Game-based meditation therapy to improve posttraumatic stress and neurobiological stress systems in traumatized adolescents:Protocol for a randomized controlled trial

Background: Many adolescents in residential care have been exposed to prolonged traumatic experiences such as violence, neglect, or abuse. Consequently, they suffer from posttraumatic stress. This not only negatively affects psychological and behavioral outcomes (eg, increased anxiety, depression, and aggression) but also has adverse effects on physiological outcomes, in particular on their neurobiological stress systems. Although current evidence-based treatment options are effective, they have their limitations. An alternative to traditional trauma treatment is meditation-based treatment that focuses on stress regulation and relaxation. Muse is a game-based meditation intervention that makes use of adolescents’ intrinsic motivation. The neurofeedback element reinforces relaxation abilities. Objective: This paper describes the protocol for a randomized controlled trial in which the goal is to examine the effectiveness of Muse (InteraXon Inc) in reducing posttraumatic stress and normalizing neurobiological stress systems in a sample of traumatized adolescents in residential care. Methods: This will be a multicenter, multi-informant, and multimethod randomized controlled trial. Participants will be adolescents (N=80), aged 10 to 18 years, with clinical levels of posttraumatic symptoms, who are randomized to receive either the Muse therapy sessions and treatment as usual (intervention) or treatment as usual alone (control). Data will be collected at 3 measurement instances: pretest (T1), posttest (T2), and at 2-month follow-up. Primary outcomes will be posttraumatic symptoms (self-report and mentor report) and stress (self-report) at posttest. Secondary outcomes will be neurobiological stress parameters under both resting and acute stress conditions, and anxiety, depression, and aggression at posttest. Secondary outcomes also include all measures at 2-month follow-up: posttraumatic symptoms, stress, anxiety, depression aggression, and neurobiological resting parameters. Results: The medical-ethical committee Arnhem-Nijmegen (NL58674.091.16) approved the trial on November 15, 2017. The study was registered on December 2, 2017. Participant enrollment started in January 2018, and the results of the study are expected to be published in spring or summer 2021. Conclusions: Study results will demonstrate whether game-based meditation therapy improves posttraumatic stress and neurobiological stress systems, and whether it is more effective than treatment as usual alone for traumatized adolescents

The Sasa-Satsuma higher order nonlinear Schrodinger equation and its bilinearization and multi-soliton solutions

Higher order and multicomponent generalizations of the nonlinear Schrodinger equation are important in various applications, e.g., in optics. One of these equations, the integrable Sasa-Satsuma equation, has particularly interesting soliton solutions. Unfortunately the construction of multi-soliton solutions to this equation presents difficulties due to its complicated bilinearization. We discuss briefly some previous attempts and then give the correct bilinearization based on the interpretation of the Sasa-Satsuma equation as a reduction of the three-component Kadomtsev-Petvishvili hierarchy. In the process we also get bilinearizations and multi-soliton formulae for a two component generalization of the Sasa-Satsuma equation (the Yajima-Oikawa-Tasgal-Potasek model), and for a (2+1)-dimensional generalization.Comment: 13 pages in RevTex, added reference

On the boundary of the dispersion-managed soliton existence

A breathing soliton-like structure in dispersion-managed (DM) optical fiber system is studied. It is proven that for negative average dispersion the breathing soliton is forbidden provided that a modulus of average dispersion exceed a threshold which depends on the soliton amplitude.Comment: LaTeX, 8 pages, to appear in JETP Lett. 72, #3 (2000

Validity of the Empatica E4 wristband to measure heart rate variability (HRV) parameters:A comparison to electrocardiography (ECG)

