McGill-Queen's University Press

Current methods of assessment in clinical psychopharmacology have several serious disadvantages, particularly for the study of social functioning. We aimed to review the strengths and weaknesses of current methods used in clinical psychopharmacology and to compare them with a group of methods, developed by personality/social psychologists, termed ecological momentary assessment (EMA), which permit the research participant to report on symptoms, affect and behaviour close in time to experience and which sample many events or time periods. EMA has a number of advantages over more traditional methods for the assessment of patients in clinical psychopharmacological studies. It can both complement and, in part, replace existing methods. EMA methods will permit more sensitive assessments and will enable more wide-ranging and detailed measurements of mood and behaviour. These types of methods should be adopted more widely by clinical psychopharmacology researchers.

If the noise component of image data is nonisotropic, i.e., if it has nonconstant smoothness or effective point spread function, then theoretical results for the P value of local maxima and the size of suprathreshold clusters of a statistical parametric map (SPM) based on random field theory are not valid. This assumption is reasonable for PET or smoothed fMRI data, but not if these data are projected onto an unfolded, inflated, or flattened 2D cortical surface. Anatomical data such as structure masks, surface displacements, and deformation vectors are also highly nonisotropic. The solution offered here is to suppose that the image can be warped or flattened (in a statistical sense) into a space where the data are isotropic. The subsequent corrected P values do not depend on finding this warping; it is sufficient only to know that such a warping exists.

[See related article at [www.cmaj.ca/lookup/doi/10.1503/cmaj.181538][2]][2] KEY POINTS Breast cancer mortality rates among Canadian women have declined from 41.7 per 100 000 in 1988 to an estimated 23.2 per 100 000 in 2017, while age-standardized incidence has remained relatively stable, at around

OBJECTIVE: To assess associations between three diet quality indices and metabolic syndrome (MetS) in the Cree (Eeyouch) of northern Québec, Canada, as well as to evaluate their pertinence in this Indigenous context. DESIGN: The alternative-Healthy Eating Index 2010 (aHEI-2010), the Food Quality Score (FQS) and the contribution of ultra-processed products (UPP) to total daily dietary energy intake using the NOVA classification were calculated from 24 h food recalls. MetS was determined with the latest harmonized definition. Logistic regressions assessed the relationship between quintiles of dietary quality scores with MetS and its components. SETTING: Study sample from the 2005-2009 cross-sectional Nituuchischaayihititaau Aschii Environment-and-Health Study. SUBJECTS: Eeyouch (n 811) from seven James Bay communities (≥18 years old). RESULTS: MetS prevalence was 56·6 % with 95·4 % abdominal adiposity, 50·1 % elevated fasting plasma glucose, 43·4 % hypertension, 38·6 % elevated TAG and 44·5 % reduced HDL cholesterol. Comparing highest and lowest quintiles of scores, adjusted OR (95 % CI) of MetS was 0·70 (0·39, 1·08; P-trend=0·05) for aHEI-2010, 1·06 (0·63, 1·76; P-trend=0·87) for FQS and 1·90 (1·14, 3·17; P-trend=0·04) for the contribution of UPP to total daily dietary energy intake. CONCLUSIONS: Although diet quality indices have been associated with cardiometabolic risk, only the dietary intake of UPP was significantly associated with MetS in the Eeyouch. Indices tailored to the food environment of northern communities are essential to further understand the impact of diet quality in this context.

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OBJECTIVES: A two-stage intervention comprising screening and a brief standardized nursing assessment and referral, for emergency department (ED) patients aged 65 years and over, reduced the rate of functional decline four months after the visit, without increasing societal costs. In this study, the authors investigated the effects of the intervention on the process of care at, and during the month after, the ED visit. METHODS: Patients at four Montreal hospital EDs were randomized by day of visit to the intervention or to usual care. Patients admitted to the hospital were excluded. Measures of process of care included: referrals and visits to the primary physician and to the local community health center, for home care or other services, and return ED visits. Data sources included hospital charts, patient questionnaires, and provincial administrative databases. RESULTS: The study sample included 166 intervention and 179 control group patients ready for discharge from the ED. Intervention group patients were more likely to have a chart-documented referral to their local community health center [adjusted odds ratio (OR) 4.0, 95% confidence interval (95% CI) = 1.7 to 9.5] and their primary physician [adjusted OR 1.9, 95% CI = 1.0 to 3.4], and to have received home care services one month after the ED visit [adjusted OR 2.3, 95% CI = 1.1 to 5.1]. Unexpectedly, they were also more likely to make a return visit to the ED [adjusted OR 1.6, 95% CI = 1.0 to 2.6]. CONCLUSIONS: The beneficial outcomes of the intervention appear to result primarily from the early provision of home care rather than early contact with the primary physician.

