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.

BACKGROUND AND PURPOSE: The gait speed that a patient selects is a well-known indicator of overall gait performance. The purpose of this study was to use multiple linear regression to assess the strength of association of temporal, kinematic, and kinetic gait variables with high walking speeds in patients with hemiplegia. SUBJECTS: Thirty-two subjects (20 male, 12 female) with an average age of 61 years took part in a sagittal-plane gait study of both sides of the body. METHODS: Data from cinematographic film and a force plate obtained during multiple walking trials were used in a seven-segment link-segment kinetic model of the walking subject to yield temporal, kinematic, and kinetic variables. RESULTS: Variables correlating significantly with self-selected speed included the maximum hip extension angle and the maximum hip flexion moment on the affected side, and the maximum ankle and hip powers on both sides. A stepwise regression identified variables most useful in predicting stride speed. For the affected side, these variables were the hip flexion moment, the ankle moment range, the knee moment range, and the proportion of double support. Together these variables explained 94% of the variation in gait speed. On the unaffected side, the variables were the percentage of stance phase, the maximum ankle power (push-off), and the maximum hip power (pull-off). They explained 92% of the variation in gait speed. CONCLUSION AND DISCUSSION: These results suggest that experimental studies are needed to assess the effects of treatment aimed at increasing ankle power and hip power and at decreasing the stance time on the affected side, and that these studies should be directed at obtaining a larger hip flexion moment and a larger ankle moment range on the unaffected side.

[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

The persistent increase in pain sensitivity observed after injury, known as hyperalgesia, depends on synaptic plasticity in the pain pathway, particularly in the spinal cord. Several potential mechanisms have been proposed, including post-synaptic exocytosis of the AMPA subclass of glutamate receptors (AMPA-R), which is known to play a critical role in synaptic plasticity in the hippocampus. AMPA-R trafficking has been described in spinal neurons in culture but it is unknown if it can also occur in spinal neurons in vivo, or if it can be induced by natural painful stimulation. Here we have induced referred mechanical hyperalgesia in vivo by intracolonic instillation of capsaicin in mice and have observed a recruitment of GluR1 AMPA-R subunits to neuronal plasma membranes in the lumbar spinal cord. Intracolonic capsaicin induced a rapid (10 min) increase in GluR1, but not GluR2/3 in the synaptosomal membrane fraction which lasted at least 3 h and a decrease in GluR1 subunit in the cytosolic fraction. Capsaicin treatment also provoked CaMKII activation and pre-treatment with a specific CaMKII inhibitor prevented the GluR1 trafficking. Brefeldin-A, an antibiotic that inhibits exocytosis of proteins, not only prevented GluR1 trafficking to the membrane but also inhibited referred hyperalgesia in capsaicin-treated mice. Our results show that delivery of GluR1 AMPA receptor subunits to the cell membrane through a CaMKII activity-dependent exocytotic regulated pathway contributes to the development of hyperalgesia after a painful stimulus. We conclude that AMPA-R trafficking contributes to the synaptic strengthening induced in the pain pathway by natural stimulation.

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.

BACKGROUND AND PURPOSE: Gait analyses yield redundant information that often is difficult to interpret. The purpose of this study was to show how principal-component analysis can provide insight into gait data obtained from persons with stroke. SUBJECTS: Twenty male and 11 female adults who were ambulatory were studied (mean age = 60.5 years, SD = 11.8, range = 24-79; mean time since stroke = 11.4 months, SD = 15.4, range = 2.0-88.0). METHODS: Spatial data were used in a 4-segment link-segment model to calculate the kinematic and kinetic variables of gait. Principal components were constructed on the averages for 40 variables. RESULTS: The first principal component was related to speed and accounted for 40.8% of the variance. The second principal component was related to differences between the 2 limbs (symmetry) and accounted for 12.8% of the variance. The third principal component was related to adoption of a postural flexion bias and accounted for 10.2% of the variance. The fourth principal component, which was not interpretable, accounted for 6.8% of the variance. CONCLUSION AND DISCUSSION: The principal-component analysis allowed clustering of related variables and simplified the complex picture presented by the large number of variables resulting from gait analysis. Examination of variables closely related to each principal component yielded insight into the nature of the strategies used in walking and their interrelationships. The method has potential for insight into similarities and differences in gait performances arising from different pathologies and for comparing the progress of individuals with similar pathologies.

This study explored the role of wild foods in the diets of children and mothers in the East Usambara Mountains (N = 274 dyads). We identified 92 wild food species. Although dietary diversity (most measures) was not different between seasons, wild foods accounted for a greater percentage of items consumed in the wet (food insecure) season. Many wild foods were obtained on farm; wild foods obtained from the forest accounted for less than 3% of food items consumed. Wild foods were used by virtually all informants but contributed only 2% of total energy in the diet. However, they contributed large percentages of vitamin A (RAE) (31%), vitamin C (20%), and iron (19.19%). Agricultural factors (e.g., hours spent in farm) were associated with greater wild food use. These findings suggest participation in agriculture may be important for the maintenance of wild food use, and that wild foods can play an important role in the nutritional resilience of local people.

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

Moisture has for a long time been recognised as a serious contributor to premature degradation of asphaltic pavements. Many studies have been performed to collect, describe and measure the moisture susceptibility of asphaltic mixes. Most of these are aimed at a comparative measure of moisture damage, either via visual observations from field data or laboratory tests or via mechanical tests, which give a so called moisture damage index parameter. The research presented in this paper is part of an ongoing effort at Delft University of Technology, to move away from such comparative or empirical measures of moisture-induced damage and start treating moisture-induced damage in a comprehensive energy based framework. Such a framework would enable realistic predictions and time-assessment of the failure pattern occurring in an asphaltic pavement under the given environmental and traffic loading which could be rutting, cracking, ravelling or any combination or manifestation thereof. The modelling of moisture-induced damage is a complex problem, which involves a coupling between physical and mechanical damage processes. This paper discusses several modes of moisture infiltration into asphaltic mixes and derives the governing equations for their simulations. Moisture diffusion into the mastic film, towards the aggregate–mastic interface and mastic erosion, due to high water pressures caused by the pumping action of traffic loading, are identified as the main moisture-induced damage processes and are implemented in a new finite element program, named RoAM. The paper discusses the necessary model parameters and gives detailed verification of the moisture diffusion and advective transport simulations. In the accompanying paper the developed finite element model is demonstrated via an elaborate parametric study and the fundamental moisture-induced damage parameters are discussed.

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: 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.

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.

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.

The 2010 clinical practice guideline for the diagnosis and management of osteoporosis in Canada[1][1] focused on the care of adults living in the community. However, the fracture rate for adults living in long-term care (residents) is two to four times that of adults of similar age living in the