bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired glucose tolerance and metabolic syndrome in idiopathic neuropathy
Authors: Gordon Smith A.
Published: May 2012

Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case–control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT‐associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies.
Autoimmune neuropathies: insights from animal models
Authors: Soliven Betty
Published: May 2012

Autoimmune neuropathies comprise a diverse group of conditions resulting from an immune attack on the peripheral nervous system. In some of these disorders, the antigenic target has been identified. In other conditions such as chronic inflammatory demyelinating polyradiculoneuropathy, the initial trigger and the antigenic target remain elusive. Animal models have provided some important information regarding their pathogenetic mechanisms. This review summarizes the background information and recent highlights from studies in animal models such as experimental autoimmune neuritis and spontaneous autoimmune polyneuropathy in B7‐2 knockout non‐obese diabetic mice.
Naltrexone Modification of Drinking Effects in a Subacute Treatment and Bar‐Lab Paradigm: Influence of OPRM1 and Dopamine Transporter (SLC6A3) Genes
Authors: Anton Raymond F. , Voronin Konstantin K. , Randall Patrick K. , Myrick Hugh , Tiffany Abraham
Published: May 2012

Background

Naltrexone is moderately effective for the treatment of alcohol dependence, but there is great individual variability. The opioid receptor (OPRM1) single nucleotide polymorphism (SNP) asn40asp has been shown to alter alcohol and naltrexone response in animals and humans. In addition, the brain opioid and dopamine systems interact and might underlie drinking and craving. This study investigated the effects of the OPRM1 SNP and dopamine transporter (DAT) variable number of tandem repeat (VNTR) genetic differences on drinking, alcohol effects, and naltrexone response under controlled conditions in nontreatment‐seeking alcoholics.

Methods

Two hundred and sixty‐five nontreatment‐seeking individuals with alcohol dependence were genotyped a priori for the OPRM1 asn40asp SNP and post hoc for DAT (SLC6A3) 9 and 10 VNTRs. Asp40 carriers (n = 43) and matched asn40 homozygotes (n = 40) were randomized to naltrexone or placebo for 7 days before receiving a priming drink and limited‐access alcohol consumption in a bar‐lab setting. Effects of genotypes on natural drinking as well as drinking, alcohol effects, and response to naltrexone in the bar‐lab setting were examined by genotype.

Results

There were no significant main effects of naltrexone or OPRM1 genotype, or any medication by OPRM1 interaction, on drinking variables. However, in individuals who had at least one DAT 9 VNTR, and who were also OPRM1 asn40 homozygotes, naltrexone reduced drinks/d consumed under natural conditions (p = 0.006), but not in the bar‐lab. OPRM1 asn40 homozygotes (p = 0.028) and DAT 9 VNTR carriers (p = 0.032) had more stimulation to alcohol after the priming drink.

Conclusions

This study does not support a salient role for the OPRM1 asp40 alone in predicting drinking or naltrexone effects. However, although exploratory and in need of replication, it introduces the possibility that epistasis between the OPRM1 gene and DAT gene might need to be taken into account when examining differential genetic response to alcohol or medication treatment, especially in early‐stage alcoholics.
Ethanol Blocks the Reversal of Prolonged Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area
Authors: Nimitvilai Sudarat , Arora Devinder S. , McElvain Maureen A. , Brodie Mark S.
Published: May 2012

Background

Dopaminergic (DAergic) neurons of the ventral tegmental area (VTA) are important for the rewarding and reinforcing properties of alcohol and other drugs of abuse. Regulation of the firing of DAergic VTA neurons is controlled by a number of factors, including autoregulation of firing by D2 dopamine (DA) receptors. The inhibitory effects of DA on these neurons exhibit concentration‐ and time‐dependent desensitization, which we have termed dopamine inhibition reversal (DIR), as it requires concurrent stimulation of D1/D5 and D2 receptors.

Methods

Extracellular recording of DAergic VTA neurons in brain slices was used to test the effects of ethanol (EtOH) (10 to 80 mM) on DIR.

Results

DIR was reduced by concentrations of EtOH as low as 10 mM and was blocked by higher EtOH concentrations. In addition, as we have shown that reversal of inhibition by the selective D2 agonist quinpirole can be observed in the presence of an activator of protein kinase C (PKC), we tested whether EtOH could antagonize the reversal of quinpirole inhibition in the presence of phorbol 12‐myristate 13‐acetate (PMA). EtOH (80 mM) blocked the reversal of quinpirole seen in the presence of PMA, suggesting that the antagonism of DIR by EtOH is owing to an action at a stage in the mechanism at or distal to PKC. Once achieved, DIR is not antagonized by EtOH.

Conclusions

The blockade by relatively low concentrations of EtOH of DIR may play an important role in the spectrum of action of EtOH on DAergic neurons of the VTA and may be important in the acute and chronic actions of EtOH on the excitability of these brain reward/reinforcement neurons.
Positron Emission Tomography Shows Elevated Cannabinoid CB1 Receptor Binding in Men with Alcohol Dependence
Authors: Neumeister Alexander , Normandin Marc D. , Murrough James W. , Henry Shannan , Bailey Christopher R. , Luckenbaugh David A. , Tuit Keri , Zheng Ming‐Qiang , Galatzer‐Levy Isaac R. , Sinha Rajita , Carson Richard E. , Potenza Marc N. , Huang Yiyun
Published: May 2012

Background

Several lines of evidence link cannabinoid (CB) type 1 (CB
1) receptor‐mediated endogenous CB (eCB) signaling to the etiology of alcohol dependence (AD). However, to date, only peripheral measures of eCB function have been collected in living humans with AD and no human in vivo data on the potentially critical role of the brain CB
1 receptor in AD have been published. This is an important gap in the literature, because recent therapeutic developments suggest that these receptors could be targeted for the treatment for AD.

