Showing papers by "Laval University published in 2011"

The Insomnia Severity Index: psychometric indicators to detect insomnia cases and evaluate treatment response.

Abstract: Background Although insomnia is a prevalent complaint with significant morbidity, it often remains unrecognized and untreated. Brief and valid instruments are needed both for screening and outcome assessment. This study examined psychometric indices of the Insomnia Severity Index (ISI) to detect cases of insomnia in a population-based sample and to evaluate treatment response in a clinical sample. Methods Participants were 959 individuals selected from the community for an epidemiological study of insomnia (Community sample) and 183 individuals evaluated for insomnia treatment and 62 controls without insomnia (Clinical sample). They completed the ISI and several measures of sleep quality, fatigue, psychological symptoms, and quality of life; those in the Clinical sample also completed sleep diaries, polysomnography, and interviews to validate their insomnia/good sleep status and assess treatment response. In addition to standard psychometric indices of reliability and validity, item response theory analyses were computed to examine ISI item response patterns. Receiver operating curves were used to derive optimal cutoff scores for case identification and to quantify the minimally important changes in relation to global improvement ratings obtained by an independent assessor. Results ISI internal consistency was excellent for both samples (Cronbach α of 0.90 and 0.91). Item response analyses revealed adequate discriminatory capacity for 5 of the 7 items. Convergent validity was supported by significant correlations between total ISI score and measures of fatigue, quality of life, anxiety, and depression. A cutoff score of 10 was optimal (86.1% sensitivity and 87.7% specificity) for detecting insomnia cases in the community sample. In the clinical sample, a change score of -8.4 points (95% CI: -7.1, -9.4) was associated with moderate improvement as rated by an independent assessor after treatment. Conclusion These findings provide further evidence that the ISI is a reliable and valid instrument to detect cases of insomnia in the population and is sensitive to treatment response in clinical patients.

Normal gut microbiota modulates brain development and behavior

Abstract: Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.

The Physiology, Signaling, and Pharmacology of Dopamine Receptors

Abstract: G protein-coupled dopamine receptors (D1, D2, D3, D4, and D5) mediate all of the physiological functions of the catecholaminergic neurotransmitter dopamine, ranging from voluntary movement and reward to hormonal regulation and hypertension. Pharmacological agents targeting dopaminergic neurotransmission have been clinically used in the management of several neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, bipolar disorder, Huntington's disease, attention deficit hyperactivity disorder (ADHD(1)), and Tourette's syndrome. Numerous advances have occurred in understanding the general structural, biochemical, and functional properties of dopamine receptors that have led to the development of multiple pharmacologically active compounds that directly target dopamine receptors, such as antiparkinson drugs and antipsychotics. Recent progress in understanding the complex biology of dopamine receptor-related signal transduction mechanisms has revealed that, in addition to their primary action on cAMP-mediated signaling, dopamine receptors can act through diverse signaling mechanisms that involve alternative G protein coupling or through G protein-independent mechanisms via interactions with ion channels or proteins that are characteristically implicated in receptor desensitization, such as β-arrestins. One of the future directions in managing dopamine-related pathologic conditions may involve a transition from the approaches that directly affect receptor function to a precise targeting of postreceptor intracellular signaling modalities either directly or through ligand-biased signaling pharmacology. In this comprehensive review, we discuss dopamine receptor classification, their basic structural and genetic organization, their distribution and functions in the brain and the periphery, and their regulation and signal transduction mechanisms. In addition, we discuss the abnormalities of dopamine receptor expression, function, and signaling that are documented in human disorders and the current pharmacology and emerging trends in the development of novel therapeutic agents that act at dopamine receptors and/or on related signaling events.

Evolution and classification of the CRISPR-Cas systems

Abstract: The CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR-Cas systems and Cas proteins. Three major types of CRISPR-Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR-Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR-cas loci.

A phase 3 trial of bevacizumab in ovarian cancer.

