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The DEAP-3600 detector searches for the scintillation signal from dark matter particles scattering on a 3.3 tonne liquid argon target. The largest background comes from 39 Ar beta decays and is suppressed using pulse-shape discrimination (PSD). We use two types of PSD estimator: the prompt-fraction, which considers the fraction of the scintillation signal in a narrow and a wide time window around the event peak, and the log-likelihood-ratio, which compares the observed photon arrival times to a signal and a background model. We furthermore use two algorithms to determine the number of photons detected at a given time: (1) simply dividing the charge of each PMT pulse by the mean single-photoelectron charge, and (2) a likelihood analysis that considers the probability to detect a certain number of photons at a given time, based on a model for the scintillation pulse shape and for afterpulsing in the light detectors. The prompt-fraction performs approximately as well as the log-likelihood-ratio PSD algorithm if the photon detection times are not biased by detector effects. We explain this result using a model for the information carried by scintillation photons as a function of the time when they are detected., (© The Author(s) 2021.)

Neutrophil killing of bacteria is mediated by oxidative and non-oxidative mechanisms. Oxidants are generated through the NADPH oxidase complex, whereas antimicrobial proteins and peptides rank amongst non-oxidative host defenses. Mucus hypersecretion, deficient hydration and poor clearance from the airways are prominent features of cystic fibrosis (CF) lung disease. CF airways are commonly infected by Pseudomonas aeruginosa and Burkholderia cepacia complex bacteria. Whereas the former bacterium is highly sensitive to non-oxidative killing, the latter is only killed if the oxidative burst is intact. Despite an abundance of neutrophils, both pathogens thrive in CF airway secretions. In this study, we report that secreted mucins protect these CF pathogens against host defenses. Mucins were purified from CF sputum and from the saliva of healthy volunteers. Whereas mucins did not alter the phagocytosis of Pseudomonas aeruginosa and Burkholderia cenocepacia by neutrophils, they completely suppressed bacterial killing. Accordingly, mucins markedly inhibited non-oxidative bacterial killing by neutrophil granule extracts, or by lysozyme and the cationic peptide, human β defensin-2 (HBD2). Mucins also suppressed the neutrophil oxidative burst through a charge-dependent mechanism that could be reversed by the cationic aminoglycoside, tobramycin. Our data indicate that airway mucins protect Gram-negative bacteria against neutrophil killing by suppressing the oxidative burst and inhibiting the bactericidal capacity of cationic proteins and peptides. Mucin hypersecretion, dehydration, stasis and anionic charge represent key therapeutic targets for improving host defenses and airway inflammation in CF and other muco-secretory airway diseases., (Copyright © 2020 Cantin, Ouellet, Cloutier and McDonald.)

Aim: No previous study has investigated interventions for homeless youth suffering from first episode psychosis and comorbid substance use disorder (HYPS). An intensive assertive community intervention team (IACIT) offering outreach interventions, housing support as well as integrated care for early psychosis and substance use disorder (SUD) was created in 2012 at the Centre Hospitalier de l'Université de Montréal (CHUM). To explore the impact of the addition of an IACIT to an early intervention for psychosis service (EIS) on housing stability, functional and symptomatic outcomes and mental health service use., Methods: A two-year longitudinal study comparing the outcome of HYPS receiving combined EIS and IACIT since 2012, to a historical cohort of HYPS receiving EIS only between 2005 and 2011. Socio-demographic data, housing stability, functioning, illness severity, SUD severity, emergency room visits and hospitalizations were assessed at admission, at 1 month, and every 3 months thereafter., Results: HYPS receiving EIS + IACIT achieved housing stability more rapidly and spent less time hospitalized than HYPS getting EIS only (RR 2.38, P = .017). HYPS with cocaine misuse were less likely to attain housing stability (RR 0.25, P = .04). No between-group differences were found for psychiatric symptoms, functioning and SUD outcomes., Conclusion: The addition of IACIT-HYPS to EIS was associated with earlier housing stability and reduced total hospitalization days compared to EIS alone., (© 2019 John Wiley & Sons Australia, Ltd.)

Current treatments for primary psychotic disorders include antipsychotics, some of which have significant side effects or suboptimal efficacy. Cannabidiol is a cannabinoid with potential antipsychotic properties. This systematic review examines the use of cannabidiol as an antipsychotic treatment for primary psychotic disorders. CINAHL, EBM, EMBASE, MEDLINE and PubMed databases were searched from 1970 to 2019 for experimental and observational studies evaluating the antipsychotic and cognitive modulation properties of cannabidiol in individuals with psychotic disorders. There were eight eligible studies evaluating the antipsychotic potential of cannabidiol, involving a total of 210 participants. Due to study heterogeneity, we present the extracted data on general psychopathology, positive and negative symptoms, cognition and functioning outcomes as a narrative synthesis. We found limited evidence supporting antipsychotic efficacy for cannabidiol and none supporting its benefits for cognition or functioning. Cannabidiol treatment had an advantageous side effect profile compared to other antipsychotics and was well tolerated across studies. Observational studies had a higher risk of bias than experimental studies. Factors potentially contributing to variability in outcome results included cannabidiol dosage, treatment duration, use as an adjunctive treatment and participant inclusion criteria, which warrant further investigation to determine whether cannabidiol can be effective as a treatment for psychosis., Competing Interests: Declaration of Competing Interest InSYS therapeutics provided study medication to Dr. Didier Jutras-Aswad's team for a clinical trial funded by the Canadian Institute of Health Research, not related to the treatment of psychosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The HydroATLAS database provides a standardized compendium of descriptive hydro-environmental information for all watersheds and rivers of the world at high spatial resolution. Version 1.0 of HydroATLAS offers data for 56 variables, partitioned into 281 individual attributes and organized in six categories: hydrology; physiography; climate; land cover & use; soils & geology; and anthropogenic influences. HydroATLAS derives the hydro-environmental characteristics by aggregating and reformatting original data from well-established global digital maps, and by accumulating them along the drainage network from headwaters to ocean outlets. The attributes are linked to hierarchically nested sub-basins at multiple scales, as well as to individual river reaches, both extracted from the global HydroSHEDS database at 15 arc-second (~500 m) resolution. The sub-basin and river reach information is offered in two companion datasets: BasinATLAS and RiverATLAS. The standardized format of HydroATLAS ensures easy applicability while the inherent topological information supports basic network functionality such as identifying up- and downstream connections. HydroATLAS is fully compatible with other products of the overarching HydroSHEDS project enabling versatile hydro-ecological assessments for a broad user community.

