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The authors report on the detection of gamma ray bursts in lightning by the Terrestrial gamma ray flash and Energetic Thunderstorm Rooftop Array (TETRA)-II. They present a description of the (TETRA)-II instrumentation, the correlations with other lightning detection networks, and the connection between the lightning and the detection of gamma rays.

Des observations effectuées directement sous l'eau ont servi durant deux étés à déterminer les principales causes favorisant la prédation effectuée par l'omble de fontaine (Salvefinus fontinalis)sur des alevins (0+) de saumons atlantiques (Salmo salar) nouvellement déversés en milieu naturel. Les mauvaises conditions prévalant durant le transport de la pisciculture aux lieux de déversement ainsi qu'une méthode d'introduction inadéquate seraient responsables en grande partie de la prédation effectuée par l'omble de fontaine. Cette prédation pourrait être minimisée en donnant aux alevins une période de récupération et en les dispersant dans des habitats qui répondent à leurs exigences, tout en respectant la capacité d'accueil de ces habitats.

Objective: An observational study showed that combining memantine with a cholinesterase inhibitor (ChEI) treatment significantly delayed admission to nursing homes in patients with Alzheimer disease (AD). Our study aimed to evaluate the economic impact of the concomitant use of memantine and a ChEI, compared with a ChEI alone, in a Canadian population of patients with AD.Method: A cost-utility analysis using a Markov model during a 7-year time horizon was performed according to a societal and Canadian health care system perspective. The Markov model includes the following states: noninstitutionalized, institutionalized, and deceased. The model includes transition probabilities for institutionalization and death, adjusted with mortality rates specific to AD. Utilities associated with institutionalization and noninstitutionalization were included. For the health care system perspective, costs of medication as well as costs of care provided in the community and in nursing homes were considered. For the societal perspective, costs of direct care and supervision provided by caregivers were added.Results: From both perspectives, the concomitant use of a ChEI and memantine is a dominant strategy, compared with the use of a ChEI alone. On a per patient basis, there was a gain of 0.26 quality-adjusted life years with the treatment including memantine and cost decreases of Can$21 391 and Can$30 512, respectively, for the societal and health care system perspective.Conclusions: This economic evaluation indicates that institutionalization is the largest cost component in AD management and that the use of memantine, combined with a ChEI, to treat AD is a cost-effective alternative, compared with the use of a ChEI alone. [ABSTRACT FROM AUTHOR]

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Dopamine-containing neurones of the ventral tegmental area express neurotensin receptors which are involved in regulating cell firing and dopamine release. Although indirect evidence suggests that some neurotensin receptors may be localised on the nerve terminals of dopaminergic neurones in the striatum and thus locally regulate dopamine release, a clear demonstration of such a mechanism is lacking and a number of indirect sites of action are possible. We have taken advantage of a simplified preparation in which cultured rat ventral tegmental area dopaminergic neurones establish nerve terminals that co-release glutamate to determine whether neurotensin can act at presynaptic sites. We recorded glutamate-mediated synaptic currents that were generated by dopaminergic nerve terminals as an index of presynaptic function. The neurotensin receptor agonist NT(8–13) caused an inward current and an enhancement of the firing rate of dopaminergic neurones together with an increase in the frequency of spontaneous glutamate receptor-mediated excitatory postsynaptic currents (EPSCs). Incompatible with a direct excitatory action on nerve terminals, NT(8–13) failed to change the amplitude of individual action potential-evoked EPSCs or the frequency of miniature EPSCs recorded in the presence of tetrodotoxin. However, NT(8–13) reduced the ability of terminal D2 dopamine receptors to inhibit action potential-evoked EPSCs in isolated dopaminergic neurones. Taken together, our results suggest that in addition to its well-known somatodendritic excitatory effect leading to an increase in firing rate, neurotensin also acts on nerve terminals. The main effect of neurotensin on nerve terminals is not to produce a direct excitation, but rather to decrease the effectiveness of D2 receptor-mediated presynaptic inhibition. [Copyright &y& Elsevier]

