bluuebunny/crossref_metadata_2025 huggingface dataset:
The FDA alert on suicidality and antiepileptic drugs: Fire or false alarm?
Authors: Hesdorffer Dale C. , Kanner Andres M.
Published: May 2009

In January 2008, the U.S. Food and Drug Administration (FDA) issued an alert about an increased risk for suicidality in 199 clinical trials of 11 antiepileptic drugs (AEDs) for three different indications, including epilepsy. An advisory panel voted against a black‐box warning on AED labels, and the FDA has accepted this recommendation. We discuss three potential problems with the alert. First, adverse event data were used rather than systematically collected data. Second, the 11 drugs grouped together as a single class of AEDs have different mechanisms of action and very different relative risks, many of which were not statistically significant and some of which were smaller than one. These facts suggest that they should not be grouped as a class. Third, the risk of adverse effects from uncontrolled seizures almost certainly outweighs the small risk of suicidality. We place our comments in the context of a review of the literature on suicidality and depression in epilepsy and the sparse literature on AEDs and suicidality. We recommend that all patients with epilepsy be routinely evaluated for depression, anxiety, and suicidality, and that future clinical trials include validated instruments to systematically assess these conditions to determine whether the possible signal observed by the FDA is real.
Periprocedural Management and In‐Hospital Outcome of Patients with Indication for Oral Anticoagulation Undergoing Coronary Artery Stenting
Authors: RUBBOLI ANDREA , COLLETTA MAURO , VALENCIA JOSÈ , CAPECCHI ALESSANDRO , FRANCO NICOLETTA , ZANOLLA LUISA , VECCHIA LUIGI LA , PIOVACCARI GIANCARLO , DI PASQUALE GIUSEPPE ,   for the WARfarin and Coronary STENTing (WAR‐STENT) Study Group
Published: May 2009

Purpose: In patients on oral anticoagulation (OAC) undergoing coronary stenting (PCI‐S), procedural management and in‐hospital outcome have never been specifically and prospectively investigated. Also, the contribution of early bleeding to the relevant hemorrhagic rate reported at follow‐up with triple therapy of OAC, aspirin, and clopidogrel is largely unknown.

Methods: Consecutive patients with indication for OAC undergoing PCI‐S at 5 centers were enrolled and prospectively evaluated.

Results: Out of 3410 patients undergoing PCI‐S in the study period, indication for OAC was present in 4.8%. Femoral approach and bare metal stents were the most frequently used. During PCI‐S, OAC was continued in about 30% of patients, whereas in about 20% heparin bridging was carried out. Glycoprotein IIb/IIIa inhibitors were rarely used (11%), whereas a standard bolus of unfractionated heparin was given in 93% of cases. Major adverse cardiovascular events (MACE) occurred in 4.8% of patients and major bleeding in 4.3%. No predictors of MACE or bleeding were identified, although the femoral approach was of borderline significance for major bleeding (OR 4.6, 95% CI 1.0–20.8; P = 0.05). A history of previous hemorrhage (OR 5.3, 95% CI 1.6–18.1; P = 0.007) predicted Carbofilm™‐coated stent implantation.

Conclusions: A limited, albeit clinically relevant, proportion of patients undergoing PCI‐S has indication for OAC. Procedural management appears not substantially different from that of common patients. In‐hospital major bleeding is relevant and should be taken into account when evaluating the overall hemorrhagic rate at a medium‐ to long‐term follow‐up.
A Robust Genome‐Wide Scan Statistic of the Wellcome Trust Case–Control Consortium
Authors: Joo Jungnam , Kwak Minjung , Ahn Kwangmi , Zheng Gang
Published: May 2009

Summary In genome‐wide association (GWA) studies, test statistics that are efficient and robust across various genetic models are preferable, particularly for studying multiple diseases in the Wellcome Trust Case–Control Consortium (WTCCC, 2007, Nature 447, 661–678). A new test statistic, the minimum of the p‐values of the trend test and Pearson's test, was considered by the WTCCC. It is referred to here as MIN2. Because the minimum of two p‐values is no longer a valid p‐value itself, the WTCCC only used it to rank single nucleotide polymorphisms (SNPs) but did not report the p‐values of the associated SNPs when MIN2 was used for ranking. Given its importance in practice, we derive the asymptotic null distribution of MIN2, study some of its analytical properties related to GWA studies, and compare it with existing methods (the trend test, Pearson's test, MAX3, and the constrained likelihood ratio test [CLRT]) by simulations across a wide range of possible genetic models: the recessive (REC), additive (ADD), multiplicative (MUL), dominant (DOM), and overdominant models. The results show that MAX3 and CLRT have greater efficiency robustness than other tests when the REC, ADD/MUL, and DOM models are possible, whereas Pearson's test and MIN2 have greater efficiency robustness if the possible genetic models also include the overdominant model. We conclude that robust tests (MAX3, MIN2, CLRT, and Pearson's test) are preferable to a single trend test for initial GWA studies. The four robust tests are applied to more than 100 SNPs associated with 11 common diseases identified by the two WTCCC GWA studies.
Predictive Model Assessment for Count Data
Authors: Czado Claudia , Gneiting Tilmann , Held Leonhard
Published: May 2009

