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Kaisa Bjuresäter,1 Mattias Bergström Andrén,2,3 Elina Mäki-Torkko,4,5 Agneta Anderzén-Carlsson,6 Per-Inge Carlsson2,5 1Institution of Health Sciences, Faculty of Health, Science and Technology, Karlstad University, Karlstad, Sweden; 2Department of Audiology, Central Hospital, Region Värmland, Karlstad, Sweden; 3School of Health Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 4Audiological Research Center, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 5School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 6University Health Care Research Center, Faculty of Medicine and Health, Örebro University, Örebro, SwedenCorrespondence: Kaisa Bjuresäter, Email kaisa.bjuresater@kau.seBackground: Hearing loss increases with age and due to increased life expectancy there is an increase in the number of individuals living with hearing loss. Older people with hearing loss residing in nursing homes are often dependent on healthcare professionals to help them with their hearing aids.Objective: The aim of the study was to translate and test the psychometric properties of a Swedish version of a Norwegian questionnaire and to assess healthcare professionals’ self-reported knowledge, experience, skills, competence, and information needs pertaining to residents’ hearing loss and hearing aids in the Swedish context.Materials and Methods: A Norwegian questionnaire was translated and adapted, and thereafter distributed to healthcare professionals in nine nursing homes in mid Sweden between 2020 and 2021, and 313 questionnaires were returned.Results: An exploratory factor analysis demonstrated adequate factorial structure in six factors, satisfying construct validity and internal consistency for the Swedish version. A confirmatory factor analysis showed a satisfactory model fit. Healthcare professionals reported having the skills required for handling hearing aids, but reported lower scores for having received information about hearing aids, taking initiatives to refer residents to hearing healthcare units, and checking for earwax. Registered nurses generally reported lower perceived knowledge and practical skills concerning hearing aids. Seventy-seven percent of the total group reported a need for information regarding hearing aid maintenance.Conclusion: Healthcare professionals reported that the majority of nursing home residents need help with their hearing aids, but only a minority of these professionals had received education on hearing loss and training in hearing aid maintenance. Enrolled nurses and care assistants demonstrated higher levels of competence in handling hearing aids compared to registered nurses. In order to ensure safe and effective care, as well as facilitate communication among older adults with hearing loss, healthcare professionals need appropriate education and training.Keywords: hearing loss, nursing homes, health care professionals, competence, instrument translation, psychometric testing

Well maintained cycleways will encourage more people to cycle, as the condition of cycleways is important for the safety, accessibility and riding comfort of cyclists. Despite that, only a few models used to describe the quality of service for cyclists take the surface condition into account. Objective measuring methods are needed to enable reliable and effective assessment of surface conditions, and measurable performance criteria related to the needs of cyclists should be developed. The purpose of this study has been to test the reliability and validity of using accelerometers in smartphones to assess the riding comfort on cycleways. A smartphone application converting three-dimensional accelerometer measurements into a single indicator for cycleways has been used to assess road surfaces in two field studies, in Sweden and Norway, respectively. Both studies assessed test sections of varying quality. To relate the measurements to subjective riding comfort assessments by cyclists, recruited cyclists collected quantitative data using the app, whilst also rating their perceived riding comfort by completing a survey. Measurements were also related to standard road surface condition indicators, generated from a road surface tester equipped with 19 laser sensors: international roughness index (IRI), mega- and macrotexture. The results show that it is possible to describe the unevenness of a cycleway using the technology present in smartphones. A software application can be used to collect and analyse data from the acceleration sensors in the phone, which can then be used to describe the riding comfort of cyclists. It is mainly the unevenness in the 50–1000 mm size-range that create the greatest discomfort for cyclists, and intermittent vibrations are perceived as more uncomfortable than more evenly distributed vibrations. Therefore, IRI is not a relevant measurement for describing the riding comfort of cyclists.

Abstract The Violaceae family is rich in metal-tolerant species and species producing cyclic peptides (cyclotides) that are linked to the resistance to biotic factors. Plants that inhabit areas polluted with heavy metals have developed various mechanisms of tolerance. To test the role of cyclotides in protection against abiotic factors, including heavy metals, cell suspension cultures of Viola species/genotypes (V. lutea ssp. westfalica, V. tricolor, V. arvensis, and V. uliginosa), representing different levels of tolerance to heavy metals (from the most tolerant-MET to the least tolerant populations/species-NMET), were used. The relative abundances of the cyclotides in the control, untreated cell suspensions of all the selected species/genotypes, and cells treated with Zn or Pb (200 µM or 2000 µM) for 24 h or 72 h were determined via MALDI-MS. Transmission electron microscopy with X-ray microanalysis was used to detect putative co-localization of the cyclotides with Zn or Pb in the cells of V. tricolor treated with the highest concentration of heavy metals for 72 h. Cyclotide biosynthesis was dependent on the type of heavy metal and its concentration, time of treatment, plant species, and population type (MET vs. NMET). It was positively correlated with the level of tolerance of particular Viola species. The increased production of cyclotides was observed in the cells of metallophyte species, mostly in Zn-treated cells. The nonmetallophyte—V. uliginosa presented a decrease in the production of cyclotides independent of the dose and duration of the metal treatment. Cyclotides co-localized with Pb more evidently than with Zn, suggesting that cyclotides have heavy metal affinity. V. lutea ssp. westfalica transcriptome mining yielded 100 cyclotide sequences, 16 known and 84 novel named viwe 1–84. These findings support the hypothesis that cyclotides are involved in certain mechanisms of plant tolerance to heavy metals.

Abstract We report a case of lichen planus pemphigoides (LPP) in a 36‐year‐old woman who presented bullous skin eruptions following both COVID‐19 infection and vaccination. The patient had a history of biopsy‐confirmed lichen planus since 2013 and had been previously investigated for suspected dermatitis herpetiformis since 2014, with inconclusive biopsy results. On two separate occasions, following her COVID‐19 vaccination and infection, she suffered the eruption of similar bullous lesions. A final diagnosis of LPP was established, believed to have been triggered by both the vaccination and the COVID‐19 infection. Treatment with prednisolone offered temporary relief, but sustained remission was achieved with methotrexate. This is, to our knowledge, the first documented case of LPP post‐COVID‐19 vaccination or infection.