Methods

Medication‐free participants were scanned during early abstinence 4 weeks after their last drink. Using positron emission tomography (PET) with a high‐resolution research tomograph and the CB
1 receptor selective radiotracer [11
C]OMAR, we determined [11
C]OMAR volume of distribution (
V

T) values, a measure of CB
1 receptor density, in a priori selected brain regions in men with AD (n = 8, age 37.4 ± 7.9 years; 5 smokers) and healthy control (HC) men (n = 8, age 32.5 ± 6.9 years; all nonsmokers). PET images reconstructed using the MOLAR algorithm with hardware motion correction were rigidly aligned to the subject‐specific magnetic resonance (MR) image, which in turn was warped to an MR template. Time–activity curves (TACs) were extracted from the dynamic PET data using a priori selected regions of interest delineated in the MR template space.

Results

In AD relative to HC, [11
C]OMAR

V

T values were elevated by approximately 20% (p = 0.023) in a circuit, including the amygdala, hippocampus, putamen, insula, anterior and posterior cingulate cortices, and orbitofrontal cortex. Age, body mass index, or smoking status did not influence the outcome.

Conclusions

These findings agree with preclinical evidence and provide the first, albeit still preliminary in vivo evidence suggesting a role for brain CB
1 receptors in AD. The current study design does not answer the important question of whether elevated CB
1 receptors are a preexisting vulnerability factor for AD or whether elevations develop as a consequence of AD.
Gross Direct and Embodied Carbon Sinks for Urban Inventories
Authors: Mohareb Eugene , Kennedy Christopher
Published: May 2012

Cities and urban regions are undertaking efforts to quantify greenhouse (GHG) emissions from their jurisdictional boundaries. Although inventorying methodologies are beginning to standardize for GHG sources, carbon sequestration is generally not quantified. This article describes the methodology and quantification of gross urban carbon sinks.

Sinks are categorized into direct and embodied sinks. Direct sinks generally incorporate natural process, such as humification in soils and photosynthetic biomass growth (in urban trees, perennial crops, and regional forests). Embodied sinks include activities associated with consumptive behavior that result in the import and/or storage of carbon, such as landfilling of waste, concrete construction, and utilization of durable wood products.

Using methodologies based on the Intergovernmental Panel on Climate Change 2006 guidelines (for direct sinks) and peer‐reviewed literature (for embodied sinks), carbon sequestration for 2005 is calculated for the Greater Toronto Area. Direct sinks are found to be 317 kilotons of carbon (kt C), and are dominated by regional forest biomass. Embodied sinks are calculated to be 234 kt C based on one year's consumption, though a complete life cycle accounting of emissions would likely transform this sum from a carbon sink to a source. There is considerable uncertainty associated with the methodologies used, which could be addressed with city‐specific stock‐change measurements. Further options for enhancing carbon sink capacity within urban environments are explored, such as urban biomass growth and carbon capture and storage.
Information and Communication Technology‐Enabled Low Carbon Technologies
Authors: Catulli Maurizio , Fryer Emma
Published: May 2012

This article outlines the subsector of the information and communication technology (ICT) industry concerned with reducing the economy's environmental impact, dubbed ICT‐enabled low carbon technologies (ICTeLCTs). The article is based on a study funded by United Kingdom (UK) Trade and Investment, a division of the UK Department for Business, Innovation and Skills. ICTeLCTs can be segmented into specialist and generalist operators. Specialists focus on one or two ICT applications to monitor or reduce environmental issues, while generalists supply products and services enabling a firm or a private household to reduce the environmental impact of its activities. The subsector can be further segmented into green ICT, energy management, building management, carbon accounting, waste management, intelligent transport systems (ITSs), and water management. The main factors driving ICTeLCTs include legislation, voluntary environmental standards, corporate social responsibility (CSR) activities, customer demand, and competitive market factors. Policy makers should continue to drive the growth of ICTeLCTs with the introduction and refinement of environmental legislation regulating energy use and markets.
Environmental Damage Assessment of Carbon Capture and Storage
Authors: Singh Bhawna , Strømman Anders H. , Hertwich Edgar G.
Published: May 2012