SummaryWe discuss tools for the evaluation of probabilistic forecasts and the critique of statistical models for count data. Our proposals include a nonrandomized version of the probability integral transform, marginal calibration diagrams, and proper scoring rules, such as the predictive deviance. In case studies, we critique count regression models for patent data, and assess the predictive performance of Bayesian age‐period‐cohort models for larynx cancer counts in Germany. The toolbox applies in Bayesian or classical and parametric or nonparametric settings and to any type of ordered discrete outcomes.
Testing Hardy–Weinberg Equilibrium and Homogeneity of Hardy–Weinberg Disequilibrium using Complex Survey Data
Authors: Li Yan , Graubard Barry I.
Published: May 2009

Summary For studies on population genetics, the use of representative random samples of the target population can avoid ascertainment bias. Genetic variation data from over a hundred genes were collected in a U.S. nationally representative sample in the Third National Health and Nutrition Examination Survey (NHANES III). Surveys such as the NHANES have complex stratified multistage cluster sample designs with sample weighting that can inflate variances and alter the expectations of test statistics. Thus, classical statistical tests of Hardy–Weinberg equilibrium (HWE) and homogeneity of HW disequilibrium (HHWD) for simple random samples are not suitable for data from complex samples. We propose using Wald tests for HWE and generalized score tests for HHWD that have been modified for complex samples. Monte Carlo simulation studies are used to investigate the finite sample properties of the proposed tests. Rao–Scott corrections applied to the tests were found to improve their type I error properties. Our methods are applied to the NHANES III genetic data for three loci involved in metabolizing lead in the body.
Bayesian Inference in Semiparametric Mixed Models for Longitudinal Data
Authors: Li Yisheng , Lin Xihong , Müller Peter
Published: May 2009

SummaryWe consider Bayesian inference in semiparametric mixed models (SPMMs) for longitudinal data. SPMMs are a class of models that use a nonparametric function to model a time effect, a parametric function to model other covariate effects, and parametric or nonparametric random effects to account for the within‐subject correlation. We model the nonparametric function using a Bayesian formulation of a cubic smoothing spline, and the random effect distribution using a normal distribution and alternatively a nonparametric Dirichlet process (DP) prior. When the random effect distribution is assumed to be normal, we propose a uniform shrinkage prior (USP) for the variance components and the smoothing parameter. When the random effect distribution is modeled nonparametrically, we use a DP prior with a normal base measure and propose a USP for the hyperparameters of the DP base measure. We argue that the commonly assumed DP prior implies a nonzero mean of the random effect distribution, even when a base measure with mean zero is specified. This implies weak identifiability for the fixed effects, and can therefore lead to biased estimators and poor inference for the regression coefficients and the spline estimator of the nonparametric function. We propose an adjustment using a postprocessing technique. We show that under mild conditions the posterior is proper under the proposed USP, a flat prior for the fixed effect parameters, and an improper prior for the residual variance. We illustrate the proposed approach using a longitudinal hormone dataset, and carry out extensive simulation studies to compare its finite sample performance with existing methods.
Analyzing Incomplete Data Subject to a Threshold using Empirical Likelihood Methods: An Application to a Pneumonia Risk Study in an ICU Setting
Authors: Yu Jihnhee , Vexler Albert , Tian Lili
Published: May 2009

Summary The initial detection of ventilator‐associated pneumonia (VAP) for inpatients at an intensive care unit needs composite symptom evaluation using clinical criteria such as the clinical pulmonary infection score (CPIS). When CPIS is above a threshold value, bronchoalveolar lavage (BAL) is performed to confirm the diagnosis by counting actual bacterial pathogens. Thus, CPIS and BAL results are closely related and both are important indicators of pneumonia whereas BAL data are incomplete. To compare the pneumonia risks among treatment groups for such incomplete data, we derive a method that combines nonparametric empirical likelihood ratio techniques with classical testing for parametric models. This technique augments the study power by enabling us to use any observed data. The asymptotic property of the proposed method is investigated theoretically. Monte Carlo simulations confirm both the asymptotic results and good power properties of the proposed method. The method is applied to the actual data obtained in clinical practice settings and compares VAP risks among treatment groups.
On the Role of Baseline Measurements for Crossover Designs under the Self and Mixed Carryover Effects Model
Authors: Liang Yuanyuan , Carriere Keumhee Chough
Published: May 2009

Summary It is well known that optimal designs are strongly model dependent. In this article, we apply the Lagrange multiplier approach to the optimal design problem, using a recently proposed model for carryover effects. Generally, crossover designs are not recommended when carryover effects are present and when the primary goal is to obtain an unbiased estimate of the treatment effect. In some cases, baseline measurements are believed to improve design efficiency. This article examines the impact of baselines on optimal designs using two different assumptions about carryover effects during baseline periods and employing a nontraditional crossover design model. As anticipated, baseline observations improve design efficiency considerably for two‐period designs, which use the data in the first period only to obtain unbiased estimates of treatment effects, while the improvement is rather modest for three‐ or four‐period designs. Further, we find little additional benefits for measuring baselines at each treatment period as compared to measuring baselines only in the first period. Although our study of baselines did not change the results on optimal designs that are reported in the literature, the problem of strong model dependency problem is generally recognized. The advantage of using multiperiod designs is rather evident, as we found that extending two‐period designs to three‐ or four‐period designs significantly reduced variability in estimating the direct treatment effect contrast.
Adjustment for Missingness Using Auxiliary Information in Semiparametric Regression
Authors: Zeng Donglin , Chen Qingxia
Published: May 2009

