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Community-based physical activity programs, such as the Recreovía, are effective in promoting healthy behaviors in Latin America. To understand Recreovías’ challenges and scalability, we characterized its social network longitudinally while studying its participants’ social cohesion and interactions. First, we constructed the Main network of the program’s Facebook profile in 2013 to determine the main stakeholders and communities of participants. Second, we studied the Temporal network growth of the Facebook profiles of three Recreovía locations from 2008 to 2016. We implemented a Time Windows in Networks algorithm to determine observation periods and a scaling model of cities’ growth to measure social cohesion over time. Our results show physical activity instructors as the main stakeholders (20.84% nodes of the network). As emerging cohesion, we found: (1) incremental growth of Facebook users (43–272 nodes), friendships (55–2565 edges), clustering coefficient (0.19–0.21), and density (0.04–0.07); (2) no preferential attachment behavior; and (3) a social cohesion super-linear growth with 1.73 new friendships per joined user. Our results underscore the physical activity instructors’ influence and the emergent cohesion in innovation periods as a co-benefit of the program. This analysis associates the social and healthy behavior dimensions of a program occurring in natural environments under a systemic approach.
Progress toward racial equality requires the engagement of the American state, centered in the presidency and the executive branch, and in fact is not possible without the state's direct and forceful intervention. The key to this transformation is what we call “Forceful Federalism,” a multidimensional understanding of the American state. Forceful Federalism has four essential dimensions: standard-setting, coercion, associationalism, and fiscal authority. These four processes rise and fall over time, each charting its own history and unfolding according to its own logic. These processes usually work against each other. But occasionally they align with each other so that the state can pursue and achieve even difficult and challenging policy aims in a focused way. We sketch the outlines of Forceful Federalism and demonstrate its explanatory power with a case study of Forceful Federalism in action: James Meredith's integration of the University of Mississippi in 1962. The Meredith case exemplifies the convergence of the four dimensions of Forceful Federalism and marks the first time the modern American state was thus mobilized on behalf of civil rights. The case offers suggestive evidence that Forceful Federalism was a necessary condition for the emergence of the Civil Rights State.
Catatonia is a psychomotor dysregulation syndrome of diverse aetiology, increasingly recognised as a prominent feature of N-methyl-d-aspartate receptor antibody encephalitis (NMDARE) in adults. No study to date has systematically assessed the prevalence and symptomatology of catatonia in children with NMDARE. We analysed 57 paediatric patients with NMDARE from the literature using the Bush-Francis Catatonia Rating Scale. Catatonia was common (occurring in 86% of patients), manifesting as complex clusters of positive and negative features within individual patients. It was both underrecognised and undertreated. Immunotherapy was the only effective intervention, highlighting the importance of prompt recognition and treatment of the underlying cause of catatonia.
The thickness of glaciers in High-Mountain Asia (HMA) is critical in determining when the ice reserve will be lost as these glaciers thin but is remarkably poorly known because very few measurements have been made. Through a series of ground-based and airborne field tests, we have adapted a low-frequency ice-penetrating radar developed originally for Antarctic over-snow surveys, for deployment as a helicopter-borne system to increase the number of measurements. The manoeuvrability provided by helicopters and the ability of our system to detect glacier beds through thick, dirty, temperate ice makes it well suited to increase greatly the sample of measurements available for calibrating ice thickness models on the regional and global scale. The Bedmap Himalayas radar-survey system can reduce the uncertainty in present-day ice volumes and therefore in projections of when HMA's river catchments will lose this hydrological buffer against drought.
Abnormal body mass index (BMI) has been associated with development of psychopathology. This association in children is well documented, for both overweight and underweight children. However, the association between change in BMI and the development of psychopathology has been less investigated.
To investigate the association between change in BMI between childhood and adolescence and psychopathology in adolescence.
Data from the Growing Up in Ireland cohort were used. We investigated the ’98 cohort (also known as the child cohort) at age 9/13. BMI, defined using internationally recognised definitions as underweight, healthy or overweight, was used as the exposure, and abnormal Strength and Difficulties Questionnaire scores were used as the outcome. Logistic regression was undertaken for the analysis. All analyses were adjusted for confounders.
