58 research outputs found

    A note on stable flow-equivalent aggregation in closed networks

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    SamhÀllet har tagit pÄ sig ett stort ansvar för de barn som placeras utanför hemmet. MÄnga av dem har upplevt svÄrigheter och inte fÄtt tillrÀcklig omvÄrdnad. Ska dessa barn fÄ samma möjlighet till ett gott liv som sina jÀmnÄriga kamrater behöver de dÀrför ett minst lika bra omhÀndertagande, av bÄde fosterförÀldrar och samhÀllet i stort. Barn som lever i fosterhem Àr en mycket heterogen grupp. De behöver olika vÄrd och bemötande i familjehemmet för att utvecklas optimalt. Just detta mycket komplexa förhÄllande berörs inte i denna kunskapsöversikt. HÀr har vi valt att fokusera pÄ samhÀllets grundlÀggande omhÀndertagande av barnen. Tre primÀra bestÄndsdelar i den nordiska vÀlfÀrdsmodellen Àr att ge barn en god och jÀmlik utbildning, förebygga hÀlsoproblem och underlÀtta övergÄngen frÄn barndom till vuxenliv. Det Àr dessa omrÄden som beskrivs hÀr. Den nordiska forskning som finns pekar pÄ att barn som vÀxer upp i fosterhem inte fÄr samma goda stöd som andra barn pÄ dessa omrÄden och det tycks inte bli bÀttre under tiden i vÄrd! Nordens VÀlfÀrdscenter och författarna presenterar konkreta rekommendationer om hur man kan förbÀttra situationen för fosterhemsplacerade barn. Det Àr rekommendationer som sannolikt förhindrar utanförskap och ohÀlsa för ett antal av dem pÄ bÄde kort och lÄng sikt.Nordens Barn - Fokus pÄ barn i fosterhe

    Internet-based interventions for parents with children 0–5 years: A scoping review

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    This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Aim: This study aims to review the existing literature on Internet-based health interventions directed to support parents of children aged 0–5 years. Methods: We systematically searched electronic databases between January 2000 and 2018. The search consisted of terms describing eHealth, intervention and families and/or children. Results: Internet-based parent support interventions were most often directed at rehabilitation and selective prevention, and we identified more studies on mental health (57%) than somatic health (41%). Developmental disorders were the most frequently studied mental health condition (n = 33), while interventions for obesity (15%) were the most studied somatic health condition. Forty-four percent of mental health studies were RCTs and 65% of interventions were theory driven. Interventions most often used a behavioural approach, included guidance and delivered content via text-based information. Conclusion: Several significant gaps were identified such as the need for more research outside of English-speaking countries, more systematic reviews and effect studies. This review also elucidates the need for researchers to improve reporting on the theoretical approaches employed in interventions, and to focus on determining the importance of guidance. Finally, program developers should consider using more audio-visual technology to avoid reinforcing social inequalities in access to healthcare.publishedVersio

    Finding the needle in the haystack: Comparison of methods for salmon louse enumeration in plankton samples

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    The economic and social implications of salmon louse (Lepeophtheirus salmonis) epidemics in salmon aquaculture drive focus of the dispersal dynamics of the planktonic larval stages. The vast spatial scale and high connectivity of the marine environment creates difficult conditions to monitor the infective planktonic louse stage, whereby the number of samples required for a representative description is bottlenecked by processing capacity. This study assessed five quantification methods for accuracy and precision in enumeration of lice in plankton samples, validated against the benchmark method of light microscopy. Visual-based (fluorescence microscopy and automated fluid imaging) and molecular-based (droplet digital PCR, quantitative fraction PCR and quantitative PCR) were tested using high- and low-density plankton samples spiked with louse copepodids, with spike numbers blind to assessors. We propose an approach to comparative assessment that uses the collective bias and deviation of a test method to determine whether it is acceptably similar to the benchmark method. Under this framework, no methods passed the comparative test, with only ddPCR comparable to light microscopy (87% mean accuracy and 74% precision). qfPCR and fluorescence microscopy were moderately efficient (88% and 67% accuracy, and 36% and 52% precision respectively). Molecular techniques are currently restricted in distinguishing between larval stages, which is an essential distinction for some research questions, but can be economical in processing numerous samples. Overall method suitability will depend on the research objectives and resources available. These results provide evidence for operational accuracy for the tested methods and highlight the direction for further development to optimize their use