An end‐point life cycle impact assessment is used to evaluate the damages of electricity generation from fossil fuel‐based power plants with carbon dioxide capture and storage (CCS) technology. Pulverized coal (PC), integrated gasification combined cycle (IGCC), and natural gas combined cycle (NGCC) power plants are assessed for carbon dioxide (CO2) capture, pipeline transport, and storage in a geological formation. Results show that the CCS systems reduce the climate change‐related damages but increase the damages from toxicity, acidification, eutrophication, and resource consumption. Based on the currently available damage calculation methods, it is concluded that the benefit of reducing damage from climate change is larger than the increases in other damage categories, such as health effects from particulates or toxic chemicals. CCS significantly reduces the overall environmental damage, with a net reduction of 60% to 70% in human health damage and 65% to 75% in ecosystem damage. Most of the damage is due to fuel production and combustion processes. The energy and infrastructure demands of CCS cause increases in the depletion of natural resources by 33% for PC, 19% for IGCC, and 18% for NGCC power plants, mostly due to increased fossil fuel consumption.
Comparison of Body Weight Distribution, Peak Vertical Force, and Vertical Impulse as Measures of Hip Joint Pain and Efficacy of Total Hip Replacement
Authors: Seibert Rachel , Marcellin‐Little Denis J. , Roe Simon C. , DePuy Venita , Lascelles B. Duncan X.
Published: May 2012

Objective

To determine whether there is a difference between the ability of peak vertical force (PVF), vertical impulse (VI), and percentage body weight distribution (%BWdist) in differentiating which leg is most affected by hip joint pain before total hip replacement (THR) surgery, and for measuring changes in limb use afterTHRsurgery.

Study Design

Prospective clinical study.

Animals

Dogs (n = 47).

Methods

Ground reaction force (GRF) data were collected using a pressure‐sensitive walkway the day beforeTHRsurgery and at ∼3, 6, and 12 months postoperatively.PVFandVIexpressed as a percentage of body weight (%PVF, %VI), and %BWdistwere recorded. Regression models performed separately for each outcome were used for statistical analysis.

Results

When comparing limb use between the affected limb (AP) and the nonaffected limb (NP) preoperatively, differences between limbs were statistically significant when evaluated usingPVF(P= .023),VI(P= .010), and %BWdist(P= .012). When evaluating the magnitude of absolute and percentage change difference inAPlimb use preoperatively versus postoperatively, differences were statistically significant when evaluated usingPVF(P< .001 andP= .001, respectively),VI(P= .001 andP< .001) and %BWdist(P< .001 andP< .001).

Conclusion

There appeared to be no difference in the sensitivity ofVI,PVF, and %BWdistfor evaluating limb use before and afterTHR.
Designing Index‐Based Livestock Insurance for Managing Asset Risk in Northern Kenya
Authors: Chantarat Sommarat , Mude Andrew G. , Barrett Christopher B. , Carter Michael R.
Published: May 2012

Abstract

This article describes a novel index‐based livestock insurance (IBLI) product piloted among pastoralists in Northern Kenya, where insurance markets are effectively absent and uninsured risk exposure is a main cause of poverty. We describe the methodology used to design the contract and its underlying index of predicted area‐average livestock mortality, established statistically using longitudinal observations of household‐level herd mortality fit to remotely sensed vegetation data. Household‐level performance analysis based on simulations finds that IBLI removes 25–40 percent of total livestock mortality risk. We describe the contract pricing and the risk exposures of the underwriter to establish IBLI's reinsurability on international markets.
China's Labyrinth: The Rise of Monitory Democracy
Authors: KEANE JOHN
Published: May 2012

The new element in governance is social media. Inexorably, its fertile networks of shared information shift power from authorities to citizens and amateurs, including to the “unknown” experts in the “dorm rooms and edges of society” who drive innovation.

Tweets may bust trust and undermine authority, but can social media also be a tool for building consensus through deliberation and negotiation among interests? When it comes to governance, is crowd‐sourcing any better than populism at generating collective intelligence instead of disruptive “dumb mobs?” Can networks aid the self‐administration of society, or does that take institutions with governing authority?

In this section, leading Silicon Valley entrepreneurs, technologists and network theorists from Google, Microsoft and the MIT Media Lab join with political scientist Francis Fukuyama and top thinkers from Asia to address these issues.
Method of Pacing Does Not Affect the Recurrence of Syncope in Carotid Sinus Syndrome
Authors: MCLEOD CHRISTOPHER J. , TRUSTY JANE M. , JENKINS SARAH M. , REA ROBERT F. , CHA YONG‐MEI , ESPINOSA RAUL A. , FRIEDMAN PAUL A. , HAYES DAVID L. , SHEN WIN‐KUANG
Published: May 2012

Introduction:

Pacemaker therapy is effective in reducing recurrent syncope in patients with symptomatic carotid sinus hypersensitivity (CSH), yet the optimal pacing modality for this syndrome is not known. The objective of this study is to prospectively investigate the impact of three pacing methods (DDDR vs DDDR with sudden bradycardia response [SBR] vs VVI) on recurrent syncope and quality of life.

Methods:

Twenty‐one patients with symptomatic CSH (syncope or near syncope) were randomized to VVI, DDDR, or DDDR with SBR on a double‐blinded basis in a sequential crossover fashion with 6 months in each mode. The primary endpoints were recurrent events and quality of life (assessed by SF‐36). The mean number of events and SF‐36 scores were compared.

Results:

At baseline, over the preceding 6 months, there were a total of 29 syncopal events and 258 presyncopal events among 21 patients. Following pacing in any mode, the total number of these syncopal events reduced to two in two patients (P < 0.001) and 17 presyncopal events (P < 0.001) in 12 patients. The mean number of events was not significantly different between the three pacing methods. SF‐36 scores revealed some minor benefits of DDDR pacing versus baseline in the categories, but no pacing method was found to be superior.