Bicycling accidents are a major traffic safety problem and are deemed ‘an unacceptable human and social price for EU citizens’. One of the major causes for bicycling accidents is loss of balance. A related influencing factor is alcohol intoxication. It is a primary, long term, safety objective to develop safety systems for the cyclist. The present work aimed to understand how to measure cyclists’ instability via steering and leaning inputs, while considering that steering and leaning might vary depending on the cycling task being performed. Of 28 participants, 19 were given doses of alcohol up to 1.0‰ and 9 remained sober (control group). Breath alcohol concentration was measured. The participants repeated the cycling test track session five times (with each block lasting 35 minutes). The track session contained three different tasks: cycling slalom, straight, and slowly. Speed, yaw rate, and roll rate were assessed continuously. Yaw rate and roll rate were relatively sensitive for the different cycling tasks. The threshold level of the angular velocity measurements was related to the cycling task performed. Alcohol intoxication at 0.7‰ had a significant impact on performance. The rather simple measurements used can detect instability. Instability should be measured differently depending on the cycling task performed. The study represents a small step towards a safety system for cyclists.

Marginal sea ecosystems, such as the Baltic Sea, are severely affected by anthropogenic pressures, such as climate warming, pollution, and eutrophication, which increased in the course of the past century. Biodiversity monitoring data and assessment of environmental status in such systems have typically been carried out only for the past few decades, if at all, and knowledge on pre-impact stability and good ecological status is limited. An extension of monitoring time series can potentially be achieved through analyses of paleoecological records, e.g. for phytoplankton, which form the base of the food web and are highly susceptible to environmental changes. Within the phytoplankton community, dinoflagellates and diatoms play a significant role as primary producers, and their relative dominance in the spring bloom, calculated as Dia/Dino index, is used as an indicator for the environmental status of the Baltic Sea. To extend time series on the dominance patterns and include non-fossilized dinoflagellates, we here establish a simple droplet digital PCR (ddPCR) reaction on ancient DNA from sediment cores that decodes phytoplankton dynamics. We focus on two common spring bloom species, the diatom Skeletonema marinoi and the dinoflagellate Apocalathium malmogiense, for which we evaluate a DNA based dominance index. It performs very well in comparison to DNA metabarcoding and modern monitoring and can elucidate past species dominance across the past century and across millennia in different basins of the Baltic. For the past century, we see a dominance shift already starting before the mid-20th century in two of the Baltic Sea basins, thus substantially predating current monitoring programs. Shifts are only partly coeval among the cores and the index shows different degrees of stability. This pattern is confirmed across millennia, where a long-term stable relationship between the diatom and the dinoflagellate is observed in the Eastern Gotland Basin, while data from the Gulf of Finland bear testimony to a much more unstable relationship. This confirms that good ecological status based on the dominance pattern of diatoms and dinoflagellates must be established locally and exemplifies how sediment core DNA can be employed to extend monitoring data.

In this, the tenth annual update for the F1000Research Tics collection, we summarize research reports from 2023 on Gilles de la Tourette syndrome and other tic disorders. The authors welcome article suggestions and thoughtful feedback from readers.

Summary: Background: γ-aminobutyric acid (GABA), known as the main inhibitory neurotransmitter in the brain, exerts immunomodulatory functions by interaction with immune cells, including T cells. Metabolic programs of T cells are closely linked to their effector functions including proliferation, differentiation, and cytokine production. The physiological molecules glucose and insulin may provide environmental cues and guidance, but whether they coordinate to regulate GABA-mediated T cell immunomodulation is still being examined. Methods: CD4+ T cells that were isolated from blood samples from healthy individuals and from patients with type 1 diabetes (T1D) were activated in vitro. We carried out metabolic assays, multiple proximity extension assay (PEA), ELISA, qPCR, immunoblotting, immunofluorescence staining, flow cytometry analysis, MS-based proteomics, as well as electrophysiology and live-cell Ca2+ imaging. Findings: We demonstrate that GABA-mediated reduction of metabolic activity and the release of inflammatory proteins, including IFNγ and IL-10, were abolished in human CD4+ T cells from healthy individuals and patients with T1D when the glucose concentration was elevated above levels typically observed in healthy people. Insulin increased GABAA receptor-subunit ρ2 expression, enhanced the GABAA receptors-mediated currents and Ca2+ influx. GABA decreased, whereas insulin sustained, hexokinase activity and glycolysis in a glucose concentration-dependent manner. Interpretation: These findings support that metabolic factors, such as glucose and insulin, influence the GABA-mediated immunomodulation of human primary T cells effector functions. Funding: The Swedish Children’s Diabetes Foundation, The Swedish Diabetes Foundation, The Swedish Research Council 2018-02952, EXODIAB, The Ernfors Foundation, The Thurings Foundation and the Science for Life Laboratory.

