Enhancement of thermovoltage and tunnel magneto-Seebeck effect in CoFeB based magnetic tunnel junctions by variation of the MgAl2_2O4_4 and MgO barrier thickness

We investigate the influence of the barrier thickness of Co$_{40}$Fe$_{40}$B$_{20}$ based magnetic tunnel junctions on the laser-induced tunnel magneto-Seebeck effect. Varying the barrier thickness from 1nm to 3nm, we find a distinct maximum in the tunnel magneto-Seebeck effect for 2.6nm barrier thickness. This maximum is independently measured for two barrier materials, namely MgAl$_2$O$_4$ and MgO. Additionally, samples with an MgAl$_2$O$_4$ barrier exhibit a high thermovoltage of more than 350$\mu$V in comparison to 90$\mu$V for the MTJs with MgO barrier when heated with the maximum laser power of 150mW. Our results allow for the fabrication of improved stacks when dealing with temperature differences across magnetic tunnel junctions for future applications in spin caloritronics, the emerging research field that combines spintronics and themoelectrics

Large magneto-Seebeck effect in magnetic tunnel junctions with half-metallic Heusler electrodes

Spin caloritronics studies the interplay between charge-, heat- and spin-currents, which are initiated by temperature gradients in magnetic nanostructures. A plethora of new phenomena has been discovered that promises, e.g., to make wasted heat in electronic devices useable or to provide new read-out mechanisms for information. However, only few materials have been studied so far with Seebeck voltages of only some {\mu}V, which hampers applications. Here, we demonstrate that half-metallic Heusler compounds are hot candidates for enhancing spin-dependent thermoelectric effects. This becomes evident when considering the asymmetry of the spin-split density of electronic states around the Fermi level that determines the spin-dependent thermoelectric transport in magnetic tunnel junctions. We identify Co$_2$FeAl and Co$_2$FeSi Heusler compounds as ideal due to their energy gaps in the minority density of states, and demonstrate devices with substantially larger Seebeck voltages and tunnel magneto-Seebeck effect ratios than the commonly used Co-Fe-B based junctions.Comment: 9 pages, 4 figure

Mental health and well-being from childhood to adulthood: design, methods and results of the 11-year follow-up of the BELLA study

Mental health and well-being are of great interest in health policy and research. Longitudinal surveys are needed to provide solid population-based data. We describe the design and methods of an 11-year follow-up of the German BELLA study in children, adolescents and young adults, and we report on age- and gender-specific courses of general health and well-being, long-term health-related outcomes of mental health problems, and mental health care use. The BELLA study is the module on mental health and well-being within the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Standardised measures were used at each of the five measurement points of the BELLA study. In the 11-year follow-up, young people aged 7–31 years participated (n = 3492). Individual growth modelling, linear regression and descriptive analyses were conducted. Self-reported general health and well-being were both better in younger (vs. older) and in male (vs. female) participants according to the data from all five measurement points. Mental health problems in childhood and adolescence (measured at baseline) predicted impaired health outcomes at 6-year and 11-year follow-ups. Approximately one out of four children with a diagnosed mental disorder was not undergoing mental health treatment. With its 11-year follow-up, the prospective longitudinal BELLA study provides new and solid data on mental health and well-being from childhood to adulthood in Germany, and these data are important for health promotion and prevention practices. These results are consistent with previous findings. Promising future analyses are planned.Peer Reviewe

Gender and Age Differences in ADHD Symptoms and Co‑occurring Depression and Anxiety Symptoms Among Children and Adolescents in the BELLA Study

Attention-deficit/hyperactivity disorder (ADHD) is one of the most diagnosed neurodevelopmental disorders of childhood. Current studies addressing gender and age differences in ADHD are lacking. The present study aims to fill this research gap by dimensionally evaluating gender and age differences in ADHD symptoms, as measured by a DSM-5-based parent rating scale, in children and adolescents who participated in the two-year follow-up of the community-based BELLA study (n = 1326). Associations between ADHD symptoms and depression symptoms and anxiety symptoms were also examined. Multiple linear regressions revealed significant associations between gender and all ADHD symptoms. Age was significantly associated with hyperactive/impulsive symptoms. Additional multiple linear regressions demonstrated significant positive associations between depression and anxiety symptoms and ADHD symptoms. Further, female gender was found to be posi- tively associated with both depression and anxiety symptoms. These findings may suggest a need for more gender-specific approaches to ADHD diagnosis and treatment, as well as more research into the intersections of ADHD and depression and anxiety symptoms in children and adolescents.Peer Reviewe

Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy

<p>Abstract</p> <p>Background</p> <p>Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic.</p> <p>Methods</p> <p>Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects.</p> <p>Results</p> <p>We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia.</p> <p>Conclusion</p> <p>Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects.</p

Child and Adolescent Mental Health During the COVID-19 Pandemic: Results of the Three-Wave Longitudinal COPSY Study

Purpose The German population-based longitudinal COVID-19 and Psychological Health study monitors changes in health-related quality of life (HRQoL) and mental health of children and adolescents during the COVID-19 pandemic and identifies vulnerable groups. Methods A nationwide, population-based survey was conducted in May 2020 to June 2020 (Wave 1), December 2020 to January 2021 (Wave 2), and September 2021 to October 2021 (Wave 3). In total, n = 2,097 children and adolescents aged 7–17 years were investigated using measures to assess HRQoL (KIDSCREEN-10), mental health problems (SDQ), anxiety (SCARED), depressive symptoms(PHQ-2), and psychosomatic complaints(HBSC-SCL). Results The prevalence of low HRQoL increased from 15% prepandemic to 40% and 48% in Waves 1 and 2 and improved slightly to 35% in Wave 3 (all differences significant). Similarly, overall mental health problems increased from 18% prepandemic to 29% in Wave 1 and 31% in Wave 2 to 28% in Wave 3 (all differences significant, except Wave 3 vs. 2), anxiety increased from 15% prepandemic to 24% and 30% in Waves 1 and 2 and was still 27% in Wave 3. Depressive symptoms increased from 10% prepandemic to 11% and 15% in Waves 1 and 2 and were 11% in Wave 3. A group with low parental education, restricted living conditions, migration background, and parental mental health problems was at significantly increased risk of HRQoL and mental health impairments. Discussion The prevalence of low HRQoL, mental health problems, and anxiety has been elevated throughout the pandemic. Thus, mental health promotion, prevention, and intervention strategies need to be implemented to support adolescents–particularly those at risk.Peer Reviewe

Factor IX Expression within the Normal Range Prevents Spontaneous Bleeds Requiring Treatment Following FLT180a Gene Therapy in Patients with Severe Hemophilia B: Long-Term Follow- up Study of the B-Amaze Program

Introduction: FLT180a (verbrinacogene setparvovec) is an investigational, liver-directed AAV gene therapy for the treatment of patients with hemophilia B (HB). FLT180a consists of a novel, potent, engineered capsid (AAVS3) containing an expression cassette encoding a Factor IX (FIX) gain-of-function protein variant ('Padua'; FIX-R338L). The B-AMAZE study was designed to identify a dose of FLT180a that maintains FIX activity within the normal range (50-150%) and thereby protect patients with severe HB from spontaneous and traumatic bleeds. Methods: B-AMAZE was a multicentre, open-label Phase 1/2 clinical trial (NCT03369444; sponsored by UCL) that evaluated FLT180a dose levels using an escalating/descending adaptive design in patients with severe (FIX activity &amp;lt;1%) or moderately severe (FIX activity 1-2%) HB who were negative for AAVS3 neutralizing antibodies. A novel regimen of prophylactic corticosteroids with/without tacrolimus was implemented to mitigate the impact of vector-related transaminitis on FIX expression. Patients who completed the 26-week B-AMAZE study were eligible for the ongoing long-term follow-up study (NCT03641703; sponsored by Freeline). Results: Ten HB patients received a single dose of FLT180a. Four FLT180a doses ranging from 3.84e11 vg/kg to 1.28e12 vg/kg were assessed. As of the data cut-off date, all patients have been followed for ≥16 months. FLT180a demonstrated a favorable safety profile, without evidence of inhibitors against FIX, infusion-related or allergic reactions. The most common treatment-related adverse event was transient elevation in alanine aminotransferase. An event of AV fistula thrombosis occurred in a 67-year-old patient who received the highest dose of 1.28e12 vg/kg (total dose of 1.15e14 vg) and had supranormal FIX levels; this patient was treated with anticoagulants. While these FIX levels demonstrate the potency of our proprietary AAVS3 capsid, this dose will not be used in future hemophilia studies. At Week 26 after FLT180a administration, a dose-response relationship was observed with mean FIX activity of 45.0%, 35.5%, 141.5%, and 175.5% for 3.84e11, 6.4e11, 8.32e11, and 1.28e12 vg/kg doses, respectively (Table); FIX activity levels ≥50% were achieved in 7 of 8 patients treated with the three highest doses. One patient (Patient 4) who received 6.4e11 vg/kg lost transgene expression early due to transaminitis and resumed routine factor prophylaxis. The 8.32e11 vg/kg cohort received an extended immune management regimen (9-18 weeks) with prophylactic tacrolimus in addition to prednisolone to prevent breakthrough vector-related transaminitis. However, after cessation of the immune management regimen, transaminitis with concomitant reductions in FIX activity was observed in all patients in the 8.32e11 vg/kg cohort. The combination of prophylactic tacrolimus and prednisolone appeared to have suppressed immune-mediated transaminitis while administered, but recurrence of transaminitis developed soon after cessation. This unique and previously unreported observation suggests that the longer-duration prophylactic immune management regimen may have prevented tolerization to the vector because this was not observed in earlier cohorts where a brief course of tacrolimus was given reactively for breakthrough transaminitis. All patients (including the 8.32e11 vg/kg cohort) have achieved steady state. Patients in the earliest cohort who received the lowest dose (3.84e11 vg/kg) have shown stable FIX activity for &amp;gt;3 years. There were no spontaneous bleeds that required FIX supplementation in patients who maintained FIX activity above 50%; Patient 4 in the 6.4e11 vg/kg cohort experienced two bleeds (cause unknown) after he lost transgene expression, which were treated with exogenous FIX. One patient received exogenous FIX for treatment of a traumatic bleed, but his FIX activity level was 57% at the time of the event. Additional efficacy and safety results with &amp;gt;3.5 years of follow-up will be presented. Conclusions: B-AMAZE is the first HB gene therapy study to achieve normal levels of FIX activity using relatively low vector doses. Results suggest that a dose of 7.7e11 vg/kg, coupled with a short course of prophylactic immune management, has the potential to achieve durable FIX activity in the normal range (50-150%) and thereby prevent spontaneous bleeds and normalize hemostasis in the event of traumatic bleeds