Dermatological diseases such as atopic dermatitis, acne, and psoriasis result in significant morbidity and decreased quality of life. The first line of treatment for such diseases is often topical medications. While topical delivery allows active drug to be delivered directly to the target site, the skin is a virtually impermeable barrier that impedes delivery of large molecules. Thus, the formulation and delivery system are integral elements of topical medications. Patients also have preferences for the properties of topical formulations and these preferences can positively or negatively impact adherence. Therefore, the choice of topical formulation is a key consideration. Recent developments in drug delivery systems have produced enhanced topical treatments that improve efficacy, safety, and patient acceptability. Awareness of the delivery system in which drugs are formulated is critical as this can have profound implications on treatment success. This paper provides an overview and clinical commentary on advances in topical delivery systems and their impact on dermatological practice., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Isabelle Delorme has been a member of advisory boards for AbbVie, Bausch Health, Eli-Lilly, Janssen, Novartis, Sanofi-Genzyme. She has been a part of clinical trials for AbbVie, Amgen, Anaptys Bio, Arcutis, Bausch Health, BMS, Celgene, Dermira, Devonian, Eli-Lilly, Galderma, Glenmark Pharmaceutical, Innovaderm Research, Janssen, Leo Pharma, Novartis, Regeneron. She has recieved honoraria from AbbVie, Amgen, Avene, Celgene, Eli-Lilly, Janssen, Novartis, UCB Pharma. She has been part of speaker’s bureaus for AbbVie, Celgene, Bausch Health, Eli-Lilly, Janssen, Medexus Inc., Novartis, Sanofi Genzyme. Melinda Gooderham has been an investigator, speaker and/or advisor for - AbbVie, Amgen, Akros, Arcutis, Aslan, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Dermira, Dermavant, Eli Lilly, Galderma, GSK, Incyte, Janssen, Kyowa Kirin, Leo Pharma, MedImmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sun Pharma, and UCB. Andrei Metelitsa has been a consultant for Bausch Health, Galderma, Leo Pharma and Pfizer. Daniel O’Sullivan, Rami Zeinab and Mark Legault are employees of Bausch Health Canada. Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

We present the Canadian Open Neuroscience Platform (CONP) portal to answer the research community's need for flexible data sharing resources and provide advanced tools for search and processing infrastructure capacity. This portal differs from previous data sharing projects as it integrates datasets originating from a number of already existing platforms or databases through DataLad, a file level data integrity and access layer. The portal is also an entry point for searching and accessing a large number of standardized and containerized software and links to a computing infrastructure. It leverages community standards to help document and facilitate reuse of both datasets and tools, and already shows a growing community adoption giving access to more than 60 neuroscience datasets and over 70 tools. The CONP portal demonstrates the feasibility and offers a model of a distributed data and tool management system across 17 institutions throughout Canada., (© 2023. The Author(s).)

The current study explored the phenomenology of emotional eating, that is, the descriptive knowledge of what one perceives, senses, and knows in one's immediate awareness and experience during emotional eating. Eight individuals with emotional eating were interviewed twice using explicitation interviewing. Data were analyzed using thematic analysis, which resulted in nine themes describing the diachronic (or temporal) unfolding of emotional eating and several sub-themes that described various synchronic (or experiential) dimensions of this unfolding. The core findings of this study support the escape theory of emotional eating and recommend future directions to investigate the self-related shifts proposed by this theory. Namely, the findings show that individuals tend to use food to regulate their emotions by reducing the unpleasant experience of negative emotions and the associated unpleasant narrative processing or ruminations about stressors that caused the negative emotions. This then leads to an urge to eat associated with a desire for the sensory experience of eating. Eating then enables individuals to reduce thoughts about their stressors and bring themselves into the present moment through embodiment. Future quantitative research could investigate this mechanism of shifting from narrative to embodied processing to regulate emotions in emotional eating to develop treatment programs, such as mindfulness-based programs, that could encourage such a shift and emotion regulation without the use of food., (© 2022. The Author(s).)

Competing Interests: Dr Vender has served as a consultant, investigator, and/or received support or honoraria from AbbVie, Actelion, Amgen, Aralez, Arcutis, Bausch Health, Boehringer Ingelheim, BMS, Celgene, Cipher, Janssen, Galderma, GSK, Kabi-Care, Leo, Lilly, Merck, Novartis, Palladin, Pfizer, Sandoz, Sun Pharma, UCB, and Viatris-Mylan. Dr Turchin has served as consultant, speaker, or investigator for AbbVie, Amgen, Arcutis, Aristea, Bausch Health, BMS, Boehringer Ingelheim, Celgene, Eli Lilly, Galderma, Incyte, Janssen, Kiniksa, LeoPharma, Mallinckrodt, Novartis, Pfizer, Sanofi, Sun Pharma, and UCB. Dr Lansang has received honoraria and consulting fees from AbbVie, Amgen, Bausch, Celgene, Galderma, Janssen, Lilly, Novartis, Pfizer, Sanofi, UCB, and Valeant. Dr Prajapati has served as an investigator for AbbVie, Amgen, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Janssen, LEO Pharma, Nimbus Lakshmi, Novartis, Pfizer, Regeneron, Reistone, Sanofi Genzyme, UCB, and Valeant and has served as a consultant, advisor, and/or speaker for AbbVie, Actelion, Amgen, Aralez, Arcutis, Aspen, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Janssen, LEO Pharma, L'Oreal, Medexus, Novartis, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant. Dr Legault is an employee of Bausch Health Canada. Dr Barakat is an employee of Bausch Health Canada. Dr Yeung has been a speaker, consultant, and investigator for AbbVie, Allergan, Amgen, Astellas, Bausch Health, Boehringer Ingelheim, Celgene, Centocor, Coherus, Dermira, Eli Lilly, Forward, Galderma, GSK, Janssen, Leo, Medimmune, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant, and Xenon.

