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Pediatric brain and spinal cancers are collectively the leading disease-related cause of death in children; thus, we urgently need curative therapeutic strategies for these tumors. To accelerate such discoveries, the Childrens Brain Tumor Network (CBTN) and Pacific Pediatric Neuro-Oncology Consortium (PNOC) created a systematic process for tumor biobanking, model generation, and sequencing with immediate access to harmonized data. We leverage these data to establish OpenPBTA, an open collaborative project with over 40 scalable analysis modules that genomically characterize 1,074 pediatric brain tumors. Transcriptomic classification reveals universal TP53 dysregulation in mismatch repair-deficient hypermutant high-grade gliomas and TP53 loss as a significant marker for poor overall survival in ependymomas and H3 K28-mutant diffuse midline gliomas. Already being actively applied to other pediatric cancers and PNOC molecular tumor board decision-making, OpenPBTA is an invaluable resource to the pediatric oncology community.

Atypical teratoid rhabdoid tumors (AT/RT) are malignant central nervous system (CNS) tumors that occur mostly in young children and have historically carried a very poor prognosis. While recent clinical trial results show that this tumor is curable, outcomes are still poor compared to other central nervous system embryonal tumors. We here review prior AT/RT clinical trials and highlight promising pre-clinical results that may inform novel clinical approaches to this aggressive cancer.

PurposeTo develop an MR multitasking-based dynamic imaging for cerebrovascular evaluation (MT-DICE) technique for simultaneous quantification of permeability and leakage-insensitive perfusion with a single-dose contrast injection.MethodsMT-DICE builds on a saturation-recovery prepared multi-echo fast low-angle shot sequence. The k-space is randomly sampled for 7.6 min, with single-dose contrast agent injected 1.5 min into the scan. MR multitasking is used to model the data into six dimensions, including three spatial dimensions for whole-brain coverage, a saturation-recovery time dimension, and a TE dimension for dynamic T1$$ {\mathrm{T}}_1 $$ and T2*$$ {\mathrm{T}}_2^{\ast } $$ quantification, respectively, and a contrast dynamics dimension for capturing contrast kinetics. The derived pixel-wise T1/T2*$$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ time series are converted into contrast concentration-time curves for calculation of kinetic metrics. The technique was assessed for its agreement with reference methods in T1$$ {\mathrm{T}}_1 $$ and T2*$$ {\mathrm{T}}_2^{\ast } $$ measurements in eight healthy subjects and, in three of them, inter-session repeatability of permeability and leakage-insensitive perfusion parameters. Its feasibility was also demonstrated in four patients with brain tumors.ResultsMT-DICE T1/T2*$$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ values of normal gray matter and white matter were in excellent agreement with reference values (intraclass correlation coefficients = 0.860/0.962 for gray matter and 0.925/0.975 for white matter ). Both permeability and perfusion parameters demonstrated good to excellent intersession agreement with the lowest intraclass correlation coefficients at 0.694. Contrast kinetic parameters in all healthy subjects and patients were within the literature range.ConclusionBased on dynamic T1/T2*$$ {\mathrm{T}}_1/{\mathrm{T}}_2^{\ast } $$ mapping, MT-DICE allows for simultaneous quantification of permeabi