Abstract: A B S T R AC T Background Angiogenesis plays a role in the biology of ovarian cancer. We examined the effect of bevacizumab, the vascular endothelial growth factor inhibitor, on survival in women with this disease. Methods We randomly assigned women with ovarian cancer to carboplatin (area under the curve, 5 or 6) and paclitaxel (175 mg per square meter of body-surface area), given every 3 weeks for 6 cycles, or to this regimen plus bevacizumab (7.5 mg per kilogram of body weight), given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 addi tional cycles or until progression of disease. Outcome measures included progressionfree survival, first analyzed per protocol and then updated, and interim overall survival. Results

Shrub expansion in tundra ecosystems: dynamics, impacts and research priorities

Abstract: Recent research using repeat photography, long-term ecological monitoring and dendrochronology has documented shrub expansion in arctic, high-latitude and alpine tundra

Bulk Heterojunction Solar Cells Using Thieno[3,4-c]pyrrole-4,6-dione and Dithieno[3,2-b:2′,3′-d]silole Copolymer with a Power Conversion Efficiency of 7.3%

Abstract: A new alternating copolymer of dithienosilole and thienopyrrole-4,6-dione (PDTSTPD) possesses both a low optical bandgap (1.73 eV) and a deep highest occupied molecular orbital energy level (5.57 eV). The introduction of branched alkyl chains to the dithienosilole unit was found to be critical for the improvement of the polymer solubility. When blended with PC71BM, PDTSTPD exhibited a power conversion efficiency of 7.3% on the photovoltaic devices with an active area of 1 cm2.

Global patterns of land-atmosphere fluxes of carbon dioxide, latent heat, and sensible heat derived from eddy covariance, satellite, and meteorological observations

Abstract: We upscaled FLUXNET observations of carbon dioxide, water, and energy fluxes to the global scale using the machine learning technique, model tree ensembles (MTE). We trained MTE to predict site-level gross primary productivity (GPP), terrestrial ecosystem respiration (TER), net ecosystem exchange (NEE), latent energy (LE), and sensible heat (H) based on remote sensing indices, climate and meteorological data, and information on land use. We applied the trained MTEs to generate global flux fields at a 0.5 degrees x 0.5 degrees spatial resolution and a monthly temporal resolution from 1982 to 2008. Cross-validation analyses revealed good performance of MTE in predicting among-site flux variability with modeling efficiencies (MEf) between 0.64 and 0.84, except for NEE (MEf = 0.32). Performance was also good for predicting seasonal patterns (MEf between 0.84 and 0.89, except for NEE (0.64)). By comparison, predictions of monthly anomalies were not as strong (MEf between 0.29 and 0.52). Improved accounting of disturbance and lagged environmental effects, along with improved characterization of errors in the training data set, would contribute most to further reducing uncertainties. Our global estimates of LE (158 +/- 7 J x 10(18) yr(-1)), H (164 +/- 15 J x 10(18) yr(-1)), and GPP (119 +/- 6 Pg C yr(-1)) were similar to independent estimates. Our global TER estimate (96 +/- 6 Pg C yr(-1)) was likely underestimated by 5-10%. Hot spot regions of interannual variability in carbon fluxes occurred in semiarid to semihumid regions and were controlled by moisture supply. Overall, GPP was more important to interannual variability in NEE than TER. Our empirically derived fluxes may be used for calibration and evaluation of land surface process models and for exploratory and diagnostic assessments of the biosphere.

Exemestane for Breast-Cancer Prevention in Postmenopausal Women

Abstract: Background Tamoxifen and raloxifene have limited patient acceptance for primary prevention of breast cancer. Aromatase inhibitors prevent more contralateral breast cancers and cause fewer side effects than tamoxifen in patients with early-stage breast cancer. Methods In a randomized, placebo-controlled, double-blind trial of exemestane designed to detect a 65% relative reduction in invasive breast cancer, eligible postmenopausal women 35 years of age or older had at least one of the following risk factors: 60 years of age or older; Gail 5-year risk score greater than 1.66% (chances in 100 of invasive breast cancer developing within 5 years); prior atypical ductal or lobular hyperplasia or lobular carcinoma in situ; or ductal carcinoma in situ with mastectomy. Toxic effects and health-related and menopause-specific qualities of life were measured. Results A total of 4560 women for whom the median age was 62.5 years and the median Gail risk score was 2.3% were randomly assigned to either exemestane or placebo. At a median follow-up of 35 months, 11 invasive breast cancers were detected in those given exemestane and in 32 of those given placebo, with a 65% relative reduction in the annual incidence of invasive breast cancer (0.19% vs. 0.55%; hazard ratio, 0.35; 95% confidence interval [CI], 0.18 to 0.70; P = 0.002). The annual incidence of invasive plus noninvasive (ductal carcinoma in situ) breast cancers was 0.35% on exemestane and 0.77% on placebo (hazard ratio, 0.47; 95% CI, 0.27 to 0.79; P = 0.004). Adverse events occurred in 88% of the exemestane group and 85% of the placebo group (P = 0.003), with no significant differences between the two groups in terms of skeletal fractures, cardiovascular events, other cancers, or treatmentrelated deaths. Minimal quality-of-life differences were observed. Conclusions Exemestane significantly reduced invasive breast cancers in postmenopausal women who were at moderately increased risk for breast cancer. During a median follow-up period of 3 years, exemestane was associated with no serious toxic effects and only minimal changes in health-related quality of life. (Funded by Pfizer and others; NCIC CTG MAP.3 ClinicalTrials.gov number, NCT00083174.)