Abstract Background Compliance with a study protocol is central to meeting its research goals. In longitudinal research studies, data loss due to missed visits limit statistical power and introduce bias. The Environmental Determinants of Diabetes in the Young (TEDDY) study is a longitudinal multinational (US, Finland, Germany, and Sweden) investigation of children at risk for type 1 diabetes (T1D) that seeks to identify the environmental triggers of islet autoimmunity and T1D. The purpose of the current study was to identify sociodemographic variables and maternal characteristics assessed in the first year of TEDDY that were associated with study visit compliance in the subsequent 3 years. Methods Sociodemographic variables, maternal life-style behaviors, post-partum depression, maternal reactions to the child’s T1D risk, and study-related variables were collected at child-age 6 months and 15 months. Multiple linear regression was used to examine the association of these variables to study visit compliance in the subsequent 3 years. Results Study visit compliance was highest in Sweden (p > 0.001), in children who were their mother’s first child (p > 0.001), and whose mothers were older (p > 0.001) and more satisfied with the TEDDY study (p > 0.001). Father participation was also associated with better study visit compliance (p > 0.001). In contrast, children whose mothers smoked (p > 0.001), suffered from post-partum depression (p = 0.034), and were more anxious about their child’s T1D risk (p = 0.002), completed fewer visits. Father’s study satisfaction was also associated with study visit compliance (p = 0.029); however, it was not significant in models that included maternal study satisfaction. Conclusions Sociodemographic variables, maternal characteristics—including study satisfaction—and fathers’ participation in the first year of a longitudinal study were associated with subsequent study visit compliance in a sample of children genetically at-risk for T1D followed for 4 years. This information can inform future strategies designed to improve study visit compliance in longitudinal pediatric studies. Trial registration: NCT00279318, 06/09/2004.

AimMacroecological studies that require habitat suitability data for many species often derive this information from expert opinion. However, expert-based information is inherently subjective and thus prone to errors. The increasing availability of GPS tracking data offers opportunities to evaluate and supplement expert-based information with detailed empirical evidence. Here, we compared expert-based habitat suitability information from the International Union for Conservation of Nature (IUCN) with habitat suitability information derived from GPS-tracking data of 1,498 individuals from 49 mammal species.LocationWorldwide.Time period1998-2021.Major taxa studiedForty-nine terrestrial mammal species.MethodsUsing GPS data, we estimated two measures of habitat suitability for each individual animal: proportional habitat use (proportion of GPS locations within a habitat type), and selection ratio (habitat use relative to its availability). For each individual we then evaluated whether the GPS-based habitat suitability measures were in agreement with the IUCN data. To that end, we calculated the probability that the ranking of empirical habitat suitability measures was in agreement with IUCN's classification into suitable, marginal and unsuitable habitat types.ResultsIUCN habitat suitability data were in accordance with the GPS data (> 95% probability of agreement) for 33 out of 49 species based on proportional habitat use estimates and for 25 out of 49 species based on selection ratios. In addition, 37 and 34 species had a > 50% probability of agreement based on proportional habitat use and selection ratios, respectively.Main conclusionsWe show how GPS-tracking data can be used to evaluate IUCN habitat suitability data. Our findings indicate that for the majority of species included in this study, it is appropriate to use IUCN habitat suitability data in macroecological studies. Furthermore, we show that GPS-tracking data can be used to identify and prioritize species and habitat types for re-evaluation of IUCN habitat suitability data.

Abstract Background Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 positively affect the fecal bacteriome in children with celiac disease autoimmunity after 6 months of supplementation. The aim of the present investigation was to study the effects of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 on the single-cell parasitome, with a primary focus on Blastocystis. Methods Stool samples were collected from 78 Swedish children with celiac disease autoimmunity participating in a randomized, double-blind, placebo-controlled clinical trial to either receive a mixture of supplementation with L. plantarum HEAL9 and L. paracasei 8700:2 (n = 38) or placebo (n = 40). A total of 227 stool samples collected at baseline and after 3 and 6 months of intervention, respectively, were retrospectively analyzed for Blastocystis by quantitative real-time PCR and subtyped by massively parallel amplicon sequencing. Other single-cell parasites were detected by untargeted 18S rDNA amplicon sequencing and verified by real-time PCR. The relation between the parasites and the bacteriome community was characterized by using 16S rDNA profiling of the V3-V4 region. Results Three different single-cell protists were identified, of which the highest prevalence was found for Dientamoeba fragilis (23.1%, 18/78 children), followed by Blastocystis (15.4%, 12/78) and Entamoeba spp. (2.6%, 2/78). The quantity of the protists was stable over time and not affected by probiotic intervention (P = 0.14 for Blastocystis, P = 0.10 for D. fragilis). The positivity of the protists was associated with increased bacteriome diversity (measured by multiple indices, P

Abstract Purpose This study aimed to increase the understanding of emotions and coping strategies used by head and neck cancer patients before cancer treatment, and to explore their emotions and coping strategies in relation to symptoms and side effects after treatment. Furthermore, we aimed to investigate the patients’ perceptions of received treatment and support. Methods Semi-structured in-depth interviews were conducted with 10 patients who had been treated for head and neck cancer, which included radiotherapy, at the Department of Oncology and the Department of Oral and Maxillofacial Surgery at Sahlgrenska University Hospital in Gothenburg. The interviews were analyzed in accordance with the method for Qualitative Content Analysis. Results The result picture revealed three head themes. The first theme “Management of simultaneously influencing mind-sets before cancer treatment” described the patients experiences of feeling “Scared and worried,” “Lonely and disappointed,” and “Relieved and confident”, and how they tried to handle the diagnosis and preparations for treatment by “Applying a positive mind-set”, “Searching for support,” and “Trusting the healthcare system”. The second theme “Experiences of becoming a pale shadow of oneself”, illustrated experiences of affecting post-treatment symptoms and side effects. To which, the last theme “Handling contextual influencing experiences after cancer treatment” displayed post-treatment emotions of being “Shocked and disappointed” and “Concerned and unsupported” but also “Grateful and forward-thinking”, where strategies such as “Appreciating Life”, “Networking socially,” and “Adapting to the new life” were used. Conclusions The results indicated the need for a more patient-centered care approach, with clearer structures and improved individual support both before and after treatment and in connection to rehabilitation. Patients’ cognitive changes after cancer treatment should be considered in the aftercare, which should also include adaptation to situation and strengthening of patients’ self-management as a goal.

