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Although behavior therapy reduces tic severity, it is unknown whether it improves co-occurring psychiatric symptoms and functional outcomes for adults with Tourette's disorder (TD). This information is essential for effective treatment planning. This study examined the effects of behavior therapy on psychiatric symptoms and functional outcomes in older adolescents and adults with TD.
A total of 122 individuals with TD or a chronic tic disorder participated in a clinical trial comparing behavior therapy to psychoeducation and supportive therapy. At baseline, posttreatment, and follow-up visits, participants completed assessments of tic severity, co-occurring symptoms (inattention, impulsiveness, hyperactivity, anger, anxiety, depression, obsessions, and compulsions), and psychosocial functioning. We compared changes in tic severity, psychiatric symptoms, and functional outcomes using repeated measure and one-way analysis of variance.
At posttreatment, participants receiving behavior therapy reported greater reductions in obsessions compared to participants in supportive therapy (
$\eta _p^2 $
= 0.04, p = 0.04). Across treatments, a positive treatment response on the Clinical Global Impression of Improvement scale was associated with a reduced disruption in family life (
$\eta _p^2 $
= 0.05, p = 0.02) and improved functioning in a parental role (
$\eta _p^2 $
= 0.37, p = 0.02). Participants who responded positively to eight sessions of behavior therapy had an improvement in tic severity (
$\eta _p^2 $
= 0.75, p < 0.001), inattention (
$\eta _p^2 $
= 0.48, p < 0.02), and functioning (
$\eta _p^2 $
= 0.39–0.42, p < 0.03–0.04) at the 6-month follow-up.
Behavior therapy has a therapeutic benefit for co-occurring obsessive symptoms in the short-term, and reduces tic severity and disability in adults with TD over time. Additional treatments may be necessary to address co-occurring symptoms and improve functional outcomes.
In recent years, the discovery of massive quasars at
has provided a striking challenge to our understanding of the origin and growth of supermassive black holes in the early Universe. Mounting observational and theoretical evidence indicates the viability of massive seeds, formed by the collapse of supermassive stars, as a progenitor model for such early, massive accreting black holes. Although considerable progress has been made in our theoretical understanding, many questions remain regarding how (and how often) such objects may form, how they live and die, and how next generation observatories may yield new insight into the origin of these primordial titans. This review focusses on our present understanding of this remarkable formation scenario, based on the discussions held at the Monash Prato Centre from November 20 to 24, 2017, during the workshop ‘Titans of the Early Universe: The Origin of the First Supermassive Black Holes’.
The overarching goal of this work is to support creative ideation in engineering design with the aim of overcoming design fixation. We study the impact of abstract representations and ways to frame the problem in design briefs on the creativity of concept sketches. Framing/Reframing involves shifting perspectives on the design purpose and to reveal insights and opportunities. Two Framing/Reframing techniques are tested: the Ishikawa/Fishbone Diagram to identify root causes and a blend of Parnes’ Restatement/SCAMPER method to encourage divergence in problem perception. Abstract representations of requirements were used as stimuli to foster transfer and associative thinking. Using a full-factorial experimental design with brief variations, C-Sketch ideas developed by first-year engineering/architecture students were evaluated for their creativity. Our results showed a positive interaction effect for novelty and usefulness when the Fishbone Reframing method was used with abstract representation, but there was no difference in creativity scores when comparing the two Framing/Reframing methods between each other.
While prototypes are critical to the creation of successful products and innovative solutions, building a prototype is characterized by large sunk costs and a plethora of unknowns. The versatility and effectiveness of prototypes paired with the ambiguous nature of developing a prototype can lead to wasted resources. Recent studies support this claim, demonstrating that under certain circumstances, designers often prototype without a clear purpose, building prototypes as a function of the design process rather than as a function of the design. These findings motivated the creation of the Prototyping Canvas, a tool to aid designers in planning for purposeful prototypes by identifying critical assumptions and questions to guide development. Business and engineering design literature influenced the development of the canvas, which was first tested with a client project in the SUTD-MIT International Design Centre (IDC). The feedback and insights from the design team guided revisions to the canvas. The updated canvas was then validated with 55 professionals during a design project sprint. The purpose of this paper is to present the Prototyping Canvas as a valid and effective design tool.