Processable Low-Bandgap Polymers for Photovoltaic Applications†

Abstract: Over the last five years, organic photovoltaic devices have emerged as a new competitor to silicon-based solar cells. In particular, the bulk heterojunction architecture (BHJ), in which the photoactive layer consists of a bicontinuous blend of an electron donor and an electron acceptor, has allowed power conversion efficiencies around 8%. We will present in this review the latest conjugated polymers used in such BHJ solar cells. We will mainly focus on electron-donating (p-type) polymers based on thiophenes, 1,3,2-benzodiathiazoles, pyrrolo[3,4-c]pyrrole-1,4-diones, benzo[1,2-b;3,4-b]dithiophenes, and few other materials with more exotic structures. This review should be helpful to evaluate which are the most promising materials and where this research field is going in the years to come.

Calcific aortic valve disease: not simply a degenerative process: A review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: Calcific aortic valve disease-2011 update.

Abstract: Calcific aortic valve disease (CAVD) encompasses the range of disease from initial alterations in the cell biology of the leaflets to end-stage calcification resulting in left ventricular outflow obstruction. The first detectable macroscopic changes in the leaflets, seen as calcification, or focal leaflet thickening with normal valve function, is termed aortic valve sclerosis, but it is likely that the initiating events in the disease process occur much earlier. Disease progression is characterized by a process of thickening of the valve leaflets and the formation of calcium nodules—often including the formation of actual bone—and new blood vessels, which are concentrated near the aortic surface. End-stage disease, eg, calcific aortic stenosis, is characterized pathologically by large nodular calcific masses within the aortic cusps that protrude along the aortic surface into the sinuses of Valsalva, interfering with opening of the cusps. There is no disease along the ventricular surface. For decades, this disease was thought to be a passive process in which the valve degenerates with age in association with calcium accumulation. Moreover, although CAVD is more common with age, it is not an inevitable consequence of aging. Instead, CAVD appears to be an actively regulated disease process that cannot be characterized exclusively as senile or degenerative. The National Heart, Lung, and Blood Institute convened a group of scientists from different fields of study, including cardiac imaging, molecular biology, cardiovascular pathology, epidemiology, cell biology, endocrinology, bioengineering, and clinical outcomes, to review the scientific studies from the past decade in the field of CAVD. The purpose was to develop a consensus statement on the current state of translational research related to CAVD. Herein, we summarize recent scientific studies and define future directions for research to diagnose, treat, and potentially prevent this complex disease process. ### Key Structure-Function Correlations Heart valves permit unobstructed, unidirectional forward flow through the circulation. …

DICER1 deficit induces Alu RNA toxicity in age-related macular degeneration

Abstract: Geographic atrophy (GA), an untreatable advanced form of age-related macular degeneration, results from retinal pigmented epithelium (RPE) cell degeneration. Here we show that the microRNA (miRNA)-processing enzyme DICER1 is reduced in the RPE of humans with GA, and that conditional ablation of Dicer1, but not seven other miRNA-processing enzymes, induces RPE degeneration in mice. DICER1 knockdown induces accumulation of Alu RNA in human RPE cells and Alu-like B1 and B2 RNAs in mouse RPE. Alu RNA is increased in the RPE of humans with GA, and this pathogenic RNA induces human RPE cytotoxicity and RPE degeneration in mice. Antisense oligonucleotides targeting Alu/B1/B2 RNAs prevent DICER1 depletion-induced RPE degeneration despite global miRNA downregulation. DICER1 degrades Alu RNA, and this digested Alu RNA cannot induce RPE degeneration in mice. These findings reveal a miRNA-independent cell survival function for DICER1 involving retrotransposon transcript degradation, show that Alu RNA can directly cause human pathology, and identify new targets for a major cause of blindness.