Background: Mentalizing, the mental capacity to understand oneself and others in terms of mental states, has been found to be reduced in some mental disorders such as Borderline Personality Disorder (BPD). Some studies have suggested that Eating Disorders (EDs) may also be associated with impairments in mentalizing, but studies have not always yielded consistent results. This is the first study to systematically investigate mentalizing impairments in patients with Bulimia Nervosa (BN) compared with controls. In addition, we investigated whether impairments in mentalizing were related to BPD features, rather than BN per se, given the high comorbidity between BPD and BN., Methods: Patients with BN (n = 53) and healthy controls (HCs; n = 87) completed a battery of measures assessing mentalizing including the Reflective Function Questionnaires (RFQ), the Object Relations Inventory (ORI; Differentiation-Relatedness Scales) and the Reading The Mind in The Eyes Test (RMET)., Results: Patients with BN scored significantly lower than HCs on all tests of mentalizing, with moderate to large between-group effect sizes. These differences were partially accounted for by BPD features as assessed with the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), and partially by bulimic symptoms measured with the Eating Disorder Examination Questionnaire (EDE-Q)., Conclusions: Patients with BN have significantly lower levels of mentalizing as assessed with a broad range of tests compared to HCs. These differences were related to both bulimic symptoms and BPD features. Although further research in larger samples is needed, if replicated, these findings suggest that poor mentalizing may be a significant factor in BN patients and should be addressed in treatment, regardless of the presence of BPD features.

It is a well-known fact that the major Canadian political parties now use political marketing tools to segment the electorate and target specific groups of voters. Positional issues are at the centre of this type of micro-targeting strategy. This article demonstrates that positional issues played a greater role in Canadian electoral politics than previously assumed. Despite the many theoretical reasons for why the effects of positional issues might have been overlooked, accounting for disaggregation error shows stable and consistent effect of positional issues on vote choice in Canada. Multi-item issue scales are used to test the stability and relative strength of positional issues compared to rival concepts, such as values and party identification. Once measured through aggregated items, the effects of positional issues on vote choice in Canada might even compare with those of conventional vote predictors, such as party identification. Hence, it shows that the actions parties take to capitalize on positional issues, as described by the political marketing literature, are justified.

In Canada, about 6,000 youth are homeless every night, many of whom suffer from addiction and psychotic disorders. To facilitate the exit out of homelessness, access to care and to improve psychosis and addiction outcomes, a new intensive outreach intervention team (EQIIP SOL) was created in Montreal (2012). It offers intensive outreach services dedicated to homeless youth suffering from first episode psychosis and addiction (HYFEPA) in addition to an early psychosis intervention service (EIS) in collaboration with the Addiction Psychiatry Unit. Our aim is to describe the characteristics, clinical, functional and housing outcomes of HYFEPA followed by EQIIP SOL. This two years long prospective longitudinal study with all HYFEPA (n = 42) admitted to EQIIP SOL between 2012-2015 reports at multiple time points, clinical (CGI, GAF), functional (SOFAS, work/study, housing autonomy) and substance use disorder (DUS, AUS) outcomes and acute services use (hospitalizations, emergency room visits). We observed that, at baseline, HYFEPA showed poor prognostic factors (eg. cluster B personality, substance use disorders, legal problems, childhood trauma and lower education level). The majority reached housing stability after 6 months and their functioning and illness severity improved with time. This suggests that HYFEPA improve with an intensive outreach intervention team integrated to an EIS., (Copyright © 2019. Published by Elsevier B.V.)

Depression is one of the most prevalent psychiatric disorders among opioid-dependent individuals. Clinical trials testing selective serotonin reuptake inhibitors among depressed patients on methadone maintenance therapy (MMT) failed to show efficacy, whereas those on tricyclic antidepressants produced mixed results with potential for cardiotoxicity. Desvenlafaxine (DESV) is a SNRI with minimal cardiotoxicity and drug interactions. This study sought to assess feasibility and tolerability of using DESV in depressed patients on MMT. A total of 18 depressed individuals on MMT received DESV (50-100 mg/day) for 8 weeks. Participants were assessed for the following: (a) Safety of DESV using Systematic Assessment for Treatment Emergent Events-GI, ECG [corrected Q-T (QTc) interval measurement] and methadone serum levels; (b) depressive symptoms using Montgomery-Äsberg Depression Rating Scale (MADRS); and (c) other outcomes including anxiety, suicidality, craving, substance use, quality of life, and other depression scales. Registration number on ClinicalTrials.gov is NCT02200406. Among participants who completed the study, MADRS scores significantly decreased at week 8 compared with baseline. Responders and remitters on MADRS at week 8 were 61 and 50%, respectively. There was no significant change in [corrected Q-T (QTc) interval measurement] between baseline and week 4. DESV was well tolerated and associated with improvement of depressive symptoms. DESV may be a promising contender to treat depression in individuals on MMT and deserves further exploration in a randomized double-blinded clinical trial.

This Letter reports the first results of a direct dark matter search with the DEAP-3600 single-phase liquid argon (LAr) detector. The experiment was performed 2 km underground at SNOLAB (Sudbury, Canada) utilizing a large target mass, with the LAr target contained in a spherical acrylic vessel of 3600 kg capacity. The LAr is viewed by an array of PMTs, which would register scintillation light produced by rare nuclear recoil signals induced by dark matter particle scattering. An analysis of 4.44 live days (fiducial exposure of 9.87 ton day) of data taken during the initial filling phase demonstrates the best electronic recoil rejection using pulse-shape discrimination in argon, with leakage <1.2×10^{-7} (90% C.L.) between 15 and 31  keV&#95;{ee}. No candidate signal events are observed, which results in the leading limit on weakly interacting massive particle (WIMP)-nucleon spin-independent cross section on argon, <1.2×10^{-44}  cm^{2} for a 100  GeV/c^{2} WIMP mass (90% C.L.).

Given the increasing prevalence of obesity and the metabolic syndrome, identification of intrinsic molecular programs responsible for ensuring fuel homeostasis and preventing metabolic disease is needed. We investigated whether the orphan nuclear receptor estrogen-related receptor α (ERRα), a major regulator of energy metabolism, plays a role in lipid homeostasis and the development of nonalcoholic fatty liver disease (NAFLD) in response to chronic high-fat diet (HFD) consumption and long-term fasting. Systemic ablation of ERRα in mice demonstrated clear beneficial effects for loss of ERRα function in protection from HFD-provoked body weight gain manifested not only from a reduction in white adipose tissue stores but also from an impediment in intrahepatic lipid accumulation. The prevention of HFD-induced NAFLD in ERRα-null mice was underscored by transcriptional repression of de novo lipogenesis, which was upregulated in wild-type mice, a known contributing factor to lipid-stimulated hepatic steatosis. Surprisingly, given these findings, ERRα deficiency had no significant impact on the degree of fasting-induced NAFLD, involving the mobilization of adipocyte triglyceride (TG) stores into the liver. However, the presence of ERRα was essential for acute refeeding-mediated reversal of fasting-induced hepatic TG accretion, underpinned by impaired downregulation of adipose TG lipolysis and reduced hepatic mitochondrial oxidative activity. Taken together, the regulation of lipid handling by ERRα depended on the nutritional state, suggesting that negative modulation of ERRα activity could be envisaged to prevent lipid-induced NAFLD, whereas inducing its activity would be useful to treat and reverse the instilled disease.

