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We describe a novel method to track fluorescent particles in three dimensions with nanometre precision and millisecond time resolution. In this method, we use our two-photon excitation microscope. The galvomotor-driven x-y scanning mirrors allow the laser beam to move repetitively in a circular path with a radius of half the width of the point spread function of the laser. When the fluorescent particle is located within the scanning radius of the laser, the precise position of the particle in the x-x plane can be determined by its fluorescence intensity distribution along the circular scanning path. A z-nanopositioner on the objective was used to change the laser focus at two planes (half width of the point spread function apart). The difference of the fluorescence intensity in the two planes is used to calculate the z-position of the fluorescent particle. The laser beam is allowed to scan multiple circular orbits before it is moved to the other plane, thus improving the signal to noise ratio. With a fast feedback mechanism, the position of the laser beam is directed to the centre of the fluorescent particle, thus allowing us to track a particle in three dimensions. In this contribution we describe some calibration experiments performed to test the three-dimensional tracking capability of our system over a large range.

Abstract Background Virtual reality (VR) is one of the most cutting-edge digital technologies currently used to extend and adapt mental health interventions. When designing therapeutic VR-applications, bias related to representational and behavioral features can be introduced. Specific bias, that could result from ethnic stereotyping, should be averted. However, structured debates and clear guidelines on how to deal with such bias are lacking. Objective In the current paper we describe our iterative, co-design process to develop an augmented version of a 360-degree VR-video that is used in the Street Temptations intervention. In this intervention, aimed at adolescents with disruptive behavior problems, the VR-video provides adolescents with an emotionally engaging situation and forms the basis of Street Temptations’ perspective-taking exercises. By presenting a detailed example of our VR developmental process, specifically focusing on ethnic representation in this virtual environment and related ethical aspects, we aim to positively contribute to the creation of ethically sound therapeutic VR-applications. Method We adopted an experience-based co-design approach. The process started by assembling professionals’ experiences with the original VR-video. Following, we conducted four co-design groups with adolescents, young adults, and professionals within the forensic youth care system, as experiential experts, to collaboratively develop an enhanced VR-scenario for the Street Temptations intervention. In total, ten adolescents, four young adults and four professionals participated. The co-design groups were alternated with sessions with a screenwriter, to reflect on the results of the co-design groups. In this way, we enabled continuous feedback on and design of the ameliorated scenario and let development and data collection reinforce each other. Results The most important adjustments that were brought forward included explicit incorporation of diversity, establishing a clear storyline for the scenario, keeping the content close to reality, casting actors in a way to avoid obvious stigmatization, and using only names for the characters that are commonly used across different cultural and ethnic backgrounds. Discussion By presenting our developmental process, we give a detailed example of how to reflectively develop ethically sound therapeutic VR-content within a forensic youth care setting. We demonstrated that including stakeholders can help in preventing socially irresponsible and conceivably hurtful stereotypes. By describing the process in detail, we hope to contribute to the responsible use of technology within mental health care.

Abstract Background The societal costs associated with juvenile delinquency and reoffending are high, emphasising the need for effective prevention strategies. A promising approach is Youth-Initiated Mentoring (YIM). In YIM, professionals support youths in selecting a non-parental adult from within their social network as their mentor. However, until now, little (quasi-)experimental research has been conducted on YIM in the field of juvenile delinquency. We will examine the effectiveness, working mechanisms, and implementation of YIM as a selective prevention strategy for juvenile delinquents. Methods This multiple-methods study consists of a quasi-experimental trial and a qualitative study. In the quasi-experimental trial, we aim to include 300 juvenile offenders referred to Halt, a Dutch juvenile justice system organisation which offers youths a diversion program. In the Netherlands, all juvenile offenders between 12 and 18 years old are referred to Halt, where they must complete the Halt intervention. Youths will be non-randomly assigned to region-matched non-YIM-trained and YIM-trained Halt professionals implementing Care as Usual (CAU, i.e., the Halt intervention) or CAU plus YIM, respectively. Despite non-random allocation, this approach may yield comparable conditions regarding (1) the characteristics of professionals delivering the intervention and (2) case type and severity. Youth and caregiver(s) self-report data will be collected at pre-and post-test and a 6-month follow-up and complemented with official Halt records data. Multilevel analyses will test whether youths following CAU plus YIM show a stronger increase in resilience factors and a stronger decline in the need for formal support and delinquency than youths following CAU. In the qualitative study, we will organise focus group interviews with YIM-trained professionals to explore boosters and barriers experienced by professionals during the implementation of YIM. Discussion The proposed study will help identify the effectiveness of YIM in strengthening resilience factors and possibly decreasing juvenile delinquency. In addition, it may offer insights into how and for whom YIM works. Finally, this study can help strengthen the implementation of YIM in the future. Trial Registration ClinicalTrials.Gov (# NCT05555472). Registered 7 September 2022. https://www.clinicaltrials.gov/ct2/show/NCT05555472?cond=Youth+Initiated+Mentoring&draw=2&rank=1 .