Background: The effects of collagen-induced arthritis (CIA), a model of systemic inflammation, on brain regional molecular markers associated with neurological disorders are uncertain. Objective: This study investigated the brain regional molecular changes in markers associated with inflammation and neuronal dysfunction in a CIA model. Methods: Fourteen male Sprague Dawley rats were divided into control (n = 5) or CIA (n = 9) groups. 10 weeks after CIA induction, brain tissue was collected. Brain regional mRNA expression of inflammatory markers (IL-1β and IL-6), apoptotic markers (BAX and Bcl2) and neurotrophic factors (BDNF, CREB and TrkB) was determined. Monoamine distribution and abundance in different brain regions were determine by mass spectrometry imaging (MSI). Results: Neuroinflammation was confirmed in the CIA group by increased IL-β mRNA expression, concurrent with an increased BAX/Bcl2 ratio. The mRNA expression of CREB was increased in the midbrain and hippocampus while BDNF was increased and TrkB was decreased across all brain regions in CIA compared to control animals. Serotonin was decreased in the midbrain and hippocampus while dopamine was decreased in the striatum of CIA rats, compared to controls. Conclusion: CIA resulted in neuroinflammation concurrent with an apoptotic state and aberrant expression of neurotrophic factors and monoamines in the brain, suggestive of neurodegeneration.

Abstract Metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to the neurotoxin MPP+ in the brain causes permanent Parkinson’s disease-like symptoms by destroying dopaminergic neurons in the pars compacta of the substantia nigra in humans and non-human primates. However, the complete molecular pathology underlying MPTP-induced parkinsonism remains poorly understood. We used dual polarity matrix-assisted laser desorption/ionization mass spectrometry imaging to thoroughly image numerous glycerophospholipids and sphingolipids in coronal brain tissue sections of MPTP-lesioned and control non-human primate brains (Macaca mulatta). The results revealed specific distributions of several sulfatide lipid molecules based on chain-length, number of double bonds, and importantly, hydroxylation stage. More specifically, certain long-chain hydroxylated sulfatides with polyunsaturated chains in the molecular structure were depleted within motor-related brain regions in the MPTP-lesioned animals, e.g., external and internal segments of globus pallidus and substantia nigra pars reticulata. In contrast, certain long-chain non-hydroxylated sulfatides were found to be elevated within the same brain regions. These findings demonstrate region-specific dysregulation of sulfatide metabolism within the MPTP-lesioned macaque brain. The depletion of long-chain hydroxylated sulfatides in the MPTP-induced pathology indicates oxidative stress and oligodendrocyte/myelin damage within the pathologically relevant brain regions. Hence, the presented findings improve our current understanding of the molecular pathology of MPTP-induced parkinsonism within primate brains, and provide a basis for further research regarding the role of dysregulated sulfatide metabolism in PD.

Introduction: The subcortical small vessel type of dementia (SSVD) is a common form of vascular dementia. There is a lack of disease-specific cerebrospinal fluid (CSF) biomarkers. We investigated whether CSF concentrations of neurofilament light chain (NFL), soluble amyloid precursor protein-α (sAPP-α), sAPP-β, and CSF/serum albumin ratio could separate SSVD from healthy controls, Alzheimer's disease (AD) and mixed dementia (combined AD and SSVD). Methods: Patients with SSVD (n = 38), AD (n = 121), mixed dementia (n = 62), and healthy controls (n = 96) were included. The CSF biomarkers were measured using immunoassays, and their independent contribution to the separation between groups were evaluated using the Wald test. Then, the area under the receiver operating characteristics curve (AUROC) and 95% confidence intervals (CIs) were calculated. Results: Elevated NFL concentrations and decreased sAPP-β concentrations independently separated SSVD from controls, and sAPP-β also distinguished SSVD from AD and mixed dementia. Furthermore, the combination of NFL and sAPP-β discriminated SSVD from controls with high accuracy (AUROC 0.903, 95% CI: 0.834 – 0.972). Additionally, sAPP-β combined with the core AD biomarkers (β-amyloid1-42, total tau, and phosphorylated tau181) had a high ability to separate SSVD from AD (AUROC 0.886, 95% CI: 0.830 – 0.942) and mixed dementia (AUROC 0.903, 95% CI: 0.838 – 0.968). Discussion: The high accuracy of NFL and sAPP-β to separate SSVD from controls supports that SSVD is a specific diagnostic entity. Moreover, sAPP-β in combination with the core AD biomarkers distinguished SSVD from AD and mixed dementia.

Introduction: There are conflicting results whether serum lipid pattern is related to the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging. Little is known of the associations between serum lipid pattern and the risk of the subcortical small vessel type of dementia (SSVD), in which WMHs are a prominent manifestation. The aim of this study was to determine wether lipid levels were associated with the risk of SSVD, Alzheimer's disease (AD), or mixed dementia (combined AD and SSVD) at a single memory clinic. Methods: This was a prospective study of 329 patients with subjective or objective mild cognitive impairment. The statistical analyses included Cox proportional hazards regression analysis. Results: During the follow-up (mean 4.1 years), 80 patients converted to dementia [SSVD, n=15 (5%); AD, n=39 (12%); mixed dementia, n=26 (8%)]. There were no associations between serum lipid levels and the risk of AD or mixed dementia after adjustment for covariates. Serum high- density lipoprotein cholesterol (HDL) was inversely associated with the risk of SSVD, whereas triglycerides (TG), low-density lipoprotein cholesterol (LDL)/HDL ratio, and TG/HDL ratio were positively associated with the risk of SSVD. In further analyses, the lowest HDL tertile was associated with a seven-fold increase in the risk of SSVD, and the highest tertile of TG/HDL ratio was associated with a three-fold increase in SSVD risk after full adjustment for covariates. Discussion: Low serum HDL and high serum TG/HDL ratio were associated with increased risk of SSVD. Furthermore, the lack of associations with the risk of AD or mixed dementia support that