Biodegradable Metals for Cardiovascular Stent Application: Interests and New Opportunities

Abstract: During the last decade, biodegradable metallic stents have been developed and investigated as alternatives for the currently-used permanent cardiovascular stents. Degradable metallic materials could potentially replace corrosion-resistant metals currently used for stent application as it has been shown that the role of stenting is temporary and limited to a period of 6–12 months after implantation during which arterial remodeling and healing occur. Although corrosion is generally considered as a failure in metallurgy, the corrodibility of certain metals can be an advantage for their application as degradable implants. The candidate materials for such application should have mechanical properties ideally close to those of 316L stainless steel which is the gold standard material for stent application in order to provide mechanical support to diseased arteries. Non-toxicity of the metal itself and its degradation products is another requirement as the material is absorbed by blood and cells. Based on the mentioned requirements, iron-based and magnesium-based alloys have been the investigated candidates for biodegradable stents. This article reviews the recent developments in the design and evaluation of metallic materials for biodegradable stents. It also introduces the new metallurgical processes which could be applied for the production of metallic biodegradable stents and their effect on the properties of the produced metals.

Observed increase in local cooling effect of deforestation at higher latitudes

Abstract: Deforestation in mid- to high latitudes is hypothesized to have the potential to cool the Earth's surface by altering biophysical processes. In climate models of continental-scale land clearing, the cooling is triggered by increases in surface albedo and is reinforced by a land albedo-sea ice feedback. This feedback is crucial in the model predictions; without it other biophysical processes may overwhelm the albedo effect to generate warming instead. Ongoing land-use activities, such as land management for climate mitigation, are occurring at local scales (hectares) presumably too small to generate the feedback, and it is not known whether the intrinsic biophysical mechanism on its own can change the surface temperature in a consistent manner. Nor has the effect of deforestation on climate been demonstrated over large areas from direct observations. Here we show that surface air temperature is lower in open land than in nearby forested land. The effect is 0.85 ± 0.44 K (mean ± one standard deviation) northwards of 45° N and 0.21 ± 0.53 K southwards. Below 35° N there is weak evidence that deforestation leads to warming. Results are based on comparisons of temperature at forested eddy covariance towers in the USA and Canada and, as a proxy for small areas of cleared land, nearby surface weather stations. Night-time temperature changes unrelated to changes in surface albedo are an important contributor to the overall cooling effect. The observed latitudinal dependence is consistent with theoretical expectation of changes in energy loss from convection and radiation across latitudes in both the daytime and night-time phase of the diurnal cycle, the latter of which remains uncertain in climate models.

Role for miR-204 in human pulmonary arterial hypertension

Abstract: Pulmonary arterial hypertension (PAH) is characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Because microRNAs have been recently implicated in the regulation of cell proliferation and apoptosis, we hypothesized that these regulatory molecules might be implicated in the etiology of PAH. In this study, we show that miR-204 expression in PASMCs is down-regulated in both human and rodent PAH. miR-204 down-regulation correlates with PAH severity and accounts for the proliferative and antiapoptotic phenotypes of PAH-PASMCs. STAT3 activation suppresses miR-204 expression, and miR-204 directly targets SHP2 expression, thereby SHP2 up-regulation, by miR-204 down-regulation, activates the Src kinase and nuclear factor of activated T cells (NFAT). STAT3 also directly induces NFATc2 expression. NFAT and SHP2 were needed to sustain PAH-PASMC proliferation and resistance to apoptosis. Finally, delivery of synthetic miR-204 to the lungs of animals with PAH significantly reduced disease severity. This study uncovers a new regulatory pathway involving miR-204 that is critical to the etiology of PAH and indicates that reestablishing miR-204 expression should be explored as a potential new therapy for this disease.

Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans.

Abstract: Context: In humans, the prevalence, mass, and glucose-uptake activity of 18F-fluorodeoxyglucose (18F-FDG)-detected brown adipose tissue (BAT), which are expectedly enhanced by a cold stimulus, also appear modulated by other factors that still have to be disentangled. Objective: The objective of the study was to investigate the factors determining the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. Research Design and Methods: We retrospectively analyzed all 18F-FDG positron emission tomography/computed tomography examinations performed between January 2007 and December 2008 at our institution for 18F-FDG uptake within the cervical/supraclavicular, mediastinal, paravertebral, and perirenal fat areas. The influence of outdoor temperature, sex, age, body mass index (BMI), plasma glucose level, diabetes diagnosis, day length, and cancer status on the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT depots was investigated. Results: Three hundred twenty-eig...