BACKGROUND/RATIONAL: Following initial irradiation sparing therapy, many young children with relapsed medulloblastoma can be salvaged with craniospinal irradiation (CSI). However, the interval to relapse is short and neurocognitive sequelae remain a major concern. The contribution of molecular subgrouping may help refine indications and modalities of salvage strategies in this population. METHOD: From a cohort of 151 young children with molecularly characterized relapsed medulloblastoma, subset analysis of the SHH medulloblastoma was conducted to describe the practice of salvage radiotherapy and associated post-relapse survival (PRS). RESULTS: Sixty-seven SHH medulloblastoma patients (46 M0; 54 GTR; 11 non-ND/MBEN) received salvage therapy with curative intent. Before relapse, 54 (80.6%) received conventional chemotherapy (CC), 13 (19.4%) high-dose chemotherapy (HDC), while seven had additional focal radiotherapy (fRT). Median time to relapse was 11.1 months (range 3.8-41.0) and 43.3% were localized. Thirty patients (16 localized relapse) underwent surgery. Forty-seven (71.2%) received salvage radiotherapy (20 with CC; 10 with HDC; 15 alone, two unknown). CSI and fRT accounted for 82% and 18% respectively. CSI median dose was 36Gy (range 18-39Gy). Ten patients (eight with localized relapse) received CSI doses ≤23.4Gy. Nineteen patients (28.8%) did not receive any radiotherapy (nine HDC; 10 CC only). Radiotherapy was associated with better 3-year PRS (73.0% versus 36.1%; p=0.001). All patients treated with CSI ≤ 23.4Gy were alive at median follow-up of 69 months(24-142). Six of nine patients treated with HDC without irradiation were alive at last follow-up. Sixty-three percent of patients received reduced dose CSI(≤23.4Gy), fRT, or no radiotherapy, and their PRS did not significantly differ from those who received CSI ≥ 30.6Gy (p = 0.54). CONCLUSION: While salvage CSI provided PRS benefit in this SHH medulloblastoma cohort, we report the use of reduced salva

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

IntroductionMedulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.MethodsGenotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.ResultsFifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10-5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10-8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10-4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10-3).ConclusionThe results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

IntroductionMedulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark.MethodsGenotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2.ResultsFifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10-5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10-8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10-4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10-3).ConclusionThe results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Atypical teratoid rhabdoid tumor (ATRT) is a rare, highly malignant central nervous system cancer arising in infants and younger children, historically considered to be homogeneous, monogenic, and incurable. Recent use of intensified therapies has modestly improved survival for ATRT; however, a majority of patients will still succumb to their disease. While ATRTs almost universally exhibit loss of SMARCB1 (BAF47/INI1/SNF5), recent whole genome, transcriptome, and epigenomic analyses of large cohorts reveal previously underappreciated molecular heterogeneity. These discoveries provide novel insights into how SMARCB1 loss drives oncogenesis and confer specific therapeutic vulnerabilities, raising exciting prospects for molecularly stratified treatment for patients with ATRT.

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Introduction: Medulloblastoma is a malignant embryonal tumor of the cerebellum that occurs predominantly in children. To find germline genetic variants associated with medulloblastoma risk, we conducted a genome-wide association study (GWAS) including 244 medulloblastoma cases and 247 control subjects from Sweden and Denmark. Methods: Genotyping was performed using Illumina BeadChips, and untyped variants were imputed using IMPUTE2. Results: Fifty-nine variants in 11 loci were associated with increased medulloblastoma risk (p < 1 × 10–5), but none were statistically significant after adjusting for multiple testing (p < 5 × 10–8). Thirteen of these variants were genotyped, whereas 46 were imputed. Genotyped variants were further investigated in a validation study comprising 249 medulloblastoma cases and 629 control subjects. In the validation study, rs78021424 (18p11.23, PTPRM) was associated with medulloblastoma risk with OR in the same direction as in the discovery cohort (ORT = 1.59, pvalidation = 0.02). We also selected seven medulloblastoma predisposition genes for investigation using a candidate gene approach: APC, BRCA2, PALB2, PTCH1, SUFU, TP53, and GPR161. The strongest evidence for association was found for rs201458864 (PALB2, ORT = 3.76, p = 3.2 × 10–4) and rs79036813 (PTCH1, ORA = 0.42, p = 2.6 × 10–3). Conclusion: The results of this study, including a novel potential medulloblastoma risk loci at 18p11.23, are suggestive but need further validation in independent cohorts.