A change to overweight from healthy BMI was significantly associated with increased risk of psychopathology (adjusted OR 1.66; 95% CI 1.19–2.32). Both change from underweight to healthy (adjusted OR 0.12; 95% CI 0.03–0.43) or from overweight to healthy (adjusted OR 0.47; 95% CI 0.79–0.8) was associated with a significantly reduced risk of developing psychopathology.
As a child’s BMI returns to within the healthy range, their risk of adolescent psychopathology is reduced. Interventions to restore healthy BMI, in both underweight and overweight, children may reduce their risk of adolescent psychopathology.
Recent advances in the measurement of bedforms beneath active ice streams have been made using ground-based grid profiling using impulse radar systems operating with centre frequencies in the 3–5 MHz range. Surveys of Rutford Ice Stream and Pine Island Glacier have shown that features such as mega-scale glacial lineations with topographic relief of as little as 3 m can be traced for many kilometres downstream under more than 2 km of fast-moving ice. In the discussion of these data, it is often asked ‘How is it possible to map such fine-scale topography with such a low-frequency radar’. In answering that question, the key point is the distinction between the precision of a radar range measurement to a single, isolated reflective interface and the ability to resolve the presence of two closely-spaced interfaces of similar reflectivity (commonly referred to as the vertical resolution). This paper will discuss and illustrate this distinction and use the case study of data acquired over Pine Island Glacier to examine the limits of precision of the radar range measurement.
Although there is growing interest in mental health problems in university students there is limited understanding of the scope of need and determinants to inform intervention efforts.
To longitudinally examine the extent and persistence of mental health symptoms and the importance of psychosocial and lifestyle factors for student mental health and academic outcomes.
Undergraduates at a Canadian university were invited to complete electronic surveys at entry and completion of their first year. The baseline survey measured important distal and proximal risk factors and the follow-up assessed mental health and well-being. Surveys were linked to academic grades. Multivariable models of risk factors and mental health and academic outcomes were fit and adjusted for confounders.
In 1530 students surveyed at entry to university 28% and 33% screened positive for clinically significant depressive and anxiety symptoms respectively, which increased to 36% and 39% at the completion of first year. Over the academic year, 14% of students reported suicidal thoughts and 1.6% suicide attempts. Moreover, there was persistence and overlap in these mental health outcomes. Modifiable psychosocial and lifestyle factors at entry were associated with positive screens for mental health outcomes at completion of first year, while anxiety and depressive symptoms were associated with lower grades and university well-being.
Clinically significant mental health symptoms are common and persistent among first-year university students and have a negative impact on academic performance and well-being. A comprehensive mental health strategy that includes a whole university approach to prevention and targeted early-intervention measures and associated research is justified.
Les troubles dépressifs concernent près de deux fois plus de femmes que d’hommes . Cette prévalence pourrait être due à une sensibilité accrue des femmes aux émotions négatives . Peu d’études d’imagerie cérébrale ont comparé l’activité cérébrale des hommes et des femmes lors de la présentation de stimuli émotionnels.
Objectif et hypothèse
Notre objectif était d’étudier les activations cérébrales des hommes et des femmes lors d’une tâche émotionnelle. Nous avons émis l’hypothèse que le pattern d’activations cérébrales diffère selon le sexe des individus et la valence des stimuli.
Nous avons mené une étude en imagerie par résonance magnétique fonctionnelle (IRMf) chez 30 participants sains (15 hommes et 15 femmes). Des stimuli à valence positive, négative et neutre étaient présentés aux sujets. Les participants ont évalué subjectivement la valence et l’intensité des stimuli.
Nous observons une activité plus importante chez les femmes que chez les hommes dans plusieurs régions clés du traitement des émotions lors de la présentation de stimuli négatifs. Aucune différence significative entre les hommes et les femmes n’a été relevée concernant l’évaluation subjective des stimuli en termes de valence et d’intensité.