Wearable monitoring devices are an innovative way to measure heart rate (HR) and heart rate variability (HRV), however, there is still debate about the validity of these wearables. This study aimed to validate the accuracy and predictive value of the Empatica E4 wristband against the VU University Ambulatory Monitoring System (VU-AMS) in a clinical population of traumatized adolescents in residential care. A sample of 345 recordings of both the Empatica E4 wristband and the VU-AMS was derived from a feasibility study that included fifteen participants. They wore both devices during two experimental testing and twelve intervention sessions. We used correlations, cross-correlations, Mann-Whitney tests, difference factors, Bland-Altman plots, and Limits of Agreement to evaluate differences in outcomes between devices. Significant correlations were found between Empatica E4 and VU-AMS recordings for HR, SDNN, RMSSD, and HF recordings. There was a significant difference between the devices for all parameters but HR, although effect sizes were small for SDNN, LF, and HF. For all parameters but RMSSD, testing outcomes of the two devices led to the same conclusions regarding significance. The Empatica E4 wristband provides a new opportunity to measure HRV in an unobtrusive way. Results of this study indicate the potential of the Empatica E4 as a practical and valid tool for research on HR and HRV under non-movement conditions. While more research needs to be conducted, this study could be considered as a first step to support the use of HRV recordings provided by wearables

Gene silencing in tick cell lines using small interfering or long double-stranded RNA

Gene silencing by RNA interference (RNAi) is an important research tool in many areas of biology. To effectively harness the power of this technique in order to explore tick functional genomics and tick-microorganism interactions, optimised parameters for RNAi-mediated gene silencing in tick cells need to be established. Ten cell lines from four economically important ixodid tick genera (Amblyomma, Hyalomma, Ixodes and Rhipicephalus including the sub-species Boophilus) were used to examine key parameters including small interfering RNA (siRNA), double stranded RNA (dsRNA), transfection reagent and incubation time for silencing virus reporter and endogenous tick genes. Transfection reagents were essential for the uptake of siRNA whereas long dsRNA alone was taken up by most tick cell lines. Significant virus reporter protein knockdown was achieved using either siRNA or dsRNA in all the cell lines tested. Optimum conditions varied according to the cell line. Consistency between replicates and duration of incubation with dsRNA were addressed for two Ixodes scapularis cell lines; IDE8 supported more consistent and effective silencing of the endogenous gene subolesin than ISE6, and highly significant knockdown of the endogenous gene 2I1F6 in IDE8 cells was achieved within 48 h incubation with dsRNA. In summary, this study shows that gene silencing by RNAi in tick cell lines is generally more efficient with dsRNA than with siRNA but results vary between cell lines and optimal parameters need to be determined for each experimental system

A dose-finding Phase 2 study of single agent isatuximab (anti-CD38 mAb) in relapsed/refractory multiple myeloma

A Phase 2 dose-finding study evaluated isatuximab, an anti-CD38 monoclonal antibody, in relapsed/refractory multiple myeloma (RRMM; NCT01084252). Patients with ?3 prior lines or refractory to both immunomodulatory drugs and proteasome inhibitors (dual refractory) were randomized to isatuximab 3 mg/kg every 2 weeks (Q2W), 10 mg/kg Q2W(2 cycles)/Q4W, or 10 mg/kg Q2W. A fourth arm evaluated 20 mg/kg QW(1 cycle)/Q2W. Patients (N = 97) had a median (range) age of 62 years (38-85), 5 (2-14) prior therapy lines, and 85% were double refractory. The overall response rate (ORR) was 4.3, 20.0, 29.2, and 24.0% with isatuximab 3 mg/kg Q2W, 10 mg/kg Q2W/Q4W, 10 mg/kg Q2W, and 20 mg/kg QW/Q2W, respectively. At doses ?10 mg/kg, median progression-free survival and overall survival were 4.6 and 18.7 months, respectively, and the ORR was 40.9% (9/22) in patients with high-risk cytogenetics. CD38 receptor density was similar in responders and non-responders. The most common non-hematologic adverse events (typically grade ?2) were nausea (34.0%), fatigue (32.0%), and upper respiratory tract infections (28.9%). Infusion reactions (typically with first infusion and grade ?2) occurred in 51.5% of patients. In conclusion, isatuximab is active and generally well tolerated in heavily pretreated RRMM, with greatest efficacy at doses ?10 mg/kg