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

Bakgrund: ADHD, Attention Deficit Hyperactivity Disorder, kännetecknas av koncentrationssvårigheter med hyperaktivitet och impulsivitet. Dessutom har ADHD påverkan på personens förmågor att hantera sitt vardagliga liv. Denna störning anses bero på både ärftliga och icke ärftliga faktorer. Ett utredningsteam på en psykiatrisk mottagning ställer diagnosen ADHD till vuxna. Teamet bedömer individens svårigheter att hantera vardagen. De svenska vårdprogrammen utgör grunden för en individanpassad behandling samt ett psykosocialt stöd. Syfte: Syftet med studien är att beskriva hur personer upplever att leva med ADHD före och efter att diagnosen ställts. Metod: En litteraturöversikt enligt Friberg har genomförts. Tretton kvalitativa artiklar har använts till analysen. Artiklarna hämtas från databaserna Cinahl, PsycInfo och PubMed. Följande sökord användes: ADHD, symptoms, adults, patients experiences, quality of life och qualitative research. Resultat: Analysen resulterade i två huvudteman Livet före diagnosen och Livet efter diagnosen. Deltagarna beskriver brist på förståelse från omgivningen, svårigheter med att anpassa sig till dagliga rutiner, låg självkänsla samt känsla av isolering före diagnosticering. Efter diagnosen beskriver deltagarna effekten av medicinsk behandling och stödet efter diagnosticering och menade att sådana åtgärder bidrog till möjligheten att fungera i den sociala miljön. Diskussion: De vuxnas upplevelser av att leva med ADHD diskuteras utifrån Erikssons teori om lidande och hälsa. Även fokuserar diskussionsdelen på sjuksköterskans professionella roll och ansvar under utredning samt behandling av patienter med ADHD., Background: ADHD, Attention Deficit Hyperactivity Disorder, is characterized by concentration difficulties with hyperactivity and impulsivity. ADHD also have an impact on a person’s ability to manage their everyday lives. This disorder is attributed to both genetic and non-genetic factors that are biological and psychosocial reasons. Current assessment of ADHD diagnosis is usually made by an investigating team at a psychiatric clinic. The team assesses the individual's extensive difficulties in managing everyday life. The Swedish health care programs are the basis for individualized treatment and psychosocial support. Aim: The purpose of this literature review was to describe how people experience living with ADHD before and after the diagnosis. Method: A literature review according to Friberg was conducted. Thirteen qualitative articles were used for the analysis. The articles were retrieved from the databases Cinahl, PsycInfo and PubMed. The following keywords were used: ADHD, symptoms, adults, patient experiences, quality of life and qualitative research. Results: The analysis resulted in two main themes Life before the diagnosis and Life after the diagnosis. Participants report difficulties in adapting to daily routines, low self-esteem and senses of isolation before diagnosis. After diagnosis, the participants described the effect of medical treatment and support and explained that this bad contributed to the ability to work in the social environment. Their increased knowledge of ADHD diagnosis and support in daily life leads to improved problem management, giving them a new meaning in life. Discussion: The adults' experiences of living with ADHD are discussed in relation to Erikson's theory of suffering and health. The discussion section also focuses on the nurses’ professional role and responsibility during the investigation and the treatment of patients with ADHD.