BACKGROUND: The prevalence of gestational diabetes mellitus has been reported to vary widely in aboriginal populations. Most of the data have come from the United States. To help determine the extent of gestational diabetes in Canada's aboriginal population, the authors assessed the prevalence in a population of Cree women in northern Quebec. METHODS: A cross-sectional study was conducted using the National Diabetes Data Group (NDDG) criteria. Information was obtained from patient charts on pregnancies between January 1995 and December 1996 among women residing in 9 Cree communities in the eastern James Bay region of northern Quebec. Women who were not Cree, had pre-existing diabetes, had spontaneous abortion or were receiving glucocorticoid treatment were excluded. RESULTS: Data on 654 pregnancies that met the inclusion criteria were available. Results of the screening oral glucose challenge test were available for 579 of the pregnancies; the remaining 75 were excluded. The mean gestational age at screening was 28.3 (standard deviation 2.6) weeks. The prevalence of gestational diabetes was 12.8% (74/579) (95% confidence interval [CI] 10.1%-15.5%). The prevalence in the inland communities was twice as high as that in the coastal communities (18.0% v. 9.3%, p = 0.002). Women with gestational diabetes or impaired glucose tolerance tended to be older, have had more pregnancies, weigh more before pregnancy and have heavier babies than those with a normal glycemic status. INTERPRETATION: The prevalence of gestational diabetes among James Bay Cree women in northern Quebec is twice as high as that among women in the general North American population and the second highest reported in an aboriginal group worldwide.

Abstract More than 60% of supratentorial ependymomas harbor a ZFTA–RELA (ZRfus) gene fusion (formerly C11orf95–RELA). To study the biology of ZRfus, we developed an autochthonous mouse tumor model using in utero electroporation (IUE) of the embryonic mouse brain. Integrative epigenomic and transcriptomic mapping was performed on IUE-driven ZRfus tumors by CUT&RUN, chromatin immunoprecipitation sequencing, assay for transposase-accessible chromatin sequencing, and RNA sequencing and compared with human ZRfus-driven ependymoma. In addition to direct canonical NFκB pathway activation, ZRfus dictates a neoplastic transcriptional program and binds to thousands of unique sites across the genome that are enriched with PLAGL family transcription factor (TF) motifs. ZRfus activates gene expression programs through recruitment of transcriptional coactivators (Brd4, Ep300, Cbp, Pol2) that are amenable to pharmacologic inhibition. Downstream ZRfus target genes converge on developmental programs marked by PLAGL TF proteins, and activate neoplastic programs enriched in Mapk, focal adhesion, and gene imprinting networks. Significance: Ependymomas are aggressive brain tumors. Although drivers of supratentorial ependymoma (ZFTA- and YAP1-associated gene fusions) have been discovered, their functions remain unclear. Our study investigates the biology of ZFTA–RELA-driven ependymoma, specifically mechanisms of transcriptional deregulation and direct downstream gene networks that may be leveraged for potential therapeutic testing. This article is highlighted in the In This Issue feature, p. 2113

Purpose The paper highlights the strategic importance of being alert to the power of the language and words used by CEOs in their various communications – their CEO‐speak. Design/methodology/approach The paper employs a close reading analysis of several contemporary examples of one of the most significant genres of CEO‐speak – the CEO's annual letter to stockholders. Findings Four perspectives important for understanding corporate strategy are highlighted: the importance of CEO‐speak as a linguistic marker of CEO narcissism; the revealing nature of metaphors chosen by CEOs; the potential rhetorical potency that arises from the way CEO‐speak is framed; and the significance of cultural keywords. Research limitations/implications Case examples, such as the close readings in this article, possess the strength of specific instance detail and interpretation, and the ostensible weakness arising from interpretation of small samples. But such research may provide for a reframing of conceptual perspectives and practical approaches. Practical implications The case examples and advice provided will help business executives and corporate stakeholders to monitor the quality of CEO‐speak, engage CEO‐speak more effectively for strategic purposes, and improve CEO text and leadership‐through‐language. Originality/value Readers are reminded of the power of CEO text, the benefits of subjecting it to greater scrutiny, and are provided with some practical, operational advice.

