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We present a stellarator configuration optimized for a large threshold (‘critical gradient’) for the onset of the ion temperature gradient (ITG) driven mode, which achieves the largest critical gradient we have seen in any stellarator. Above this threshold, gyrokinetic simulations show that the configuration has low turbulence levels over an experimentally relevant range of the drive strength. The applied optimization seeks to maximize the drift curvature, leading to enhanced local-shear stabilization of toroidal ITG modes, and the associated turbulence. These benefits are combined with excellent quasi-symmetry, yielding low neoclassical transport and vanishingly small alpha particle losses. Analysis of the resulting configuration suggests a trade-off between magnetohydrodynamic (MHD) and ITG stability, as the new configuration possesses a vacuum magnetic hill.
Global electromagnetic turbulence is simulated in stellarator geometry using the gyrokinetic particle-in-cell code EUTERPE. The evolution of the turbulent electromagnetic field and the plasma profiles is considered at different values of the plasma beta and for different magnetic configurations. It is found that turbulence is linearly driven at relatively high toroidal mode numbers. In the nonlinear regime, lower toroidal mode numbers, including zonal flows, are excited resulting in a quench of the linear instability drive. The turbulent heat flux is outward and leads to the nonlinear relaxation of the plasma temperature profile. The particle flux is inward for the parameters considered. The effect of the parallel perturbation of the magnetic field on the stellarator turbulence is addressed.
CyberKnife radiosurgery (RS), as an initial first treatment, is recognized as an efficient and safe modality for trigeminal neuralgia (TN). However, knowledge on repeat CyberKnife RS in refractory cases is limited. The objective was to evaluate the clinical outcomes of repeat CyberKnife RS for TN.
Methods:
A retrospective review of 33 patients with refractory TN treated a second time with CyberKnife RS from 2009 to 2021. The median follow-up period after the second RS was 26.0 months (range 0.3–115.8). The median dose for the repeat RS was 60 Gy (range 60.0–70.0). Pain relief after the intervention was assessed using the Barrow Neurological Institute scale for pain (I–V). Scores I to IIIb were classified as an adequate pain relief and scores IV–V were classified as a treatment failure
Results:
After the second RS, initial adequate pain relief was achieved in 87.9% of cases. The actuarial probabilities of maintaining an adequate pain relief at 6, 12, 24, and 36 months were 92.1%, 74.0%, 58.2%, and 58.2%, respectively. Regarding sustained pain relief, there was no significant difference between the first and the second RS. Sensory toxicity after the first RS was predictive of a better outcome following the second RS. The onset of hypesthesia rate was the same after the first or the second RS (21%).
Conclusion:
Repeat RS is an effective and safe method for the treatment of refractory TN.
This article investigates the emergence of recursive DPs in child language. In certain languages, DP modification can be achieved via diverse structures and any number of different embedding markers (prepositions, particles, case-marker, etc.), each having to be learned; this diversity may impact the L1 development of recursive DP modification. Japanese, in contrast, relies on two uniform unrestricted strategies: the adnominal particle の (no) or a relative clause. We report the results of an elicited production study comparing the production of recursive DPs in Japanese-speaking children and adults. Our results show that Japanese children were much like adults in the types of semantic modificational relations that elicited the most target responses. Children were different from adults in that they were: a) much less successful overall, and b) they preferred no, independently of whether the condition was biased toward no. We review the implications of these findings for analyses of no.
This economic evaluation supplements a pragmatic randomized controlled trial conducted in community care settings, which showed superior improvement in the symptoms of adults with anxiety disorders who received 12 sessions of transdiagnostic cognitive-behavioural group therapy in addition to treatment as usual (tCBT + TAU) compared to TAU alone.
Methods
This study evaluates the cost-utility and cost-effectiveness of tCBT + TAU over an 8-month time horizon. For the reference case, quality-adjusted life years (QALYs) obtained using the EQ-5D-5L, and the health system perspective were chosen. Alternatively, anxiety-free days (AFDs), derived from the Beck Anxiety Inventory, and the limited societal perspective were considered. Unadjusted incremental cost-effectiveness/utility ratios were calculated. Net-benefit regressions were done for a willingness-to-pay (WTP) thresholds range to build cost-effectiveness acceptability curves (CEAC). Sensitivity analyses were included.