Conclusions:

The study was unable to confirm the initial study hypothesis of a superiority of one pacing modality over another. Quality of life measures allude to potential benefit from DDDR pacing alone. (PACE 2012;xx;1–7)
Magnetic Resonance Imaging in Patients with Implanted Devices
Authors: BEINART ROY , NAZARIAN SAMAN
Published: May 2012

Techniques and Technology.  The use of magnetic resonance (MR) imaging as a diagnostic technique is rapidly expanding. In parallel, the number of patients with cardiac devices is constantly growing and many of them may be referred for MR examinations. However, implantable cardiac devices are subject to multiple effects from MR, and numerous safety issues need to be considered prior to scanning. In this review, we will summarize our experience with MR imaging of patients with implantable cardiac devices, and outline our safety protocol. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1040‐1042, September 2012)
Feasibility of Early Discharge After Implantable Cardioverter‐Defibrillator Procedures
Authors: CHOUDHURI INDRAJIT , DESAI DIPAN , WALBURG JON , AUGUST PHYLLIS , KELLER SETH I , SURI RANJIT
Published: May 2012

Early Discharge After ICD Implantation. Introduction: Registry data demonstrate considerably low complication rates after implantable cardioverter‐defibrillator (ICD) procedures for primary prevention of sudden death. Yet standard of care includes postimplant overnight in‐hospital observation that may levy substantial unnecessary financial burden on health care systems. In appropriate patients, discharge soon after implant could translate into significant cost savings, if such practice does not result in complications. We applied a simple clinical algorithm to assess feasibility of discharge on the same day of ICD implantation in patients at low risk for procedural complications.

Methods: We prospectively randomized primary prevention ICD candidates at low risk for complications (not pacing‐dependent or requiring bridging heparin anticoagulation) to next‐day discharge with overnight in‐hospital observation, or same‐day discharge with remote monitoring for 24 hours after ICD implant. Implants were performed via cephalic vein access, and randomization occurred after 4‐hours clinical observation and device interrogation. All patients were followed for a minimum of 6 weeks to assess acute procedural complications.

Results: 71 patients comprised the study cohort (mean age 62, 79% male) after 3 were excluded. The most common indication for ICD implant was ischemic cardiomyopathy with ejection fraction ≤35%. Device data obtained through 24‐hour remote monitoring was comparable to 4‐hour postimplant parameters in same‐day discharge patients. No acute complications occurred in same‐day discharge patients; 1 next‐day discharge patient developed pneumothorax.

Conclusion: ICD implantation with same‐day discharge is reasonable in patients at low risk for complications. Remote monitoring can be useful in indicating lead‐parameter stability during the immediate postoperative period. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1123‐1129, October 2012)
Left Ventricular Diastolic Dysfunction in Atrial Fibrillation: Predictors and Relation with Symptom Severity
Authors: KOSIUK JEDRZEJ , VAN BELLE YVES , BODE KERSTIN , KORNEJ JELENA , ARYA ARASH , ROLF SASCHA , HUSSER DANIELA , HINDRICKS GERHARD , BOLLMANN ANDREAS
Published: May 2012

Left Ventricular Diastolic Dysfunction in Atrial Fibrillation Background: Left ventricular diastolic dysfunction (LVDD) is common in the general population, but its prevalence in atrial fibrillation (AF), predictors for LVDD in AF and the association between LVDD and AF‐related symptom severity has not been well studied.

Methods: In 124 consecutive patients (mean age 61 ± 11years, 60% male) with paroxysmal (n = 70) or persistent AF (n = 54) referred for AF catheter ablation, LVDD was evaluated according to current guidelines using transthoracic echocardiography. AF‐related symptom severity was quantified using the European Heart Rhythm Association score.

Results: LVDD was present in 46 patients (37%). In uni‐ and multivariable regression analysis, age (OR 1.068 per year, 95% CI 1.023–1.115, P = 0.003) and persistent AF (OR 2.427 vs. paroxysmal AF, 95% CI 1.112–5.3, P = 0.026) were associated with LVDD. LVDD was found in 11% with mild AF symptoms (n = 27) as opposed to 44% in patients with moderate–severe AF symptoms (n = 97, P = 0.002). Thus, the OR for moderate–severe AF symptoms was 6.368 (1.797–22.568, P = 0.004) in the presence of LVDD.

Conclusions: LVDD (1) occurs frequently in AF, (2) is associated with advancing age and AF progression and (3) is correlated with symptom severity in AF. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1073‐1077, October 2012)
The Prevalence of Mutations in KCNQ1, KCNH2, and SCN5A in an Unselected National Cohort of Young Sudden Unexplained Death Cases
Authors: WINKEL BO GREGERS , LARSEN MAIKEN KUDAHL , BERGE KNUT ERIK , LEREN TROND PAUL , NISSEN PETER HENRIK , OLESEN MORTEN SALLING , HOLLEGAARD MADS VILHELM , JESPERSEN THOMAS , YUAN LEI , NIELSEN NIKOLAJ , HAUNSØ STIG , SVENDSEN JESPER HASTRUP , WANG YINMAN , KRISTENSEN INGRID BAYER , JENSEN HENRIK KJÆRULF , TFELT‐HANSEN JACOB , BANNER JYTTE
Published: May 2012

Introduction: Sudden unexplained death account for one‐third of all sudden natural deaths in the young (1–35 years). Hitherto, the prevalence of genopositive cases has primarily been based on deceased persons referred for postmortem genetic testing. These deaths potentially may represent the worst of cases, thus possibly overestimating the prevalence of potentially disease causing mutations in the 3 major long‐QT syndrome (LQTS) genes in the general population. We therefore wanted to investigate the prevalence of mutations in an unselected population of sudden unexplained deaths in a nationwide setting.