Background: There are conflicting results whether serum lipid pattern is related to the amount of white matter hyperintensities (WMHs) on magnetic resonance imaging. Little is known of the associations between lipid concentrations and the subsequent risk of the subcortical small vessel type of dementia (SSVD), in which WMHs are a prominent manifestation. Here, we determined whether lipid levels are associated with the risk of SSVD, Alzheimer's disease (AD), or mixed dementia (combined AD and SSVD). Methods: This was a longitudinal, prospective study of 329 patients with subjective or objective mild cognitive impairment at baseline. The statistical analyses included Cox proportional hazards regression with adjustments for age, gender, education, body mass index, current smoking, hypertension, diabetes mellitus, and APOE ε4 genotype. Results: During the follow-up (mean 4.1 years), 80 patients converted to dementia [SSVD, n = 15 (5 %); AD, n = 39 (12 %); and mixed dementia, n = 26 (8 %)]. Serum high-density lipoprotein cholesterol (HDL, per SD increase) was inversely associated with the risk of SSVD, whereas triglycerides (TG), low-density lipoprotein cholesterol (LDL)/HDL ratio, and TG/HDL ratio were positively associated with SSVD risk. Furthermore, the lowest HDL tertile was associated with a sevenfold, and the highest tertile of TG/HDL ratio with a threefold, increase in SSVD risk. There were no associations with the risk of AD or mixed dementia after adjustment for covariates. Conclusion: In a memory clinic population, low HDL and high TG/HDL ratio were independent risk factors of SSVD, but not of AD or mixed dementia.

Body dysmorphic disorder (BDD) is a prevalent and impairing psychiatric condition that typically debuts in adolescence and is associated with risky behaviours. The disorder can be effectively treated with cognitive behaviour therapy (CBT). However, CBT for BDD is seldom available primarily due to a shortage of trained therapists. Internet-delivered CBT (ICBT) can be a way to increase treatment availability. The aim of this feasibility trial was to evaluate the feasibility, safety, and preliminary efficacy of a CBT protocol for adolescents with BDD, adapted to be delivered over the Internet with minimal therapist support. A total of 20 participants (12–17-year-olds) meeting criteria for BDD were recruited nationally to a specialist outpatient clinic in Stockholm, Sweden. One participant withdrew consent and their data could not be analysed. Nineteen participants were offered 12 modules of therapist-guided ICBT for BDD and were followed up to 12 months post-treatment. Preliminary efficacy was measured at the a priori primary endpoint (3-month follow-up) and at the 12-month follow-up with the clinician-rated Yale-Brown Obsessive Compulsive Scale Modified for BDD for Adolescents. The treatment was rated as both credible and satisfactory and was associated with a large and statistically significant reduction in BDD symptom severity (d = 2.94). The proportion of participants classified as responders at the primary endpoint was 73.7%, and the proportion of full or partial remitters was 63.2%. The average therapist support time was 8 min per participant per week. Treatment gains continued to accrue up to the 12-month follow-up. Two participants attempted suicide and another two reported non-suicidal self-injuries during the study period. ICBT with minimal therapist support is a feasible, potentially efficacious, and durable treatment for adolescents with BDD. Risky behaviours typical of this patient group should be carefully monitored during treatment.