OBJECTIVE: We hypothesized that increasing brain serotonin in healthy individuals with high scores on 2 self-report measures of trait quarrelsomeness would reduce quarrelsome behaviours and enhance agreeable behaviours when measured ecologically using an event-contingent recording method. METHODS: We conducted a double-blind crossover study, in which participants took tryptophan (3 g/d) and placebo for 15 days each and recorded how they behaved, felt and perceived others during everyday social interactions. RESULTS: Tryptophan significantly decreased quarrelsome behaviours and increased agreeable behaviours and perceptions of agreeableness. Men also behaved less dominantly, whereas both men and women perceived others as more dominant. CONCLUSION: Tryptophan's effects on behaviours and perceptions, while more marked in the men, were generally positive and accompanied by improved affect. Increasing serotonin in quarrelsome people may not only reduce behaviours associated with a predisposition to various mental and physical disorders but also enhance socially constructive behaviours and improve social perceptions.

Abstract An analysis of the extensive literature on non‐steady drag forces supports the correlation of the data by means of a total drag coefficient, which appears to be a function of the Reynolds Number and of a reduced time parameter which is related to the number of particle diameters traversed since the initiation of the motion. The added mass concept is shown to be both completely inadequate and theoretically unsound. An increase in wake turbulence resulting from Reynolds Number increases or from the occurrence of surface roughness seems to diminish the acceleration effects. Fundamental studies of the flow fields around blunt bodies reveal the extreme complexity of the phenomena occurring during acceleration. Explanations offered for the characteristics of the non‐steady drag coefficient behavior re shown to be frequently at variances with these findings.

BACKGROUND: Clinical data on patients admitted to hospital with coronavirus disease 2019 (COVID-19) provide clinicians and public health officials with information to guide practice and policy. The aims of this study were to describe patients with COVID-19 admitted to hospital and intensive care, and to investigate predictors of outcome to characterize severe acute respiratory infection. METHODS: This observational cohort study used Canadian data from 32 selected hospitals included in a global multisite cohort between Jan. 24 and July 7, 2020. Adult and pediatric patients with a confirmed diagnosis of COVID-19 who received care in an intensive care unit (ICU) and a sampling of up to the first 60 patients receiving care on hospital wards were included. We performed descriptive analyses of characteristics, interventions and outcomes. The primary analyses examined in-hospital mortality, with secondary analyses of the length of hospital and ICU stay. RESULTS: Between January and July 2020, among 811 patients admitted to hospital with a diagnosis of COVID-19, the median age was 64 (interquartile range [IQR] 53-75) years, 495 (61.0%) were men, 46 (5.7%) were health care workers, 9 (1.1%) were pregnant, 26 (3.2%) were younger than 18 years and 9 (1.1%) were younger than 5 years. The median time from symptom onset to hospital admission was 7 (IQR 3-10) days. The most common symptoms on admission were fever, shortness of breath, cough and malaise. Diabetes, hypertension and cardiac, kidney and respiratory disease were the most common comorbidities. Among all patients, 328 received care in an ICU, admitted a median of 0 (IQR 0-1) days after hospital admission. Critically ill patients received treatment with invasive mechanical ventilation (88.8%), renal replacement therapy (14.9%) and extracorporeal membrane oxygenation (4.0%); 26.2% died. Among those receiving mechanical ventilation, 31.2% died. Age was an influential predictor of mortality (odds ratio per additional year of life 1.06, 95% confidence interval 1.03-1.09). INTERPRETATION: Patients admitted to hospital with COVID-19 commonly had fever, respiratory symptoms and comorbid conditions. Increasing age was associated with the development of critical illness and death; however, most critically ill patients in Canada, including those requiring mechanical ventilation, survived and were discharged from hospital.