Methods: DNA for genetic testing was available for 44 cases of sudden unexplained death in Denmark in the period 2000–2006 (equaling 33% of all cases of sudden unexplained death in the age group). KCNQ1, KCNH2, and SCN5A were sequenced and in vitro electrophysiological studies were performed on novel mutations.

Results: In total, 5 of 44 cases (11%) carried a mutation in 1 of the 3 genes corresponding to 11% of all investigated cases (R190W KCNQ1, F29L KCNH2 (2 cases), P297S KCNH2 and P1177L SCN5A). P1177L SCN5A has not been reported before. In vitro electrophysiological studies of P1177L SCN5A revealed an increased sustained current suggesting a LQTS phenotype.

Conclusion: In a nationwide setting, the genetic investigation of an unselected population of sudden unexplained death cases aged 1–35 years finds a lower than expected number of mutations compared to referred populations previously reported. We therefore conclude that the prevalence of mutations in the 3 major LQTS associated genes may not be as abundant as previously estimated. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1092‐1098, October 2012)
A Method of Moments Estimator for Random Effect Multivariate Meta‐Analysis
Authors: Chen Han , Manning Alisa K. , Dupuis Josée
Published: May 2012

SummaryMeta‐analysis is a powerful approach to combine evidence from multiple studies to make inference about one or more parameters of interest, such as regression coefficients. The validity of the fixed effect model meta‐analysis depends on the underlying assumption that all studies in the meta‐analysis share the same effect size. In the presence of heterogeneity, the fixed effect model incorrectly ignores the between‐study variance and may yield false positive results. The random effect model takes into account both within‐study and between‐study variances. It is more conservative than the fixed effect model and should be favored in the presence of heterogeneity. In this paper, we develop a noniterative method of moments estimator for the between‐study covariance matrix in the random effect model multivariate meta‐analysis. To our knowledge, it is the first such method of moments estimator in the matrix form. We show that our estimator is a multivariate extension of DerSimonian and Laird’s univariate method of moments estimator, and it is invariant to linear transformations. In the simulation study, our method performs well when compared to existing random effect model multivariate meta‐analysis approaches. We also apply our method in the analysis of a real data example.
A Robust Bayesian Random Effects Model for Nonlinear Calibration Problems
Authors: Fong Y. , Wakefield J. , De Rosa S. , Frahm N.
Published: May 2012

Summary In the context of a bioassay or an immunoassay, calibration means fitting a curve, usually nonlinear, through the observations collected on a set of samples containing known concentrations of a target substance, and then using the fitted curve and observations collected on samples of interest to predict the concentrations of the target substance in these samples. Recent technological advances have greatly improved our ability to quantify minute amounts of substance from a tiny volume of biological sample. This has in turn led to a need to improve statistical methods for calibration. In this article, we focus on developing calibration methods robust to dependent outliers. We introduce a novel normal mixture model with dependent error terms to model the experimental noise. In addition, we propose a reparameterization of the five parameter logistic nonlinear regression model that allows us to better incorporate prior information. We examine the performance of our methods with simulation studies and show that they lead to a substantial increase in performance measured in terms of mean squared error of estimation and a measure of the average prediction accuracy. A real data example from the HIV Vaccine Trials Network Laboratory is used to illustrate the methods.
A Robust Method for Estimating Optimal Treatment Regimes
Authors: Zhang Baqun , Tsiatis Anastasios A. , Laber Eric B. , Davidian Marie
Published: May 2012

Summary A treatment regime is a rule that assigns a treatment, among a set of possible treatments, to a patient as a function of his/her observed characteristics, hence “personalizing” treatment to the patient. The goal is to identify the optimal treatment regime that, if followed by the entire population of patients, would lead to the best outcome on average. Given data from a clinical trial or observational study, for a single treatment decision, the optimal regime can be found by assuming a regression model for the expected outcome conditional on treatment and covariates, where, for a given set of covariates, the optimal treatment is the one that yields the most favorable expected outcome. However, treatment assignment via such a regime is suspect if the regression model is incorrectly specified. Recognizing that, even if misspecified, such a regression model defines a class of regimes, we instead consider finding the optimal regime within such a class by finding the regime that optimizes an estimator of overall population mean outcome. To take into account possible confounding in an observational study and to increase precision, we use a doubly robust augmented inverse probability weighted estimator for this purpose. Simulations and application to data from a breast cancer clinical trial demonstrate the performance of the method.
Bayesian Model Selection for Incomplete Data Using the Posterior Predictive Distribution
Authors: Daniels Michael J. , Chatterjee Arkendu S. , Wang Chenguang
Published: May 2012