Background Behavioural therapy for tics is difficult to access, and little is known about its effectiveness when delivered online. Objective To investigate the clinical and cost-effectiveness of an online-delivered, therapist- and parent-supported therapy for young people with tic disorders. Design Single-blind, parallel-group, randomised controlled trial, with 3-month (primary end point) and 6-month post-randomisation follow-up. Participants were individually randomised (1 : 1), using on online system, with block randomisations, stratified by site. Naturalistic follow-up was conducted at 12 and 18 months post-randomisation when participants were free to access non-trial interventions. A subset of participants participated in a process evaluation. Setting Two hospitals (London and Nottingham) in England also accepting referrals from patient identification centres and online self-referrals. Participants Children aged 9–17 years (1) with Tourette syndrome or chronic tic disorder, (2) with a Yale Global Tic Severity Scale-total tic severity score of 15 or more (or > 10 with only motor or vocal tics) and (3) having not received behavioural therapy for tics in the past 12 months or started/stopped medication for tics within the past 2 months. Interventions Either 10 weeks of online, remotely delivered, therapist-supported exposure and response prevention therapy (intervention group) or online psychoeducation (control). Outcome Primary outcome: Yale Global Tic Severity Scale-total tic severity score 3 months post-randomisation; analysis done in all randomised patients for whom data were available. Secondary outcomes included low mood, anxiety, treatment satisfaction and health resource use. Quality-adjusted life-years are derived from parent-completed quality-of-life measures. All trial staff, statisticians and the chief investigator were masked to group allocation. Results Two hundred and twenty-four participants were randomised to the intervention (n = 112) or control (n = 112) group. Participants were mostly male (n = 177; 79%), with a mean age of 12 years. At 3 months the estimated mean difference in Yale Global Tic Severity Scale-total tic severity score between the groups adjusted for baseline and site was −2.29 points (95% confidence interval −3.86 to −0.71) in favour of therapy (effect size −0.31, 95% confidence interval −0.52 to −0.10). This effect was sustained throughout to the final follow-up at 18 months (−2.01 points, 95% confidence interval −3.86 to −0.15; effect size −0.27, 95% confidence interval −0.52 to −0.02). At 18 months the mean incremental cost per participant of the intervention compared to the control was £662 (95% confidence interval −£59 to £1384), with a mean incremental quality-adjusted life-year of 0.040 (95% confidence interval −0.004 to 0.083) per participant. The mean incremental cost per quality-adjusted life-year gained was £16,708. The intervention was acceptable and delivered with high fidelity. Parental engagement predicted child engagement and more positive clinical outcomes. Harms Two serious, unrelated adverse events occurred in the control group. Limitations We cannot separate the effects of digital online delivery and the therapy itself. The sample was predominately white and British, limiting generalisability. The design did not compare to face-to-face services. Conclusion Online, therapist-supported behavioural therapy for young people with tic disorders is clinically and cost-effective in reducing tics, with durable benefits extending up to 18 months. Future work Future work should compare online to face-to-face therapy and explore how to embed the intervention in clinical practice. Trial registration This trial is registered as ISRCTN70758207; ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information. Plain language summary It can be difficult for children and young people with tics to access therapy. This is because there are not enough trained tic therapists. Online remote behavioural intervention for tics was a clinical trial to see whether an online platform that delivered two different types of interventions could help tics. One intervention focused on techniques to control tics; this type of therapy is called exposure and response prevention. The other intervention was psychoeducation, where participants learned about the nature of tics but not how to control them. The online remote behavioural intervention for tics interventions also involved help from a therapist and support from a parent. Participants were aged 9–17 years with Tourette syndrome/chronic tic disorder and were recruited from 16 clinics, two study sites (Nottingham and London) or via online self-referral. All individuals who were eligible for the online remote behavioural intervention for tics trial were randomised in a 50/50 split by researchers who were unaware of which treatment was being given. Participants received either 10 weeks of online exposure and response prevention or 10 weeks of online psychoeducation. A total of 224 children and young people participated: 112 allocated to exposure and response prevention and 112 to psychoeducation. Tics decreased more in the exposure and response prevention group (16% reduction) than in the psychoeducation group (6% reduction) 3 months after treatment. This difference is considered a clinically important difference in tic reduction. The treatment continued to have a positive effect on tic symptoms at 6, 12 and 18 months, showing that the effects are durable. This was achieved with minimal therapist involvement. The cost of online exposure and response prevention to treat young people with tics within this study was less when compared to the cost of face-to-face therapy. The results show that exposure and response prevention is an effective behavioural therapy for tics in this specific patient group. Delivering exposure and response prevention online with minimal therapist contact can be a successful and cost-effective treatment to improve access to behavioural therapy. Scientific summary Background Tic disorders including Tourette syndrome and chronic tic disorders are common conditions that affect approximately 1% of the population in the UK. Young people with tics often report substantial impairment, thus it is important that they have access to evidence-based treatment. Face-to-face behavioural therapy (BT) such as exposure and response prevention (ERP) may be offered to some young people. However, due to a lack of trained therapists, there are often difficulties accessing BT, and there is a better need to understand the clinical and cost-effectiveness of the online delivery of such therapy. Objectives The primary objective of this study was to evaluate the clinical effectiveness of therapist-guided, parent-assisted, internet-based ERP BT for tics in young people with tic disorders compared to online psychoeducation. Secondary objectives included (1) optimising the design of the intervention, (2) undertaking an internal pilot, (3) evaluating cost-effectiveness, (4) establishing whether the efficacy is maintained longer term, (5) understanding the mechanisms of impact of the intervention and (6) identifying barriers to implementation. Methods We conducted an individually randomised (1 : 1 ratio), multicentre trial, with an internal pilot and embedded process evaluation. Participants were assigned to either receive online, remotely delivered, therapist- and parent-supported ERP for tics or online, remotely delivered, therapist- and parent-supported psychoeducation for tics. Participants were recruited from the two study sites, 16 patient identification centres in England or could self-refer online via the study webpage or via Tourettes Action (a national charity for tics). The inclusion criteria were age between 9 and 17 years, with tics assessed on the Yale Global Tic Severity Scale (YGTSS), able to provide written informed consent (parental consent for children aged < 16 years) and with a suitable device they could use to access the internet. Exclusion criteria included receiving a therapy for tics in the past 12 months, starting or stopping tic medication within the past 2 months and intellectual disability/substance use/anorexia nervosa/psychosis/suicidality, moderate/severe intellectual disability, risk to self or others or parent or young person unable to speak or read/write English. All potential participants attended a screening/baseline appointment at one of the two study centres. Participants who were eligible and consented were randomised into one of two study groups. In the intervention group participants received 10 weeks of the remotely delivered, therapist-guided ERP behaviour