Summary In this article, we study the estimation of mean response and regression coefficient in semiparametric regression problems when response variable is subject to nonrandom missingness. When the missingness is independent of the response conditional on high‐dimensional auxiliary information, the parametric approach may misspecify the relationship between covariates and response while the nonparametric approach is infeasible because of the curse of dimensionality. To overcome this, we study a model‐based approach to condense the auxiliary information and estimate the parameters of interest nonparametrically on the condensed covariate space. Our estimators possess the double robustness property, i.e., they are consistent whenever the model for the response given auxiliary covariates or the model for the missingness given auxiliary covariate is correct. We conduct a number of simulations to compare the numerical performance between our estimators and other existing estimators in the current missing data literature, including the propensity score approach and the inverse probability weighted estimating equation. A set of real data is used to illustrate our approach.
Determination of Sample Sizes for Demonstrating Efficacy of Radiation Countermeasures
Authors: Kodell Ralph L. , Lensing Shelly Y. , Landes Reid D. , Kumar K. Sree , Hauer‐Jensen Martin
Published: May 2009

Summary In response to the ever increasing threat of radiological and nuclear terrorism, active development of nontoxic new drugs and other countermeasures to protect against and/or mitigate adverse health effects of radiation is ongoing. Although the classical LD50 study used for many decades as a first step in preclinical toxicity testing of new drugs has been largely replaced by experiments that use fewer animals, the need to evaluate the radioprotective efficacy of new drugs necessitates the conduct of traditional LD50 comparative studies (FDA, 2002, Federal Register 67, 37988–37998). There is, however, no readily available method to determine the number of animals needed for establishing efficacy in these comparative potency studies. This article presents a sample‐size formula based on Student's t for comparative potency testing. It is motivated by the U.S. Food and Drug Administration's (FDA's) requirements for robust efficacy data in the testing of response modifiers in total body irradiation experiments where human studies are not ethical or feasible. Monte Carlo simulation demonstrated the formula's performance for Student's t, Wald, and likelihood ratio tests in both logistic and probit models. Importantly, the results showed clear potential for justifying the use of substantially fewer animals than are customarily used in these studies. The present article may thus initiate a dialogue among researchers who use animals for radioprotection survival studies, institutional animal care and use committees, and drug regulatory bodies to reach a consensus on the number of animals needed to achieve statistically robust results for demonstrating efficacy of radioprotective drugs.
Double‐Observer Line Transect Methods: Levels of Independence
Authors: Buckland Stephen T. , Laake Jeffrey L. , Borchers David L.
Published: May 2009

SummaryDouble‐observer line transect methods are becoming increasingly widespread, especially for the estimation of marine mammal abundance from aerial and shipboard surveys when detection of animals on the line is uncertain. The resulting data supplement conventional distance sampling data with two‐sample mark–recapture data. Like conventional mark–recapture data, these have inherent problems for estimating abundance in the presence of heterogeneity. Unlike conventional mark–recapture methods, line transect methods use knowledge of the distribution of a covariate, which affects detection probability (namely, distance from the transect line) in inference. This knowledge can be used to diagnose unmodeled heterogeneity in the mark–recapture component of the data. By modeling the covariance in detection probabilities with distance, we show how the estimation problem can be formulated in terms of different levels of independence. At one extreme, full independence is assumed, as in the Petersen estimator (which does not use distance data); at the other extreme, independence only occurs in the limit as detection probability tends to one. Between the two extremes, there is a range of models, including those currently in common use, which have intermediate levels of independence. We show how this framework can be used to provide more reliable analysis of double‐observer line transect data. We test the methods by simulation, and by analysis of a dataset for which true abundance is known. We illustrate the approach through analysis of minke whale sightings data from the North Sea and adjacent waters.
Impact of Population Substructure on Trend Tests for Genetic Case–Control Association Studies
Authors: Zheng Gang , Li Zhaohai , Gail Mitchell H. , Gastwirth Joseph L.
Published: May 2009

SummaryHidden population substructure in case–control data has the potential to distort the performance of Cochran–Armitage trend tests (CATTs) for genetic associations. Three possible scenarios that may arise are investigated here: (i) heterogeneity of genotype frequencies across unidentified subpopulations (PSI), (ii) heterogeneity of genotype frequencies and disease risk across unidentified subpopulations (PSII), and (iii) cryptic correlations within unidentified subpopulations. A unified approach is presented for deriving the bias and variance distortion under the three scenarios for any CATT in a general family. Using these analytical formulas, we evaluate the excess type I errors of the CATTs numerically in the presence of population substructure. Our results provide insight into the properties of some proposed corrections for bias and variance distortion and show why they may not fully correct for the effects of population substructure.
A Novel Approach to the Examination of Soil Evidence: Mineral Identification Using Infrared Microprobe Analysis*
Authors: Weinger Brooke A. , Reffner John A. , De Forest Peter R.
Published: May 2009