Textual idea data from online crowdsourcing contains rich information of the concepts that underlie the original ideas and can be recombined to generate new ideas. But representing such information in a way that can stimulate new ideas is not a trivial task, because crowdsourced data are often vast and in unstructured natural languages. This paper introduces a method that uses natural language processing to summarize a massive number of idea descriptions and represents the underlying concept space as word clouds with a core-periphery structure to inspire recombinations of such concepts into new ideas. We report the use of this method in a real public-sector-sponsored project to explore ideas for future transportation system design. Word clouds that represent the concept space underlying original crowdsourced ideas are used as ideation aids and stimulate many new ideas with varied novelty, usefulness and feasibility. The new ideas suggest that the proposed method helps expand the idea space. Our analysis of these ideas and a survey with the designers who generated them shed light on how people perceive and use the word clouds as ideation aids and suggest future research directions.
The inhabitants of the overseas departments and collectivities of France have, of late, been reconsidering their relationships both to each other and to the former imperial metropole. In 2011 Mayotte, previously classified as an overseas collectivity, acceded to full French and European status as an overseas department of France following a referendum. This decision to, in the words of the social scientist François Taglioni, further ‘anchor’ the island in the republic has commonly been understood as a pragmatic decision as much as an ideological one. It was a way of distancing Mayotte from the political turmoil in neighbouring independent Comoros, as well as an indicator of the improbability of a small island nation achieving full sovereignty in a multipolar, resource hungry world. The narrative that self-determination must necessarily be obtained through national independence is still prevalent in the language of certain independence movements, including that of the Kanak people of New Caledonia. But it has been repeatedly tested at the ballot box, not least in November 2018 when New Caledonians voted in a referendum on their constitutional future. This referendum – and the further two due to follow it before 2022 – will be observed with interest by other self declared nations in waiting. Some anticipate, not a reclaiming of local sovereignty in the event of independence, but rather a transferral of economic hegemony from France to China, a prospect hinted at by Emmanuel Macron during a visit to Nouméa in 2018. However, the demographic minority status of the Kanak people whom the independentist Kanak and Socialist Liberation Front (Front de libération nationale kanak et socialiste; FLNKS) claims to represent, coupled with divisions within the movement, means it is very hard to predict the contours of a future independent New Caledonian state.
Innovation Concept: The fairness of the Canadian Residency Matching Service (CaRMS) selection process has been called into question by rising rates of unmatched medical students and reports of bias and subjectivity. We outline how the University of Saskatchewan Royal College emergency medicine program evaluates CaRMS applications in a standardized, rigorous, equitable and defensible manner. Methods: Our CaRMS applicant evaluation methods were first utilized in the 2017 CaRMS cycle, based on published Best Practices, and have been refined yearly to ensure validity, standardization, defensibility, rigour, and to improve the speed and flow of data processing. To determine the reliability of the total application scores for each rater, single measures intraclass correlation coefficients (ICCs) were calculated using a random effects model in 2017 and 2018. Curriculum, Tool or Material: A secure, online spreadsheet was created that includes applicant names, reviewer assignments, data entry boxes, and formulas. Each file reviewer entered data in a dedicated sheet within the document. Each application was reviewed by two staff physicians and two to four residents. File reviewers used a standardized, criterion-based scoring rubric for each application component. The file score for each reviewer-applicant pair was converted into a z-score based on each reviewer's distribution of scores. Z-scores of all reviewers for a single applicant were then combined by weighted average, with the group of staff and group of residents each being weighted to represent half of the final file score. The ICC for the total raw scores improved from 0.38 (poor) in 2017 to 0.52 (moderate) in 2018. The data from each reviewer was amalgamated into a master sheet where applicants were sorted by final file score and heat-mapped to offer a visual aid regarding differences in ratings. Conclusion: Our innovation uses heat-mapped and formula-populated spreadsheets, scoring rubrics, and z-scores to normalize variation in scoring trends between reviewers. We believe this approach provides a rigorous, defensible, and reproducible process by which Canadian residency programs can appraise applicants and create a rank order list.