Les résultats suggèrent qu’il existe bien une différence de patterns d’activation entre les hommes et les femmes lors de la perception des émotions négatives, qui irait dans le sens d’une sensibilité accrue chez les femmes. Celle-ci pourrait expliquer leur plus grande vulnérabilité aux troubles dépressifs. Il pourrait être intéressant de répliquer cette étude chez des patients qui souffrent de troubles de l’humeur.
La stimulation magnétique transcrânienne répétitive (SMTr) appliquée sur le cortex préfrontal dorso-latéral (CPFDL) a prouvé son efficacité dans le traitement de la dépression résistante . En plus d’une amélioration sur la symptomatologie, des études rapportent des effets positifs sur le fonctionnement cognitif , dont la mémoire de travail. Cependant, cet effet ne semble pas être retrouvé chez des sujets sains  lors d’une tâche de N-back sans leurre. L’objectif de notre étude est donc d’évaluer l’impact de la SMTr sur le CPFDL, région plus sensible à une tâche de N-back avec leurre .
Une étude randomisée en double insu a été menée chez 30 participants sains. Une stimulation de type iTBS (intermittent theta burst stimulation) a été effectuée pendant 5 jours à raison de 2 séances/jour appliquée au niveau du CPFDL gauche ciblé par neuro-navigation sur les coordonnées MNI (X, Y, Z = –50,30,36). Nous avons observé l’impact de la SMTr sur le comportement des participants durant la tâche de N-back. Pour cela, les participants ont effectué cette tâche, composée de blocs de 0-back, 3-back et 3-back contenant des leurres, lors de deux sessions d’IRMf (une avant et une après la semaine de stimulation active ou placebo). La performance, le temps de réaction ainsi que les données d’imageries ont été recueillis.
Les 2 groupes ne montrent pas de différence au niveau de l’âge ou du genre. Au niveau comportemental, les premières analyses sur la performance ainsi que sur le temps de réaction ne montrent pas d’effet d’interaction Groupe (actif/placebo) * Temps (avant/après SMTr). Au niveau des données de neuro-imagerie, une analyse d’interaction Groupe * Temps en prenant en compte la condition leurre nous permettra de mieux comprendre l’impact de la SMTr sur la mémoire de travail impliquant le CPFDL.
With one in ten young people being affected by ill mental health and stigma regularly cited as a factor affecting access to early intervention services, focussing resources on school based stigma reduction strategies seems prudent. ‘Headucate’, a student society, designed a 50 minute workshop which aims to increase mental health literacy and decrease stigma.
Repeated, cross sectional surveys were carried out at three time points; 1) immediately before (n=77), 2) Immediately after (n=81) and 3) three months post workshop (n=73). The surveys were paper based versions of the Reported Intended Behaviours Score (RIBS) and Mental Health Knowledge Scale (MAKS) utilising a social distance scale.
Four year 10 classed (pupils aged 14-15) were recruited. Post hoc t-tests were carried out when one-way ANOVAS were significant.
Disorder knowledge (from MAKS) and intended contact (from RIBS) significantly increased between time points one and two (p<0.01 and <0.004 respectively) but then decreased.
Analysis of the question pertaining to knowing where to access help showed a statistically significant increase (p<0.001) between time points one and two and then a decrease at time three, albeit to a higher value than at time point one (3.45 compared to 3.13, P=0.088).
Headucate workshops offer a low resource option which is well accepted by students. Like other school based stigma reduction strategies, a dramatic increase was seen between immediately before and after indicating that the workshop resonates with the pupils, but there was little sustained change in attitudes.
A total of 38 long-term care facilities within a region participated in a 3-month quality improvement initiative focused on environmental cleaning and disinfection. Significant improvements in daily and discharge cleaning were observed during the project period. Further study of the sustainability and clinical impact of this type of initiative is warranted.
In 2016, the US FDA issued an industry guidance document “Quality Attribute Considerations for Chewable Tablets” which describes the quality attributes to be considered when developing chewable tablets. It includes recommendations on selection of acceptance criteria for measuring palatability (having a taste acceptable to the patient or has adequate masking). These data are now recommended as part of ANDA submissions. Palatability is a known positive contributing factor to drug adherence and persistence. We summarize here palatability data for a new amphetamine extended-release tablet (Dyanavel XR® Extended Release Tablet; AMPH ER TAB).