Aim: Immigration is a risk factor for psychosis emergence, and previous studies show that immigrants are less likely to engage in treatment for psychosis. However, the literature on outcome is scant and heterogeneous. This study was designed to compare first-generation (FGI) and second-generation immigrants (SGI) to non-immigrants' symptomatic and functional outcomes 2 years after a first-episode psychosis (FEP)., Methods: A 2-year prospective longitudinal study of 223 FEP patients between 18 and 30 years took place in two early intervention services (EIS) in Montreal, Canada., Results: Forty-two per cent of the sample were immigrants (FGI (n = 56), SGI (n = 38)). Compared with non-immigrants, immigrants had similar symptomatic and functioning profiles at baseline, 1 and 2 years, except that fewer SGI had a history of homelessness and more were living with their families. FGI were less likely to have a substance use disorder but more likely to pursue their studies and to present depressive symptoms., Conclusions: Even if immigrants are known to be at greater risk of developing psychosis, probably secondary to stress related to immigration, their symptomatic and functional outcomes, once engaged in EIS treatment, are similar to or sometimes better than non-immigrants' outcomes. Because immigrants tend to be less engaged in their follow-up, understanding why they disengage from treatment is crucial to develop better therapeutic approaches to better engage them as EIS treatment can improve their outcomes effectively., (© 2015 Wiley Publishing Asia Pty Ltd.)

Conditions leading to unrepaired DNA double-stranded breaks are potent inducers of genetic instability. Systemic conditions may lead to fluctuation of hydrogen ions in the cellular microenvironment, and we show that small variations in extracellular pH, termed suboptimal pHe, can decrease the efficiency of DNA repair in the absence of intracellular pH variation. Recovery from bleomycin-induced DNA double-stranded breaks in fibroblasts proceeded less efficiently at suboptimal pHe values ranging from 7.2 to 6.9, as shown by the persistence of repair foci, reduction of H4K16 acetylation, and chromosomal instability, while senescence or apoptosis remained undetected. By allowing escape from these protective mechanisms, suboptimal pHe may therefore enhance the genotoxicity of double-stranded breaks, leading to genetic instability.

While considerable attention has been given to the measurement of mercury (Hg) and lead (Pb) concentrations and accumulation in detailed peat cores in central Canada, the geographic distribution and density of sampling are generally limited. Here, we use the Ontario Peatland Inventory to examine broad patterns of Hg and Pb concentration with depth, based on 338 peat cores (containing >1500 analyzed samples) from 127 bogs, fens and swamps located in southeastern, northeastern and northwestern sections of Ontario. Overall, Hg concentrations averaged 0.05 μg g -1 and that of Pb averaged 10.8 μg g -1 . Maximum values in the top 50 cm of the profiles are 0.08 μg g -1 and 26.2 μg g -1 for Hg and Pb, respectively. The ratio between these values (surface) and the values from below 100 cm (background), where peat likely accumulated before 1850 and industrial activities were limited, are 2.3 and 6.6 for Hg and Pb, respectively. The highest surface:background concentration ratios are generally found in the westernmost part of the province and in the southeast for Hg and around areas that are more heavily populated for Pb. Our results show that a vast amount of Hg and Pb are stored in Ontarian peatlands, although the spatial distribution of these stores varies. The rapid decomposition of peat in a changing climate could release these pollutants to the atmosphere., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The use of a Kerr nonlinearity to generate squeezed light is a well-known way to surpass the quantum noise limit along a given field quadrature. Nevertheless, in the most common regime of weak nonlinearity, a single Kerr resonator is unable to provide the proper interrelation between the field amplitude and squeezing required to induce a sizable deviation from Poissonian statistics. We demonstrate experimentally that weakly coupled bosonic modes allow exploration of the interplay between squeezing and displacement, which can give rise to strong deviations from the Poissonian statistics. In particular, we report on the periodic bunching in a Josephson junction formed by two coupled exciton-polariton modes. Quantum modeling traces the bunching back to the presence of quadrature squeezing. Our results, linking the light statistics to squeezing, are a precursor to the study of nonclassical features in semiconductor microcavities and other weakly nonlinear bosonic systems.

Background: Many studies have concluded that cannabis use disorder (CUD) negatively influences outcomes in first-episode psychosis (FEP). However, few have taken into account the impact of concurrent misuse of other substances., Methods: This 2-year, prospective, longitudinal study of FEP patients, aged between 18 and 30 years, admitted to early intervention programs in Montreal, Quebec, Canada, examined the specific influence of different substance use disorders (SUD) (alcohol, cannabis, cocaine, amphetamines) on service utilization, symptomatic and functional outcomes in FEP., Results: Drugs and alcohol were associated with lower functioning, but drugs had a greater negative impact on most measures at 2-year follow-up. Half of CUD patients and more than 65% of cocaine or amphetamine abusers presented polysubstance use disorder (poly-SUD). The only group that deteriorated from years 1 to 2 (symptoms and functioning) were patients with persistent CUD alone. Outcome was worse in CUD than in the no-SUD group at 2 years. Cocaine, amphetamines and poly-SUD were associated with worse symptomatic and functional outcomes from the 1st year of treatment, persisting over time with higher service utilization (hospitalization)., Conclusion: The negative impact attributed to CUD in previous studies could be partly attributed to methodological flaws, like including polysubstance abusers among cannabis misusers. However, our investigation confirmed the negative effect of CUD on outcome. Attention should be paid to persistent cannabis misusers, since their condition seems to worsen over time, and to cocaine and amphetamine misusers, in view of their poorer outcome early during follow-up and high service utilization.