Diagnosis and treatment of pediatric acquired aplastic anemia (AAA): An initial survey of the North American Pediatric Aplastic Anemia Consortium (NAPAAC)

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106711/1/pbc24875.pd

Adolescents perception of the COVID-19 pandemic restrictions and associated mental health and well-being: gender, age and socioeconomic differences in 22 countries

Background: The COVID-19-pandemic has had a profound impact on the lives of adolescents worldwide. This study examined the subjective perception of the COVID-19 pandemic measures and its association with mental health and well-being (i.e., loneliness, life satisfaction and multiple health complaints) among 13- and 15-years-old adolescents from 22 countries. Methods: Data from the cross-national Health Behaviour in School-aged Children (HBSC) 2021/22 study were used from representative samples of 22 countries (N = 67,544; 51.9% girls). The self-perceived impact of COVID-19 measure comprised 10 items asking about the impact on several dimensions of adolescent lives (e.g., relationships with family and friends, health, or eating behaviours). Measures of loneliness, multiple health complaints, and life satisfaction were included as indicators of mental health and well-being. A non-parametric multilevel latent class analysis considering individual and country-levels was conducted to identify classes of self-perceived impact of the COVID-19 measures. Multilevel logistic regression models adjusted by age and socioeconomic status were applied to assess the association between COVID-19 measure impact classes and mental health. Results: Three classes were identified on individual level encompassing a neutral (51%), positive (31%), or negative (18%) perception of COVID-19 measures. A third of the adolescents reported a positive impact of the pandemic measures. The distribution of classes was heterogeneous within and across countries. Within the positive COVID-19 measure impact class, social relationships were the most important dimension, whereas mental health problems were mostly represented within the negative COVID-19 measure impact class. Girls with a negative perception of pandemic measures showed higher levels of loneliness and multiple health complaints and lower life satisfaction. 15-year-old adolescents and those with a low socioeconomic status reported higher levels of loneliness and lower life satisfaction. Conclusions: The majority of adolescents perceived the pandemic measures as neutral or positive. Girls, 15-year-old adolescents, and those with low socioeconomic status were at higher risk of suffering from pandemic measures and associated problems of loneliness, multiple health complaints, and low life satisfaction. We conclude that adolescent’s mental health and well-being should be considered in the decision-making process by ensuring that the unique challenges of adolescents are adequately addressed in policies