This was a 2-arm preplanned secondary analysis from a comparative bioavailability study: single-dose AMPH ER TAB 20 mg chewed under fasting (Treatment A) and fed (Treatment B) conditions. Subjects rated the palatability of AMPH ER TAB (Treatments A+B) through a 5-question palatability questionnaire. The questions included in the palatability questionnaire were as follows:
1. Oral sensation/mouth feel of the drug product
2. Taste of the drug product
3. How strong is the taste?
4. Aftertaste of the product
5. How strong is the aftertaste?
Subjects completed the questionnaire within 10 minutes from the time of drug administration, which was evaluated and scored according to the rubric below:
Q1, Q2, Q4: palatability- Very unpleasant (score of 1), Unpleasant (2), No sensation or mouthfeel (3), Pleasant (4), and Very pleasant (5)
Q3, Q5 (Taste/aftertaste strength): Very strong (score of 1), Strong (2), Moderate (3), Mild (4), No aftertaste (5).
Scores of 1-2 for both categories were Negative; score of 3 was Neutral, and 4-5 were Positive.
35 subjects comprised the palatability dataset (completed one question on the questionnaire). In the palatability analysis, for treatments A and B, most of the subjects rated the oral sensation/mouth feel of AMPH ER TAB (Question 1) and the taste of AMPH ER TAB (Question 2) as positive (pleasant to very pleasant) (70.1% and 83.6%, respectively).
When evaluating taste strength (Question 3): 43.3% rated the strength as positive (mild/no taste) and 43.3% of subjects rated the strength as neutral (moderate taste). Also, 82.1% rated the aftertaste of AMPH ER TAB (Question 4) as positive (pleasant/very pleasant) and 52.2% rated the strength of the aftertaste as positive (mild/no taste).
Most subjects rated the oral sensation and taste as pleasant or very pleasant, whether chewed under fasted conditions or after a meal. With respect to the taste strength, most subjects rated it as moderate (chewed under fasted conditions) or mild/no taste (chewed after a meal). Aftertaste was rated as pleasant or very pleasant in most subjects, with the strength as moderate (chewed under fasted conditions) or mild/no aftertaste (chewed after a meal). AMPH ER Tablets provided an overall pleasant taste and mouthfeel experience for patients.
Evaluate comparative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB, Tris Pharma, Inc., Monmouth Junction, NJ) 20 mg, swallowed whole or chewed and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; and evaluate whether a PK food effect exists on AMPH ER TAB (contains a 3.2:1 ratio of d- to l-amphetamine).
Healthy volunteers (18-55 yr) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted).
A crossover design was used. Samples were collected each period pre-dose and at time points to 60 h post-dose. D-and l-amphetamine were measured, and PK was calculated (90% CIs of the ratios of the geometric mean plasma levels) for Cmax, AUCt, and AUC0∞. Comparative bioavailability was determined when ratios were within 80 and 125%. Safety was also assessed.
32 subjects completed the study. Based on the calculated bioavailability ratios, for AMPH ER TAB swallowed vs. AMPH EROS fasted: d-amphetamine total and peak exposures were found to be similar: AUC0-t: 100.68-108.08%, AUC0-∞:101.47-109.52%, Cmax: 98.10-103.17%. For l-amphetamine, the total and peak exposures were similar: AUC0-t: 100.31-108.57%, AUC0-∞:101.27-111.09%, Cmax: 98.2-103.37%.
AMPH ER TAB chewed vs. AMPH EROS fasted: For d-amphetamine, the total and peak exposures were similar: AUC0-t: 99.23-106.62%, AUC0-∞: 99.58-107.59%, Cmax: 99.91-105.14%. For l-amphetamine, the total and peak exposure was similar: AUC0-t: 98.16-106.35%, AUC0-∞: 98.44-108.11%, Cmax: 99.53-104.75%.
