corresponds to adding approximately 20 bp to the classical 147 bp length of nucleosomal DNA. Conclusions/Significance: The increase in nucleosomal DNA length is predicted to stabilize the association of DNA with histones and therefore to prevent nucleosomes from unwrapping. This provides a mechanistic explanation for the gene silencing associated with K12Bio-H4. The proposed single-molecule AFM approach will be instrumental for studying the effects of various epigenetic modifications of nucleosomes, in addition to biotinylation