Abstract: Identification of minerals using the infrared microprobe with a diamond internal reflection objective is a rapid and reliable method for forensic soil examinations. Ninety‐six mineral varieties were analyzed, and 77 were differentiated by their attenuated total reflection (ATR) spectra. Mineral grains may be mounted in oil for conventional polarized light microscope characterization and their ATR spectrum obtained with little or no interference by the liquid. This infrared microprobe method can be used to identify silicates, phosphates, nitrates, carbonates, and other covalent minerals; however, ionic minerals, metal oxide and sulfide minerals, and minerals with refractive indexes greater than diamond do not produce identifiable spectra, but the lack of a spectrum or one with high absorbance values does provide useful information. This research demonstrates the overall utility that infrared microprobe analysis brings mineral identification in soil evidence.
An Analysis of Possible Mechanisms of Unexpected Death Occurring in Hydatid Disease (Echinococcosis)
Authors: Byard Roger W.
Published: May 2009

Abstract: Most cases of hydatid disease in human populations are due toEchinococcus granulosus.The hydatid life cycle involves passage between definitive hosts such as dogs and intermediate hosts such as sheep. Humans become accidental intermediate hosts following ingestion of food or water contaminated with eggs or by contact with infected dogs. Although hydatid disease may remain asymptomatic, occasional cases of sudden and unexpected death present to autopsy. Causes of rapid clinical decline involve a wide range of mechanisms including anaphylaxis (with or without cyst rupture), cardiac outflow obstruction or conduction tract disturbance, pulmonary and cerebral embolism, pericarditis, cardiac tamponade, myocardial ischemia, pulmonary hypertension, peritonitis, hollow organ perforation, intracerebral mass effect, obstructive hydrocephalus, seizures, cerebral ischemia/infarction, and pregnancy complications. The autopsy assessment of cases therefore requires careful examination of all organ systems for characteristic cystic lesions, as multiorgan involvement is common, with integration of findings so that possible mechanisms of death can be determined. Measurement of serum tryptase and specific IgE levels should be undertaken for possible anaphylaxis.
Validation of the Short Amplicon Multiplex Q8 Including the German DNA Database Systems*
Authors: Müller Kathrin , Braunschweiger Günter , Klein Rachel , Miltner Erich , Wiegand Peter
Published: May 2009

Abstract:  We have developed a concept to enable the analyzing of degraded stains with limited DNA template quantity. Therefore we have constructed a short tandem repeat (STR) multiplex including the German DNA database systems (Q8). The amplicon lengths are smaller than 280 bp. For the validation of Q8 over 50 degraded samples were investigated. Amplifications were performed with “low copy number” PCR, the number of PCR cycles was increased to 33 and the reaction volume was decreased to 12.5 μL. Compared with the MPX2 and Nonaplex kit, the average success rate was increased using the Q8 kit by approximately 20% and 30%, respectively. The efficiency of a sensitive STR multiplex with reduced amplicon lengths was confirmed in comparing the success rates of Q8 for typing degraded samples and samples with limited amount of DNA template while partial profiles were observed with the majority of the samples using commercially available kits.
Practical Aspects of Analyzing Vegetable Oils in Fire Debris*
Authors: Schwenk Lisa M. , Reardon Michelle R.
Published: May 2009

Abstract:  Vegetable oils undergo burning, self‐heating, and spontaneous ignition, resulting in their presence in fire debris. As these processes can affect the fatty acid content of vegetable oils, it is important that debris be properly handled in order to obtain reliable and informative data. This research investigated changes in vegetable oil content as a result of storage conditions and different types of burning. Material spiked with vegetable oils and burned was stored under various long‐term conditions, and debris was tested by heating overnight using passive headspace concentration. Results indicated that refrigeration is ideal for fire debris samples suspected of containing vegetable oils and that including passive headspace concentration in the analytical scheme would not affect oils. Spontaneous ignition experiments were conducted to compare the effects of various burning processes on vegetable oil content. Vegetable oils that experienced nonpiloted ignition, self‐heating, and spontaneous ignition produced noticeably different chromatograms from those that underwent piloted ignition.
A history of childhood attention‐deficit hyperactivity disorder (ADHD) impacts clinical outcome in adult bipolar patients regardless of current ADHD
Authors: Rydén E. , Thase M. E. , Stråht D. , Åberg‐Wistedt A. , Bejerot S. , Landén M.
Published: May 2009

Objective:  The occurrence of comorbid attention‐deficit hyperactivity disorder (ADHD) might have an impact of the course of the bipolar disorder.

Method:  Patients with bipolar disorder (n = 159) underwent a comprehensive evaluation with respect to affective symptoms. Independent psychiatrists assessed childhood and current ADHD, and an interview with a parent was undertaken.

Results:  The prevalence of adult ADHD was 16%. An additional 12% met the criteria for childhood ADHD without meeting criteria for adult ADHD. Both these groups had significantly earlier onset of their first affective episode, more frequent affective episodes (except manic episodes), and more interpersonal violence than the bipolar patients without a history of ADHD.