Abstract Background Children from multi-problem families have an increased risk for experiencing mental health problems. These families face problems in several domains that are often found to be chronic and intergenerational. Yet, the effects of mental health care for youths from multi-problem families are small at best, urging research on new treatment programs. The InConnection approach is an integrated care program to improve resilience of youths with mental health needs from multi-problem families by connecting professional expertise from multiple disciplines with the informal social network of the youth. Youths are asked to nominate a youth-initiated mentor (YIM) from the supportive adults in their network. Methods This quasi-experimental study compared the effectiveness of the InConnection approach to treatment as usual in a sample of 107 families (n = 66 intervention group, n = 41 control group) with n = 115 youths receiving treatment (cases). Youths (n = 102 reports, M age = 15.59 years), parents (n = 85 reports) and case managers (n = 107 reports) responded to questionnaires four times over 15 months. Using these data, we measured youth resilience as the primary outcome, seven secondary outcomes, and three intermediate outcomes. Results Latent growth models showed only one significant change in outcomes over time across conditions, namely a decrease in case manager-reported child unsafety, and only two condition effects, which were both parent-reported. Parents in the InConnection group reported improvements over time in youth’s emotional and behavioral problems and their own positive parenting, whereas control parents reported no changes (ps ≤ 0.013). Discussion The treatment conditions were not effective in improving most of the youth and parental outcomes over time, except for child safety reported by the case manager. The InConnection approach only outperformed care as usual on two parent-reported outcomes. Future research should examine for whom and under what circumstances the InConnection approach works more convincingly. Trial registration Netherlands Trial Register NL7565. Retrospectively registered on 05/03/2019.

Durante los últimos años, las TIC se han convertido en una herramienta esencial con potencialidades en la educación y con efectos diversos que son parte del debate en medio de las nuevas tendencias de enseñanza y aprendizaje. A tal efecto, se plantea como objetivo determinar la influencia del uso de las TIC en el aprendizaje de estudiantes de nivel secundaria. El estudio se desarrolló bajo una revisión sistemática en fuentes de Scopus, Scielo, ScienceDirect y Dialnet; apoyándose en la metodología PRISMA. Fueron seleccionados 18 artículos para el análisis. En los criterios de inclusión se consideraron artículos con antigüedad menor a cinco años. En los resultados se encontró que la gran mayoría de los estudios fueron realizados entre el año 2019 y otros en 2022. De ese modo, se concluye que en el 72 % de los artículos se mostró una influencia positiva de las TIC en el aprendizaje; asimismo, destacaron las redes sociales y los formatos digitales como los recursos entre las TIC con mayor uso, develando que poseen un gran potencial en una etapa de tecnificación que solo ha iniciado para los docentes, pero cuyas experiencias previsiblemente se irán sumando en el tiempo, lo cual permite alcanzar mejores resultados.

BackgroundWe developed Street Temptations (ST) as an add-on intervention to increase the treatment responsivity of adolescents with disruptive behavior problems. ST’s primary aim is to improve adolescents’ mentalizing abilities in order to help them engage in and benefit from psychotherapy. Additionally, virtual reality (VR) is used to work in a more visual, less verbal, fashion. ObjectiveBy recapping the lessons learned while developing ST so far, we aim to design the following study on ST. Furthermore, we aim to enhance the development and study of new health care interventions in clinical practice, together with adolescents as their end users. MethodsWe followed an iterative co-creation process to develop a prototype of ST, in collaboration with adolescents and professionals from a secured residential facility in Amsterdam, the Netherlands. The prototype was tested during a pilot phase, involving 2 test runs, in which 4 adolescents and 4 professionals participated. Qualitative data were collected through interviews with the adolescents and by conducting a group interview with the professionals, in order to gain first insights into ST’s usability, feasibility, and its added value to clinical practice. In between the first and second test runs, the prototype was enhanced. On the basis of the complete pilot phase, we reflected on the future development and implementation of ST to design a subsequent study. ResultsOver the course of 6 months, ST’s first prototype was developed during multiple creative sessions. Included was the development of a short 360° VR video, to serve as a base for the mentalization exercises. The final version of ST consisted of 7 individual therapy sessions, incorporating both the VR video and a VR StreetView app. On the basis of the qualitative data collected during the pilot phase, we found preliminary signs of ST’s potential to support adolescents’ perspective-taking abilities specifically. Additionally, using VR to focus on real-life situations that adolescents encounter in their daily lives possibly helps to facilitate communication. However, several challenges and requests concerning the VR hardware and software and the implementation of ST emerged, pointing toward further development of ST as an add-on intervention. These challenges currently limit large-scale implementation, resulting in specific requirements regarding a subsequent study. ConclusionsIn order to gather more extensive information to shape further development and study treatment effects, a small-scale and individually oriented research design seems currently more suitable than a more standard between-subjects design. Using the reflection on the lessons learned described in this report, a research protocol for a forthcoming study on ST has been developed. By presenting our co-creation journey thus far, we hope to be of inspiration for a more co-creative mindset and in that way contribute to the mutual reinforcement of science and clinical practice.