In January 2016, the Montreal Neurological Institute-Hospital (The Neuro) declared itself an Open Science organization. This vision extends beyond efforts by individual scientists seeking to release individual datasets, software tools, or building platforms that provide for the free dissemination of such information. It involves multiple stakeholders and an infrastructure that considers governance, ethics, computational resourcing, physical design, workflows, training, education, and intra-institutional reporting structures. The C-BIG repository was built in response as The Neuro's institutional biospecimen and clinical data repository, and collects biospecimens as well as clinical, imaging, and genetic data from patients with neurological disease and healthy controls. It is aimed at helping scientific investigators, in both academia and industry, advance our understanding of neurological diseases and accelerate the development of treatments. As many neurological diseases are quite rare, they present several challenges to researchers due to their small patient populations. Overcoming these challenges required the aggregation of datasets from various projects and locations. The C-BIG repository achieves this goal and stands as a scalable working model for institutions to collect, track, curate, archive, and disseminate multimodal data from patients. In November 2020, a Registered Access layer was made available to the wider research community at https://cbigr-open.loris.ca , and in May 2021 fully open data will be released to complement the Registered Access data. This article outlines many of the aspects of The Neuro's transition to Open Science by describing the data to be released, C-BIG's full capabilities, and the design aspects that were implemented for effective data sharing., (© 2021. The Author(s).)

Background: Rare diseases are estimated to affect 150-350 million people worldwide. With advances in next generation sequencing, the number of known disease-causing genes has increased significantly, opening the door for therapy development. Rare disease research has therefore pivoted from gene discovery to the exploration of potential therapies. With impending clinical trials on the horizon, researchers are in urgent need of natural history studies to help them identify surrogate markers, validate outcome measures, define historical control patients, and design therapeutic trials., Results: We customized a browser-accessible multi-modal (e.g. genetics, imaging, behavioral, patient-determined outcomes) database to increase cohort sizes, identify surrogate markers, and foster international collaborations. Ninety data entry forms were developed including family, perinatal, developmental history, clinical examinations, diagnostic investigations, neurological evaluations (i.e. spasticity, dystonia, ataxia, etc.), disability measures, parental stress, and quality of life. A customizable clinical letter generator was created to assist in continuity of patient care., Conclusions: Small cohorts and underpowered studies are a major challenge for rare disease research. This online, rare disease database will be accessible from all over the world, making it easier to share and disseminate data. We have outlined the methodology to become Title 21 Code of Federal Regulations Part 11 Compliant, which is a requirement to use electronic records as historical controls in clinical trials in the United States. Food and Drug Administration compliant databases will be life-changing for patients and families when historical control data is used for emerging clinical trials. Future work will leverage these tools to delineate the natural history of several rare diseases and we are confident that this database will be used on a larger scale to improve care for patients affected with rare diseases., (© 2021. The Author(s).)

Severe obesity is associated with major health issues and bariatric surgery is still the only treatment to offer significant and durable weight loss. Assessment of dietary intakes is an important component of the bariatric surgery process., Objective: To document the dietary assessment tools that have been used with patients targeted for bariatric surgery and patients who had bariatric surgery and explore the extent to which these tools have been validated., Methods: A literature search was conducted to identify studies that used a dietary assessment tool with patients targeted for bariatric surgery or who had bariatric surgery., Results: 108 studies were included. Among all studies included, 27 used a dietary assessment tool that had been validated either as part of the study per se ( n = 11) or in a previous study ( n = 16). Every tool validated per se in the cited studies was validated among a bariatric population, while none of the tools validated in previous studies were validated in this population., Conclusion: Few studies in bariatric populations used a dietary assessment tool that had been validated in this population. Additional studies are needed to develop valid and robust dietary assessment tools to improve the quality of nutritional studies among bariatric patients.