BACKGROUND: Low-function alleles of the serotonin transporter promoter polymorphism (5HTTLPR) have been linked to various psychopathological entities, especially in individuals exposed to prior stressors. In women with bulimic syndromes, we explored associations with personality pathology of 5HTTLPR and prior sexual or physical maltreatment. METHODS: Ninety-two women with bulimic syndromes were genotyped for 5HTTLPR short (S) and long (L(G) and L(A)) alleles and were then assessed for eating symptoms, dimensional personality disturbances, history of sexual or physical abuse and borderline personality disorder (BPD). RESULTS: With a classification based on a biallelic model of 5HTTLPR (i.e., presence or absence of at least 1 S-allele copy), multiple regression analyses indicated significant proportions of variance in stimulus seeking and insecure attachment to be explained by abuse x genotype interaction effects, with greater psychopathology always occurring in S-allele carriers who had been abused. Likewise, a logistic regression analysis linked BPD to significant main effects of genotype and abuse. Analyses that aggregated carriers according to a triallelic model of 5HTTLPR (i.e., presence or absence of at least 1 copy of a presumably low-function S or LG allele) produced similar patterns but no statistically significant effects. CONCLUSIONS: Traits such as sensation seeking and insecure attachment are, on average, elevated in 5HTTLPR S-allele carriers with bulimic syndromes who report prior physical or sexual maltreatment. These results add to the literature associating pronounced psychopathological manifestations, with conjoint effects of stress and the 5HTTLPR polymorphism.

BACKGROUND: Few pharmacological treatments for alcohol dependence are available. Moreover, the best supported treatment, naltrexone hydrochloride, appears to work for only some. METHODS: To investigate potential predictors of these differential responses, 40 social drinkers (20 women) were administered 6 days of treatment with naltrexone vs. placebo in a double-blind, counterbalanced, crossover design. At the end of each treatment period, participants received a single dose of their preferred alcoholic beverage followed by the opportunity to work for additional alcohol units using a progressive ratio (PR) breakpoint paradigm. All subjects but one were genotyped for the A118G polymorphism of the mu opioid receptor gene (OPRM1). RESULTS: Naltrexone decreased the ethanol-induced 'euphoria' to a priming dose of alcohol in two subgroups: (i) in women, and (ii) in subjects with the A118G polymorphism of the mu opioid receptor gene (OPRM1). Naltrexone did not decrease motivation to work for additional alcoholic beverages on the PR task regardless of gender or genotype. CONCLUSIONS: The results add to the evidence that naltrexone decreases positive subjective effects of alcohol, with preferential effects in distinct subgroups. Similar effects in heavier drinkers might decrease alcohol use.

Abstract Objectives: A two‐stage intervention comprising screening and a brief standardized nursing assessment and referral, for emergency department (ED) patients aged 65 years and over, reduced the rate of functional decline four months after the visit, without increasing societal costs. In this study, the authors investigated the effects of the intervention on the process of care at, and during the month after, the ED visit. Methods: Patients at four Montreal hospital EDs were randomized by day of visit to the intervention or to usual care. Patients admitted to the hospital were excluded. Measures of process of care included: referrals and visits to the primary physician and to the local community health center, for home care or other services, and return ED visits. Data sources included hospital charts, patient questionnaires, and provincial administrative databases. Results: The study sample included 166 intervention and 179 control group patients ready for discharge from the ED. Intervention group patients were more likely to have a chart‐documented referral to their local community health center [adjusted odds ratio (OR) 4.0, 95% confidence interval (95% CI) = 1.7 to 9.5] and their primary physician [adjusted OR 1.9, 95% CI = 1.0 to 3.4], and to have received home care services one month after the ED visit [adjusted OR 2.3, 95% CI = 1.1 to 5.1]. Unexpectedly, they were also more likely to make a return visit to the ED [adjusted OR 1.6, 95% CI = 1.0 to 2.6]. Conclusions: The beneficial outcomes of the intervention appear to result primarily from the early provision of home care rather than early contact with the primary physician.

OBJECTIVE: We previously reported that patients with systemic lupus erythematosus (SLE) in the US incurred approximately 19% and 12% higher direct medical costs than patients in Canada and the UK, respectively, without experiencing superior outcomes expressed as disease damage or quality of life. In the present study, we compared cumulative indirect costs over 4 years in these patients. METHODS: A total of 715 patients with SLE (269 US, 231 Canada, 215 UK) were surveyed semiannually for 4 years on employment status and time lost from labor and nonlabor market activities. Cross-country comparisons of indirect costs were performed. RESULTS: In the US, Canada, and the UK, mean 4-year cumulative indirect costs (95% confidence interval [95% CI]) due to diminished labor market activity were $56,745 ($49,919, $63,571), $38,642 ($32,785, $44,500), and $42,213 ($35,859, $48,567), respectively, and cumulative indirect costs due to diminished nonlabor market activity were $5,249 ($2,766, $7,732), $5,455 ($3,290, $7,620), and $8,572 ($5,626, $11,518), respectively. Regression results showed that cumulative indirect costs (95% CI) due to diminished labor market activity in the US were $6,750 ($580, $12,910) greater than in Canada and $10,430 ($4,050, $16,800) greater than in the UK. Indirect costs due to diminished nonlabor market activity in the US were $280 (-$2,950, $3,520) less than in Canada and $2,010 (-$1,490, $5,510) less than in the UK, both results insignificant due to wide CIs. CONCLUSION: Despite American patients incurring greater direct medical costs than Canadian and British patients, they do not experience superior health outcomes in terms of less productivity loss in either labor market or nonlabor market activities.