Workplace Learning in Dual Higher Professional Education

Workplace learning is considered an effective strategy for the development of vocation, career and professional identity. Dual training programs, in which learning at a vocational school and learning at work in a company are combined, are seen as strong carriers for skill formation processes. In this study we explore workplace learning in dual training programs in Dutch higher professional education. To gain an understanding of these learning environments and processes, a qualitative multiple case study was conducted in seven sectors. The findings show substantial differences in learning environments between and within sectors. However, cooperation between school and practice is minimal in all of the cases. Although students develop personal and job-related competencies that are useful for daily work routines, they acquire hardly any profound theoretical knowledge at the workplace. School fails to direct workplace learning. Given the considerable share of workplace learning in dual training programs, and the demands to higher professional education graduates in terms of being able to solve complex problems and develop new knowledge during their career as reflective practitioners, it is important that these shortcomings are resolved. More promising alternatives for workplace learning environments and questions for further research to improve workplace learning in higher professional education are discussed

Children’s experiences following a CBT intervention to reduce dental anxiety: one year on

Objective: To investigate children’s ongoing experiences of dental care and use of strategies to manage their dental anxiety following cognitive behavioural therapy (CBT). Design: A child self-completed postal questionnaire. Settings: Hospital, community and general dental practice. Subjects: Questionnaires were sent to 44 children, aged 10-17 years who had been referred to specialist services due to their dental anxiety. Intervention: Children had all previously received a guided CBT self-help intervention to reduce their dental anxiety and, on completion of treatment, had been discharged to their referring dentist. Questionnaires were sent out 12-18 months later to ascertain dental attendance patterns and application of any strategies learnt from the previous CBT intervention. Results: 22 responses (50%) were received from 16 girls and 6 boys. 82% had subsequently accessed follow up care with a general dental practitioner and over half of these had undergone a dental procedure, other than a check-up. 91% reported feeling less worried about dental visits, than previously, and described a change in cognition, behaviours, and feelings that allowed them to manage their anxiety better. Conclusions: CBT has positive immediate and longitudinal effects in reducing children’s dental anxiety. The challenge of adopting this evidence-based approach within primary care settings remains

Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma

The efficacy of daratumumab depends partially on CD38 expression on multiple myeloma (MM) cells. We have previously shown that all-trans retinoic acid (ATRA) upregulates CD38 expression and reverts daratumumab-resistance ex vivo. We therefore evaluated the optimal dose, efficacy, and safety of daratumumab combined with ATRA in patients with daratumumab-refractory MM in a phase 1/2 study (NCT02751255). In part A of the study, 63 patients were treated with daratumumab monotherapy. Fifty patients with daratumumabrefractory MM were subsequently enrolled in part B and treated with daratumumab (reintensified schedule) combined with ATRA until disease progression. The recommended phase 2 dose of ATRA in combination with daratumumab was defined as 45 mg/m2. At this dose, the overall response rate (ORR) was 5%, indicating that the primary endpoint (ORR $15%) was not met. However, most patients (66%) achieved at least stable disease. After a median follow-up of 43 months, the median progression-free survival (PFS) for all patients was 2.8 months. Patients who previously achieved at least a partial response or minimal response/stable disease with prior daratumumab monotherapy had a significantly longer PFS compared with patients who immediately progressed during daratumumab as single agent (median PFS 3.4 and 2.8 vs 1.3 months). The median overall survival was 19.1 months. The addition of ATRA did not increase the incidence of adverse events. Flow cytometric analysis revealed that ATRA temporarily increased CD38 expression on immune cell subsets. In conclusion, the addition of ATRA and reintensification of daratumumab had limited activity in patients with daratumumab-refractory MM, which may be explained by the transient upregulation of CD38 expression. This trial was registered at www.clinicaltrials.gov as #NCT02751255