SummaryWe explore the use of a posterior predictive loss criterion for model selection for incomplete longitudinal data. We begin by identifying a property that most model selection criteria for incomplete data should consider. We then show that a straightforward extension of the Gelfand and Ghosh (1998,Biometrika,85, 1–11) criterion to incomplete data has two problems. First, it introduces an extra term (in addition to the goodness of fit and penalty terms) that compromises the criterion. Second, it does not satisfy the aforementioned property. We propose an alternative and explore its properties via simulations and on a real dataset and compare it to the deviance information criterion (DIC). In general, the DIC outperforms the posterior predictive criterion, but the latter criterion appears to work well overall and is very easy to compute unlike the DIC in certain classes of models for missing data.
Adenomyosis: A Challenge in Clinical Gynecology
Authors: Cockerham Anne Z.
Published: May 2012

Adenomyosis is a prevalent, benign gynecologic condition in which endometrial tissue invades the myometrium, causing myometrial inflammation and hypertrophy. Although some women with adenomyosis are asymptomatic, the condition often causes menorrhagia and dysmenorrhea. This article provides women's health providers with a review of causes and risk factors for developing adenomyosis, clinical presentations of women with the condition, diagnostic modalities and criteria, and medical and surgical treatment options.
An Integrative Review of Relationships Between Discrimination and Asian American Health
Authors: Nadimpalli Sarah B. , Hutchinson M. Katherine
Published: May 2012

Purpose: Many ethnic minorities in the United States experience disproportionate rates of adverse health outcomes or health disparities. Factors such as socioeconomic status do not fully explain how these disparities are generated and maintained. Research has demonstrated that chronic experiences of discrimination are harmful to the health of African Americans and Latinos. However, there is a dearth of research examining Asian Americans’ experiences with discrimination and health disparities. The purpose of this integrative review was to summarize the current literature examining discrimination and the mental and physical health of Asian Americans.

Design and Methods: Combinations of search terms related to discrimination, health, and Asian Americans were used to search five electronic databases. Inclusion criteria were primary research studies, published in English between 1980 and 2011, Asian American adults, and discrimination examined in relationship to a physical or mental health outcome. The search initially yielded 489 results; 14 quantitative studies met inclusion criteria.

Findings and Conclusions: Quantitative studies in this review revealed several significant associations between discrimination and health outcomes in Asian Americans. Discrimination was significantly associated with depressive symptoms in seven studies. Three studies found associations between discrimination and physical health, including cardiovascular disease, respiratory conditions, obesity, and diabetes. Although the literature was limited by self‐reported data, cross‐sectional designs, and inconsistent definitions and measurement of discrimination, the findings suggest that discrimination is a significant contributor to poorer health and health disparities for Asian Americans. The findings clearly demonstrate the need for further nursing research in this area to inform evidence‐based practice and social policy.

Clinical Relevance: Patient care providers can recognize discrimination as a significant stressor or purveyor of illness and explore ways to facilitate coping and resilience with their Asian American patients. Community‐based participatory research approaches can be implemented by clinicians, academicians, and Asian American community partners to address the issue of discrimination and Asian American health outcomes.
Fundamental Aspects of Spark Plasma Sintering: I. Experimental Analysis of Scalability
Authors: Olevsky Eugene A. , Bradbury William L. , Haines Christopher D. , Martin Darold G. , Kapoor Deepak
Published: May 2012

Scalability experiments on the spark plasma sintering (SPS) of similarly shaped alumina specimens of the four different sizes are conducted. The utilized experimental methodology, based on the principle of rigorous proportionality of all the specimen and tooling dimensions, employs two different SPS devices of different scales. The processed specimens are characterized in terms of relative density and grain‐pore structure.

Overall, SPS shows good scalability potential within a single SPS device, but indicates substantial structure changes when switching between different SPS devices. Despite deviations in some cases, by and large, the experimental results obtained for different tooling sizes and temperature regimes are rather similar for specimens processed by the same SPS device. The obtained density and grain size spatial distributions are relatively uniform. High final densities with moderate grain growth are common. At the same time, due to the demonstrated possibility of a significant size impact in case of high heating rates and large specimen sizes, as well as the demonstrated differences of the processing outcomes based on different SPS devices, the predictive capability of reliable modeling approaches is of great importance for the industrial implementation of SPS techniques.
The Governance of Things: Documenting Limbo in the Greek Asylum Procedure
Authors: Cabot Heath
Published: May 2012

Some anthropological examinations of documents have emphasized their role as regulatory technologies that enact control and legibility over both citizens and “aliens.” This article shows, however, that documentary practices and forms both reinforce and undermine attempts to make persons governable. My analysis centers on the “pink card,” the identity document issued to asylum seekers in Greece, which in 2010 was the European country with the highest number of asylum cases pending in limbo. Examining how both state functionaries and asylum seekers engage with it, I show how the pink card takes on unpredictable meanings with indeterminate effects, which can disrupt the regulatory functions of the asylum procedure. Through ethnographic data drawn from encounters between asylum seekers and police, interviews with asylum seekers, and case material, I argue for a consideration of how things themselves govern—that is, dispose, position, and shape—the activities and tools of state regulation.
The Hope Crusades: Culturalism and Reform in the Arab World
Authors: Sukarieh Mayssoun
Published: May 2012

