| 1. |
- Alimena, Juliette, et al.
(författare)
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Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
- 2020
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Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
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Tidskriftsartikel (refereegranskat)abstract
- Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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| 2. |
- Bousquet, Jean, et al.
(författare)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Forskningsöversikt (refereegranskat)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 3. |
- Cable, Jennifer, et al.
(författare)
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Progress in vaccine development for infectious diseases : a Keystone Symposia report
- 2023
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Ingår i: Annals of the New York Academy of Sciences. - : John Wiley & Sons. - 0077-8923 .- 1749-6632. ; 1524:1, s. 65-86
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Tidskriftsartikel (refereegranskat)abstract
- The COVID-19 pandemic has taught us many things, among the most important of which is that vaccines are one of the cornerstones of public health that help make modern longevity possible. While several different vaccines have been successful at stemming the morbidity and mortality associated with various infectious diseases, many pathogens/diseases remain recalcitrant to the development of effective vaccination. Recent advances in vaccine technology, immunology, structural biology, and other fields may yet yield insight that will address these diseases; they may also help improve societies' preparedness for future pandemics. On June 1-4, 2022, experts in vaccinology from academia, industry, and government convened for the Keystone symposium "Progress in Vaccine Development for Infectious Diseases" to discuss state-of-the-art technologies, recent advancements in understanding vaccine-mediated immunity, and new aspects of antigen design to aid vaccine effectiveness.
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| 4. |
- Guintivano, Jerry, et al.
(författare)
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Meta-Analyses of Genome-Wide Association Studies for Postpartum Depression
- 2023
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Ingår i: American Journal of Psychiatry. - : American Psychiatric Association Publishing. - 0002-953X .- 1535-7228. ; 180:12, s. 884-895
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.METHOD: Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.RESULTS: No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.CONCLUSIONS: While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
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| 5. |
- Johansson, Angelica, 1990-, et al.
(författare)
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Evaluating progress on loss and damage: an assessment of the Executive Committee of the Warsaw International Mechanism under the UNFCCC
- 2022
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Ingår i: Climate Policy. - : Taylor & Francis. - 1469-3062 .- 1752-7457. ; 22:9-10, s. 1199-1212
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Tidskriftsartikel (refereegranskat)abstract
- The Warsaw International Mechanism for Loss and Damage Associated with Climate Change Impacts (WIM) was established in 2013, and its Executive Committee (ExCom) is developing a new five-year workplan. Seizing this opportune moment to assess institutional progress on the issue of loss and damage under the United Nations Framework Convention on Climate Change (UNFCCC) we address two research questions: (1) Has the ExCom delivered on its workplans to date, and (2) how has the ExCom’s progress varied across thematic areas? Drawing on public documentary sources, we assess the effectiveness and timeliness of the delivery of activities across five thematic areas: slow onset events; non-economic losses; comprehensive risk management approaches; human mobility; and finance, action and support. We find that there has been progress across the thematic areas, but that it has varied in pace. Delays are associated with activities from the two-year workplan being moved into the first five-year workplan or being devolved to the more recently established expert groups. Our results also show that decisions from the Conference of the Parties (COP) or the COP serving as the Meeting of the Parties to the Paris Agreement (CMA) have played a critical role in accelerating specific aspects of the ExCom’s work. Finally, we note that the ExCom is increasingly relying on its expert groups and their members to deliver many activities. This research advances our understanding of the nature and pace of progress on this issue, and raises new questions about the politics of global climate policy implementation.KEY POLICY INSIGHTSThe WIM ExCom’s workplans are characterized by broad goals and are ambiguous about start dates and deadlines. To enhance accountability, future workplans would benefit from clearly defined objectives, outcomes, and timelines.The workplans do not seem to constitute strong commitments: Parties make use of COP/CMA decisions to strengthen the workplans by mandating specific activities or deadlines, adding new activities and prioritizing among existing ones.The politics of implementation merits greater attention: wider political dynamics around loss and damage shape the pace of the ExCom’s supposedly technical work. One example is the delayed establishment of the expert group on action and support.
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| 6. |
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| 7. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 8. |
- Ma, Wenjie, et al.
(författare)
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Cancer risk in patients with diverticular disease : A nationwide cohort study
- 2022
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105.
