| 1. |
- de Rojas, I., et al.
(author)
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Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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| 2. |
- Marconi, A., et al.
(author)
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ANDES, the high resolution spectrograph for the ELT : science case, baseline design and path to construction
- 2022
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In: GROUND-BASED AND AIRBORNE INSTRUMENTATION FOR ASTRONOMY IX. - : SPIE - International Society for Optical Engineering. - 9781510653504 - 9781510653498
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Conference paper (peer-reviewed)abstract
- The first generation of ELT instruments includes an optical-infrared high resolution spectrograph, indicated as ELT-HIRES and recently christened ANDES (ArmazoNes high Dispersion Echelle Spectrograph). ANDES consists of three fibre-fed spectrographs (UBV, RIZ, YJH) providing a spectral resolution of similar to 100,000 with a minimum simultaneous wavelength coverage of 0.4-1.8 mu m with the goal of extending it to 0.35-2.4 mu m with the addition of a K band spectrograph. It operates both in seeing- and diffraction-limited conditions and the fibre-feeding allows several, interchangeable observing modes including a single conjugated adaptive optics module and a small diffraction-limited integral field unit in the NIR. Its modularity will ensure that ANDES can be placed entirely on the ELT Nasmyth platform, if enough mass and volume is available, or partly in the Coude room. ANDES has a wide range of groundbreaking science cases spanning nearly all areas of research in astrophysics and even fundamental physics. Among the top science cases there are the detection of biosignatures from exoplanet atmospheres, finding the fingerprints of the first generation of stars, tests on the stability of Nature's fundamental couplings, and the direct detection of the cosmic acceleration. The ANDES project is carried forward by a large international consortium, composed of 35 Institutes from 13 countries, forming a team of more than 200 scientists and engineers which represent the majority of the scientific and technical expertise in the field among ESO member states.
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| 3. |
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| 4. |
- Callaway, EM, et al.
(author)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Journal article (peer-reviewed)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 5. |
- Scott, Whitney, et al.
(author)
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A qualitative study of the experience and impact of neuropathic pain in people living with HIV
- 2020
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In: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 161:5, s. 970-978
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Journal article (peer-reviewed)abstract
- Painful distal symmetrical polyneuropathy is common in HIV and is associated with reduced quality of life. Research has not explored the experience of neuropathic pain in people with HIV from a person-centred perspective. Therefore, a qualitative interview study was conducted to more deeply understand the experience and impact of neuropathic pain in this population. Semi-structured interviews were conducted with 26 people with HIV and peripheral neuropathic pain symptoms. Interviews explored the impact of pain and participants' pain management strategies. Interviews were transcribed verbatim and analysed using thematic analysis. Four themes and 11 subthemes were identified. Theme one reflects the complex characterisation of neuropathic pain, including the perceived unusual nature of this pain and diagnostic uncertainty. Theme two centred on the interconnected impacts of pain on mood and functioning and includes how pain disrupts relationships and threatens social inclusion. Theme three reflects the struggle for pain relief, including participants' attempts to 'exhaust all options' and limited success in finding lasting relief. The final theme describes how pain management is complicated by living with HIV; this theme includes the influence of HIV stigma on pain communication and pain as an unwanted reminder of HIV. These data support the relevance of investigating and targeting psychosocial factors to manage neuropathic pain in HIV.
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| 6. |
- Scott, Whitney, et al.
(author)
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Acceptability of psychologically-based pain management and online delivery for people living with HIV and chronic neuropathic pain : a qualitative study
- 2021
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In: Scandinavian Journal of Pain. - : Walter de Gruyter. - 1877-8860 .- 1877-8879. ; 21:2, s. 296-307
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Journal article (peer-reviewed)abstract
- Objectives: Chronic neuropathic pain is common in people living with HIV. Psychological treatments can improve quality of life for people with chronic pain in general, and online delivery can increase access to these treatments. However, the acceptability of psychological treatment and online delivery have not been investigated in-depth in people living with HIV and chronic neuropathic pain. Therefore, a qualitative study was undertaken to explore views about a psychological treatment for pain management in this population and to investigate the acceptability of online treatment delivery.Methods: Qualitative interviews were conducted and analysed using inductive thematic analysis, adopting a critical realist perspective. Twenty-six people living with HIV and chronic neuropathic pain completed semi-structured interviews. Their views about a psychological treatment for pain management and online delivery were explored in-depth.Results: Three themes and 12 subthemes were identified. Theme one represents a desire for a broader approach to pain management, including not wanting to take more pills and having multidimensional goals that were not just focussed on pain relief. Theme two includes barriers to online psychologically-based pain management, including concerns about using the Internet and confidentiality. Theme three describes treatment facilitators, including accessibility, therapist support, social connection, and experiencing success.Conclusions: A psychological treatment for chronic neuropathic pain management appears acceptable for people living with HIV. Therapist-supported online delivery of cognitive-behavioural pain management may be acceptable for people living with HIV given appropriate development of the treatment to address identified barriers to engagement. These data can inform developments to enhance engagement in online psychologically-informed pain management in people living with HIV and more broadly in remote delivery of psychological treatments.
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| 8. |
- James, SL, et al.
(author)
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The global burden of falls: global, regional and national estimates of morbidity and mortality from the Global Burden of Disease Study 2017
- 2020
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In: Injury prevention : journal of the International Society for Child and Adolescent Injury Prevention. - : BMJ. - 1475-5785. ; 26:SUPP_1Supp 1, s. 3-11
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Journal article (peer-reviewed)abstract
- Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls.MethodsEstimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records.ResultsGlobally, the age-standardised incidence of falls was 2238 (1990–2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622–5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5–9.8) per 100 000 which equated to 695 771 (644 927–741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897–17 636 830) YLLs, 19 252 699 (13 725 429–26 140 433) YLDs and 35 940 787 (30 185 695–42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age.ConclusionsThis study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.
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| 9. |
- Micah, Angela E., et al.
(author)
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Tracking development assistance for health and for COVID-19 : a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050
- 2021
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In: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 398:10308, s. 1317-1343
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Research review (peer-reviewed)abstract
- Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$ per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached $8. 8 trillion (95% uncertainty interval [UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total, $40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this, $13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and $1.4 billion was repurposed from existing health projects. $3.1 billion (22.4%) of the funds focused on country-level coordination and $2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7%) of COVID-19 development assistance for health went to Latin America, despite this region reporting 34.3% of total recorded COVID-19 deaths in low-income or middle-income countries in 2020. Spending on health is expected to rise to $1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.
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| 10. |
- Storch, Eric A., et al.
(author)
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Little Doubt That CBT Works for Pediatric OCD
- 2020
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In: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567. ; 59:7, s. 785-787
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Journal article (peer-reviewed)abstract
- We write with great concern in response to the recent systematic review and meta-analysis of cognitive-behavioral therapy (CBT) in pediatric obsessive-compulsive disorder (OCD) by Uhre et al.1 Although the authors’ results consistently support the clinical efficacy of CBT for pediatric OCD, we expect that, much like ourselves, readers will be confused by the discordant and inappropriate conclusions that they put forward. These conclusions stem from the authors’ application and interpretation of their particular qualitative methods, which could lead important stakeholders (eg, parents, patients, clinicians, and payers) to wrongly discount clear evidence for what is known to be the best evidence-based therapy for pediatric OCD.
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