Food effect: AMPH ER TAB, chewed, fasted vs. fed: For d-amphetamine, the total and peak exposure was similar: AUC0-t: 92.57-99.49%, AUC0-∞: 91.12-98.48%, Cmax: 94.22-99.17%.
For l-amphetamine, the total and peak exposure was similar: AUC0-t: 91.27-98.91%, AUC0-∞: 88.44-97.17%, Cmax: 94.52-99.50%).
No serious AEs were reported during the conduct of this study, and the AE profiles were observed to be similar in frequency of events and severity to other amphetamine formulations used in ADHD.
Bioavailability of single dose of AMPH ER TAB for both d- and l-amphetamine was comparable, swallowed whole or chewed, to an equivalent 20 mg dose of the reference product AMPH EROS, 2.5 mg/mL fasted, and showed equivalent peak and overall exposure.
No food effect was observed for AMPH ER TAB administered chewed. All AEs were mild in severity and AE profiles were similar to other amphetamine formulations used for treatment of ADHD.
Evaluate the relative bioavailability of single-dose amphetamine extended-release tablet (AMPH ER TAB) 20 mg, swallowed whole or chewed, and amphetamine extended-release oral suspension (AMPH EROS) 2.5 mg/mL; evaluate food effect on AMPH ER TAB.
Healthy volunteers (18–55 years) were randomized to 1 dose of AMPH ER TAB 20 mg swallowed (fasted), chewed (fed/fasted), or 20 mg AMPH EROS (fasted). A crossover study design was used. Plasma samples were collected each period predose and at time points to 60 hours postdose. d- and l-amphetamine were measured and pharmacokinetic (PK) was calculated (90% confidence intervals of the ratios of the plasma levels) for AUC0-t, AUC0-∞, and Cmax. Comparative relative bioavailability between formulations was determined when ratios were within 80% and 125%. Safety was also assessed.
Thirty-two subjects completed the study. AMPH ER TAB swallowed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 100.68% to 108.08%, AUC0-∞: 101.47% to 109.52%, Cmax: 98.10% to 103.17%; l: AUC0-t: 100.31% to 108.57%, AUC0-∞: 101.27% to 111.09%, Cmax: 98.2% to 103.37%. For d- and l-amphetamine when the tablet is swallowed whole, Tmax was 5.00 hours (with a range of 2.00–9.00 hours). AMPH ER TAB chewed versus AMPH EROS (fasted): for d- and l-amphetamine, the total and peak exposure was similar: d: AUC0-t: 99.23% to 106.62%, AUC0-∞: 99.58% to 107.59%, Cmax: 99.91% to 105.14%; l: AUC0-t: 98.16% to 106.35%, AUC0-∞: 98.44% to 108.11%, Cmax: 99.53% to 104.75%. For d- and l-amphetamine when the tablet has been chewed, Tmax was 5.00 hours (with a range of 3.00-7.00 hours). PK results were similar for patients in the fasted and fed groups, indicative of no presence of food effect. No serious adverse events (AEs) were reported, overall AE profiles between the tablet and oral suspension were comparable without any unanticipated safety concerns.
Single doses of AMPH ER TAB for both d- and l-amphetamine demonstrated comparable bioavailability to a 20 mg dose of AMPH EROS, 2.5 mg/mL under fasted conditions when chewed and swallowed whole, and demonstrated equivalent peak and overall exposure without apparent food effect. AMPH ER TAB was well-tolerated and consistent with adverse events noted in other amphetamine formulations.
Rigid bronchoscopy is an important procedure practiced primarily by otolaryngologists and thoracic surgeons, which allows visualization of the trachea and proximal bronchi. The bronchoscope was introduced in 1806 by Bozzini. Its first successful reported use was in 1897 when Gustav Killian retrieved an aspirated pork bone from the right mainstem bronchus, avoiding a tracheostomy. Around the same period, Chevalier Jackson created his own illuminated endoscopes, and in 1907 published his findings in his landmark book, Tracheobronchoscopy, Esophagoscopy and Bronchoscopy.
Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic–pituitary–adrenal axis function should be a focus of continued research.
Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol (‘low-level response’) imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: http://clinicaltrials.gov/ct2/show/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.