In vivo imaging of Treg cells providing immune privilege to the haematopoietic stem-cell niche

Abstract: A new study identifies the bone marrow haematopoietic stem cell (HSC) niche — a specialized microenvironment where stem cells reside — as an immune privileged site. This property is known to exist in the testis, ovary and hair follicle but has not been universally demonstrated in all stem cell niches. High-resolution in vivo imaging shows the accumulation of regulatory T cells in the HSC niche, enabling transplanted allo-HSCs to escape from allogeneic rejection. As well as supporting stem-cell function, the niche may provide a relative sanctuary from immune attack that could extend to malignant cells in some instances. Stem cells reside in a specialized regulatory microenvironment or niche1,2, where they receive appropriate support for maintaining self-renewal and multi-lineage differentiation capacity1,2,3. The niche may also protect stem cells from environmental insults3 including cytotoxic chemotherapy and perhaps pathogenic immunity4. The testis, hair follicle and placenta are all sites of residence for stem cells and are immune-suppressive environments, called immune-privileged sites, where multiple mechanisms cooperate to prevent immune attack, even enabling prolonged survival of foreign allografts without immunosuppression4. We sought to determine if somatic stem-cell niches more broadly are immune-privileged sites by examining the haematopoietic stem/progenitor cell (HSPC) niche1,2,5,6,7 in the bone marrow, a site where immune reactivity exists8,9. We observed persistence of HSPCs from allogeneic donor mice (allo-HSPCs) in non-irradiated recipient mice for 30 days without immunosuppression with the same survival frequency compared to syngeneic HSPCs. These HSPCs were lost after the depletion of FoxP3 regulatory T (Treg) cells. High-resolution in vivo imaging over time demonstrated marked co-localization of HSPCs with Treg cells that accumulated on the endosteal surface in the calvarial and trabecular bone marrow. Treg cells seem to participate in creating a localized zone where HSPCs reside and where Treg cells are necessary for allo-HSPC persistence. In addition to processes supporting stem-cell function, the niche will provide a relative sanctuary from immune attack.

Toward a Physical Internet: meeting the global logistics sustainability grand challenge

Abstract: This paper starts with the assertion that the way physical objects are currently transported, handled, stored, realized, supplied, and used throughout the world is unsustainable economically, environmentally, and socially. Evidence supporting this assertion is exposed through a set of key unsustainability symptoms. Then, the paper expresses the goal to revert this situation, thus meeting the global logistics sustainability grand challenge. It suggests exploiting the Digital Internet metaphor to develop a Physical Internet vision toward meeting this grand challenge. The paradigm breaking vision is introduced through a set of its key characteristics. The paper then proceeds with addressing the implications and requirements for implementing the Physical Internet vision as a means to meet the grand challenge. It concludes with a call for further research, innovation, and development to really shape and assess the vision and, much more important, to give it flesh through real initiatives and projects so as to really influence in a positive way the collective future. For this to happen, it emphasizes the requirement for multidisciplinary collaboration among and between academia, industry, and government across localities, countries, and continents.

Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children

Abstract: Background: The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n=218,166) and nine studies of children and adolescents (n=19,268). Methods and Findings: All studies identified to have data on the FTO rs9939609 variant (or any proxy [r(2)>0.8]) and PA were invited to participate, regardless of ethnicity or age of the participants. PA was standardized by categorizing it into a dichotomous variable (physically inactive versus active) in each study. Overall, 25% of adults and 13% of children were categorized as inactive. Interaction analyses were performed within each study by including the FTOxPA interaction term in an additive model, adjusting for age and sex. Subsequently, random effects meta-analysis was used to pool the interaction terms. In adults, the minor (A-) allele of rs9939609 increased the odds of obesity by 1.23-fold/allele (95% CI 1.20-1.26), but PA attenuated this effect (p(interaction) = 0.001). More specifically, the minor allele of rs9939609 increased the odds of obesity less in the physically active group (odds ratio = 1.22/allele, 95% CI 1.19-1.25) than in the inactive group (odds ratio = 1.30/allele, 95% CI 1.24-1.36). No such interaction was found in children and adolescents. Conclusions: The association of the FTO risk allele with the odds of obesity is attenuated by 27% in physically active adults, highlighting the importance of PA in particular in those genetically predisposed to obesity.