Posterior fossa ependymomas (EPN_PF) in children comprise two morphologically identical, but biologically distinct tumor entities. Group-A (EPN_PFA) tumors have a poor prognosis and require intensive therapy. In contrast, group-B tumors (EPN_PFB) exhibit excellent prognosis and the current consensus opinion recommends future clinical trials to test the possibility of treatment de-escalation in these patients. Therefore, distinguishing these two tumor subtypes is critical. EPN_PFA and EPN_PFB can be distinguished based on DNA methylation signatures, but these assays are not routinely available. We have previously shown that a subset of poorly prognostic childhood EPN_PF exhibits global reduction in H3K27me3. Therefore, we set out to determine whether a simple immunohistochemical assay for H3K27me3 could be used to segregate EPN_PFA from EPN_PFB tumors. We assembled a cohort of 230 childhood ependymomas and H3K27me3 immunohistochemistry was assessed as positive or negative in a blinded manner. H3K27me3 staining results were compared with DNA methylation-based subgroup information available in 112 samples [EPN_PFA (n = 72) and EPN_PFB tumors (n = 40)]. H3K27me3 staining was globally reduced in EPN_PFA tumors and immunohistochemistry showed 99% sensitivity and 100% specificity in segregating EPN_PFA from EPN_PFB tumors. Moreover, H3K27me3 immunostaining was sufficient to delineate patients with worse prognosis in two independent, non-overlapping cohorts (n = 133 and n = 97). In conclusion, immunohistochemical evaluation of H3K27me3 global reduction is an economic, easily available and readily adaptable method for defining high-risk EPN_PFA from low-risk posterior fossa EPN_PFB tumors to inform prognosis and to enable the design of future clinical trials.

Bakgrund: ADHD, Attention Deficit Hyperactivity Disorder, kännetecknas av koncentrationssvårigheter med hyperaktivitet och impulsivitet. Dessutom har ADHD påverkan på personens förmågor att hantera sitt vardagliga liv. Denna störning anses bero på både ärftliga och icke ärftliga faktorer. Ett utredningsteam på en psykiatrisk mottagning ställer diagnosen ADHD till vuxna. Teamet bedömer individens svårigheter att hantera vardagen. De svenska vårdprogrammen utgör grunden för en individanpassad behandling samt ett psykosocialt stöd. Syfte: Syftet med studien är att beskriva hur personer upplever att leva med ADHD före och efter att diagnosen ställts. Metod: En litteraturöversikt enligt Friberg har genomförts. Tretton kvalitativa artiklar har använts till analysen. Artiklarna hämtas från databaserna Cinahl, PsycInfo och PubMed. Följande sökord användes: ADHD, symptoms, adults, patients experiences, quality of life och qualitative research. Resultat: Analysen resulterade i två huvudteman Livet före diagnosen och Livet efter diagnosen. Deltagarna beskriver brist på förståelse från omgivningen, svårigheter med att anpassa sig till dagliga rutiner, låg självkänsla samt känsla av isolering före diagnosticering. Efter diagnosen beskriver deltagarna effekten av medicinsk behandling och stödet efter diagnosticering och menade att sådana åtgärder bidrog till möjligheten att fungera i den sociala miljön. Diskussion: De vuxnas upplevelser av att leva med ADHD diskuteras utifrån Erikssons teori om lidande och hälsa. Även fokuserar diskussionsdelen på sjuksköterskans professionella roll och ansvar under utredning samt behandling av patienter med ADHD., Background: ADHD, Attention Deficit Hyperactivity Disorder, is characterized by concentration difficulties with hyperactivity and impulsivity. ADHD also have an impact on a person’s ability to manage their everyday lives. This disorder is attributed to both genetic and non-genetic factors that are biological and psychosocial reasons. Current assessment of ADHD diagnosis is usually made by an investigating team at a psychiatric clinic. The team assesses the individual's extensive difficulties in managing everyday life. The Swedish health care programs are the basis for individualized treatment and psychosocial support. Aim: The purpose of this literature review was to describe how people experience living with ADHD before and after the diagnosis. Method: A literature review according to Friberg was conducted. Thirteen qualitative articles were used for the analysis. The articles were retrieved from the databases Cinahl, PsycInfo and PubMed. The following keywords were used: ADHD, symptoms, adults, patient experiences, quality of life and qualitative research. Results: The analysis resulted in two main themes Life before the diagnosis and Life after the diagnosis. Participants report difficulties in adapting to daily routines, low self-esteem and senses of isolation before diagnosis. After diagnosis, the participants described the effect of medical treatment and support and explained that this bad contributed to the ability to work in the social environment. Their increased knowledge of ADHD diagnosis and support in daily life leads to improved problem management, giving them a new meaning in life. Discussion: The adults' experiences of living with ADHD are discussed in relation to Erikson's theory of suffering and health. The discussion section also focuses on the nurses’ professional role and responsibility during the investigation and the treatment of patients with ADHD.