Conclusion:  The fact that bipolar patients with a history of childhood ADHD have a different clinical outcome than the pure bipolar group, regardless of whether the ADHD symptoms remained in adulthood or not, suggests that it represent a distinct early‐onset phenotype of bipolar disorder.
Glossopharyngeal pistoning for lung insufflation in children with spinal muscular atrophy type II
Authors: Nygren‐Bonnier Malin , Markström Agneta , Lindholm Peter , Mattsson Eva , Klefbeck Brita
Published: May 2009

Aim:  To evaluate whether children with spinal muscular atrophy (SMA) type II were able to learn glossopharyngeal pistoning for lung insufflation (GI), and to evaluate the effects of GI on pulmonary function and chest expansion.

Methods:  Eleven children with SMA type II were recruited. They performed 10 cycles of GI, four times per week, for 8 weeks. Lung function and chest expansion were measured before and after the 8‐week period.

Results:  Five of the 11 children learned the technique. The median GI volume was 0.28 (range 0.15–0.98) L. Four of the children who completed the study showed a mean increase in inspiratory vital capacity (IVC) of 0.13 L (95% confidence interval (CI) 0.03–0.23) and peak expiratory flow (PEF) of 116 L/min (95% CI 60–173). They also had an increased chest expansion with GI at the level of the xiphoid process of 1.50 cm (95% CI 0.16–2.84) and at the level of the fourth costa of 1.79 cm (95% CI 0.85–2.73). The children reported temporary symptoms of dizziness and tension in the chest.

Conclusion:  Five of the 11 children were able to learn the technique of GI and for the four who fulfilled the training, it had positive effects on IVC, PEF and chest expansion. GI did not cause major discomfort.
A comparison of patient satisfaction between treatment with conventional complete dentures and overdentures in the elderly: a literature review
Authors: Assunção Wirley Gonçalves , Barão Valentim Adelino Ricardo , Delben Juliana Aparecida , Gomes Érica Alves , Tabata Lucas Fernando
Published: May 2009

doi:10.1111/j.1741‐2358.2009.00299.x
 
A comparison of patient satisfaction between treatment with conventional complete dentures and overdentures in the elderly: a literature review

Background:  It has been stated that mandibular overdentures are more satisfactory than conventional dentures, but problems relating to the use of retrospective ratings, lack of control group and sequential provision of treatment may compromise the findings.

Objective:  To establish a comparison between treatment with conventional complete dentures and implant‐retained overdentures in elderly patients by conducting a literature review.

Materials and methods:  A search of English language peer‐review literature was completed using Medline up to 2008 focusing on evidence‐based research. Randomised clinical trials (RCTs) and longitudinal prospective studies were favoured in the review, using a general hierarchical classification. Articles that did not focus exclusively on the comparison of patient satisfaction between complete dentures and overdentures were excluded from further evaluation. The last search was conducted in February 2008. Key terms included quality of life, patient satisfaction, edentulism, complete denture and overdenture.

Results:  Among the 90 articles found in the initial search, 27 met the inclusion criteria. This included 18 RCTs and eight prospective and one cohort study. Most of the articles stated superiority of the mandibular implant‐retained overdenture therapy over the conventional complete denture regarding patient satisfaction and quality of life.

Conclusion:  Even with implant treatment presenting higher patient satisfaction and improvement of quality of life, it was not possible to establish a direct comparison between the studies due to differences in adopted methodologies.
A Survey on Prevention of Surgical Infections in Operating Theaters
Authors: Demir Fatma
Published: May 2009

Background: It is well known that surgical site infections (SSIs) contribute significantly to the cost of nosocomial infections. Although many guidelines and recommendations exist, research has demonstrated that practices for preventing SSIs in operating theaters (OT) vary.

Aim: The purpose of this study was to describe the current infection control practices for SSIs, formerly called surgical wound infections, in OTs, and compare these findings with evidence‐based practice guidelines.

Methods: In order to accomplish the purpose, a prospective, cross‐sectional descriptive survey was conducted. Data were collected by interviewing the charge nurses in 24 OTs of 11 hospitals in the city of Izmir, Turkey. The results were tabulated and compared with an evidence‐based guideline.

Results: Data showed that there is a lack of adherence to the guideline. The most compliant areas to the guideline were hand/forearm antisepsis and the use of surgical gowns and drapes.

Implications: It is suggested that increased compliance to infection control guidelines for surgical infections in OTs would facilitate providing best practice and evidence‐based care. There is a need for further research to determine why there is a difference between what is practiced and what guidelines indicate should be practiced.
The pivotal regulator GlnB of Escherichia coli is engaged in subtle and context‐dependent control
Authors: van Heeswijk Wally C. , Molenaar Douwe , Hoving Sjouke , Westerhoff Hans V.
Published: May 2009