This study aimed to explore the impact of an awareness tool for relatives of older drivers (OSCARPA) on i) their interest, openness and knowledge, ii) changes of abilities required for safe driving, and iii) utilization of compensatory strategies. A pre-experimental design with pretest (T0) and post-test (T1) eight to ten weeks after the intervention was realized with 45 relatives in contact with an older driver of 65 years old or older and who was driving at least once a week. Overall, the results demonstrated that OSCARPA increased i) interest, openness and knowledge of relatives (p<0.001), as well as their perceptions of ii) changes of abilities of older drivers (p=0.02), and iii) their utilization of compensatory strategies (p=0.001). Future studies would be relevant to further evaluate and increase the effectiveness of OSCARPA.

Background: Accurate and practical biologic tools to estimate HIV incidence is crucial to better monitor the epidemic and evaluate the effectiveness of HIV prevention and treatment programs., Methods: We evaluated two avidity assays to measure recent HIV infection: the Sedia HIV-1 LAg-Avidity EIA (Sedia Biosciences, Portland) and the Centers for Disease Control and Prevention (CDC)-modified Bio-Rad-Avidity assay (Bio-Rad Laboratories, Mississauga, ON). Longitudinal specimens (n = 473) obtained from 123 treatment-naive seroconverted individuals enrolled in the Primary HIV-1 Infection (PHI) cohort of Quebec were used to determine the average time an individual is considered to be recently infected (mean duration of recent infection; MDRI), for the two avidity assays alone and in combination using a nonparametric survival method analysis. A total of 420 specimens from individuals with established HIV infection (90 individuals from the PHI cohort of Quebec and 330 individuals from the Laboratoire de santé publique du Quebec (LSPQ) serobank) were also tested to investigate false recency rate (FRR)., Results: The CDC-modified Bio-Rad-Avidity gave an estimated MDRI of 234 days (95% CI 220-249) at the avidity index cutoff of 30% while the Sedia-LAg-Avidity assay gave an estimated MDRI of 120 days (95% CI 109-132) at the normalized optical density (ODn) cutoff of 1.5. The FRR among individuals with established HIV infection was 10.2% (7.5%-13.5%) with the CDC-modified Bio-Rad-Avidity assay as compared to 6.0% (3.9%-8.7%) with the Sedia-LAg-Avidity assay. When optimizing a multiassay algorithm (MAA) that includes sequentially the CDC-modified Bio-Rad-Avidity assay then the Sedia-LAg-Avidity assay EIA (avidity index/ODn: 30%/1.7), the MDRI was 136 days (95% CI 123-148) and the FRR, 3.3% (95% CI 1.8-5.6)., Conclusion: Multiassay algorithms that include the CDC-modified Bio-Rad-Avidity assay and the Sedia-LAg-Avidity assay performed better than each avidity assay alone. Such 2-assay algorithm that starts with the CDC-modified Bio-Rad-Avidity assay followed by the Sedia-LAg-Avidity assay allowed a better classification of HIV-1 infections.

The North-east American Rainbow smelt (Osmerus mordax) is composed of two glacial races first identified through the spatial distribution of two distinct mtDNA lineages. Contemporary breeding populations of smelt in the St. Lawrence estuary comprise contrasting mixtures of both lineages, suggesting that the two races came into secondary contact in this estuary. The overall objective of this study was to assess the role of intraspecific genetic admixture in the morphological diversification of the estuarine rainbow smelt population complex. The morphology of mixed-ancestry populations varied as a function of the relative contribution of the two races to estuarine populations, supporting the hypothesis of genetic admixture. Populations comprising both ancestral mtDNA races did not exhibit intermediate morphologies relative to pure populations but rather exhibited many traits that exceeded the parental trait values, consistent with the hypothesis of transgressive segregation. Evidence for genetic admixture at the level of the nuclear gene pool, however, provided only partial support for this hypothesis. Variation at nuclear AFLP markers revealed clear evidence of the two corresponding mtDNA glacial races. The admixture of the two races at the nuclear level is only pronounced in mixed-ancestry populations dominated by one of the mtDNA lineages, the same populations showing the greatest degree of morphological diversification and population structure. In contrast, mixed-ancestry populations dominated by the alternate mtDNA lineage showed little evidence of introgression of the nuclear genome, little morphological diversification and little contemporary population genetic structure. These results only partially support the hypothesis of transgressive segregation and may be the result of the differential effects of natural selection acting on admixed genomes from different sources.