Results
Compared to TAU (n = 114), tCBT + TAU (n = 117) generated additional QALYs, AFDs, and higher mental health care costs from the health system perspective. From the health system and the limited societal perspectives, at a WTP of Can$ 50 000/QALY, the CEACs showed that the probability of tCBT + TAU v. TAU being cost-effective was 97 and 89%. Promising cost-effectiveness results using AFDs are also presented. The participation of therapists from the public health sector could increase cost-effectiveness.
Conclusions
From the limited societal and health system perspectives, this first economic evaluation of tCBT shows favourable cost-effectiveness results at a WTP threshold of Can$ 50 000/QALY. Future research is needed to replicate findings in longer follow-up studies and different health system contexts to better inform decision-makers for a full-scale implementation.
The self-report version of the Panic Disorder Severity Scale (PDSS-SR) is a reliable and valid instrument to assess panic disorder, but is unavailable in French.
Objectives
The aim of this study was to conduct a transcultural validation of the French-Canadian PDSS-SR and examine its psychometric properties.
Methods
This study is part of a pragmatic RCT of group transdiagnostic CBT for anxiety disorders, and includes 272 adults meeting DSM-5 panic disorder diagnostic criteria. At baseline, participants completed the Anxiety and Related Disorders Interview Schedule (ADIS-5), the French-Canadian PDSS-SR and self-report measures. Convergent validity was assessed with Spearman correlations, Cronbach’s α was used to analyse internal consistency, and confirmatory factor analysis (CFA) evaluated its factor structure. Sensitivity to change was assessed with paired sample t-tests in patients (n = 72) meeting DSM-5 criteria for panic disorder at baseline with posttreatment data.
Results
108 patients met DSM-5 criteria for panic disorder, including 58 with agoraphobia. The majority were women (85.3%) and mean age was 37.1 (SD = 12.4). Internal consistency (Cronbach’s α) was 0.91. For convergent validity, the highest correlation was with the Beck Anxiety Inventory (r = 0.64). CFA suggested a two-factor model. Optimal threshold for probable diagnosis was 10. Analyses support sensitivity to change when comparing transdiagnostic group CBT and control conditions.
Conclusions
With its good psychometric properties in primary care patients, the French-Canadian self-report version of the Panic Disorder Severity Scale is an efficient and practical instrument for both clinicians and researchers working in the field of mental health.
Cognitive-behavioral therapy (CBT) is recognized as an effective treatment for anxiety disorders. Transdiagnostic group CBT (tCBT) targets cognitive and behavioural intervention strategies common to anxiety disorders. tCBT allows the treatment of a larger number of patients simultaneously and therapists only need to master a single intervention protocol. However, tCBT may present several challenges for therapists, particularly regarding group management.
Objectives
To explore therapists’ perceptions and experience of group management during tCBT for mixed anxiety disorders.
Methods
A qualitative study embedded in a randomized controlled trial of group tCBT (Roberge & Provencher; CIHR, 2015-2021). Semi-structured interviews were conducted with 18 of the 21 therapists to document their perceptions and to identify improvements for tCBT delivery. The data were analyzed using a deductive approach and based on the interactive cyclical process of data reduction, display and conclusion drawing.
Results
Therapists raised the challenge of the heterogeneous characteristics of participants’ anxious profile, since they had to be creative to provide exercises that were suitable for a whole group. Exposure exercises, a key component of tCBT, were particularly affected by the composition of the groups. Previous group animation experience and the ability to establish a therapeutic alliance from a group perspective were important facilitators. Co-therapy also facilitated the intervention, since it allowed the therapists to be more vigilant to group dynamics and favored the organization of tCBT.
Conclusions
This study highlights the importance of exploring therapists’ perceptions and experience about group management in order to identify facilitators and barriers of group tCBT in community-based care.
We compared entorhinal cortex atrophy (ERICA) score vs. medial temporal atrophy (MTA) score’s ability to predict conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer’s disease (AD) using magnetic resonance imaging (MRI). We hypothesized that ERICA would show higher specificity. Data from 61 aMCI patients were analyzed. Positive ERICA was associated with AD conversion with a sensitivity of 56% (95% CI: 30–80%) and a specificity of 78% (63–89%) vs. 69% (41–89%) SE and 60% (44–74%) SP for the MTA. Results suggest that ERICA is superior to MTA in predicting conversion from aMCI to AD in a small sample of participants.
In response to the treatment gap for anxiety and depressive disorders, psychological treatments with innovative modalities and high implementation potential are essential. Internet CBT (iCBT) is a cost/effective approach that could improve access to a low-intensity evidence-based CBT intervention.