This study tests the purported signal amplification capability of the glutamine synthetase (GS) regulatory cascade in Escherichia coli. Intracellular concentrations of the pivotal regulatory protein GlnB were modulated by varying expression of its gene (glnB). Neither glnB expression nor PII* (i.e. the sum of the concentration of the PII‐like proteins GlnB and GlnK) had control over the steady‐state adenylylation level of GS when cells were grown in the presence of ammonia, in which glnK is not activated. Following the removal of ammonia, the response coefficient of the transient deadenylylation rate of GS–AMP was again zero with respect to both glnB expression and PII* concentration. This was at wild‐type PII* levels. A 20% decrease in the PII* level resulted in the response coefficients increasing to 1, which was quite significant yet far from expected for zero‐order ultrasensitivity. The transient deadenylylation rate of GS–AMP after brief incubation with ammonia was also measured in cells grown in the absence of ammonia. Here, GlnK was present and both glnB expression and PII* lacked control throughout. Because at wild‐type levels of PII*, the molar ratio of PII*‐trimer/adenylyltransferase‐monomer was only slightly above 1, it is suggested that the absence of control by PII* is caused by saturation of adenylyltransferase by PII*. The difference in the control of deadenylylation by PII* under the two different growth conditions indicates that control of signal transduction is adjusted to the growth conditions of the cell. Adjustment of regulation rather than ultrasensitivity may be the function of signal transduction chains such as the GS cascade. We discuss how the subtle interplay between GlnB, its homologue GlnK and the adenylyltransferase may be responsible for the ‘redundant’, but quantitative, phenotype of GlnB.
Characterization of the NAD(P)H oxidase and metronidazole reductase activities of the RdxA nitroreductase of Helicobacter pylori
Authors: Olekhnovich Igor N. , Goodwin Avery , Hoffman Paul S.
Published: May 2009

Metronidazole (MTZ) is widely used in combination therapies against the human gastric pathogen Helicobacter pylori. Resistance to this drug is common among clinical isolates and results from loss‐of‐function mutations in rdxA, which encodes an oxygen‐insensitive nitroreductase. The RdxA‐associated MTZ‐reductase activity of H. pylori is lost upon cell disruption. Here we provide a mechanistic explanation for this phenomenon. Under aerobic conditions, His6‐tagged RdxA protein (purified from Escherichia coli), catalyzed NAD(P)H‐dependent reductions of nitroaromatic and quinone substrates including nitrofurazone, nitrofurantoin, furazolidone, CB1954 and 1,4‐benzoquinone, but not MTZ. Unlike other nitroreductases, His6–RdxA exhibited potent NAD(P)H‐oxidase activity (kcat = 2.8 s−1) which suggested two possible explanations for the role of oxygen in MTZ reduction: (a) NAD(P)H‐oxidase activity promotes cellular hypoxia (nonspecific reduction of MTZ), and (b) molecular oxygen out‐competes MTZ for reducing equivalents. The first hypothesis was eliminated upon finding that rdxA expression, although increasing MTZ toxicity in both E. coli and H. pylori constructs, did not increase paraquat toxicity, even though both are of similar redox potential. The second hypothesis was confirmed by demonstrating NAD(P)H‐dependent MTZ‐reductase activity (apparent Km = 122 ± 58 μm, kcat = 0.24 s−1) under strictly anaerobic conditions. The MTZ‐reductase activity of RdxA was 60 times greater than for NfsB (E. coli NTR), but 10 times lower than the NADPH‐oxidase activity. Whether molecular oxygen directly competes with MTZ or alters the redox state of the FMN cofactors is discussed.
Penile Prosthesis Implantation Compares Favorably in Malpractice Outcomes to Other Common Urological Procedures: Findings from a Malpractice Insurance Database
Authors: Chason Juddson , Sausville Justin , Kramer Andrew C.
Published: May 2009

Introduction

Some urologists choose not to offer penile prostheses because of concern over malpractice liability.

Aim

The aim of this study was to assess whether urologists performing penile prosthesis surgery are placed at a greater malpractice risk.

Main Outcome Measures

Percentage of malpractice suits from prosthesis surgery and other urological procedures that result in payment, average resulting payout from these cases, and category of legal issue that ultimately resulted in payout.

Methods

A database from the Physician Insurers Association of America, an association of malpractice insurance companies covering physicians in North America, was analyzed to quantitatively compare penile implant surgery to other urological procedures in medicolegal terms.

Results

Compared to other common urological procedures, penile implant is comparable and on the lower end of the spectrum in terms of both the percentage of malpractice suits that result in payment and the amount ultimately paid in indemnity from those cases. Additionally, issues of informed consent play the largest role in indemnities for all urological procedures, whereas surgical technique is the most important issue for prosthesis surgery.

Conclusions

Urologists who are adequately trained in prosthetic surgery should not avoid penile implant procedures for fear of malpractice suits. A focus on communication and informed consent can greatly reduce malpractice risk for urological procedures.
Prevalence and Characteristics of Vibrator Use by Women in the United States: Results from a Nationally Representative Study
Authors: Herbenick Debra , Reece Michael , Sanders Stephanie , Dodge Brian , Ghassemi Annahita , Fortenberry J. Dennis
Published: May 2009

Introduction

Although vibrators are commonly recommended by clinicians as adjunct to treatment for female sexual dysfunction, and for sexual enhancement, little is known about their prevalence or correlates of use.

Aim

The aim of this study was to determine the lifetime and recent prevalence of women’s vibrator use during masturbation and partnered sex, and the correlates of use related to sociodemographic variables, health behaviors, and sexual function.

Methods

A nationally representative sample of 3,800 women aged 18–60 years were invited to participate in a cross-sectional Internet-based survey; 2,056 (54.1%) participated.

Main Outcome Measures

The prevalence of vibrator use, the relationship between vibrator use and physical and psychological well-being (as assessed by the Centers for Disease Control and Prevention [CDC] Healthy Days measure) and health-promoting behaviors, the relationship between vibrator use and women’s scores on the Female Sexual Function Index, and an assessment of the frequency and severity of side effects potentially associated with vibrator use.