The potential of enzyme catalysis in organic solvents for synthetic applications has been overshadowed by the fact that their catalytic properties are affected by organic solvents. In addition, it has recently been shown that an enzyme's initial activity diminishes considerably after prolonged exposure to organic media. Studies geared towards understanding this last drawback have yielded unclear results. In the present work we decided to use electron paramagnetic resonance spectroscopy (EPR) to study the motion of an active site spin label (a nitroxide free radical) during 96 h of exposure of the serine protease subtilisin Carlsberg to four different organic solvents. Our EPR data shows a typical two component spectra that was quantified by the ratio of the anisotropic and isotropic signals. The isotropic component, associated with a mobile nitroxide free radical, increases during prolonged exposure to all solvents used in the study. The maximum increase (of 43%) was observed in 1,4-dioxane. Based on these and previous studies we suggest that prolonged exposure of the enzyme to these solvents provokes a cascade of events that could induce substrates to adopt different binding conformations. This is the first EPR study of the motion of an active-site spin label during prolonged exposure of an enzyme to organic solvents ever reported.

Objective: Data were analyzed from 2 prospective, double-blind, placebo-controlled trials of escitalopram in obsessive-compulsive disorder (OCD) to characterize the baseline levels of functional disability and impairment in health-related quality of life (HRQoL) and to assess the relationship between treatment outcomes (response or relapse) and disability or HRQoL., Method: Data from a 24-week, placebo-controlled, fixed-dose trial (N = 466) of escitalopram (10-20 mg/d) or paroxetine (40 mg/d) and from a 40-week, flexible-dose (escitalopram 10-20 mg/d), placebo-controlled relapse-prevention trial (N = 468) were analyzed. Obsessive-compulsive disorder symptoms (DSM-IV criteria) were assessed using the Yale-Brown Obsessive Compulsive Scale (YBOCS), functioning was assessed using the Sheehan Disability Scale (SDS), and HRQoL was assessed using the Medical Outcomes Study Short Form (SF-36). Baseline data were pooled for patients across both studies. For patients in the fixed-dose study, SDS and SF-36 scores were compared across treatment groups and for responders versus nonresponders. In the relapse-prevention trial, SDS and SF-36 scores were compared for relapsed versus nonrelapsed patients., Results: Patients with more severe baseline symptoms (YBOCS > or = 27) reported significantly greater impairment on the SDS (P < .001) and SF-36 (except for bodily pain). Patients receiving escitalopram or paroxetine reported significant improvements on most SF-36 dimensions and on the SDS compared to placebo; however, improvements in work-related functioning were seen earlier for patients receiving escitalopram (20 mg/d). At the study endpoints, SDS and SF-36 scores were significantly better for patients who were responders (versus nonresponders) and for patients who did not relapse (versus relapsers)., Conclusions: Obsessive-compulsive disorder is associated with significant impairment in functioning and HRQoL. Significant differences in disability and HRQoL between responders and nonresponders or relapsers and nonrelapsers suggest a relationship between symptomatic and functional outcomes., Trial Registration: lundbecktrials.com Identifiers: 10205 and 10193., (2010 Physicians Postgraduate Press, Inc.)

Objective: To evaluate the effectiveness and tolerability of escitalopram (10-20 mg/day) in adult outpatients suffering from major depressive disorder in naturalistic settings., Methods: An open-label, 3-month, surveillance study was conducted in 434 investigative sites in Greece enrolling 5175 patients. Clinical Global Impression-Severity (CGI-S) scale and patient-rated Sheehan Disability Scale (SDS) were used as efficacy measurements and treatment discontinuation rates due to adverse events was used to assess tolerability., Results: Clinically significant improvement in CGI-S scores was recorded after 3 months. At baseline, patients reported marked or extreme disability for work (38%), social life (41%) and family life (37%), whereas after 3 months of treatment, 80.6%, 79.5% and 83.5% of patients indicated either no or mild disability, respectively. Escitalopram had good tolerability, demonstrated by a very low rate of discontinuations due to adverse events., Conclusion: In this large naturalistic study, escitalopram was well tolerated and improved both depressive symptoms and function.

Background: The present trial was designed to assess the efficacy and safety of escitalopram prescribed to patients seeking treatment of major depressive disorder (MDD) in a Canadian primary-care setting., Methods: Investigators (mainly primary-care physicians) enrolled patients with MDD from their daily practice. Patients were treated with escitalopram (flexible dose 10-20 mg/day) for up to 24 weeks. Efficacy assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Clinical Global Impression-Improvement and -Severity scales (CGI-I, CGI-S), the Patient Global Evaluation (PGE), and the Medical Outcome Study 36-item Short Form (SF-36)., Results: Out of the 647 patients enrolled, 461 (71%) completed 24 weeks of treatment. The most common reason for discontinuation was adverse events (10%). The mean MADRS score decreased from 30.7 at baseline to 10.9 at the end of 24 weeks (last observation carried forward, LOCF). Remission (MADRS