This article is an in depth analysis of three public relations (PR) campaigns in the Arab region that promote the slogans of “Hope,”“Life,” and “Optimism.” These PR campaigns are the most visible manifestations of a broader set of social and economic reform programs that have been launched throughout the Arab world during the post‐9/11 era. The article argues that all these PR campaigns and the broader reform projects to which they are linked are shaped by a hegemonic culturalist way of thinking about the Arab world, not only in the West but among transnational Arab elites as well. Culturalism is an ideology that sees the world's population as being divided into discrete and homogeneous “cultures,” which are determinative of individual thought and action, as well as broader social, economic, and political structures and processes. In these PR campaigns and in key policy reform documents such as the Arab Human Development Report and the Alexandria Charter, the problems of the Arab world are construed primarily as matters of culture. The Arab world and the West are constructed in terms of a stereotyped and Orientalist opposition, and solutions to contemporary problems in the region are presented as involving a key set of cultural reforms. Not coincidentally, these cultural reforms both facilitate and legitimate a simultaneous set of neoliberal economic, political, and legal reforms.
Culture of rat endometrial telocytes
Authors: Hatta Kota , Huang Ming‐Li , Weisel Richard D. , Li Ren‐Ke
Published: May 2012

Previous studies have shown that telocytes are found in a variety of tissues. Here, we report the presence of telocytes in the human endometrium. In addition, telocytes were isolated from the rat endometrium and cultured. Immunohistochemistry was performed in vitro and in vivo. Cultured cells showed that telocytes expressed CD34, and similar results were found in the uterine tissue. In both species, telocytes also stained positive for vimentin and connexin 43. Telopodes were observed connecting cell colonies and connecting distant cells. Our findings suggest that telocytes may have a role in cell‐to‐cell communication over short and long distances within the endometrium.
Survival after stage IA endometrial cancer; can follow‐up be altered? A prospective nationwide Danish survey
Authors: LAJER HENRIK , ELNEGAARD SANDRA , CHRISTENSEN RENÉ D. , ORTOFT GITTE , SCHLEDERMANN DORIS E. , MOGENSEN OLE
Published: May 2012

Objective. To present Danish national survival data on women with early stage endometrial cancer and use these data to discuss the relevance of postoperative follow‐up. Design. Prospective study. Setting. Danish Endometrial Cancer Study (DEMCA). Population. Five hundred and seventy‐one FIGO stage IA (1988 classification) endometrial cancer patients prospectively included between 1986 and 1999. All patients had total abdominal hysterectomy and bilateral salpingo‐oophorectomy without adjuvant therapy. Methods. The patient and the disease characteristics were drawn from the DEMCA database with cross‐references to the national death registry and the national pathology database. Statistical methods included Kaplan–Meier, log‐rank and Cox regression analysis. Main outcome measures. Survival rates in relation to histopathology. Results. The five year overall survival rate was 88.9% and five year disease‐specific survival was 97.3%. Patients with low‐ (91.8%) and high‐risk histopathology (8.2%) were compared. The age‐adjusted overall and disease‐specific survival differed significantly between women with low‐ and high‐risk histopathology (p = 0.039 and p = 0.004, respectively). The disease‐specific survival adjusted for age between patients with well‐differentiated endometrioid tumors differed from those with moderately differentiated tumors (p = 0.008, hazard ratio = 3.75, 95% confidence interval 1.41–10.00). Recurrence data were available on 464 patients. Twenty‐three (3.9%) experienced recurrence. Of these recurrences, 15 of 23 (65%) were vaginal. Death from recurrence was observed in nine of 23 (39%) patients, and five of these nine had vaginal recurrences. Conclusions. Women with FIGO stage IA endometrial cancer have a very high disease‐specific five year survival. Survival was related to histopathology. Follow‐up at a highly specialized tertiary care center for patients with an extremely good prognosis may be questioned.
Molecular markers provide insights into contemporary and historic gene flow for a non‐migratory species
Authors: Graham Brendan A. , Burg Theresa M.
Published: May 2012

Hairy woodpeckers Picoides villosus are a common, year round resident with distinct plumage and morphological variation across North America. We genotyped 335 individuals at six variable microsatellite loci and analyzed 322 mtDNA control region sequences in order to examine the role of contemporary and historical barriers to gene flow. In addition we combined genetic analyses with ecological niche modelling to test if hairy woodpeckers were isolated in northern refugia (Alaska, Newfoundland and the Queen Charlotte Islands) during the last glacial maximum. Genetic analyses revealed that gene flow among North American hairy woodpecker populations is restricted, but not to the extent predicted for a sedentary species. Populations clustered into two main genetic groups, east and west of the Great Plains in the south and the Rocky Mountains in the north. Contact zones between the two main genetic groups exist in central British Columbia and Washington, but are narrow. Within each group we found additional population structure with genetic breaks between subgroups in the geographic west corresponding to breaks in forested habitat and physical barriers like open expanses of water. Population genetic patterns for hairy woodpeckers have resulted from isolation in multiple southern refugia with the current distribution of genetic groups resulting from post‐glacial expansion and subsequent reduction in gene flow. While populations in Alaska, Newfoundland and the Queen Charlotte Islands are genetically distinct from other populations, we found no evidence of these areas acting as refugia throughout the Pleistocene. Atlantic Canada populations contained unique haplotypes raising the possibility of a separate colonization from the rest of eastern Canada. The endemic subspecies on the island of Newfoundland is not genetically distinct from their closest mainland population unlike the Queen Charlotte Island subspecies.
Differential susceptibility of Cx26 mutations associated with epidermal dysplasias to peptidoglycan derived from Staphylococcus aureus and Staphylococcus epidermidis
Authors: Donnelly Steven , English Grant , de Zwart‐Storm Eugene A. , Lang Sue , van Steensel Maurice A. M. , Martin Patricia E.
Published: May 2012