Objectives
To assess the feasibility and acceptability of the French adaptation of the physician-prescribed six-lesson This Way Up transdiagnostic iCBT program for mixed anxiety and depressive disorders developed in Australia.
Methods
Feasibility study with pre- post-intervention evaluations, including an embedded qualitative study in Family Medicine Groups (Quebec, Canada). Inclusion criteria comprise a family physician diagnosis of Major Depression, Panic Disorder, Agoraphobia, Social Anxiety Disorder or Generalized Anxiety Disorder. Primary self-reported outcomes: PHQ-9 (depression) and GAD-7 (anxiety); secondary measures include diagnostic-specific scales and health service utilisation.
Results
Family physicians (N=21) from five Family Medicine Groups prescribed iCBT to 45 patients (30 women, 15 men; mean age = 39.7), 31 initiated the program. To date, 20 patients completed 5 or 6 lessons, nine completed between 2 and 4. Intervention and post-treatment assessments are ongoing, results forthcoming. Results of semi-structured interviews with patients (N=15) and family physicians (ongoing) on iCBT acceptability indicate it is beneficial, practical and easy to use. Program adherence requires patient readiness and determination and could be fostered by motivational support from clinicians.
Conclusions
Results support this French iCBT program’s scaling-up potential to contribute to reducing the gap in evidence-based treatments for common mental disorders. Its implementation in primary care could improve the effectiveness, efficiency and equity to a rapidly accessible treatment.
A first-principles method to calculate the critical temperature gradient for the onset of the ion-temperature-gradient mode (ITG) in linear gyrokinetics is presented. We find that conventional notions of the connection length previously invoked in tokamak research should be revised and replaced by a generalized correlation length to explain this onset in stellarators. Simple numerical experiments and gyrokinetic theory show that localized ‘spikes’ in shear, a hallmark of stellarator geometry, are generally insufficient to constrain the parallel correlation length of the mode. ITG modes that localize within bad drift curvature wells that have a critical gradient set by peak drift curvature are also observed. A case study of near-helical stellarators of increasing field period demonstrates that the critical gradient can indeed be controlled by manipulating the magnetic geometry, but underscores the need for a general framework to evaluate the critical gradient. We conclude that average curvature and global shear set the correlation length of resonant ITG modes near the absolute critical gradient, the physics of which is included through direct solution of the gyrokinetic equation. Our method, which handles the general geometry and is more efficient than conventional gyrokinetic solvers, could be applied to future studies of stellarator ITG turbulence optimization.
Alzheimer’s disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic.
Methods:
We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aβ1–42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient’s diagnosis and management.
Results:
The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP.
Interpretation:
Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.
Transdiagnostic group cognitive-behavioral therapy (tCBT) is a delivery model that could help overcome barriers to large-scale implementation of evidence-based psychotherapy for anxiety disorders. The aim of this study was to assess the effectiveness of combining group tCBT with treatment-as-usual (TAU), compared to TAU, for the treatment of anxiety disorders in community-based mental health care.
Methods
In a multicenter single-blind, two-arm pragmatic superiority randomized trial, we recruited participants aged 18–65 who met DSM-5 criteria for principal diagnoses of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Group tCBT consisted of 12 weekly 2 h sessions. There were no restrictions for TAU. The primary outcome measures were the Beck Anxiety Inventory (BAI) and clinician severity rating from the Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5) for the principal anxiety disorder at post-treatment, with intention-to-treat analysis.
Results
A total of 231 participants were randomized to either tCBT + TAU (117) or TAU (114), with outcome data available for, respectively, 95 and 106. Results of the mixed-effects regression models showed superior improvement at post-treatment for participants in tCBT + TAU, compared to TAU, for BAI [p < 0.001; unadjusted post-treatment mean (s.d.): 13.20 (9.13) v. 20.85 (10.96), Cohen's d = 0.76] and ADIS-5 [p < 0.001; 3.27 (2.19) v. 4.93 (2.00), Cohen's d = 0.79].
Conclusions
Our findings suggest that the addition of group tCBT into usual care can reduce symptom severity in patients with anxiety disorders, and support tCBT dissemination in routine community-based care.