Giardia intestinalis is a protozoan parasite that causes giardiasis, a form of severe and infectious diarrhea. Despite the importance of the cell cycle in the control of proliferation and differentiation during a giardia infection, it has been difficult to study this process due to the absence of a synchronization procedure that would not induce cellular damage resulting in artifacts. We utilized counterflow centrifugal elutriation (CCE), a size-based separation technique, to successfully obtain fractions of giardia cultures enriched in G 1 , S, and G 2 . Unlike drug-induced synchronization of giardia cultures, CCE did not induce double-stranded DNA damage or endoreplication. We observed increases in the appearance and size of the median body in the cells from elutriation fractions corresponding to the progression of the cell cycle from early G 1 to late G 2 . Consequently, CCE could be used to examine the dynamics of the median body and other structures and organelles in the giardia cell cycle. For the cell cycle gene expression studies, the actin-related gene was identified by the program geNorm as the most suitable normalizer for reverse transcription-quantitative PCR (RT-qPCR) analysis of the CCE samples. Ten of 11 suspected cell cycle-regulated genes in the CCE fractions have expression profiles in giardia that resemble those of higher eukaryotes. However, the RNA levels of these genes during the cell cycle differ less than 4-fold to 5-fold, which might indicate that large changes in gene expression are not required by giardia to regulate the cell cycle. IMPORTANCE Giardias are among the most commonly reported intestinal protozoa in the world, with infections seen in humans and over 40 species of animals. The life cycle of giardia alternates between the motile trophozoite and the infectious cyst. The regulation of the cell cycle controls the proliferation of giardia trophozoites during an active infection and contains the restriction point for the differentiation of trophozoite to cyst. Here, we developed counterflow centrifugal elutriation as a drug-free method to obtain fractions of giardia cultures enriched in cells from the G 1 , S, and G 2 stages of the cell cycle. Analysis of these fractions showed that the cells do not show side effects associated with the drugs used for synchronization of giardia cultures. Therefore, counterflow centrifugal elutriation would advance studies on key regulatory events during the giardia cell cycle and identify potential drug targets to block giardia proliferation and transmission.

How androgen signaling contributes to the oncometabolic state of prostate cancer remains unclear. Here, we show how the estrogen-related receptor γ (ERRγ) negatively controls mitochondrial respiration in prostate cancer cells. Sustained treatment of prostate cancer cells with androgens increased the activity of several metabolic pathways, including aerobic glycolysis, mitochondrial respiration, and lipid synthesis. An analysis of the intersection of gene expression, binding events, and motif analyses after androgen exposure identified a metabolic gene expression signature associated with the action of ERRγ. This metabolic state paralleled the loss of ERRγ expression. It occurred in both androgen-dependent and castration-resistant prostate cancer and was associated with cell proliferation. Clinically, we observed an inverse relationship between ERRγ expression and disease severity. These results illuminate a mechanism in which androgen-dependent repression of ERRγ reprograms prostate cancer cell metabolism to favor mitochondrial activity and cell proliferation. Furthermore, they rationalize strategies to reactivate ERRγ signaling as a generalized therapeutic approach to manage prostate cancer. Cancer Res; 77(2); 378-89. ©2016 AACR., (©2016 American Association for Cancer Research.)

Substance use disorders (SUD) in first-episode psychosis (FEP) are highly prevalent and linked with poor outcomes. However, most longitudinal studies investigating their impacts in FEP have not reported proportions of patients who ceased SUD. Our aim was to examine the influence of SUD course on functional and symptomatic outcomes as well as service use in FEP. We performed a 2-year longitudinal study of 212 FEP patients, aged between 18 and 30 years, admitted to 2 early psychosis services in Montréal, Québec, Canada. We observed that cannabis was the first substance abused (42.9% at baseline), followed by alcohol (19.3%). The SUD rate decreased by approximately 30% during the first year. Patients with persistent SUD had worse functional outcomes (Quality of Life Scale, Social and Occupational Functioning Assessment Scale, employment), more symptoms (Positive and Negative Symptoms Scale) and heavier service use (emergency and hospitalization). SUD persistence was associated with illness severity, homelessness and cluster-B personality. Those living with their parents and financially supported by them were more likely to cease SUD. Our results indicate that SUD course was more significant than having SUD at admission; persistent SUD was associated with worse outcomes. SUD decreased during a general early psychosis intervention program (with no specialized SUD treatment). An integrated, specialized approach targeting FEP patients with predictive factors of SUD persistence during the first years of treatment might increase SUD cessation and possibly improve outcomes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: In this multi-centre randomized controlled trial (RCT) we compared modified mentalisation-based treatment (MBT-ED) to specialist supportive clinical management (SSCM-ED) in patients with eating disorders (EDs) and borderline personality disorder symptoms (BPD). This group of patients presents complex challenges to clinical services, and a treatment which addresses their multiple problems has the potential to improve outcome. MBT has been shown to be effective in improving outcome in patients with BPD, but its use has not been reported in ED., Methods: Sixty-eight eligible participants were randomised to MBT-ED or SSCM-ED. The primary outcome measure was the global score on the Eating Disorder Examination. Secondary outcomes included measures of BPD symptoms (the Zanarini Rating Scale for Borderline Personality Disorder), general psychiatric state, quality of life and service utilisation. Participants were assessed at baseline and at 6, 12 and 18 months after randomisation. Analysis was performed using linear mixed models., Results: Only 15 participants (22 %) completed the 18 month follow-up. Early drop-out occurred significantly more in the SSCM-ED group. Drop-out did not vary with treatment model later in therapy and was sometimes attributed to participants moving away. There was higher drop--out amongst smokers and those with higher neuroticism scores. 47.1 % of participants in the MBT-ED arm and 37.1 % in the SSCM-ED arm attended at least 50 % of therapy sessions offered. Amongst those remaining in the trial, at 12 and 18 months MBT-ED was associated with a greater reduction in Shape Concern and Weight Concern in the Eating Disorder Examination compared to SSCM-ED. At 6, 12 and 18 months there was a decline of ED and BPD symptoms in both groups combined. Ten participants were reported as having had adverse events during the trial, mostly self-harm, and there was one death, attributed as 'unexplained' by the coroner., Conclusions: The high drop-out rate made interpretation of the results difficult. Greater involvement of research staff in clinical management might have improved compliance with both therapy and research assessment. MBT-ED may have had an impact on core body image psychopathology., Trial Registration: Current Controlled Trials: ISRCTN51304415 . Registered on 19 April 2011.

Bmps are morphogens involved in various gastric cellular functions. Studies in genetically-modified mice have shown that Bmp disruption in gastric epithelial and stromal cell compartments leads to the development of tumorigenesis. Our studies have demonstrated that abrogation of gastric epithelial Bmp signaling alone was not sufficient to recapitulate the neoplastic features associated with total gastric loss of Bmp signaling. Thus, epithelial Bmp signaling does not appear to be a key player in gastric tumorigenesis initiation. These observations suggest a greater role for stromal Bmp signaling in gastric polyposis initiation. In order to identify the specific roles played by mesenchymal Bmp signaling in gastric homeostasis, we generated a mouse model with abrogation of Bmp signaling exclusively in the gastro-intestinal mesenchyme (Bmpr1a(ΔMES)). We were able to expose an unsuspected role for Bmp loss of signaling in leading normal gastric mesenchyme to adapt into reactive mesenchyme. An increase in the population of activated-fibroblasts, suggesting mesenchymal transdifferentiation, was observed in mutant stomach. Bmpr1a(ΔMES) stomachs exhibited spontaneous benign polyps with presence of both intestinal metaplasia and spasmolytic-polypeptide-expressing metaplasia as early as 90 days postnatal. These results support the novel concept that loss of mesenchymal Bmp signaling cascade acts as a trigger in gastric polyposis initiation.