Mutations in Connexin26 (Cx26) give rise to a spectrum of dominantly inherited hyperproliferating skin disorders, the severest being keratitis–ichthyosis–deafness (KID) syndrome, an inflammatory skin disorder, with patients prone to opportunistic infections. We compared the effects of peptidoglycan (PGN) extracted from the skin commensal Staphylococcus epidermidis and the opportunistic pathogen Staphylococcus aureus on interleukin‐6 and connexin expression in HaCaT cells (a keratinocyte cell line) and connexin channel activity in HaCaT and HeLa (connexin deficient) cells transfected to express KID and non‐KID Cx26 mutations. In both cell types, PGN from S. aureus induced hemichannel activity in cells expressing KID mutants as monitored by ATP release assays following 15‐min challenge, while that from S. epidermidis evoked a response in HeLa cells. In KID mutant expressing cells, ATP release was significantly higher than in cells transfected with wild‐type Cx26. No ATP release was observed in non‐KID mutant transfected cells or in the presence of carbenoxolone, a connexin channel blocker. PGN isolated from S. aureus but not S. epidermidis induced interleukin‐6 and Cx26 expression in HaCaT cells following 6‐h challenge. Challenge by PGN from S. aureus evoked a greater interleukin‐6 response in cells expressing KID mutants than in cells expressing wtCx26 or non‐KID mutants. This response returned to basal levels if acute KID hemichannel signalling was blocked prior to PGN challenge. Thus, KID mutants form channels that can be triggered by the pro‐inflammatory mediator PGN from opportunistic pathogens but not skin commensals, providing further insight into the genotype–phenotype relationship of Cx26 disorders.
Sunburn protection as a function of sunscreen application thickness differs between high and low SPFs
Authors: Liu Wei , Wang Xuemin , Lai Wei , Yan Tian , Wu Yanyu , Wan Miaojian , Yi Jinling , Matsui Mary S.
Published: May 2012

Background

Sunscreens are an important component of healthy sun‐protection behavior. To achieve satisfactory protection, sunscreens must be applied consistently, evenly and correctly. Consumers do not apply sunscreen properly and, therefore, do not achieve the protection indicated by the label ‘sun protection factor’ (SPF). The objective of the present study was to determine the actual sun(burn) protection given by a range of sunscreen application thickness levels for both low and high SPF formulas.

Subjects and Methods

Forty study subjects were recruited from each of three geographical regions in China. Sunscreens with label SPFs of 4, 15, 30, and 55 were tested at application levels of 0.5, 1.0, 1.5, and 2.0 mg/cm2 in three laboratories using a standard SPF protocol.

Results

Sunscreens with lower SPFs (4 and 15) showed a linear dose–response relationship with application level, but higher SPF (30 and 55) product protection was exponentially related to application thickness.

Conclusion

Sunscreen protection is not related in one uniform way to the amount of product applied to human skin. Consumers may achieve an even lower than expected sunburn protection from high SPF products than from low SPF sunscreens.
Ultraviolet B radiation differentially modifies catechol‐O‐methyltransferase activity in keratinocytes and melanoma cells
Authors: Magina Sofia , Vieira‐Coelho Maria Augusta , Serrão Maria Paula , Kosmus Carina , Moura Eduardo , Moura Daniel
Published: May 2012

Background

Catechol‐O‐methyltransferase (COMT) is a ubiquitous enzyme inactivating catecholic compounds. COMT is expressed also in human skin samples, and in melanoma cells it may be cytoprotective. A role of COMT in keratinocytes (HaCat) is unknown.

Objective: The objective of this study is

to investigate whether ultraviolet‐B (UVB) radiation modifies COMT activity in melanocytes and HaCat and whether COMT inhibition plays a role in UVB‐induced cell death.

Methods

Human cell lines of melanotic melanoma (SK‐mel‐1) and HaCat were used. COMT activity was evaluated under basal conditions and after UVB irradiation (311 nm) at a low (8 mJ/cm2) and a high dose (60 mJ/cm2). Tolcapone 1 μM was used to inhibit COMT.

Results

Both SK‐mel‐1 and Ha‐Cat cells express COMT activity. In SK‐mel‐1, COMT activity is reduced nearly 50% both 24 h and 48 h after a high dose UVB. In Ha‐Cat cells, COMT activity increased 24 h after a high dose UVB but decreased at 48 h. Tolcapone increases significantly the cytotoxic effect of high dose UVB irradiation only in HaCat. High concentrations of tolcapone reduced melanin levels in melanoma cells parallel to reduced cell numbers.

Conclusions

Ultraviolet radiation differentially modifies COMT activity in melanoma cells and HaCat. Furthermore, tolcapone increased death of HaCat after irradiation but did not affect melanoma cells.