Estimation of effective population sizes (N(e)) and temporal gene flow (N(e)m, m) has many implications for understanding population structure in evolutionary and conservation biology. However, comparative studies that gauge the relative performance of N(e), N(e)m or m methods are few. Using temporal genetic data from two salmonid fish population systems with disparate population structure, we (i) evaluated the congruence in estimates and precision of long- and short-term N(e), N(e)m and m from six methods; (ii) explored the effects of metapopulation structure on N(e) estimation in one system with spatiotemporally linked subpopulations, using three approaches; and (iii) determined to what degree interpopulation gene flow was asymmetric over time. We found that long-term N(e) estimates exceeded short-term N(e) within populations by 2-10 times; the two were correlated in the system with temporally stable structure (Atlantic salmon, Salmo salar) but not in the highly dynamic system (brown trout, Salmo trutta). Four temporal methods yielded short-term N(e) estimates within populations that were strongly correlated, and these were higher but more variable within salmon populations than within trout populations. In trout populations, however, these short-term N(e) estimates were always lower when assuming gene flow than when assuming no gene flow. Linkage disequilibrium data generally yielded short-term N(e) estimates of the same magnitude as temporal methods in both systems, but the two were uncorrelated. Correlations between long- and short-term geneflow estimates were inconsistent between methods, and their relative size varied up to eightfold within systems. While asymmetries in gene flow were common in both systems (58-63% of population-pair comparisons), they were only temporally stable in direction within certain salmon population pairs, suggesting that gene flow between particular populations is often intermittent and/or variable. Exploratory metapopulation N(e) analyses in trout demonstrated both the importance of spatial scale in estimating N(e) and the role of gene flow in maintaining genetic variability within subpopulations. Collectively, our results illustrate the utility of comparatively applying N(e), N(e)m and m to (i) tease apart processes implicated in population structure, (ii) assess the degree of continuity in patterns of connectivity between population pairs and (iii) gauge the relative performance of different approaches, such as the influence of population subdivision and gene flow on N(e) estimation. They further reiterate the importance of temporal sampling replication in population genetics, the value of interpreting N(e)or m in light of species biology, and the need to address long-standing assumptions of current N(e), N(e)m or m models more explicitly in future research.

Background: A population-based phylogenetic approach was used to characterize human immunodeficiency virus (HIV)-transmission dynamics in Quebec., Methods: HIV-1 pol sequences included primary HIV infections (PHIs; <6 months after seroconversion) from the Quebec PHI cohort (1998-2005; n=215) and the provincial genotyping program (2001-2005; n=481). Phylogenetic analysis determined sequence interrelationships among unique PHIs (n=593) and infections from untreated (n=135) and treated (n=660) chronically infected (CI) potential transmitter populations (2001-2005). Clinical features, risk factors, and drug resistance for clustered and nonclustered transmission events were ascertained., Results: Viruses from 49.4% (293/593) of PHIs cosegregated into 75 transmission chains with 2-17 transmissions/cluster. Half of the clusters included 2.7+/-0.8 (mean+/-SD) transmissions, whereas the remainder had 8.8+/-3.5 transmissions. Maximum periods for onward transmission in clusters were 15.2+/-9.5 months. Coclustering of untreated and treated CIs with PHIs were infrequent (6.2% and 4.8%, respectively). The ages, viremia, and risk factors were similar for clustered and nonclustered transmission events. Low prevalence of drug resistance in PHI supported amplified transmissions at early stages., Conclusions: Early infection accounts for approximately half of onward transmissions in this urban North American study. Therapy at early stages of disease may prevent onward HIV transmission.

Neurotensin (NT) increases neurotransmission within the mesolimbic dopamine system by enhancing the firing rate of dopaminergic (DAergic) neurons and by acting at the nerve terminal level. The signal transduction pathways involved in these effects have not been characterized, but NT receptors are coupled to the phospholipase C pathway and Ca(2+) mobilization. However, an enhancement of intracellular Ca(2+) concentration ([Ca(2+)](i)) evoked by NT in DAergic neurons has yet to be demonstrated. Furthermore, the hypothesis that the excitatory effects of NT in DAergic neurons are Ca(2+) dependent is currently untested. In whole-cell recording experiments, DAergic neurons in culture were identified by their selective ability to express a cell-specific green fluorescent protein reporter construct. These experiments confirmed that NT increases firing rate in cultured DAergic neurons. This effect was Ca(2+) dependent because it was blocked by intracellular dialysis with BAPTA. Using Ca(2+) imaging, we showed that NT caused a rapid increase in [Ca(2+)](i) in DAergic neurons. Most of the Ca(2+) originated from the extracellular medium. NT-induced excitation and Ca(2+) influx were blocked by SR48692, an antagonist of the type 1 NT receptor. Blocking IP(3) receptors using heparin prevented the excitatory effect of NT. Moreover, Zn(2+) and SKF96365 both blocked the excitatory effect of NT, suggesting that nonselective cationic conductances are involved. Finally, although NT can also induce a rise in [Ca(2+)](i) in astrocytes, we find that NT-evoked excitation of DAergic neurons can occur independently of astrocyte activation.