First-order rate coefficients at three temperatures, and energies and entropies of activation, have been determined for the acid-catalyzed hydrolysis of methyl glucopyranosides containing various substituents at C-5 and for glycopyranosiduronic acids with different aglycones. Substitution at C-5 increased the stability towards acids of methyl α- and β-D-glucopyranosides, but there was no correlation between either the polarity or the size of the substituent and the rates of hydrolysis. The operation of either an inductive or a conformational effect alone was accordingly deemed unlikely.Methyl α- and β-D-glucopyranosiduronic acids and methyl α-D-galactopyranosiduronic acid were only slightly more stable towards acids than the glycoside analogs, while benzyl β-D-glucopyranosiduronic acid was three times more stable. The presence of a methyl ester group at the carboxyl function increased the stability of the glycuronide bond. Isopropyl, n-butyl, isobutyl, and neopentyl β-D-glucopyranosiduronic acids were hydrolyzed approximately twice and cyclohexy β-D-glucopyranosiduronic acid five times as fast as the corresponding glucosides. This appears to be the first time that glycuronides have been found to be hydrolyzed by dilute acid at a higher rate than their glycoside analogs.The energies and, especially, the entropies of activation were, throughout, lower for the glycuronides than for the glycosides. The difference in entropy suggests that the two classes of compounds are hydrolyzed by different mechanisms.

A bstract Mark‐recapture analyses were performed on photo‐identification data for Indo‐Pacific humpback dolphins ( Sousa chinensis ) inhabiting Algoa Bay, on the Eastern Cape coast of South Africa. Boat‐based photo‐ID surveys were undertaken between May 1991 and May 1994. The rate of discovery of newly identified dolphins, distribution of sightings and frequency of resightings of known individuals indicate a high level of seasonal immigration of humpback dolphins into, and emigration from, the Algoa Bay region in summer. Consequently, humpback dolphins from Algoa Bay appear to be part of a substantially larger population that uses a considerable length of the coastal zone. The minimum population size is estimated to be about 466 dolphins.

Estimates of the effect of increased global atmospheric CO(2) levels on oceanic primary productivity depend on the physiological responses of contemporary phytoplankton populations. However, microalgal populations will possibly adapt to rising CO(2) levels in such a way that they become genetically different from contemporary populations. The unknown properties of these future populations introduce an undefined error into predictions of C pool dynamics, especially the presence and size of the biological C pump. To address the bias in predictions introduced by evolution, we measured the kinetics of CO(2) uptake in populations of Chlamydomonas reinhardtii that had been selected for growth at high CO(2) for 1000 generations. Following selection at high CO(2), the populations were unable to induce high-affinity CO(2) uptake, and one line had a lower rate of net CO(2) uptake. We attribute this to conditionally neutral mutations in genes affecting the C concentrating mechanism (CCM). Lower affinity CO(2) uptake, in addition to smaller population sizes, results in a significant reduction in net CO(2) uptake of about 38% relative to contemporary populations under the same conditions. This shows how predictions about the properties of communities in the future can be influenced by the effect of natural selection.

Carbon dots have attracted great attention from the research community given their very attractive luminescent properties. However, the recent discovery that some of these properties may result from fluorescent impurities originating from the synthesis process, and not from the carbon dots themselves, constitute a significant setback to our knowledge of these materials. Herein, we proceeded to the study of carbon dots generated from citric acid and urea via a microwave-assisted synthesis, focusing on their analysis by AFM, HR-TEM, XPS, FT-IR, ESI-MS, UV-Vis and fluorescence spectroscopy. We have found that this synthesis process does generate molecular fluorophores that can mask the luminescence of the carbon dots. More importantly, our data demonstrates that when present in the same solution, the carbon dots and these fluorophores do not behave as separated species with individual emission. Instead, they interact to produce a hybrid luminescence, which excited state properties and reactivity are different from the properties of the individual species. These results indicate the possibility for the development of hybrid materials composed by carbon dots and related molecular fluorophores with new and improved properties.