Maximum Likelihood Estimation of the Negative Binomial Dispersion Parameter for Highly Overdispersed Data, with Applications to Infectious Diseases

BACKGROUND: The negative binomial distribution is used commonly throughout biology as a model for overdispersed count data, with attention focused on the negative binomial dispersion parameter, k. A substantial literature exists on the estimation of k, but most attention has focused on datasets that are not highly overdispersed (i.e., those with k≥1), and the accuracy of confidence intervals estimated for k is typically not explored. METHODOLOGY: This article presents a simulation study exploring the bias, precision, and confidence interval coverage of maximum-likelihood estimates of k from highly overdispersed distributions. In addition to exploring small-sample bias on negative binomial estimates, the study addresses estimation from datasets influenced by two types of event under-counting, and from disease transmission data subject to selection bias for successful outbreaks. CONCLUSIONS: Results show that maximum likelihood estimates of k can be biased upward by small sample size or under-reporting of zero-class events, but are not biased downward by any of the factors considered. Confidence intervals estimated from the asymptotic sampling variance tend to exhibit coverage below the nominal level, with overestimates of k comprising the great majority of coverage errors. Estimation from outbreak datasets does not increase the bias of k estimates, but can add significant upward bias to estimates of the mean. Because k varies inversely with the degree of overdispersion, these findings show that overestimation of the degree of overdispersion is very rare for these datasets

Polyhydroxy Fullerenes (Fullerols or Fullerenols): Beneficial Effects on Growth and Lifespan in Diverse Biological Models

Recent toxicological studies on carbon nanomaterials, including fullerenes, have led to concerns about their safety. Functionalized fullerenes, such as polyhydroxy fullerenes (PHF, fullerols, or fullerenols), have attracted particular attention due to their water solubility and toxicity. Here, we report surprisingly beneficial and/or specific effects of PHF on model organisms representing four kingdoms, including the green algae Pseudokirchneriella subcapitata, the plant Arabidopsis thaliana, the fungus Aspergillus niger, and the invertebrate Ceriodaphnia dubia. The results showed that PHF had no acute or chronic negative effects on the freshwater organisms. Conversely, PHF could surprisingly increase the algal culture density over controls at higher concentrations (i.e., 72% increase by 1 and 5 mg/L of PHF) and extend the lifespan and stimulate the reproduction of Daphnia (e.g. about 38% by 20 mg/L of PHF). We also show that at certain PHF concentrations fungal growth can be enhanced and Arabidopsis thaliana seedlings exhibit longer hypocotyls, while other complex physiological processes remain unaffected. These findings may open new research fields in the potential applications of PHF, e.g., in biofuel production and aquaculture. These results will form the basis of further research into the mechanisms of growth stimulation and life extension by PHF

Knowledge about complementary, alternative and integrative medicine (CAM) among registered health care providers in Swedish surgical care: a national survey among university hospitals

<p>Abstract</p> <p>Background</p> <p>Previous studies show an increased interest and usage of complementary and alternative medicine (CAM) in the general population and among health care workers both internationally and nationally. CAM usage is also reported to be common among surgical patients. Earlier international studies have reported that a large amount of surgical patients use it prior to and after surgery. Recent publications indicate a weak knowledge about CAM among health care workers. However the current situation in Sweden is unknown. The aim of this study was therefore to explore perceived knowledge about CAM among registered healthcare professions in surgical departments at Swedish university hospitals.</p> <p>Method</p> <p>A questionnaire was distributed to 1757 registered physicians, nurses and physiotherapists in surgical wards at the seven university hospitals in Sweden from spring 2010 to spring 2011. The questionnaire included classification of 21 therapies into conventional, complementary, alternative and integrative, and whether patients were recommended these therapies. Questions concerning knowledge, research, and patient communication about CAM were also included.</p> <p>Result</p> <p>A total of 737 (42.0%) questionnaires were returned. Therapies classified as complementary; were massage, manual therapies, yoga and acupuncture. Alternative therapies; were herbal medicine, dietary supplements, homeopathy and healing. Classification to integrative therapy was low, and unfamiliar therapies were Bowen therapy, iridology and Rosen method. Therapies recommended by > 40% off the participants were massage and acupuncture. Knowledge and research about CAM was valued as minor or none at all by 95.7% respectively 99.2%. Importance of possessing knowledge about it was valued as important by 80.9%. It was believed by 61.2% that more research funding should be addressed to CAM research, 72.8% were interested in reading CAM-research results, and 27.8% would consider taking part in such research. Half of the participants (55.8%) were positive to learning such therapy. Communication about CAM between patients and the health care professions was found to be rare.</p> <p>Conclusion</p> <p>There is a lack of knowledge about CAM and research about it among registered health care professions in Swedish surgical care. However, in contrast to previous studies the results revealed that the majority perceived it as important to gain knowledge in this field.</p

Change in Blood Pressure Variability Among Treated Elderly Hypertensive Patients and Its Association With Mortality