Metacognition refers to the ability to evaluate and control our cognitive processes. While studies have investigated metacognition in schizophrenia and clinical high risk for psychosis (CHR), less is known about the potential mechanisms which result in metacognitive deficits.
We aimed to investigate whether neurocognitive functions including attention, working memory, verbal learning and executive functions predicted the tendency to focus on one’s thoughts (cognitive self-consciousness) and beliefs in the efficacy of one’s cognitive skills (cognitive confidence).
Participants (130 CHR individuals) were recruited as part of the multi-site PREDICT study. They were assessed using the Metacognitions Questionnaire (MCQ) as well as measures of executive function (WCST), attention (N-Back), working memory (LNS) and verbal learning (AVLT).
Cognitive competence was negatively correlated with N-Back while cognitive self-consciousness was positively correlated with N-Back and LNS. Linear regression analysis with N-Back, AVLT, LNS and WCST as predictors showed that neurocognition significantly predicted cognitive self-consciousness, with N-Back, LNS and WCST as significant predictors. The model accounted for 14% of the variance in cognitive self-consciousness. However, neurocognition did not result in a significant predictive model of cognitive competence.
Neurocognition was associated with an increased focus on one’s thoughts, but it was not associated with higher confidence in one’s cognitive skills. Neurocognition accounted for less than one-sixth of the variance in metacognition, suggesting that interventions that target neurocognition are unlikely to improve metacognitive abilities.
X-ray excitation causes rare-earth impurities in yttrium oxide and gadolinium oxide to emit intense and highly characteristic optical line fluorescence, which enables their analyses at low concentrations. The limits of detection for praseodymium, ncodymium, samarium, europium, gadolinium, terbium, dysprosium. holmium, erbium, thulium, and ytterbium in these two oxides range from 1 to 100 parts per billion (ppb). In other rare-earth oxides which have been investigated. the fluorescent intensities arc greatly reduced. Successful analyses can be made only by dilution in high-purity Y2O3. This dilution raises the detection limits for rare earths in these other oxides to the part per million range. X-rays from the chromium target of a cual-target X-ray tube are about two times more efficient in exciting rareeaith optical fluorescence than are the tungsten-target X-rays, even though the total energy output of the chromium target is only about one-third that of the tungsten target. With either target material, the rare-earth intensities vary linearly with the X-ray tube current, but a plot of intensity versus the square of the accelerating potential is not linear; it drops off at higher voltages.
To evaluate the impact of changes to urine testing orderables in computerized physician order entry (CPOE) system on urine culturing practices.
Retrospective before-and-after study.
A 1,250-bed academic tertiary-care referral center.
Hospitalized adults who had ≥1 urine culture performed during their stay.
The intervention (implemented in April 2017) consisted of notifications to providers, changes to order sets, and inclusion of the new urine culture reflex tests in commonly used order sets. We compared the urine culture rates before the intervention (January 2015 to April 2016) and after the intervention (May 2016 to August 2017), adjusting for temporal trends.
During the study period, 18,954 inpatients (median age, 62 years; 68.8% white and 52.3% female) had 24,569 urine cultures ordered. Overall, 6,662 urine cultures (27%) were positive. The urine culturing rate decreased significantly in the postintervention period for any specimen type (38.1 per 1,000 patient days preintervention vs 20.9 per 1,000 patient days postintervention; P < .001), clean catch (30.0 vs 18.7; P < .001) and catheterized urine (7.8 vs 1.9; P < .001). Using an interrupted time series model, urine culture rates decreased for all specimen types (P < .05).
Our intervention of changes to order sets and inclusion of the new urine culture reflex tests resulted in a 45% reduction in the urine cultures ordered. CPOE system format plays a vital role in reducing the burden of unnecessary urine cultures and should be implemented in combination with other efforts.
To evaluate the long-term safety and tolerability of deutetrabenazine in patients with tardive dyskinesia (TD) at 2years.
In the 12-week ARM-TD and AIM-TD studies, deutetrabenazine showed clinically significant improvements in Abnormal Involuntary Movement Scale scores compared with placebo, and there were low rates of overall adverse events (AEs) and discontinuations associated with deutetrabenazine.
Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration period and a long-term maintenance phase. Safety measures included incidence of AEs, serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD). This analysis reports results up to 2 years (Week106).
343 patients were enrolled (111 patients received placebo in the parent study and 232 received deutetrabenazine). There were 331.4 patient-years of exposure in this analysis. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term deutetrabenazine and placebo, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was similar to those observed with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33) treatment. AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
These results confirm the safety outcomes seen in the ARM-TD and AIM-TD parent studies, demonstrating that deutetrabenazine is well tolerated for long-term use in TD patients.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California,USA
Funding Acknowledgements: Funding: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel
To evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.
In the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.
Patients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.
343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.
Patients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.
Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.
Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.
A point-prevalence study of antimicrobial use among inpatients at 5 public hospitals in Sri Lanka revealed that 54.6% were receiving antimicrobials: 43.1% in medical wards, 68.0% in surgical wards, and 97.6% in intensive care wards. Amoxicillin-clavulanate was most commonly used for major indications. Among patients receiving antimicrobials, 31.0% received potentially inappropriate therapy.
The north-west European population of Bewick’s Swan Cygnus columbianus bewickii declined by 38% between 1995 and 2010 and is listed as ‘Endangered’ on the European Red List of birds. Here, we combined information on food resources within the landscape with long-term data on swan numbers, habitat use, behaviour and two complementary measures of body condition, to examine whether changes in food type and availability have influenced the Bewick’s Swan’s use of their main wintering site in the UK, the Ouse Washes and surrounding fens. Maximum number of Bewick’s Swans rose from 620 in winter 1958/59 to a high of 7,491 in winter 2004/05, before falling to 1,073 birds in winter 2013/14. Between winters 1958/59 and 2014/15 the Ouse Washes supported between 0.5 and 37.9 % of the total population wintering in north-west Europe (mean ± 95 % CI = 18.1 ± 2.4 %). Swans fed on agricultural crops, shifting from post-harvest remains of root crops (e.g. sugar beet and potatoes) in November and December to winter-sown cereals (e.g. wheat) in January and February. Inter-annual variation in the area cultivated for these crops did not result in changes in the peak numbers of swans occurring on the Ouse Washes. Behavioural and body condition data indicated that food supplies on the Ouse Washes and surrounding fens remain adequate to allow the birds to gain and maintain good body condition throughout winter with no increase in foraging effort. Our findings suggest that the recent decline in numbers of Bewick’s Swans at this internationally important site was not linked to inadequate food resources.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Psychosocial disability affects a number of individuals with psychosis and often begins years before the formal onset of disorder. This suggests that for many, their psychosocial disability is enduring, and targeted interventions are therefore needed earlier in their developmental trajectories to ensure that psychosocial disability does not become entrenched. Poor psychosocial functioning also affects individuals with a range of different emerging mental health problems, putting these young people at risk of long-term social marginalisation and economic disadvantage; all of which are known risk factors for the development of psychosis. Identification of the markers of poor psychosocial functioning will help to inform effective treatments. This editorial will discern the early trajectories and markers of poor psychosocial outcome in psychosis, and highlight which individuals are most at risk of having a poor outcome. This editorial will also discuss whether early interventions are currently being targeted appropriately and will propose how intervention and preventative strategies can be implemented, to restore psychosocial trajectories in a way that enables young people to maximise their life chances.
Adolescence is a critical time point in the lifecourse. LifeLab is an educational intervention engaging adolescents in understanding Developmental Origins of Health and Disease (DOHaD) concepts and the impact of the early life environment on future health, benefitting both their long-term health and that of the next generation. We aimed to assess whether engaging adolescents with DOHaD concepts improves scientific literacy and whether engagement alone improves health behaviours.
Six schools were randomized, three to intervention and three to control. Outcome measures were changed in knowledge, and intended and actual behaviour in relation to diet and lifestyle. A total of 333 students completed baseline and follow-up questionnaires. At 12 months, intervention students showed greater understanding of DOHaD concepts. No sustained changes in behaviours were identified.
Adolescents’ engagement with DOHaD concepts can be improved and maintained over 12 months. Such engagement does not itself translate into behaviour change. The intervention has consequently been revised to include additional components beyond engagement alone.