therapy. In the control group participants received 10 weeks of remotely delivered, therapist-guided psychoeducation about tics. Participants completed measures at the mid-treatment point (5 weeks) and at 3 and 6 months (this formed phase 1, per-protocol design). For phase 2 (a naturalist design), follow-up measures were obtained at 12 and 18 months. The primary outcome (at 3 months) was the total tic severity score (TTSS) on the YGTSS. Secondary outcomes included measures of tics (parent tic questionnaire), general difficulties (strengths and difficulties questionnaire), mood and anxiety (moods and feelings questionnaire and Spence Child Anxiety Scale), global functioning (Children’s Global Assessment Scale, Clinical Global Impressions-Improvement), adverse events, need for further treatment, treatment credibility and satisfaction and the Child and Adolescent Version of the Gilles de la Tourette Syndrome Quality of Life Scale. Quality of life [child health utility 9D (CHU9D)] and resource use (modified child and adolescent service use schedule) data were also collected for the economic evaluation. Follow-up assessments were completed online or via telephone/Webex videoconferencing (YGTSS). The trial internal pilot evaluated recruitment rate, engagement with the intervention and retention to the primary outcome at 9 months into the trial and the results were reported to the relevant oversight committees (Trial Steering Committees and Data Monitoring Committee). A sub-sample of parents and young people in the intervention arm, clinicians and therapists were interviewed to explore barriers/facilitators to implementation and refine the intervention for future use, which formed part of the mixed-methods process evaluation. The quantitative data for the process evaluation included intervention usage metrics, clinical and demographic trial data and therapist contacts. Intervention The intervention was delivered via Barninternetprojektet (Child Internet Project; Swedish digital platform) (BIP), a Swedish web-based digital platform. The BT intervention (ERP) was translated from the Swedish original intervention (BIP TIC), refined and adapted for UK use by our trial team. The active control intervention (psychoeducation) was created by our trial team. Both interventions consisted of 10 web-based chapters, designed to last 10 weeks. Participants had regular contact with a therapist during this time via messages that could be sent inside the treatment platform (resembling an email). The therapist’s role was to give specific feedback to motivate the patient and not to deliver therapeutic content. The young person and the parent/carer were provided with their own separate logins to the BIP platform. For both the intervention and the comparator, treatment completion was defined as completion of the first four child chapters. Results The trial recruited and retained participants exceeding the pre-specified criteria for the internal pilot and therefore proceeded to the full trial. In total 445 candidates signed up to the study and were assessed for eligibility, of which 221 potential participants were excluded (90 did not meet inclusion criteria, 84 declined to participate and 47 were unable to contact family). This meant 224 participants were enrolled and randomly assigned (1 : 1) to either the ERP BT group (n = 112) or psychoeducation group (n = 112). The characteristics of the two groups were similar at baseline. The enrolled patients were mostly male (n = 177; 79%) and of white ethnicity (n = 195; 87%). Only 13% of participants were receiving tic medication. Adherence to the intervention was good in 99 (88%) of the 112 participants in the ERP group, and 105 (94%) of the 112 participants in the psychoeducation group were classified as treatment completers (i.e. completing at least the first four chapters). Retention to the primary outcome at the 3-month primary end point (90%) and 6-month follow-up (> 80%) was excellent. Retention to the primary outcome measure remained high at 12 months (81% in both arms) and 18 months (> 79% in both arms). The primary analysis showed that participants in the ERP group [16% reduction, standard deviation (SD) 1.1] had a greater decrease in tics than those in the psychoeducation group (6% reduction, SD 1.0) at 3 months (primary end point). The estimated mean difference in YGTSS-TTSS change between the groups adjusted for baseline and site was −2.29 points [95% confidence interval (CI) −3.86 to −0.71] in favour of ERP, with an effect size of −0.31 (95% CI −0.52 to −0.10). This effect was sustained at 6 months, with a mean decrease of 6.9 points (24%, SD 1.2) in the ERP group versus 3.4 points (12%, SD 1.0) in the psychoeducation group. For phase 2, participants in the ERP group continued to have a greater decrease in tics than the control group. The estimated mean difference in YGTSS-TTSS between groups adjusting for baseline and site at 12 months was −2.64 points (95% CI −4.48 to −0.79), with an effect size of −0.36 (95% CI −0.61 to −0.11), at 18 months it was −2.01 points (95% CI −3.86 to −0.15), with an effect size of −0.27 (95% CI −0.52 to −0.02), in favour of the ERP group. In addition, extended follow-up showed those receiving online ERP compared with online psychoeducation had reduced scores for low mood and anxiety at 12 and 18 months and superior tic-specific quality of life, with the largest effects seen at 18 months. The direct cost of the intervention was £155 per person, including £104.57 for the online platform, supervision and training and a mean variable cost of £50.43 per participant for therapist time in the trial. At 18 months, using proxy parent-completed CHU9D responses, there were a mean additional 0.040 (95% CI −0.004 to 0.083) quality-adjusted life-years (QALYs) per participant in the ERP group compared with psychoeducation, with an addition mean cost per participant of £662 (95% CI −£59 to £1384). The incremental cost-effectiveness ratio in the primary analysis was £16,708 per QALY gained from a health and social care cost perspective at 18 months. In the 10-year long-term decision model, online ERP cost £537 less per participant than face-to-face BT and resulted in 0.02 fewer QALYs. Two serious adverse events (SAEs) occurred (hospital attendance due to one ‘collapse’ and one ‘tic attack’), both in the active control psychoeducation group, neither of which were related to the study intervention. The process evaluation found that the ERP intervention was implemented with high fidelity, and participants found the intervention acceptable and satisfactory. Engagement was high, with child participants completing an average of 7.5/10 chapters and 99/112 (88.4%) participants completing the minimum of the first four chapters (the predefined threshold for effective dose). Parental engagement was the only significant independent predictor of child engagement. Improvement in tic severity and overall clinical condition was not moderated by the relationship between demographic or baseline clinical factors and engagement and no mediators were found. However, level of parental engagement was associated with overall clinical improvement, and this relationship was illuminated by the qualitative data. Conclusion Implications for health care The findings demonstrate that online, therapist-supported ERP for young people with chronic tic disorders is clinically effective at reducing tic severity. Therefore, this is an efficient public mental health approach to supporting young people with tics. The intervention can be delivered at lower cost than standard face-to-face BT and may also result in improved service efficiencies, allowing a greater number of young people to access evidence-based care. Future research implications Further ‘field trials’ should be conducted to explore the clinical and service implications of delivering the intervention in real-world settings. Given that online interventions are context dependent, exploring the validity of these findings in different cultures/countries is important. Future research should explore where online, therapist-supported ERP best fits in the tic disorder care pathway and how online and face-to-face therapy can be best combined (e.g. non-responders to online ERP are ‘stepped up’ to face-to-face therapy). Trial registrations This trial is registered as ISRCTN70758207 and ClinicalTrials.gov (NCT03483493). The trial is now complete. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Technology Assessment programme (project number 16/19/02) and will be published in full in Health and Technology Assessment; Vol. 27, No. 18. See the NIHR Journals Library website for further project information.