    A reproducible brain tumour model established from human glioblastoma biopsies

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    Background: Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates. Methods: In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features. Results: The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages in vivo, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 in vivo passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms. Conclusions: In vivo passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to in vitro propagated cell lines for dissecting mechanisms of brain tumour progression.publishedVersio

    Ipilimumab in a real-world population: A prospective Phase IV trial with long-term follow-up

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    Ipilimumab was the first treatment that improved survival in advanced melanoma. Efficacy and toxicity in a real-world setting may differ from clinical trials, due to more liberal eligibility criteria and less intensive monitoring. Moreover, high costs and lack of biomarkers have raised cost-benefit concerns about ipilimumab in national healthcare systems and limited its use. Here, we report the prospective, interventional study, Ipi4 (NCT02068196), which aimed to investigate the toxicity and efficacy of ipilimumab in a real-world population with advanced melanoma. This national, multicentre, phase IV trial included 151 patients. Patients received ipilimumab 3 mg/kg intravenously and were followed for at least 5 years or until death. Treatment interruption or cessation occurred in 38%, most frequently due to disease progression (19%). Treatment-associated grade 3 to 4 toxicity was observed in 28% of patients, and immune-related toxicity in 56%. The overall response rate was 9%. Median overall survival was 12.1 months (95% CI: 8.3-15.9); and progression-free survival 2.7 months (95% CI: 2.6-2.8). After 5 years, 20% of patients were alive. In a landmark analysis from 6 months, improved survival was associated with objective response (HR 0.16, P = .001) and stable disease (HR 0.49, P = .005) compared to progressive disease. Poor performance status, elevated lactate dehydrogenase and C-reactive protein were identified as biomarkers. This prospective trial represents the longest reported follow-up of a real-world melanoma population treated with ipilimumab. Results indicate safety and efficacy comparable to phase III trials and suggest that the use of ipilimumab can be based on current cost-benefit estimates.publishedVersio

    Tumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenografts

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    Background: Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. Methods: We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b+ immune and CD31+ endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors. This cell population was subsequently characterised using gene expression analyses and immunocytochemistry. Furthermore, sphere formation was assessed in vitro and their glioma growth-promoting ability was examined in vivo. Finally, the expression of TAG related markers was validated in human GBMs. Results: TAGs were highly enriched for the expression of glial cell proteins including GFAP and myelin basic protein (MBP), and immature markers such as Nestin and O4. A fraction of TAGs displayed sphere formation in stem cell medium. Moreover, TAGs promoted brain tumour growth in vivo when co-implanted with glioma cells, compared to implanting only glioma cells, or glioma cells and unconditioned glial cells from mice without tumours. Genome-wide microarray analysis of TAGs showed an expression profile distinct from glial cells from healthy mice brains. Notably, TAGs upregulated genes associated with immature cell types and self-renewal, including Pou3f2 and Sox2. In addition, TAGs from highly angiogenic tumours showed upregulation of angiogenic factors, including Vegf and Angiopoietin 2. Immunohistochemistry of three GBMs, two patient biopsies and one GBM xenograft, confirmed that the expression of these genes was mainly confined to TAGs in the tumour bed. Furthermore, their expression profiles displayed a significant overlap with gene clusters defining prognostic subclasses of human GBMs. Conclusions: Our data demonstrate that glial host cells in brain tumours are functionally distinct from glial cells of healthy mice brains. Furthermore, TAGs display a gene expression profile with enrichment for genes related to stem cells, immature cell types and developmental processes. Future studies are needed to delineate the biological mechanisms regulating the brain tumour-host interplay.publishedVersio