How Prevalent Are Anxiety Disorders in Schizophrenia? A Meta-Analysis and Critical Review on a Significant Association

Abstract: Objective: The presence of anxiety disorders (AD) in schizophrenia (SZ) is attracting increasing interest. However, published studies have yielded very broad variations in prevalence rates across studies. The current meta-analysis sought to (1) investigate the prevalence of co-occurring AD in SZ by reporting pooled prevalence rates and (2) identify potential sources of variations in reported rates that could guide our efforts to identify and treat these co-occurring disorders in patients with SZ. Methods: We performed a systematic search of studies reporting prevalence of AD in SZ and related psychotic disorders. Mean prevalence rates and 95% confidence intervals (CIs) were first computed for each disorder. We then examined the impact of potential moderators related to patient sampling or to AD assessment methods on these rates. Results: Fifty-two eligible studies were identified. Pooled prevalence rates and CIs were 12.1% (7.0%–17.1%) for obsessive-compulsive disorders, 14.9% (8.1%–21.8%) for social phobia, 10.9% (2.9%–18.8%) for generalized AD, 9.8% (4.3%–15.4%) for panic disorders, and 12.4% (4.0%–20.8%) for post-traumatic stress disorders. For all disorders, we found significant heterogeneity in rates across studies. This heterogeneity could at least partially be explained by the effect of moderator variables related to patient characteristics or assessment methods. Conclusions: AD are highly prevalent in SZ, but important variations in rates are observed between studies. This meta-analysis highlights several factors that affect risk for, or detection of AD in SZ, and could, thus, have an important impact on treatment and outcome of SZ patients.

Resistance of Herpes Simplex Viruses to Nucleoside Analogues: Mechanisms, Prevalence, and Management

Abstract: Herpes simplex viruses (HSV) type 1 and type 2 are responsible for recurrent orolabial and genital infections. The standard therapy for the management of HSV infections includes acyclovir (ACV) and penciclovir (PCV) with their respective prodrugs valacyclovir and famciclovir. These compounds are phosphorylated by the viral thymidine kinase (TK) and then by cellular kinases. The triphosphate forms selectively inhibit the viral DNA polymerase (DNA pol) activity. Drug-resistant HSV isolates are frequently recovered from immunocompromised patients but rarely found in immunocompetent subjects. The gold standard phenotypic method for evaluating the susceptibility of HSV isolates to antiviral drugs is the plaque reduction assay. Plaque autoradiography allows the associated phenotype to be distinguished (TK-wild-type, TK-negative, TK-lowproducer, or TK-altered viruses or mixtures of wild-type and mutant viruses). Genotypic characterization of drug-resistant isolates can reveal mutations located in the viral TK and/or in the DNA pol genes. Recombinant HSV mutants can be generated to analyze the contribution of each specific mutation with regard to the drug resistance phenotype. Most ACV-resistant mutants exhibit some reduction in their capacity to establish latency and to reactivate, as well as in their degree of neurovirulence in animal models of HSV infection. For instance, TK-negative HSV mutants establish latency with a lower efficiency than wild-type strains and reactivate poorly. DNA pol HSV mutants exhibit different degrees of attenuation of neurovirulence. The management of ACV- or PCV-resistant HSV infections includes the use of the pyrophosphate analogue foscarnet and the nucleotide analogue cidofovir. There is a need to develop new antiherpetic compounds with different mechanisms of action. Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for recurrent orolabial and genital infections. In the United States, the seroprevalence of HSV-1 and HSV-2 infections has been estimated to be approximately 50% and 20%, respectively (243). Transmission occurs by contact with secretions from an infected person with either overt infection or asymptomatic excretion of virus. After primary infection, HSV establishes long-term latency in the ganglia of sensory nerves, from which it can reactivate episodically. These reactivations may be accompanied by symptoms or may be clinically silent. The most common clinical manifestations of HSV infections are vesicular lesions affecting the mucous membranes principally of the mouth, nose, or eyes for HSV-1 and the anogenital region for HSV-2. However, an increasing proportion of genital infections are caused by HSV-1 (243). The symptoms associated with both viruses are usually self-limiting, and the goals of treatment are to accelerate lesion healing and to prevent transmission in immunocompetent individuals (61). Both HSV-1 and HSV-2 can also cause infrequent but serious diseases, such as encephalitis and disseminated neonatal infections. HSV infections may be severe in immunocompromised patients, particularly those with defects in cell-mediated immunity. In patients with HIV infection and in recipients of solid organ or bone marrow transplants, herpetic lesions can be extensive, tend to persist for longer periods, and have the potential to disseminate. Recurrences tend to be more frequent and may be atypical in appearance (140). In addition to persistent mucocutaneous lesions, HSV can also lead to disseminated visceral infections, such as esophagitis, hepatitis, or pneumonia, as well as meningoencephalitis, in immunocompromised hosts (94, 99, 174).