The current coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) pandemic has resulted in severe shortages of personal protective equipment, including respiratory protective equipment, such as N95 respirators. This has led some government agencies to suggest the use of cloth face coverings (CFCs) by health-care providers and the general public as a last resort when standard respiratory protective equipment is unavailable. Although such coverings have been in use for over a century and have found widespread use during some previous pandemics, research data are relatively scant for the protective value of this measure. This article, a literature review, explores the development of CFCs and reviews available scientific research regarding the efficacy of this intervention as a preventive measure in the spread of airborne infectious diseases
Breast cancer treatment and prognosis is informed by biomarker expression. Expression of Oestrogen Receptor-alpha (ERα) for example influences whether the patient receives endocrine- or chemo-therapy. Nutritional status is a modifier of disease free survival and elevated circulating cholesterol associates with increased risk of relapse. Cholesterol hydroxylation produces ‘oxysterols’ which are selective Liver X Receptor alpha (LXRα) modulators and ERα agonists. In ER-positive breast cancer, oxysterols induce proliferation and resistance to endocrine therapy, whilst in ER-negative disease oxysterols are anti-proliferative and pro-metastatic suggesting that there are breast cancer subtype specific differences in the genomic targets of the oxysterol-LXR pathway. This study explored the regulation of LXRα signalling in ER-positive and ER-negative breast cancer, and how ligand, receptor and co-factors combine to regulate LXRα target gene expression in different breast cancer types.
In vitro, MDA.MB.468 (ER-negative) cells were more responsive than MCF-7 (ER-positive) cells to synthetic LXRα agonists (T0901317, GW3965) and six oxysterols (22-hydroxycholesterol [22-OHC], 24-OHC, 25-OHC, 27-OHC, 7-ketocholesterol and 24,25-epoxycholesterol), as measured by MTT, LXR-luciferase reporter, and qPCR of canonical targets ABCA1 and APOE (Students t-tests: p < 0.01). Responses to the antagonist GSK2033 was comparable across cell lines. In vivo, LXRa expression correlated with 48/146 target genes in ER-negative (n = 81), but with just 9/146 in ER-positive tumours (n = 234) (Fischer exact test: p < 0.0001) indicating greater LXRa-mediated transcription of target genes in the aggressive subtype. This was not explained by ligand concentration, as we developed a novel fast oxysterol detection system and found no difference in concentration of 22-OHC, 24-OHC, 25-OHC or 27-OHC between ER-negative (n = 11) and ER-positive (n = 11) primary tumours obtained from the Leeds Breast Tissue Bank. However, we did observe that expression of LXRa and 2/7 of its co-activators (SRC, TRRAP) were higher in ER-negative relative to ER-positive disease (using TCGA data from cBioPortal) (Mann-Whitney U test: p < 0.001), and that expression of all LXRa co-repressors were lowest in ER-negative disease (NCOR1, NCOR2, LCOR: Mann-Whitney U test: p < 0.001 for all). siRNA knock-down of NCOR1 and NCOR2 resulted in MCF-7 cells that mimicked the response of MDA.MB.468 cells to oxysterols (as measured by LXR-luciferase and qPCR assay).
These data indicate that despite the anti-proliferative actions of oxysterol-LXRa signalling, there is a, yet to be identified, selective advantage for retention and enhancement of this pathway in ER-negative breast cancer. Dietary routes to selective LXRa modulation (such as plant sterols) may provide patient-led routes to improving ER-negative survival rates.
Historically, language contact has taken place under conditions of trade, imported slave and contract labor, military service, conquest, colonialism, migration, and urbanization. The linguistic outcomes are determined in large part by the social relations among populations — including economic, political, and demographic factors — and by the duration of contact. In some times and places, interactions between linguistically heterogeneous groups have generated (depending on one’s theoretical orientation) new languages or radically different language varieties. This article examines the formation of contact languages — understood here primarily as pidgins, creoles, and bilingual mixed languages — the history of which involves a Germanic language in a significant way.
An important feature of German-language general music periodicals during the first half of the twentieth century is the frequency with which the editors made use of special issues, most often called Sonderhefte. Such special issues served to focus the readers' attention by devoting most, if not all, of the article section of an issue to a specific composer or topic. An editor might have decided to publish a special issue for the following reasons: (i) to commemorate the anniversary of the birth or death of a major figure; (ii) to provide intensive coverage of an important topic or new field of interest; (iii) to survey musical life in a given area or country; or (iv) to introduce a group of young composers whose works were to be presented as part of a festival of contemporary music. In addition to these types of special issues, some journals offered, once a year, a Carnival issue consisting of humouristic or satirical texts.