The FLEXGRID project develops a digital platform designed to offer Digital Energy Services (DESs) that facilitate energy sector stakeholders (i.e. Distribution System Operators - DSOs, Transmission System Operators - TSOs, market operators, Renewable Energy Sources - RES producers, retailers, flexibility aggregators) towards: i) automating and optimizing the planning and operation/management of their systems/assets, and ii) interacting in a dynamic and efficient way with their environment (electricity system) and the rest of the stakeholders. In this way, FLEXGRID envisages secure, sustainable, competitive, and affordable smart grids. A key objective is the incentivization of large-scale bottom-up investments in Distributed Energy Resources (DERs) through innovative smart grid management. Towards this goal, FLEXGRID develops innovative data models and energy market architectures (with high liquidity and efficiency) that effectively manage smart grids through an advanced TSO-DSO interaction as well as interactions between Transmission Network and Distribution Network level energy markets. Consequently, and through intelligence that exploits the innovation of the proposed market architecture, FLEXGRID develops investment tools able to examine in depth the emerging energy ecosystem and allow in this way: i) the financial sustainability of DER investors, and ii) the market liquidity/efficiency through advanced exploitation of DERs and intelligent network upgrades.

This is the ninth yearly article in the Tourette Syndrome Research Highlights series, summarizing selected research reports from 2022 relevant to Tourette syndrome. The authors briefly summarize reports they consider most important or interesting.

BackgroundEarly conduct problems and school failure are prominent risk factors for several adverse outcomes in later life. With the potential of reaching many children at early stages of their life, school-based interventions constitute a valuable approach to universal prevention. Good behavior game (GBG) is a promising school-based behavior management program, having shown immediate reductions in conduct problems along with several long-term positive effects. Adapting interventions to new contexts may however affect their effectiveness. The current study aims to evaluate the effectiveness of a Swedish adaption of GBG under pragmatic conditions. The intervention is hypothesized to reduce conduct problems in the classroom (primary outcome). Secondary analyses will investigate changes in conduct problems in common school areas, classroom climate, teacher collective efficacy, on-task behavior, as well as investigating behavioral management practices, implementation, and barriers to implementation.MethodsThis is a cluster-randomized trial with two parallel groups. Schools will be randomized (1,1, stratified by their areas sociodemographic index score) to be provided training in GBG or perform business-as-usual. The intervention and data collection lasts for a school year. Data will be collected at three time points: at baseline in the beginning of the school year (prior to training in GBG), after three months, and after nine months (at the end of the school year; primary endpoint). Data consists of teacher-rated measures of conduct problems, classroom climate, teacher collective efficacy, behavior management practices, and implementation factors, along with demographic factors. In addition, data will be collected by independent and blinded observers using corresponding measures in a subset of randomly chosen classrooms. Procedural fidelity will be rated and collected by GBG-trainers during nine observations throughout the school year. Statistical analysis will include frequentist intention-to-treat analysis, and comparisons of estimates with a corresponding Bayesian model using weakly informative priors. The study has currently completed data collection.DiscussionThis study will provide knowledge in universal prevention and school-based interventions with high reach, as well as specific knowledge concerning the effectiveness of an adapted version of GBG under real-world conditions, along with factors affecting its implementation and effects.Clinical trial registrationClinicalTrials.gov, identifier NCT05794893.

The development of coatings for accident-tolerant fuels (ATFs) for light water reactor (LWR) applications promises improved corrosion resistance under accident conditions and better performances during operation. CrN and TiN coatings are characterized by high wear resistance coupled with good corrosion resistance properties. They are generally used to protect materials in applications where extreme conditions are involved and represent promising candidates for ATF. Zr cladding tubes coated with 5 µm-thick CrN or TiN, exposed in an autoclave to simulated PWR chemistry and BWR chemistry, were characterized with SEM, EDS, and STEM. The investigation focused on the performance and oxidation mechanisms of the coated claddings under simulated reactor chemistry. Both coatings provided improved oxidation resistance in a simulated PWR environment, where passivating films of Cr2O3 and TiO2, less than 1 µm-thick, formed on the CrN and TiN outer surfaces, respectively. Under the more challenging BWR conditions, any formed Cr2O3 dissolved into the oxidizing water, resulting in the complete dissolution of the CrN coating. For the TiN coating, the formation of a stable TiO2 film was observed under BWR conditions, but the developed oxide film was unable to stop the flux of oxygen to the substrate, causing the oxidation of the substrate.

I många samhälleliga sammanhang återkommer en uppmaning att lyssna på barn, inte sällan med hänvisning till FN:s barnkonvention och kanske särskilt artikel 12 om rätten att bli hörd. Men vad innebär det att lyssna på barn? Mängder av böcker om lyssnande till barn som riktar sig till yrkespraktiker och andra som möter barn i sitt vardagsliv publiceras kontinuerligt. Vi saknar emellertid en kritisk diskussion som sätter frågor om lyssnande, lyssnande på barn och det goda lyssnandet i en större teoretisk kontext. Mot den bakgrunden har föreliggande artikel tillkommit. Lyssnandets problematik diskuteras här primärt i relation till monologiska och dialogiska perspektiv på kommunikation samt i relation till olika synsätt på barn (barnsyn) som lika eller olika vuxna. Avslutningsvis pekar vi på etiska implikationer som följer i kölvattnet av olika teoretiska perspektiv på lyssnande och lyssnande på barn.

This is the ninth yearly article in the Tourette Syndrome Research Highlights series, summarizing selected research reports from 2022 relevant to Tourette syndrome. The authors briefly summarize reports they consider most important or interesting.

IntroductionCoeliac disease is a lifelong immune-mediated enteropathy manifested as gluten intolerance in individuals carrying specific human leukocyte antigen (HLA) molecules. Other factors than genetics and gluten intake, however, may play a role in triggering the disease. The gut internal environment is thought to be one of these potential contributing factors, and it can be influenced throughout life.MethodsWe examine the impact of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 supplementation on the faecal metabolome in genetically predisposed children having tissue transglutaminase autoantibodies, i.e., coeliac disease autoimmunity. Probiotic strains were selected based on their beneficial properties, including mucosal permeability and immune modulation effects. The intervention group (n = 40) and control group (n = 38) took the probiotics or placebo daily for 6 months in a double-blinded randomised trial. Faecal samples were collected at baseline and after 3 and 6 months and analysed using the 1H NMR for metabolome. The incorporation of 16S rRNA sequencing as a supportive dataset complemented the analysis of the metabolome data.ResultsDuring the 6 months of intervention, the stool concentrations of 4-hydroxyphenylacetate increased in the intervention group as compared to controls, whereas concentrations of threonine, valine, leucine, isoleucine, methionine, phenylalanine, aspartate, and fumarate decreased. Additionally, a noteworthy effect on the glycine, serine, and threonine metabolic pathway has been observed.ConclusionThe findings suggest a modest yet significant impact of the probiotics on the faecal metabolome, primarily influencing proteolytic processes in the gut.Clinical trial registrationClinicalTrials.gov, NCT03176095.