Dynamic State Estimation in Power System by Applying the Extended Kalman Filter With Unknown Inputs to Phasor Measurements

Abstract: Availability of the synchronous machine angle and speed variables give us an accurate picture of the overall condition of power networks leading therefore to an improved situational awareness by system operators. In addition, they would be essential in developing local and global control schemes aimed at enhancing system stability and reliability. In this paper, the extended Kalman filter (EKF) technique for dynamic state estimation of a synchronous machine using phasor measurement unit (PMU) quantities is developed. The simulation results of the EKF approach show the accuracy of the resulting state estimates. However, the traditional EKF method requires that all externally observed variables, including input signals, be measured or available, which may not always be the case. In synchronous machines, for example, the exciter output voltage Efd may not be available for measuring in all cases. As a result, the extended Kalman filter with unknown inputs, referred to as EKF-UI, is proposed for identifying and estimating the states and the unknown inputs of the synchronous machine simultaneously. Simulation results demonstrate the efficiency and accuracy of the EKF-UI method under noisy or fault conditions, compared to the classic EKF approach and confirms its great potential in cases where there is no access to the input signals of the system.

A biopsychosocial formulation of pain communication

Abstract: We present a detailed framework for understanding the numerous and complicated interactions among psychological and social determinants of pain through examination of the process of pain communication. The focus is on an improved understanding of immediate dyadic transactions during painful events in the context of broader social phenomena. Fine-grain consideration of social transactions during pain leads to an appreciation of sociobehavioral events affecting both suffering persons as well as caregivers. Our examination considers knowledge from a variety of perspectives, including clinical health psychology, social and developmental processes, evolutionary psychology, communication studies, and behavioral neuroscience.

Discriminant diagrams for iron oxide trace element fingerprinting of mineral deposit types

Abstract: Magnetite and hematite are common minerals in a range of mineral deposit types. These minerals form partial to complete solid solutions with magnetite, chromite, and spinel series, and ulvospinel as a result of divalent, trivalent, and tetravalent cation substitutions. Electron microprobe analyses of minor and trace elements in magnetite and hematite from a range of mineral deposit types (iron oxide-copper-gold (IOCG), Kiruna apatite–magnetite, banded iron formation (BIF), porphyry Cu, Fe-Cu skarn, Fe-Ti, V, Cr, Ni-Cu-PGE, Cu-Zn-Pb volcanogenic massive sulfide (VMS) and Archean Au-Cu porphyry and Opemiska Cu veins) show compositional differences that can be related to deposit types, and are used to construct discriminant diagrams that separate different styles of mineralization. The Ni + Cr vs. Si + Mg diagram can be used to isolate Ni-Cu-PGE, and Cr deposits from other deposit types. Similarly, the Al/(Zn + Ca) vs. Cu/(Si + Ca) diagram can be used to separate Cu-Zn-Pb VMS deposits from other deposit types. Samples plotting outside the Ni-Cu-PGE and Cu-Zn-Pb VMS fields are discriminated using the Ni/(Cr + Mn) vs. Ti + V or Ca + Al + Mn vs. Ti + V diagrams that discriminate for IOCG, Kiruna, porphyry Cu, BIF, skarn, Fe-Ti, and V deposits.

Extent and scale of local adaptation in salmonid fishes: review and meta-analysis

Abstract: What is the extent and scale of local adaptation (LA)? How quickly does LA arise? And what is its underlying molecular basis? Our review and meta-analysis on salmonid fishes estimates the frequency of LA to be ∼55–70%, with local populations having a 1.2 times average fitness advantage relative to foreign populations or to their performance in new environments. Salmonid LA is evident at a variety of spatial scales (for example, few km to>1000 km) and can manifest itself quickly (6–30 generations). As the geographic scale between populations increases, LA is generally more frequent and stronger. Yet the extent of LA in salmonids does not appear to differ from that in other assessed taxa. Moreover, the frequency with which foreign salmonid populations outperform local populations (∼23–35%) suggests that drift, gene flow and plasticity often limit or mediate LA. The relatively few studies based on candidate gene and genomewide analyses have identified footprints of selection at both small and large geographical scales, likely reflecting the specific functional properties of loci and the associated selection regimes (for example, local niche partitioning, pathogens, parasites, photoperiodicity and seasonal timing). The molecular basis of LA in salmonids is still largely unknown, but differential expression at the same few genes is implicated in the convergent evolution of certain phenotypes. Collectively, future research will benefit from an integration of classical and molecular approaches to understand: (i) species differences and how they originate, (ii) variation in adaptation across scales, life stages, population sizes and environmental gradients, and (iii) evolutionary responses to human activities.