Steroid sulfatase (STS), the enzyme which converts inactive sulfated steroid precursors into active hormones, is a promising therapeutic target for the treatment of estrogen-sensitive breast cancer. We report herein the synthesis and in vitro study of dual-action STS inhibitors with selective estrogen-receptor modulator (SERM) effects. A library of tetrahydroisoquinoline-N-substituted derivatives (phenolic compounds) was synthesized by solid-phase chemistry and tested on estrogen-sensitive breast cancer T-47D cells. Three phenolic compounds devoid of estrogenic activity and toxicity emerged from this screening. Their sulfamate analogs were then synthesized, tested in STS-transfected HEK-293 cells, and found to be potent inhibitors of the enzyme (IC50 of 3.9, 8.9, and 16.6 nM). When tested in T-47D cells they showed no estrogenic activity and produced a moderate antiestrogenic activity. The compounds were further tested on osteoblast-like Saos-2 cells and found to significantly stimulate their proliferation as well as their alkaline phosphatase activity, thus suggesting a SERM activity. These results are supported by molecular docking experiments., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

In the colon, myofibroblasts are primary contributors in the establishment of the microenvironment involved in tissue homeostasis. Alterations in myofibroblast functions lead to changes resulting in a toxic microenvironment nurturing tumorigenesis. Bone morphogenetic proteins (Bmps) are morphogens known to play key roles in adult gut homeostasis. Studies in genetically-modified mice have shown that Bmp disruption in all cell layers leads to the development of gut polyposis. In contrast, our studies showed that loss of Bmp exclusively in the gastrointestinal epithelium resulted in increased epithelial proliferation without polyposis initiation, thus suggesting a key role for mesenchymal Bmp signaling in polyposis initiation. In order to identify the role of mesenchymal Bmp signaling on the microenvironment and its impact on colonic mucosa, a mouse model was generated with suppression of Bmp signaling exclusively in myofibroblasts (Bmpr1aΔMES). Bmpr1aΔMES mice exhibited increased subepithelial proliferation with changes in cellular composition leading to the development of a primed stroma with modulation of extracellular matrix proteins, immune cells and cytokines as early as 90 days of age. This microenvironmental deregulation was associated with increased polyposis initiation at one year of age. These results are the first to demonstrate that mesenchymal Bmpr1a inactivation alone is sufficient to prompt an expansion of myofibroblasts leading to the development of a reactive mesenchyme that contributes to polyposis initiation in the colon. These findings support the novel concept that inhibition of Bmp signaling in mesenchymal cells surrounding the normal epithelium leads to important changes instructing a toxic microenvironment sufficient to induce colonic polyposis., (© 2016 UICC.)

Introduction: As the health consequences of climate change (CC) will likely become more manifest in the future, family physicians have to be knowledgeable about these impacts and the ways in which they can affect their patients. The main aim of this study was to propose a competency framework and questionnaire used to conduct a needs analysis to identify and prioritize family physicians' real educational needs regarding the health impacts of CC., Methods: A mixed method combining a qualitative interview and a quantitative online questionnaire was used (n = 24 physicians). The interview assessed key beliefs related to participating in an online continuing medical education (eCME) activity on the health impacts of climate change, and the perception of the key factors or conditions required to ensure the family physicians' satisfaction with this eCME activity. The questionnaire assessed the current and desired levels of competency on five general training themes: general knowledge about CC; heat-related illnesses; CC, extreme weather events and modification of vector-borne and zoonotic diseases; CC, extreme weather events and modification of water-borne diseases; and mental health impacts of natural disasters., Results: Results revealed the need for improved medical education on climate change and health. Results also add to the literature by showing that a 3-hour eCME activity covering these topics would be useful and would allow family physicians to use this knowledge in their daily practice, notably through prevention and counseling., Discussion: Introducing a CME needs assessment framework and a generic instrument that reflects family physicians' needs regarding the health impacts of CC has the added advantage of standardizing the assessment procedure.

Background: Thought-Shape Fusion (TSF) and Thought-Action Fusion (TAF) are cognitive distortions that are associated with eating and obsessional pathology respectively. Both involve the underlying belief that mere thoughts and mental images can lead to negative outcomes. TSF involves the belief that food-related thoughts lead to weight gain, body dissatisfaction, and perceptions of moral wrong-doing. TAF is more general, and involves the belief that merely thinking about a negative event (e.g., a loved one getting into a car accident) can make this event more likely to happen, and leads to perceptions of moral wrong-doing. However, the shared susceptibility across related cognitive distortions-TAF and TSF-has not yet been studied., Method: The effects of TSF and TAF inductions in women with an eating disorder (n = 21) and a group of healthy control women with no history of an eating disorder (n = 23) were measured. A repeated-measures design was employed, with all participants exposed to a TSF, TAF and neutral induction during three separate experimental sessions. Participants' cognitive and behavioral responses were assessed., Results: Individuals with eating disorders were more susceptible to TSF and TAF than were control participants, demonstrating more neutralization behavior after TSF and TAF inductions (i.e., actions to try to reduce the negative effects of the induction), and reporting higher levels of trait TAF and TSF than did controls., Conclusions: Individuals with eating disorders are particularly susceptible to both TAF and TSF. Clinical implications of these findings will be discussed.

The manner and extent to which normal aging affects the ability to speak are not fully understood. While age-related changes in voice fundamental frequency and intensity have been documented, changes affecting the planning and articulation of speech are less well understood. In the present study, 76 healthy, cognitively normal participants aged between 18 and 93 years old were asked to produce auditorily and visually triggered sequences of finely controlled movements (speech, oro-facial, and manual movement). These sequences of movements were either (1) simple, in which at least two of the three movements were the same, or (2) complex, in which three different movements were produced. For each of the resulting experimental condition, accuracy was calculated. The results show that, for speech and oro-facial movements, accuracy declined as a function of age and complexity. For these movements, the negative effect of complexity on performance accuracy increased with age. No aging or complexity effects were found for the manual movements on accuracy, but a significant slowing of movement was found, particularly for the complex sequences. These results demonstrate that there is a significant deterioration of fine motor control in normal aging across different response modalities.