    SARS-CoV-2 vaccines are not associated with hypercoagulability in apparently healthy people

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    Background: SARS-CoV-2 adenoviral vector DNA vaccines have been linked to the rare but serious thrombotic postvaccine complication vaccine-induced immune thrombotic thrombocytopenia. This has raised concerns regarding the possibility of increased thrombotic risk after any SARS-CoV-2 vaccines. Objectives: To investigate whether SARS-CoV-2 vaccines cause coagulation activation leading to a hypercoagulable state. Methods: This observational study included 567 health care personnel; 521 were recruited after the first dose of adenoviral vector ChAdOx1-S (Vaxzevria, AstraZeneca) vaccine and 46 were recruited prospectively before vaccination with a messenger RNA (mRNA) vaccine, either Spikevax (Moderna, n = 38) or Comirnaty (Pfizer-BioNTech, n = 8). In the mRNA group, samples were acquired before and 1 to 2 weeks after vaccination. In addition to the prevaccination samples, 56 unvaccinated blood donors were recruited as controls (total n = 102). Thrombin generation, D-dimer levels, and free tissue factor pathway inhibitor (TFPI) levels were analyzed. Results: No participant experienced thrombosis, vaccine-induced immune thrombotic thrombocytopenia, or thrombocytopenia (platelet count 9 /L) 1 week to 1 month postvaccination. There was no increase in thrombin generation, D-dimer level, or TFPI level in the ChAdOx1-S vaccine group compared with controls or after the mRNA vaccines compared with baseline values. Eleven of 513 (2.1%) participants vaccinated with ChAdOx1-S had anti-PF4/polyanion antibodies without a concomitant increase in thrombin generation. Conclusion: In this study, SARS-CoV-2 vaccines were not associated with thrombosis, thrombocytopenia, increased thrombin generation, D-dimer levels, or TFPI levels compared with baseline or unvaccinated controls. These findings argue against the subclinical activation of coagulation post-COVID-19 vaccination

    A reproducible brain tumour model established from human glioblastoma biopsies

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    <p>Abstract</p> <p>Background</p> <p>Establishing clinically relevant animal models of glioblastoma multiforme (GBM) remains a challenge, and many commonly used cell line-based models do not recapitulate the invasive growth patterns of patient GBMs. Previously, we have reported the formation of highly invasive tumour xenografts in nude rats from human GBMs. However, implementing tumour models based on primary tissue requires that these models can be sufficiently standardised with consistently high take rates.</p> <p>Methods</p> <p>In this work, we collected data on growth kinetics from a material of 29 biopsies xenografted in nude rats, and characterised this model with an emphasis on neuropathological and radiological features.</p> <p>Results</p> <p>The tumour take rate for xenografted GBM biopsies were 96% and remained close to 100% at subsequent passages <it>in vivo</it>, whereas only one of four lower grade tumours engrafted. Average time from transplantation to the onset of symptoms was 125 days ± 11.5 SEM. Histologically, the primary xenografts recapitulated the invasive features of the parent tumours while endothelial cell proliferations and necrosis were mostly absent. After 4-5 <it>in vivo </it>passages, the tumours became more vascular with necrotic areas, but also appeared more circumscribed. MRI typically revealed changes related to tumour growth, several months prior to the onset of symptoms.</p> <p>Conclusions</p> <p><it>In vivo </it>passaging of patient GBM biopsies produced tumours representative of the patient tumours, with high take rates and a reproducible disease course. The model provides combinations of angiogenic and invasive phenotypes and represents a good alternative to <it>in vitro </it>propagated cell lines for dissecting mechanisms of brain tumour progression.</p

    Chronic fatigue syndromes: real illnesses that people can recover from

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    The ‘Oslo Chronic Fatigue Consortium’ consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brain's response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation. Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them
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