Childhood posterior fossa (PF) ependymomas cause substantial morbidity and mortality. These tumors lack recurrent genetic mutations, but a subset of these ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)], implicating epigenetic alterations in their pathogenesis. Further, histological grade does not reliably predict prognosis, highlighting the importance of developing more robust prognostic markers. We discovered global H3K27me3 reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M mutant gliomas. PF-ve tumors exhibited many clinical and biological similarities with PFA ependymomas. Genomic H3K27me3 distribution showed an inverse relationship with CpGi methylation, suggesting that CpGi hypermethylation drives low H3K27me3 in PF-ve ependymomas. Despite CpGi hypermethylation and global H3K27me3 reduction, these tumors showed DNA hypomethylation in the rest of the genome and exhibited increased H3K27me3 genomic enrichment at limited genomic loci similar to H3K27M mutant gliomas. Combined integrative analysis of PF-ve ependymomas with H3K27M gliomas uncovered common epigenetic deregulation of select factors that control radial glial biology, and PF radial glia in early human development exhibited reduced H3K27me3. Finally, H3K27me3 immunostaining served as a biomarker of poor prognosis and delineated radiologically invasive tumors, suggesting that reduced H3K27me3 may be a prognostic indicator in PF ependymomas.

Childhood posterior fossa (PF) ependymomas cause substantial morbidity and mortality. These tumors lack recurrent genetic mutations, but a subset of these ependymomas exhibits CpG island (CpGi) hypermethylation [PF group A (PFA)], implicating epigenetic alterations in their pathogenesis. Further, histological grade does not reliably predict prognosis, highlighting the importance of developing more robust prognostic markers. We discovered global H3K27me3 reduction in a subset of these tumors (PF-ve ependymomas) analogous to H3K27M mutant gliomas. PF-ve tumors exhibited many clinical and biological similarities with PFA ependymomas. Genomic H3K27me3 distribution showed an inverse relationship with CpGi methylation, suggesting that CpGi hypermethylation drives low H3K27me3 in PF-ve ependymomas. Despite CpGi hypermethylation and global H3K27me3 reduction, these tumors showed DNA hypomethylation in the rest of the genome and exhibited increased H3K27me3 genomic enrichment at limited genomic loci similar to H3K27M mutant gliomas. Combined integrative analysis of PF-ve ependymomas with H3K27M gliomas uncovered common epigenetic deregulation of select factors that control radial glial biology, and PF radial glia in early human development exhibited reduced H3K27me3. Finally, H3K27me3 immunostaining served as a biomarker of poor prognosis and delineated radiologically invasive tumors, suggesting that reduced H3K27me3 may be a prognostic indicator in PF ependymomas.

Genetic analysis of familial forms of Alzheimer's disease (AD) causally links the proteolytic processing of the amyloid precursor protein (APP) and AD. However, the specific type of amyloid and mechanisms of amyloid pathogenesis remain unclear. We conducted a detailed analysis of intracellular amyloid with an aggregation specific conformation dependent monoclonal antibody, M78, raised against fibrillar Aß42. M78 immunoreactivity colocalizes with Aß and the carboxyl terminus of APP (APP-CTF) immunoreactivities in perinuclear compartments at intermediate times in 10month 3XTg-AD mice, indicating that this represents misfolded and aggregated protein rather than normally folded APP. At 12months, M78 immunoreactivity also accumulates in the nucleus. Neuritic plaques at 12months display the same spatial organization of centrally colocalized M78, diffuse chromatin and neuronal nuclear NeuN staining surrounded by peripheral M78 and APP-CTF immunoreactivity as observed in neurons, indicating that neuritic plaques arise from degenerating neurons with intracellular amyloid immunoreactivity. The same staining pattern was observed in neuritic plaques in human AD brains, showing elevated intracellular M78 immunoreactivity at intermediate stages of amyloid pathology (Braak A and B) compared to no amyloid pathology and late stage amyloid pathology (Braak 0 and C, respectively). These results indicate that intraneuronal protein aggregation and amyloid accumulation is an early event in AD and that neuritic plaques are initiated by the degeneration and death of neurons by a mechanism that may be related to the formation of extracellular traps by neutrophils.