Objective: The study compared engagement in treatment and medication adherence of immigrants and nonimmigrants in early intervention services for persons with first-episode psychosis., Methods: This two-year longitudinal prospective cohort study recruited patients with first-episode psychosis who were entering early intervention services in Montreal, Canada (N=223). Data on sociodemographic characteristics, symptoms, and social functioning were collected annually., Results: At two years, immigrants had more than three times the odds of attrition than nonimmigrants after the analysis controlled for potential confounding factors (first-generation immigrants: odds ratio [OR]=3.11, 95% confidence interval [CI]=1.01-9.57, p=.049); second-generation immigrants: OR=3.65, CI=1.07-12.50, p=.039). Medication adherence was similar among those who remained in the programs., Conclusions: During the two years after entering a program for first-episode psychosis, immigrants were more likely than nonimmigrants to disengage from treatment. Further research is warranted to understand this phenomenon and to improve the ability of services to engage immigrants with first-episode psychosis.

Selective estrogen receptor modulators (SERMs) are currently in use in the hormonal therapy of breast cancer. In that respect, a new hormone-related approach is the therapeutical inhibition of steroid sulfatase (STS), which converts inactive, sulfated steroids into active hormones. We investigated the potential of 6-EO-14, a non-steroidal STS inhibitor with SERM potential. The latter compound, which exhibits a sulfamate moiety, releases the phenol derivative 8-EO-14 after the irreversible inhibition of STS. STS was inhibited by 6-EO-14 (IC50 = 0.3 μM), but not 8-EO-14, in HEK-293 cells transfected with an STS expression vector. The SERM potential of 8-EO-14 was assessed in osteoblast-like Saos-2 cells by investigating its effect on cell proliferation and on the activity of alkaline phosphatase (ALP), a specific differentiation marker. Saos-2 cell proliferation was increased by 21 % following 8-EO-14 addition (1 μM), and 8-EO-14 induced ALP activity (31 % increase at 0.1 nM) via estrogen receptor alpha (ERα) similarly to the SERM raloxifene. As compared to estradiol (E2) (100 %), the relative binding affinity of 6-EO-14 and 8-EO-14) for ERα was found to be weak (0.09 and 0.01 %, respectively). When assessed in two estrogen-dependent human breast cancer cell lines (MCF-7 and T-47D), 8-EO-14 did not support MCF-7 cell proliferation, whereas both 8-EO-14 and 6-EO-14 exhibited estrogen-like growth stimulation in T-47D cells. These two compounds were also unable to block E2-induced cell proliferation, suggesting their lack of antiestrogenic activity. Despite the known potency of 6-EO-14 as an STS inhibitor, the observed trophic activity of this new scaffold towards ERα-positive cells needs to be carefully considered prior to its potential utilization as a therapeutic agent.

Biological composites are typically based on an adhesive matrix that interlocks rigid reinforcing elements in fiber composite or brick-and-mortar assemblies. In nature, the adhesive matrix is often made up of proteins, which are also interesting model systems, as they are unique among polymers in that we know how to engineer their structures with atomic detail and to select protein elements for specific interactions with other components. Here we studied how fusion proteins that consist of cellulose binding proteins linked to proteins that show a natural tendency to form multimer complexes act as an adhesive matrix in combination with nanofibrillated cellulose. We found that the fusion proteins are retained with the cellulose and that the proteins mainly affect the plastic yield behavior of the cellulose material as a function of water content. Interestingly, the proteins increased the moisture absorption of the composite, but the well-known plastifying effect of water was clearly decreased. The work helps to understand the functional basis of nanocellulose composites as materials and aims toward building model systems for molecular biomimetic materials.

Epidemiology Canada now has the second highest number of opioid prescriptions per capita in the world. The rate of prescriptions has increased over the last decade, most notably in adults over 55 years of age. A recognition of the importance of treating pain has influenced this increase, but higher rates of opioid prescribing have produced undesirable outcomes including the misuse of medication as well as an increased number of deaths and emergency department visits attributable to opioids. Diverse psychiatric disorders, such as major depression, now also occur in 40% of those with an opioid use disorder (OUD). Neuroscience We now understand that addictive behaviors are caused by both environmental and genetic factors. Although OUD has historically been perceived as a weakness of character, it is now clear that it is a chronic disease, which results from a complex interaction between a substance, such as opioid, environmental factors, and an individual's genotype. Unfortunately, this evidence has yet to be successfully translated into clinical practice and most physicians are unable to diagnose and manage OUD patients appropriately.Clinical guidelines Many clinical guidelines for the management of chronic, non-cancer pain are available. All guidelines identify the need to assess the patient appropriately and screen for factors associated with misuse before prescribing opioids. Guidelines generally acknowledge that patients should not be denied appropriate pain management, but that some patients will require close supervision and frequent follow-up to prevent the misuse of prescription opioids.

Objective: Observed by physicians and often reported by patients, craving is a core symptom of addiction, although not well defined nor understood completely. In the last several years, functional imaging as well as the measurement of different biological substrates of addiction have greatly evolved, allowing for a better understanding of the underlying neurobiological pathways of craving. Furthermore, with the development of the DSM-V and its inclusion as a diagnostic criterion for substance use disorders, craving has gained a whole new level of interest. Hence, the general objective of this article is to examine findings of studies that have led to a better understanding of craving and its implications. First, we address the definition of craving and its epidemiology in individuals with substance use disorders. We then summarize the results of the research conducted on the neurobiological substrates of craving. Finally, we present the role of craving in the cycle of addiction and its potential as a therapeutic target for pharmacological and non-pharmacological interventions., Methods: Narrative review of the literature., Results: The definition of craving has greatly evolved throughout the years, and it is commonly described as an abnormal desire or need to take a drug. While its conscious aspect is well known, whereas it is expressed subjectively, it is growingly also defined as an unconscious phenomenon illustrated by a physiologic activation that is not perfectly correlated with subjective measures. Available data on craving have also demonstrated the presence of this symptom in all three phases of the addiction cycle, including early and prolonged abstinence, long after the acute physical withdrawal syndrome. Three factors have been identified as potent craving inducers: the drug itself, drug related cues and stress. PET scan studies and fMRI studies confirmed the implication of dopaminergic pathways in craving, and have more recently shed light on the contribution of other neurotransmission systems, such as GABA, norepinephrine as well as the endocannabinoid and opioid systems, but their roles are not yet fully understood. Furthermore, craving-related activations of specific areas of the brain involved in learned habits and behavior as well as memory have been demonstrated by various studies; in contrast, regions associated with regulation and control of emotion have been demonstrated to be hypoactive during craving episodes. Finally, several studies have demonstrated that craving is a valid predictive indicator of relapse, making it an interesting target for pharmacological and non-pharmacological treatment. Several anti-craving medications have been shown to decrease craving, including varenicline for tobacco and naltrexone for alcohol dependence. Studies examining the efficacy of other anti-craving medications for other substances are growing in numbers., Conclusions: Available data on craving support its role as a core symptom of addiction and allow for a better understanding of the underlying neurobiological substrates. Studies tend to show that it is a valid indicator of relapse during early and prolonged abstinence. Further research is needed to truly understand the complexity of the neurobiological substrates involved in craving as well as to develop new anti-craving interventions to facilitate long-term abstinence in individuals with substance use disorders.