In this study, we investigate the relative role of historical factors and evolutionary forces in promoting population differentiation in a new case of sympatric dwarf and normal ecotypes of the rainbow smelt (Osmerus mordax Mitchill) in Lac Saint-Jean (Québec, Canada). Our first objective was to test the hypothesis that the evolution of sympatric smelt ecotypes in Lac Saint-Jean has been contingent upon the secondary contact between two evolutionary lineages in postglacial times. Secondly, the QST method was applied to test the null hypothesis that the extent of phenotypic differences relative to that of neutral marker variation would be similar in comparisons involving populations within and among ecotypes. Thirdly, we applied a quantitative-genetic method as an exploratory assessment as to whether the amount of gene flow observed between populations could affect divergence in adaptive traits under specific conditions. This study revealed a unique situation of dwarf and normal smelt ecotypes that are, respectively, characterized by selmiparous and iteroparous life histories and the occurrence in each of two genetically distinct populations that synchronously use the same spawning habitat in two tributaries. Historical contingency has apparently played little role in the origin of these populations. In contrast, an important role of divergent natural selection in driving their phenotypic divergence was suggested. While divergent selection has apparently been strong enough to maintain phenotypic differentiation in the face of migration, this study suggests that gene flow has been sufficiently important to modulate the extent of adaptive differentiation being achieved between ecotypes, unless the extent of stabilizing selection acting on smelt ecotypes is much more pronounced than usually reported in natural populations.

In BRET2 (Bioluminescence Resonance Energy Transfer), a Renilla luciferase (RLuc) is used as the donor protein, while a Green Fluorescent Protein (GFP2) is used as the acceptor protein. In the presence of the cell permeable substrate DeepBlueC, RLuc emits blue light at 395 nm. If the GFP2 is brought into close proximity to RLuc via a specific biomolecular interaction, the GFP2 will absorb the blue light energy and reemit green light at 510nm. BRET2 signals are therefore easily determined by measuring the ratio of green over blue light (510/395nm) using appropriate dual channel luminometry instruments (e.g., Fusion Universal Microplate Analyzer, Packard BioScience). Since no light source is required for BRET2 assays, the technology does not suffer from high fluorescent background or photobleaching, the common problems associated with standard FRET-based assays. Using BRET2, we developed a generic G Protein-Coupled Receptor (GPCR) assay based on the observation that activation of the majority of GPCRs by agonists leads to the interaction of beta-arrestin (a protein that is involved in receptor desensitization and sequestration) with the receptor. We established a cell line stably expressing the GFP2:beta-arrestin 2 fusion protein, and showed that it can be used to monitor the activation of various transiently expressed GPCRs, in BRET2/arrestin assays. In addition, using the HEK 293/GFP2:beta-arrestin 2 cell line as a recipient, we generated a double-stable line co-expressing the vasopressin 2 receptor (V2R) fused to RLuc (V2R:RLuc) and used it for the pharmacological characterization of compounds in BRET2/arrestin assays. This approach yields genuine pharmacology and supports the BRET2/arrestin assay as a tool that can be used with recombinant cell lines to characterize ligand-GPCR interactions which can be applied to ligand identification for orphan receptors.

In vivo microdialysis in freely moving rats was used to monitor novelty-evoked elevations in extracellular dopamine in the nucleus accumbens septi (NAS) and to examine the role of the ventral subiculum of the hippocampus and glutamatergic transmission in the ventral tegmental area (VTA) on these elevations. Exposure to novel stimuli evoked investigatory activity and increased nucleus accumbens dopamine. Unilateral injections of the sodium channel blocker tetrodotoxin (0.16 ng/0.5 microL) into the ventral subiculum ipsilateral to the dialysed NAS abolished novelty-evoked elevations in dopamine. Injections of tetrodotoxin into the contralateral VS did not prevent novelty-evoked elevations in nucleus accumbens dopamine. Unilateral perfusion (via microdialysis) of the ionotropic glutamate receptor antagonists kynurenic acid (1 mM) into the ipsilateral but not the contralateral VTA blocked novelty-evoked elevations in nucleus accumbens dopamine. Neither unilateral injections of tetrodotoxin nor unilateral perfusion of kynurenic acid disrupted investigatory behaviour. These data indicate that phasic elevations in nucleus accumbens dopamine evoked by exposure to unconditioned novel stimuli are dependent on impulse flow from the hippocampus and glutamatergic transmission in the VTA.