Poly(ADP-Ribose) (PAR) Binding to Apoptosis-Inducing Factor Is Critical for PAR Polymerase-1–Dependent Cell Death (Parthanatos)

Abstract: Overactivation of the DNA repair enzyme PARP-1 [poly(ADP-ribose) (PAR) polymerase-1] leads to “parthanatos,” a form of cell death that is distinct from apoptosis and necrosis and that depends on release of apoptosis-inducing factor (AIF) from mitochondria. Here, Wang et al . showed that PAR bound directly to AIF, disrupting AIF’s association with the mitochondria and allowing it to translocate to the nucleus to mediate cell death. Moreover, mutation of the PAR binding site of AIF enabled the authors to separate AIF’s role in parthanatos from its function in mitochondrial respiration. Identification of AIF as a PAR-binding protein could potentially lead to the development of compounds that inhibit this interaction, protecting against parthanatos, or compounds that mimic it and thereby promote parthanatos as an agent of death in malignant cells.

Efficacy of a home-visiting intervention aimed at improving maternal sensitivity, child attachment, and behavioral outcomes for maltreated children: A randomized control trial

Abstract: The efficacy of a short-term attachment-based intervention for changing risk outcomes for children of maltreating families was examined using a randomized control trial. Sixty-seven primary caregivers reported for maltreatment and their children (1-5 years) were randomly assigned to an intervention or control group. The intervention group received 8 weekly home visits directed at the caregiver-child dyad and focused on improving caregiver sensitivity. Intervention sessions included brief discussions of attachment-emotion regulation-related themes and video feedback of parent-child interaction. Comparison of pre- and posttest scores revealed significant improvements for the intervention group in parental sensitivity and child attachment security, and a reduction in child disorganization. Older children in the intervention group also showed lower levels of internalizing and externalizing problems following intervention. This is the first study to demonstrate the efficacy of short-term attachment-based intervention in enhancing parental sensitivity, improving child security, and reducing disorganization for children in the early childhood period.

Comparison of user groups' perspectives of barriers and facilitators to implementing electronic health records: a systematic review.

Abstract: Electronic health record (EHR) implementation is currently underway in Canada, as in many other countries. These ambitious projects involve many stakeholders with unique perceptions of the implementation process. EHR users have an important role to play as they must integrate the EHR system into their work environments and use it in their everyday activities. Users hold valuable, first-hand knowledge of what can limit or contribute to the success of EHR implementation projects. A comprehensive synthesis of EHR users' perceptions is key to successful future implementation. This systematic literature review was aimed to synthesize current knowledge of the barriers and facilitators influencing shared EHR implementation among its various users. Covering a period from 1999 to 2009, a literature search was conducted on nine electronic databases. Studies were included if they reported on users' perceived barriers and facilitators to shared EHR implementation, in healthcare settings comparable to Canada. Studies in all languages with an empirical study design were included. Quality and relevance of the studies were assessed. Four EHR user groups were targeted: physicians, other health care professionals, managers, and patients/public. Content analysis was performed independently by two authors using a validated extraction grid with pre-established categorization of barriers and facilitators for each group of EHR users. Of a total of 5,695 potentially relevant publications identified, 117 full text publications were obtained after screening titles and abstracts. After review of the full articles, 60 publications, corresponding to 52 studies, met the inclusion criteria. The most frequent adoption factors common to all user groups were design and technical concerns, ease of use, interoperability, privacy and security, costs, productivity, familiarity and ability with EHR, motivation to use EHR, patient and health professional interaction, and lack of time and workload. Each user group also identified factors specific to their professional and individual priorities. This systematic review presents innovative research on the barriers and facilitators to EHR implementation. While important similarities between user groups are highlighted, differences between them demonstrate that each user group also has a unique perspective of the implementation process that should be taken into account.