We describe a system to transport and identify barium ions produced in liquid xenon, as part of R&D towards the second phase of a double beta decay experiment, nEXO. The goal is to identify the Ba ion resulting from an extremely rare nuclear decay of the isotope (136)Xe, hence providing a confirmation of the occurrence of the decay. This is achieved through Resonance Ionization Spectroscopy (RIS). In the test setup described here, Ba ions can be produced in liquid xenon or vacuum and collected on a clean substrate. This substrate is then removed to an analysis chamber under vacuum, where laser-induced thermal desorption and RIS are used with time-of-flight mass spectroscopy for positive identification of the barium decay product.

Cigarette smoking is the leading preventable cause of death in the Western world, with a considerably higher prevalence observed in schizophrenia compared to the general population. Despite the negative health consequences of smoking heavily, it has been proposed that individuals with schizophrenia may maintain smoking behaviors to remediate symptoms associated with the disorder. Neurocognitive deficits are a core feature of schizophrenia and are present in approximately 80% of patients. Further, these deficits constitute an endophenotype of schizophrenia, as they are stable across disease phases, and are heritable. The neurocognitive deficits that are present in schizophrenia are especially debilitating, since they are associated with poor clinical and functional outcomes and community integration. Interestingly, these deficits may also constitute a vulnerability factor towards the initiation and maintenance of tobacco use. Contributing to the potential shared vulnerability between schizophrenia and tobacco dependence is a dysregulation of the nicotinic acetylcholine receptor (nAChR) system. Pre-clinical evidence has shown that nicotine affects several neurotransmitter systems, including dopamine (DA), glutamate, and γ-aminobutyric acid (GABA), and certain neuropsychological deficits associated with these neurotransmitters (reaction time, spatial working memory, sustained attention, and sensory gating) are improved after nicotine administration in patients with schizophrenia. These positive effects on neurocognition appear to be more pronounced in smokers with schizophrenia, and may be an important mechanism that explains the co-morbidity of schizophrenia and tobacco dependence., (© 2013 Elsevier Inc. All rights reserved.)

Objective: Conventional vaginal applicators with a single apical hole do not distribute vaginal formulations homogenously and do not cover the entire vaginal and cervical mucosa. To overcome this problem and offer women further protection against vaginal infections, we designed a unique vaginal applicator with multiple apical and lateral holes. We have previously shown that the new applicator distributes an investigational vaginal gel homogenously over the entire vaginal and cervical mucosa. In this study, we investigated (using MRI) whether the new applicator works as well with marketed vaginal gels and creams., Methods: Eighteen women participated in the study and six vaginal gels and creams were tested. Each woman used a marketed vaginal product with its own commercial applicator (CA) once and with our universal vaginal applicator (UVA) once to deliver the same product. The applications were separated by a one-week period. Pelvic MRI was performed immediately after vaginal application to evaluate the product's distribution and mucosal coverage., Results: Immediately after application of the vaginal product, the UVA homogenously distributed the six products (3 gels and 3 creams) over the entire vaginal and cervical mucosa. On the other hand, the tested CA delivered four products (3 gels and 1 cream) mainly to the cervix and the upper vagina, but not to the mid and lower vagina; for the other two creams, the distribution was similar to that of UVA. Furthermore, the UVA received the highest acceptability score., Conclusion: The UVA can be used to deliver different vaginal gel and cream products homogenously throughout the vagina. This was the first time the UVA had been tested with marketed vaginal gels and creams. This applicator, giving uniform mucosal coverage and being highly acceptable, may help women to better protect themselves against sexually transmitted infections.

We report on a search for neutrinoless double-beta decay of 136Xe with EXO-200. No signal is observed for an exposure of 32.5 kg yr, with a background of ∼1.5×10(-3)  kg(-1) yr(-1)  keV(-1) in the ±1σ region of interest. This sets a lower limit on the half-life of the neutrinoless double-beta decay T(1/2)(0νββ)(136Xe)>1.6×10(25)  yr (90% C.L.), corresponding to effective Majorana masses of less than 140-380 meV, depending on the matrix element calculation.

The first episode of a psychotic disorder typically occurs in late adolescence or young adulthood, a critical time of development with respect to personality, social role, education, and vocation. The first few years of psychosis appear to be a critical period during which intervention needs to be initiated before the consequences of psychosis become more severe. Early intervention is therefore crucial in maximizing outcomes. Although response rates to antipsychotic medication in first-episode psychosis (FEP) are good, there is a relatively high risk of relapse. The greatest challenges that physicians face in treating FEP and preventing relapse are engaging patients in treatment and preventing non-adherence to therapy. Overall rates of non-adherence to antipsychotic medications for FEP patients are estimated to be at or higher than 50% within the first year of treatment, suggesting that malleable factors linked to non-adherence need to be targeted in interventions provided. Factors influencing adherence can be categorized into four groups: (1) environment-related, (2) patient-related, (3) medication-related, and (4) illness-related. This paper will review the factors associated with adherence and discuss solutions to optimize engagement, adherence to medication, and treatment in order to prevent relapse. Factors like social and family support, therapeutic alliance, attitudes and beliefs toward illness and medication, insight, substance use disorders, medication efficacy, tolerability, and accessibility will be discussed. Solutions, such as early psychosis specialized services integrating psychosocial therapies and careful selection of appropriate antipsychotic medication, will be proposed., (Copyright © 2012. Published by Elsevier B.V.)

We report the observation of two-neutrino double-beta decay in (136)Xe with T(1/2) = 2.11 ± 0.04(stat) ± 0.21(syst) × 10(21) yr. This second-order process, predicted by the standard model, has been observed for several nuclei but not for (136)Xe. The observed decay rate provides new input to matrix element calculations and to the search for the more interesting neutrinoless double-beta decay, the most sensitive probe for the existence of Majorana particles and the measurement of the neutrino mass scale.

Untreated psychosis causes a lot of suffering and its impact echoes on different aspects of the affected individual's functioning. In city centers, youths presenting early psychosis face additional challenges because many of them live in precarious, unstable conditions and are isolated. Reorganisation of mental health care access and delivery is necessary to avoid delay for psychosis identification and treatment initiation. This article describes possible solutions which have been applied at Clinique JAP, a specialized early psychosis intervention clinic at the CHUM, which offers integrated services to optimize outcome. To increase engagement and adherence to treatment, treatment setting must include a welcoming and youth-friendly atmosphere, individualized and flexible interventions, and nourishing optimistic but realistic hope. Intensive interventions by a specialized interdisciplinary team, in collaboration with community organizations, must be offered in a proactive way to reduce delay in treatment and therefore avoid disastrous consequences of psychosis.