Results

The prevalence of women’s vibrator use was found to be 52.5% (95% CI 50.3–54.7%). Vibrator users were significantly more likely to have had a gynecologic exam during the past year (P < 0.001) and to have performed genital self-examination during the previous month (P < 0.001). Vibrator use was significantly related to several aspects of sexual function (i.e., desire, arousal, lubrication, orgasm, pain, overall function) with recent vibrator users scoring higher on most sexual function domains, indicating more positive sexual function. Most women (71.5%) reported having never experienced genital symptoms associated with vibrator use. There were no significant associations between vibrator use and participants’ scores on the CDC Healthy Days Measures.

Conclusions

Vibrator use among women is common, associated with health-promoting behaviors and positive sexual function, and rarely associated with side effects. Clinicians may find these data useful in responding to patients’ sexual issues and recommending vibrator use to improve sexual function. Further research on the relationships between vibrator use and sexual health is warranted.
The Prevalence of Hypoactive Sexual Desire Disorder in Surgically Menopausal Women: An Epidemiological Study of Women in Four European Countries
Authors: Graziottin Alessandra , Koochaki Patricia E. , Rodenberg Cynthia A. , Dennerstein Lorraine
Published: May 2009

Introduction

Insufficient documentation exists regarding the prevalence of hypoactive sexual desire disorder (HSDD) in surgically menopausal (SM) women in European countries. Women who have undergone hysterectomy and bilateral oophorectomy experience a loss of ovarian hormones. Inclusion of these women in an epidemiological study provided the opportunity to study biological and cultural impacts on sexual function.

Aim

The aim of this study was to compare the prevalence of HSDD among SM women in France, Germany, Italy, and the United Kingdom, as well as the relationship between low sexual desire and sexual activity or behavior, and sexual or partner relationship satisfaction.

Methods

Cross-sectional survey of a convenience sample of 427 SM women aged 20–70 years.

Main Outcome Measures

The desire domain of the Profile of Female Sexual Function (PFSF) to identify women with low sexual desire, Personal Distress Scale (PDS) to measure distress caused by low sexual desire, and a sexual activities measure. Women with low sexual desire who were distressed were classified as having HSDD.

Results

SM women having low sexual desire ranged from 35% (United Kingdom) to 44% (Italy); of these women, 16% (Germany) to 56% (France) were distressed because of their low sexual desire. Overall, SM women classified with HSDD ranged from 7% (Germany) to 22% (France). A strong positive correlation was observed between sexual desire and arousal, orgasm, and sexual pleasure in all countries (P < 0.001). Low sexual desire leads to less sexual activity, more dissatisfaction with sex life and partner relationship, and more negative emotional or psychological states, than normal desire in each country.

Conclusions

A similar percentage of SM women with low sexual desire were found across countries suggesting the role of biological factors (i.e., losing ovarian hormones) in determining sexual desire. Differences in the percentage of SM women with HSDD suggest a role for cultural factors in determining how low sexual desire is perceived.
A Conceptual Framework for the Evolution of Sexual Medicine and a Model for the Development of Alternative Sexual Health Services: 10-Year Experience of the Center for Sexual and Reproductive Health
Authors: Kirana Paraskevi-Sofia , Papaharitou Stamatis , Athanasiadis Loukas , Nakopoulou Evangelia , Salpiggidis George , Moysidis Kyriakos , Pipilaki Chryssa , Hatzimouratidis Konstantinos , Tzotstzis Vassilios , Portseli Aleka , Iraklidou Maria , Apostolidis Apostolos , Bekos Athanasios , Hatzichristou Dimitrios
Published: May 2009

Introduction

Sexual health services are limited and inadequate to reduce factors that hinder treatment and adequate care, despite the growing interest for public awareness and prevention strategies.

Aim

The aim of this study was to present an integrative conceptual framework, which led to the development of a model of alternative sexual health services and the 10-year experience of the practice of the service.

Main Outcome Measures

Multiple-level needs assessments.

Methods

The conceptual framework is composed of four distinct elements: (i) it adopts a social/ecological perspective; (ii) it assumes that results are optimal when multiple interventions are used; (iii) interventions are influenced by behavioral theories; and (iv) sexual health is conceptualized through the biopsychosocial model. Based on this model, a Sexual and Reproductive Health Center was developed, dedicated to research, education, and public awareness.

Results

Over 10 years of experience show that the present approach constitutes a process which: (i) facilitates our understanding of the needs at individual, community, and system level; and (ii) increases the individuals’, community and systems’ capacity to control sexual health.

Conclusion. 

Alternative models for sexual and reproductive health services should be encouraged, in order for best practices to be explored and identified. In addition, future research in the effectiveness of such interventions shall be beneficial in order for evidence-based interventions to be designed.
Role of shear stress on nitrite and NOS protein content in different size conduit arteries of swine
Authors: Guo X. , Kassab G. S.
Published: May 2009

Aim:  Inherent fundamental difference exists among arteries of different sizes. The purpose of this study was to evaluate the relation between regional difference of wall shear stress (WSS) in various sizes arteries and contents of nitrite and NO synthase (NOS) isoforms.