Genetic analysis of familial forms of Alzheimer's disease (AD) causally links the proteolytic processing of the amyloid precursor protein (APP) and AD. However, the specific type of amyloid and mechanisms of amyloid pathogenesis remain unclear. We conducted a detailed analysis of intracellular amyloid with an aggregation specific conformation dependent monoclonal antibody, M78, raised against fibrillar Aß42. M78 immunoreactivity colocalizes with Aß and the carboxyl terminus of APP (APP-CTF) immunoreactivities in perinuclear compartments at intermediate times in 10month 3XTg-AD mice, indicating that this represents misfolded and aggregated protein rather than normally folded APP. At 12months, M78 immunoreactivity also accumulates in the nucleus. Neuritic plaques at 12months display the same spatial organization of centrally colocalized M78, diffuse chromatin and neuronal nuclear NeuN staining surrounded by peripheral M78 and APP-CTF immunoreactivity as observed in neurons, indicating that neuritic plaques arise from degenerating neurons with intracellular amyloid immunoreactivity. The same staining pattern was observed in neuritic plaques in human AD brains, showing elevated intracellular M78 immunoreactivity at intermediate stages of amyloid pathology (Braak A and B) compared to no amyloid pathology and late stage amyloid pathology (Braak 0 and C, respectively). These results indicate that intraneuronal protein aggregation and amyloid accumulation is an early event in AD and that neuritic plaques are initiated by the degeneration and death of neurons by a mechanism that may be related to the formation of extracellular traps by neutrophils.

Background: Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular A beta and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results: We immunized rabbits with a morphologically homogeneous population of A beta 42 fibrils. The resulting immune serum (OC) specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 x G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type II diabetes, demons

Background: Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular A beta and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results: We immunized rabbits with a morphologically homogeneous population of A beta 42 fibrils. The resulting immune serum (OC) specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 x G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type II diabetes, demons

Background: Amyloid-related degenerative diseases are associated with the accumulation of misfolded proteins as amyloid fibrils in tissue. In Alzheimer disease (AD), amyloid accumulates in several distinct types of insoluble plaque deposits, intracellular A beta and as soluble oligomers and the relationships between these deposits and their pathological significance remains unclear. Conformation dependent antibodies have been reported that specifically recognize distinct assembly states of amyloids, including prefibrillar oligomers and fibrils. Results: We immunized rabbits with a morphologically homogeneous population of A beta 42 fibrils. The resulting immune serum (OC) specifically recognizes fibrils, but not random coil monomer or prefibrillar oligomers, indicating fibrils display a distinct conformation dependent epitope that is absent in prefibrillar oligomers. The fibril epitope is also displayed by fibrils of other types of amyloids, indicating that the epitope is a generic feature of the polypeptide backbone. The fibril specific antibody also recognizes 100,000 x G soluble fibrillar oligomers ranging in size from dimer to greater than 250 kDa on western blots. The fibrillar oligomers recognized by OC are immunologically distinct from prefibrillar oligomers recognized by A11, even though their sizes overlap broadly, indicating that size is not a reliable indicator of oligomer conformation. The immune response to prefibrillar oligomers and fibrils is not sequence specific and antisera of the same specificity are produced in response to immunization with islet amyloid polypeptide prefibrillar oligomer mimics and fibrils. The fibril specific antibodies stain all types of amyloid deposits in human AD brain. Diffuse amyloid deposits stain intensely with anti-fibril antibody although they are thioflavin S negative, suggesting that they are indeed fibrillar in conformation. OC also stains islet amyloid deposits in transgenic mouse models of type II diabetes, demons