The Agricultural Safety and Health Best Management Practices (ASHBMP) Manual was developed as an alternative intervention tool to help identify and correct farmwork hazards. A modified pretest-posttest control group experimental design was used to test the effectiveness of the manual with three intervention groups and a control. Testing consisted of conducting baseline and post-intervention audits on 150 farms in Pennsylvania. Significant differences were found among groups of farmers who were given the ASHBMP Manual and those who were not given the manual. The results of the data analysis also showed a positive significant difference among farmers who reduced their farm hazard levels through use of the ASHBMP Manual over farmers who received the Control (traditional safety fact sheets). The data supports the conclusion that the ASHBMP Manual is an effective tool for helping farmers reduce workplace hazards.

Dual-probe microdialysis (with HPLC and electrochemical detection) in freely moving rats and single-unit recording in anesthetized rats were used to study the extent to which impulse flow through the ventral tegmental area (VTA) contributes to elevations in nucleus accumbens (NAS) dopamine (DA) evoked by stimulation of the ventral subiculum (VS). During perfusion of artificial extracellular fluid into the VTA, injections of 0.74 microgram of the excitatory amino acid NMDA into the VS elevated accumbens DA to >150% of basal values. During intra-VTA perfusion of either 1 microM tetrodotoxin (which blocks impulse flow) or 1 mM kynurenic acid (which blocks excitatory glutamate receptors), injections of NMDA into the VS failed to elevate accumbens DA. Thus, increased impulse flow through VTA DA neurons, mediated by excitatory glutamate inputs to this region, appears critical for VS stimulation to elevate NAS DA. Increased impulse flow through VTA DA neurons was confirmed using single-unit recording in anesthetized rats. Intra-VS NMDA injections increased the firing rates of 45% (14 of 31), decreased the firing rates of 13% (4 of 31), and had no effect on 42% (13 of 31) of VTA DA neurons. Increases in firing rates were evident within 15 min of NMDA injections, a time at which VS NMDA injections elevate accumbens DA in awake animals. The results of the present experiments identify the VTA as a critical site through which outputs from the VS modulate NAS dopaminergic neurotransmission.

The nucleus accumbens septi receives inputs from dopaminergic neurons of the ventral tegmental area (VTA) and glutamatergic neurons of the ventral subiculum (VS). The convergence of these inputs in the NAS is important for the normal expression of exploratory locomotion; stimulation of the VS by injection of the glutamate receptor agonist N-methyl-D-aspartate (NMDA) causes dopamine-dependent increases in locomotion. In the present study, in vivo microdialysis in conjunction with high-performance liquid chromatography and electrochemical detection (HPLC-EC) was used to estimate changes in extracellular dopamine in the VTA and NAS in response to intra-VS injections of NMDA (0.074, 0.28, 0.74 microg). NMDA injections caused dose-dependent elevations in extracellular dopamine in each region. Each dose of NMDA clearly increased extracellular dopamine in the NAS, whereas only the two higher doses increased dopamine significantly in the VTA. The highest dose of NMDA elevated extracellular dopamine to approximately 180% of baseline in each region. Whereas elevations in NAS dopamine might be induced by impulse-independent local mechanisms, elevations of dopamine in the VTA are presumed to reflect increased somatodendritic release associated with increased impulse flow through dopamine neurons. Thus, the present study suggests that the modulation of dopaminergic neurotransmission by the ventral subiculum results from a trans-synaptic activation of dopamine cell bodies in the VTA.

Objective: To compare the kangaroo and traditional methods of removing an infant from an incubator in terms of four physiologic parameters, mother's satisfaction, and mother's preference., Design: Time-series design (quasi-experimental), with infant-mother dyads subjected to both methods., Setting: Intermediate neonatal care unit in a tertiary hospital in Canada., Participants: A convenience sample of 71 infant-mother dyads. INTERVENTION AND MEASURES: The intervention was use of the kangaroo or traditional method of maintaining body temperature of preterm infants. The dependent variables were physiologic parameters (skin temperature, heart rate, respiratory rate, and oxygen saturation) measured five times with each method. Mother's satisfaction was measured at the end of each testing period and mother's preference at the end of the experiment., Results: The kangaroo method produced less variation in oxygen saturation and longer duration of testing, and it was preferred by most of the mothers., Conclusions: The kangaroo method is safe for the preterm infant and allows for early contact between parents and infants.