In this article, the authors discuss the difficulties and opportunities of psychiatric training in an urban setting. Based on the example of Montréal, they ponder the interest and the relevance of this contextual framework for the training of future psychiatrists and other mental health professionals, regardless of the nature and location of their practice after their residency. The authors examine the advantages of this teaching environment and how to overcome its limits.

The half-life of the important radioisotope (198)Au is evaluated by using several different statistical methods, such as weighted mean (WM), limitation of statistical weights method (LWM), normalized residuals method (NRM), Rajeval technique (RT), Bootstrap median (BM) and Mandel-Paule method (MP). After comparing and analyzing the results from these methods, a final value of 2.6948±0.0012d is recommended based on the stability and sensitivity of the methods and the resulting uncertainties., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Myocardial infarction (MI) is characterized by irreversible loss of cardiomyocytes, resulting in impaired ventricular function. Stem cell therapy using autologous progenitor cells has emerged as a promising approach. Experimental studies have demonstrated that highly selected hematopoeitic stem cells, which are characterized by the presence of the surface markers CD34 and CD133, may contribute to repair of the acutely infarcted myocardium by inducing neovascularization, inhibiting apoptosis, and promoting cardiomyogenesis. We sought, to evaluate the intracoronary injection of CD133+ stem cells for cardiac repair in patients with dysfunctional myocardium after an acute MI., Patients and Methods: In this Canadian randomized, double-blind, placebo-controlled, Phase I-II study ("COMPARE-AMI"), we are evaluating the feasibility, safety, and efficacy of intracoronary injection of selected CD133+ stem cells for cardiac repair in patients with impaired cardiac function after successfully stented acute MI. Since November 2007, we have enrolled 14 patients in the study. Their mean age was 50.5 +/- 9.1 years, including 93% men. The culprit lesion was always on the left anterior descending artery (LAD). Their maximum troponin and CKMB levels were 8.4 +/- 6.1 microg/L and 322 +/- 225 U/L, respectively., Results: Compared with the baseline, we observed a significant 8.7% improvement in left ventricular ejection fraction at 4 months follow-up, namely, from 41.3 +/- 5.5% to 50.0 +/- 8.2% (n = 7; P = .008). There were no protocol-related complications. Our trial is designed to recruit 40 patients who are randomized 1:1 to receive CD133+ cells or placebo., Perspective: There is a need to seek out new therapeutics for the treatment of ischemic heart disease addressing the early loss of viable myocytes. Stem cell transplantation has shown early promise; this appraisal needs well-designed, controlled studies.

Background: Hand hygiene compliance improves when alcohol-based hand products (ABHP) are provided at the point-of-care (POC). However, it is not known how many facilities have the infrastructure available to provide easy access to ABHP currently., Objectives: To describe the extent to which facilities in the Champlain Infection Control Network (CICN) provide POC access to ABHP., Methods: A survey was conducted of all healthcare facilities in the CICN in October 2007. Sites were asked to complete a one-page questionnaire regarding number and location of ABHP dispensers on one ward in their facilities. The primary outcome measures included: the proportion of facilities providing any POC access to ABHP and the proportion of ABHP dispensers that were at POC, hallways and other areas., Results: A total of 18 of 59 (31%) long-term care facilities (LTCF) and 14 of 18 (78%) acute-care facilities (ACF) participated in the survey. Intensive care units (ICUs) were present in seven (50%) of the ACF. POC access to ABHP was provided in 44% of LTCF, 50% of ACF and 71% of ICUs surveyed. In LTCF 20% of ABHP dispensers were at the POC compared to 23% in ACF and 42% in ICUs., Conclusions: Although ABHP is available in these settings, most dispensers are not provided at the POC. Hospitals and LTCF need to increase the number of ABHP dispensers available, with a particular emphasis on placing them at the POC in accordance with provincial guidelines.

We present the design of a confocal microscope adapted for optical spectroscopy and imaging at cryogenic temperatures. This system is based on the existing approach of partly inserting the optical components of the microscope inside a helium-bath cryostat. It provides a spatial resolution approaching the diffraction limit with a mechanical stability allowing uninterrupted integration times exceeding 10 h and allows keeping track of a single emitter for unlimited periods of time. Furthermore, our design allows scanning the excitation spot and detection area independently of the sample position. This feature provides the means to perform probeless transport experiments on one-dimensional nanostructures. The scanning capabilities of this microscope are fully detailed and characterized using the photoluminescence of single nitrogen dyads at 4.5 K.

Background: Factors influencing community pharmacists' interventions have been identified, but little information is available regarding these factors in asthma care., Objective: To describe the type and frequency of pharmacists' asthma care interventions and to identify factors influencing those interventions., Methods: A pretested, self-administered questionnaire was mailed to all community pharmacists registered with the Ordre des pharmaciens du Québec in 2006. The form included questions about the pharmacists' interventions in asthma care in the community setting (21 questions), factors influencing the provision of those interventions (13 questions), and the responders' characteristics (17 questions)., Results: A total of 4587 questionnaires were sent; 917 pharmacists returned the questionnaires (response rate 20%), and 877 were eligible for analysis. Overall, community pharmacists who completed the questionnaire appeared to intervene frequently when the initial prescription for asthma medication was filled. About 98% of responders reported providing verbal information always or often on new asthma medication prescriptions. Furthermore, checking for overuse of rescue medication and underuse of maintenance therapy always or often was reported by 91% and 85.8% of responders, respectively. Other interventions at follow-up were not as frequently reported. For example, only 8.4% of pharmacists reported reassessing inhalation technique always or often. Lack of time was reported to be an important barrier to the type and frequency of intervention, while interest on the part of the patient appeared to be a significant facilitator. About 99% of pharmacists agreed with the statement that they have an important role in asthma care., Conclusions: Community pharmacists appear to intervene with patients with asthma mostly at the initiation of treatment, but some interventions at follow-up are not frequently done, which could be attributed to organizational factors.

The identification of a potent series of IKK-beta selective inhibitors based on an imidazothienopyrazine template and the oral efficacy of one such analog (22j) in the LPS-induced TNF-alpha release mouse model are described.

We have recently identified BMS-345541 (1) as a highly selective and potent inhibitor of IKK-2 (IC50 = 0.30 microM), which however was considerably less potent against IKK-1 (IC50 = 4.0 microM). In order to further explore the SAR around the imidazoquinoxaline tricyclic structure of 1, we prepared a series of tetracyclic analogues (7, 13, and 18). The synthesis and biological activities of these potent IKK inhibitors are described.