Introduction: substantial resources are required to provide lifelong post-operative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. Objectives: to assess the feasibility of comparing a remote care pathway to the standard pathway in adults using cochlear implants. Design: two-arm Randomised Controlled Trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. Setting: University of Southampton Auditory Implant Service: provider of NHS care. Participants: 60 adults who had used cochlear implants for at least 6 months. Interventions: control group (n = 30) followed usual care pathway. Remote care group (n = 30) received care remotely for 6 months incorporating: •Home hearing in noise test •Online support tool •Self-adjustment of device (only 10 had compatible equipment) Main outcome measures: Primary: change in patient activation; measured using the Patient Activation Measure® Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. Results: one participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Conclusions: adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-t

Introduction: substantial resources are required to provide lifelong post-operative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. Objectives: to assess the feasibility of comparing a remote care pathway to the standard pathway in adults using cochlear implants. Design: two-arm Randomised Controlled Trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. Setting: University of Southampton Auditory Implant Service: provider of NHS care. Participants: 60 adults who had used cochlear implants for at least 6 months. Interventions: control group (n = 30) followed usual care pathway. Remote care group (n = 30) received care remotely for 6 months incorporating: •Home hearing in noise test •Online support tool •Self-adjustment of device (only 10 had compatible equipment) Main outcome measures: Primary: change in patient activation; measured using the Patient Activation Measure® Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. Results: one participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Conclusions: adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-t

Introduction: substantial resources are required to provide lifelong post-operative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. Objectives: to assess the feasibility of comparing a remote care pathway to the standard pathway in adults using cochlear implants. Design: two-arm Randomised Controlled Trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. Setting: University of Southampton Auditory Implant Service: provider of NHS care. Participants: 60 adults who had used cochlear implants for at least 6 months. Interventions: control group (n = 30) followed usual care pathway. Remote care group (n = 30) received care remotely for 6 months incorporating: •Home hearing in noise test •Online support tool •Self-adjustment of device (only 10 had compatible equipment) Main outcome measures: Primary: change in patient activation; measured using the Patient Activation Measure® Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. Results: one participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Conclusions: adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-t

Introduction: substantial resources are required to provide lifelong post-operative care to people with cochlear implants. Most patients visit the clinic annually. We introduced a person-centred remote follow-up pathway, giving patients telemedicine tools to use at home so they would only visit the centre when intervention was required. Objectives: to assess the feasibility of comparing a remote care pathway to the standard pathway in adults using cochlear implants. Design: two-arm Randomised Controlled Trial. Randomisation used a minimisation approach, controlling for potential confounding factors. Participant blinding was not possible, but baseline measures occurred before allocation. Setting: University of Southampton Auditory Implant Service: provider of NHS care. Participants: 60 adults who had used cochlear implants for at least 6 months. Interventions: control group (n = 30) followed usual care pathway. Remote care group (n = 30) received care remotely for 6 months incorporating: •Home hearing in noise test •Online support tool •Self-adjustment of device (only 10 had compatible equipment) Main outcome measures: Primary: change in patient activation; measured using the Patient Activation Measure® Secondary: change in hearing and quality of life; qualitative feedback from patients and clinicians. Results: one participant in the remote care group dropped out. The remote care group showed a greater increase in patient activation than the control group. Changes in hearing differed between the groups. The remote care group improved on the Triple Digit Test hearing test; the control group perceived their hearing was worse on the Speech, Spatial and Qualities of Hearing questionnaire. Quality of life remained unchanged in both groups. Patients and clinicians were generally positive about remote care tools and wanted to continue. Conclusions: adults with cochlear implants were willing to be randomised and complied with the protocol. Personalised remote care for long-t