Background: Information is scarce regarding effects of antihypertensive medication on blood pressure variability (BPV) and associated clinical outcomes. We examined whether antihypertensive treatment changes BPV over time and whether such change (decline or increase) has any association with long-term mortality in an elderly hypertensive population. Methods and Results: We used data from a subset of participants in the Second Australian National Blood Pressure study (n=496) aged ≥65 years who had 24-hour ambulatory blood pressure recordings at study entry (baseline) and then after a median of 2 years while on treatment (follow-up). Weighted day-night systolic BPV was calculated for both baseline and follow-up as a weighted mean of daytime and nighttime blood pressure standard deviations. The annual rate of change in BPV over time was calculated from these BPV estimates. Furthermore, we classified both BPV estimates as high and low based on the baseline median BPV value and then classified BPV changes into stable: low BPV, stable: high BPV, decline: high to low, and increase: low to high. We observed an annual decline (mean±SD: −0.37±1.95; 95% CI, −0.54 to −0.19; P<0.001) in weighted day-night systolic BPV between baseline and follow-up. Having constant stable: high BPV was associated with an increase in all-cause mortality (hazard ratio: 3.03; 95% CI, 1.67–5.52) and cardiovascular mortality (hazard ratio: 3.70; 95% CI, 1.62–8.47) in relation to the stable: low BPV group over a median 8.6 years after the follow-up ambulatory blood pressure monitoring. Similarly, higher risk was observed in the decline: high to low group. Conclusions: Our results demonstrate that in elderly hypertensive patients, average BPV declined over 2 years of follow-up after initiation of antihypertensive therapy, and having higher BPV (regardless of any change) was associated with increased long-term mortality

Rapidity and Centrality Dependence of Proton and Anti-proton Production from Au+Au Collisions at sqrt(sNN) = 130GeV

We report on the rapidity and centrality dependence of proton and anti-proton transverse mass distributions from Au+Au collisions at sqrt(sNN) = 130GeV as measured by the STAR experiment at RHIC. Our results are from the rapidity and transverse momentum range of |y|<0.5 and 0.35 <p_t<1.00GeV/c. For both protons and anti-protons, transverse mass distributions become more convex from peripheral to central collisions demonstrating characteristics of collective expansion. The measured rapidity distributions and the mean transverse momenta versus rapidity are flat within |y|<0.5. Comparisons of our data with results from model calculations indicate that in order to obtain a consistent picture of the proton(anti-proton) yields and transverse mass distributions the possibility of pre-hadronic collective expansion may have to be taken into account.Comment: 4 pages, 3 figures, 1 table, submitted to PR

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

BAF complex-mediated chromatin relaxation is required for establishment of X chromosome inactivation

The process of epigenetic silencing, while fundamentally important, is not yet completely understood. Here we report a replenishable female mouse embryonic stem cell (mESC) system, Xmas, that allows rapid assessment of X chromosome inactivation (XCI), the epigenetic silencing mechanism of one of the two X chromosomes that enables dosage compensation in female mammals. Through a targeted genetic screen in differentiating Xmas mESCs, we reveal that the BAF complex is required to create nucleosome-depleted regions at promoters on the inactive X chromosome during the earliest stages of establishment of XCI. Without this action gene silencing fails. Xmas mESCs provide a tractable model for screen-based approaches that enable the discovery of unknown facets of the female-specific process of XCI and epigenetic silencing more broadly.Andrew Keniry ... Jose M. Polo ... et al

Modulation of the surface proteome through multiple ubiquitylation pathways in African Trypanosomes

Recently we identified multiple suramin-sensitivity genes with a genome wide screen in Trypanosoma brucei that includes the invariant surface glycoprotein ISG75, the adaptin-1 (AP-1) complex and two deubiquitylating enzymes (DUBs) orthologous to ScUbp15/HsHAUSP1 and pVHL-interacting DUB1 (type I), designated TbUsp7 and TbVdu1, respectively. Here we have examined the roles of these genes in trafficking of ISG75, which appears key to suramin uptake. We found that, while AP-1 does not influence ISG75 abundance, knockdown of TbUsp7 or TbVdu1 leads to reduced ISG75 abundance. Silencing TbVdu1 also reduced ISG65 abundance. TbVdu1 is a component of an evolutionarily conserved ubiquitylation switch and responsible for rapid receptor modulation, suggesting similar regulation of ISGs in T. brucei. Unexpectedly, TbUsp7 knockdown also blocked endocytosis. To integrate these observations we analysed the impact of TbUsp7 and TbVdu1 knockdown on the global proteome using SILAC. For TbVdu1, ISG65 and ISG75 are the only significantly modulated proteins, but for TbUsp7 a cohort of integral membrane proteins, including the acid phosphatase MBAP1, that is required for endocytosis, and additional ISG-related proteins are down-regulated. Furthermore, we find increased expression of the ESAG6/7 transferrin receptor and ESAG5, likely resulting from decreased endocytic activity. Therefore, multiple ubiquitylation pathways, with a complex interplay with trafficking pathways, control surface proteome expression in trypanosomes

Transverse-momentum and collision-energy dependence of high-p(T) hadron suppression in Au+Au collisions at ultrarelativistic energies

We report high statistics measurements of inclusive charged hadron production in Au+Au and p+p collisions at rootS(NN)=200 GeV. A large, approximately constant hadron suppression is observed in central Au+Au collisions for 5<p(T)<12 GeV/c. The collision energy dependence of the yields and the centrality and p(T) dependence of the suppression provide stringent constraints on theoretical models of suppression. Models incorporating initial-state gluon saturation or partonic energy loss in dense matter are largely consistent with observations. We observe no evidence of p(T)-dependent suppression, which may be expected from models incorporating jet attenuation in cold nuclear matter or scattering of fragmentation hadrons