Abstract Background The Covid-19 pandemic may have had negative effects on youth and parental mental health, especially in high-risk populations such as multi-problem families (i.e., families that experience problems in multiple domains, such as mental health and social network problems). Using one to four assessments during all phases of the Covid-19 pandemic up until January 2022, we examined the associations between pandemic-related stress and mental health (resilience and well-being) of youth and parents from multi-problem families. We also investigated whether experienced informal (i.e., youth informal mentoring) and formal support (i.e., therapist support) served as protective factors in this association. Methods A total of 92 youth aged 10–19 years (46.7% girls; mean age 16.00 years) and 78 parents (79.5% female; mean age 47.17 years) filled in one to four questionnaires between March 2020 and January 2022. Multi-level analyses were conducted to account for the nested structure of the data. Results For youth, pandemic-related stress was associated with lower well-being, but not with resilience. Perceived support from both mentors and therapists was positively associated with youth mental health. Furthermore, high perceived therapist support protected youth from the negative effect of pandemic-related stress on resilience. For parents, pandemic-related stress was not related to mental health, irrespective of therapist support. Yet, therapist support was directly and positively associated with parental mental health. Conclusions Youth from multi-problem families who experience pandemic-related stress are at risk of (elevated) mental health problems during the pandemic, specifically if they have no or weak therapist support. The mental health of parents, however, was minimally affected by pandemic-related stress, indicating strength and flexibility. Youth and parents who experienced support during the pandemic reported higher levels of resilience and well-being, demonstrating the importance of support for individuals’ mental health during stressful times such as a pandemic.

The US President’s Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries.

Summary: Spatial transcriptomics is a novel technique that provides RNA-expression data with tissue-contextual annotations. Quality assessments of such techniques using end-user generated data are often lacking. Here, we evaluated data from the NanoString GeoMx Digital Spatial Profiling (DSP) platform and standard processing pipelines. We queried 72 ROIs from 12 glioma samples, performed replicate experiments of eight samples for validation, and evaluated five external datasets. The data consistently showed vastly different signal intensities between samples and experimental conditions that resulted in biased analysis. We evaluated the performance of alternative normalization strategies and show that quantile normalization can adequately address the technical issues related to the differences in data distributions. Compared to bulk RNA sequencing, NanoString DSP data show a limited dynamic range which underestimates differences between conditions. Weighted gene co-expression network analysis allowed extraction of gene signatures associated with tissue phenotypes from ROI annotations. Nanostring GeoMx DSP data therefore require alternative normalization methods and analysis pipelines.

BackgroundSerious disruptive behavior among adolescents is a prevalent and often persistent problem. This highlights the importance of adequate and effective treatment to help adolescents with disruptive behavior problems react less hostile and aggressive. In order to create a treatment environment in which behavioral change can be enhanced, treatment motivation plays an essential role. Regarding treatment itself, a focus on challenging self-serving cognitive distortions in order to achieve behavioral change is important. Street Temptations (ST) is a new training program that was developed to address both treatment motivation and cognitive distortions in adolescents with disruptive behavior problems. One of the innovative aspects of ST is the use of virtual reality (VR) techniques to provide adolescents during treatment with visually presented daily social scenarios to activate emotional engagement and dysfunctional cognitions. By using the VR scenarios as an integral starting point of ST’s sessions and transferring the power of the VR experience into playful and dynamic exercises to practice social perspective–taking, adolescents are encouraged to reflect on both their own behavior and that of others. This focus on reflection is grounded in ST’s main treatment mechanism to influence treatment motivation and cognitive distortions, namely, mentalizing (ie, reflective functioning). ObjectiveThe aim of this study is to describe the research protocol to evaluate the effects of ST on treatment motivation and cognitive distortions. We take a closer look at the use of ST and the methodology used, namely, the repeated single-case experimental design (SCED). MethodsThe effects of ST are studied through a multiple baseline SCED, using both quantitative and qualitative data. In total, 18 adolescents from secure residential youth care facilities and secondary special education schools are randomly assigned to 1 of the 3 different baseline conditions. Throughout the baseline phase (1, 2, or 3 weeks), intervention phase (4 weeks), and follow-up phase (1, 2, or 3 weeks), daily measurements on treatment motivation and cognitive distortions are conducted. Secondary study parameters are assessed before baseline, after intervention, and after follow-up. Qualitative data are collected after intervention, as well as at 3 months and 6 months after the intervention. ResultsData collection for this study started in November 2021 and is planned to be completed by August 2023. The results will be published in peer-reviewed journals and presented at national and international conferences. ConclusionsST aims to improve the disruptive behavior problems of adolescents. This study will be the first to gain insights into the effectiveness of ST. The strengths of this study include its thorough and individually focused design (SCED), the focus on a residential as well as a secondary special education setting, and the ecological validity. The implications for practice are discussed. Trial RegistrationCentral Committee on Research Involving Human Subjects NL75545.029.20. Netherlands Trial Register NL9639; https://www.trialregister.nl/trial/9639 International Registered Report Identifier (IRRID)PRR1-10.2196/33555