Methods:  Five different conduit arteries in a wide range of diameter (1–8 mm) were examined in the hind limbs of 13 pigs. Blood flow rate and outer diameter were measured in vivo to determine WSS. Arterial tissues were harvested for the measurement of nitrite and NOS protein contents. The concentration of nitrite, a product of NO synthesis, was determined by high‐performance liquid chromatography method. Western blot analysis was used to assess the protein contents of endothelial NOS (eNOS), inducible NOS (iNOS) and neuronal NOS (nNOS).

Results:  Our data show that WSS increases with a decrease in artery diameter. Nitrite level increases with increasing WSS and hence decreases with artery diameter. The eNOS protein contents decrease with an increase in diameter. No significant difference for iNOS and nNOS protein contents was found with different artery diameter. A significant positive correlation between tissue nitrite and eNOS protein contents was also observed. Finally, the WSS‐normalized eNOS is not significantly different in various size vessels.

Conclusion:  Regional difference in blood flow has no effect on iNOS and nNOS protein contents in these conduit arteries. Regional difference in eNOS expression and nitrite contents may be related to the WSS‐induced NO by the endothelium under normal physiological conditions.
Post‐ischaemic activation of kinases in the pre‐conditioning‐like cardioprotective effect of the platelet‐activating factor
Authors: Penna C. , Mognetti B. , Tullio F. , Gattullo D. , Mancardi D. , Moro F. , Pagliaro P. , Alloatti G.
Published: May 2009

Aim:  Platelet‐activating factor (PAF) triggers cardiac pre‐conditioning against ischemia/reperfusion injury. The actual protection of ischaemic pre‐conditioning occurs in the reperfusion phase. Therefore, we studied in this phase the kinases involved in PAF‐induced pre‐conditioning.

Methods:  Langendorff‐perfused rat hearts underwent 30 min of ischaemia and 2 h of reperfusion (group 1, control). Before ischaemia, group 2 hearts were perfused for 19 min with PAF (2 × 10−11 m); groups 3–5 hearts were co‐infused during the initial 20 min of reperfusion, with the protein kinase C (PKC) inhibitor chelerythrine (5 × 10−6 m) or the phosphoinositide 3‐kinase (PI3K) inhibitor LY294002 (5 × 10−5 m) and atractyloside (2 × 10−5 m), a mitochondrial permeability transition pore (mPTP) opener respectively. Phosphorylation of PKCε, PKB/Aκt, GSK‐3β and ERK1/2 at the beginning of reperfusion was also checked. Left ventricular pressure and infarct size were determined.

Results:  PAF pre‐treatment reduced infarct size (33 ± 4% vs. 64 ± 5% of the area at risk of control hearts) and improved pressure recovery. PAF pre‐treatment enhanced the phosphorylation/activation of PKCε, PKB/Aκt and the phosphorylation/inactivation of GSK‐3β at reperfusion. Effects on ERK1/2 phosphorylation were not consistent. Infarct‐sparing effect and post‐ischaemic functional improvement induced by PAF pre‐treatment were abolished by post‐ischaemic infusion of either chelerythrine, LY294002 or atractyloside.

Conclusions:  The cardioprotective effect exerted by PAF pre‐treatment involves activation of PKC and PI3K in post‐ischaemic phases and might be mediated by the prevention of mPTP opening in reperfusion via GSK‐3β inactivation.
Patterns and Processes of Tree Islands in Two Transitional Environments: Alpine Treeline and Bog Forest‐Meadow Ecotones
Authors: Resler Lynn M. , Stine Melanie B.
Published: May 2009

Clusters of trees surrounded by a dissimilar type of vegetation are known as ‘tree islands’. Vegetation patterns at ecotones are often comprised of tree islands. Many studies, primarily from ecology and botany, have helped researchers understand tree islands from an ecological perspective. However, a look at tree islands in the context of pattern–process relationships helps to frame these important landscape features within a geographic perspective. At alpine treelines and bog forest‐meadow ecotones, tree islands are distinctive, finite, close to the environmental limits of trees, and relatively easy to observe. Therefore, they are interesting features with which to examine the effects of broader environmental change, and internal dynamics, such as positive plant interactions. In this article, we first broadly describe tree island patterns and their growth forms at the Cranberry Glades Botanical Area in West Virginia, and at alpine treelines of the North American Rocky Mountains. Internal and external factors that affect tree island distributions are then discussed. Finally, we examine how the fundamental similarities and contrasts between tree islands at treelines and bogs increase our understanding of broader environmental change, controls, and constraints.
Biophysical Remote Sensing and Climate Data in Famine Early Warning Systems
Authors: Brown Molly E.
Published: May 2009

Famine early warning systems use remote sensing in combination with socioeconomic and household food economy analysis to provide timely and rigorous information on emerging food security crises. The Famine Early Warning Systems Network (FEWS NET) is the US Agency for International Development's decision support system in 20 African countries, as well as in Guatemala, Haiti and Afghanistan. FEWS NET provides early and actionable policy guidance for the US government and its humanitarian aid partners. As we move into an era of climate change where weather hazards will become more frequent and severe, understanding how to provide quantitative and actionable scientific information for policy‐makers using biophysical data is critical for an appropriate and effective response.