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are little data on diverticular disease and cancer development other than colorectal cancer.Methods: We conducted a population-based, matched cohort study with linkage of nationwide registers to the Epidemiology Strengthened by histoPathology Reports in Sweden histopathology cohort. We included 75 704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313 480 reference individuals from the general population matched on age, sex, calendar year, and county. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) for associations between diverticular disease and overall cancer and specific cancers.Results: Over a median follow-up of 6 years, we documented 12 846 incident cancers among patients with diverticular disease and 43 354 incident cancers among reference individuals from the general population. Compared with reference individuals, patients with diverticular disease had statistically significantly increased overall cancer incidence (24.5 vs 18.1 per 1000 person-years), equivalent to 1 extra cancer case in 16 individuals with diverticular disease followed-up for 10 years. After adjusting for covariates, having a diagnosis of diverticular disease was associated with a 33% increased risk of overall cancer (95% confidence interval [CI] = 1.31 to 1.36). The risk increases also persisted compared with siblings as secondary comparators (HR = 1.26, 95% CI = 1.21 to 1.32). Patients with diverticular disease also had an increased risk of specific cancers, including colon cancer (HR = 1.71, 95% CI = 1.60 to 1.82), liver cancer (HR = 1.72, 95% CI = 1.41 to 2.10), pancreatic cancer (HR = 1.62, 95% CI = 1.42 to 1.84), and lung cancer (HR = 1.50, 95% CI = 1.39 to 1.61). The increase in colorectal cancer risk was primarily restricted to the first year of follow-up, and especially early cancer stages.Conclusions: Patients with diverticular disease who have colorectal histopathology have an increased risk of overall incident cancer.
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| 9. |
- Margaryan, Ashot, et al.
(författare)
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Population genomics of the Viking world
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 585:7825, s. 390-396
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Tidskriftsartikel (refereegranskat)abstract
- The maritime expansion of Scandinavian populations during the Viking Age (about ad750–1050) was a far-flung transformation in world history1,2. Here we sequenced the genomes of 442humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci—including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response—in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.
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| 10. |
- Vanhala, Lisa, et al.
(författare)
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Reflections on the Global Governance of Climate Change Loss and Damage at COP26.
- 2021
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Annan publikation (populärvet., debatt m.m.)abstract
- What happened on the issue of loss and damage atthe 26th Conference of the Parties (COP26) held inGlasgow in November 2021 and why does it matter?In many ways COP26 was the moment when lossand damage was transformed from being an issueof importance to certain states and communities –for example the small island states – to one that hasbecome centre stage for much of the world. Thedeveloping countries grouping, known as the G77plus China, were united in unprecedented ways onthe issue of loss and damage in Glasgow. We alsowitnessed a host of different non-state and substate stakeholders taking up the mantle of loss anddamage from those marching in the streets, to theFirst Minister of Scotland to the Trade Unionconstituency of the UNFCCC.Given the growing frequency and intensity of theadverse impacts of climate change globally and thelaunch of the most recent assessment of theIntergovernmental Panel on Climate Change(IPCC), the Working Group I contribution to the 6thAssessment Report, this is an issue that is now onthe political agenda. This set of short reflectionsfrom our inter-disciplinary team of expertsadvances our understanding of the globalgovernance of climate change loss and damage.Coming from different disciplinary perspectives,from anthropology and law to geography andpolitical science, we explore the topic of climatechange loss and damage governance focusing onissues of finance, science and expertise, policy, lawand litigation.
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| 11. |
- Wagner, Jessica, et al.
(författare)
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Medin co-aggregates with vascular amyloid-beta in Alzheimers disease
- 2022
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Ingår i: Nature. - : Nature Portfolio. - 0028-0836 .- 1476-4687. ; 612, s. 123-131
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Tidskriftsartikel (refereegranskat)abstract
- Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age(1,)(2), making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction(3). Here we demonstrate in amyloid-beta precursor protein (APP) transgenic mice and in patients with Alzheimers disease that medin co-localizes with vascular amyloid-beta deposits, and that in mice, medin deficiency reduces vascular amyloid-beta deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-beta burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimers disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-beta to promote its aggregation, as medin forms heterologous fibrils with amyloid-beta, affects amyloid-beta fibril structure, and cross-seeds amyloid-beta aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-beta deposition in the blood vessels of the brain.
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| 12. |
- Welch, Vivian, et al.
(författare)
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Health, social care and technological interventions to improve functional ability of older adults living at home : An evidence and gap map
- 2021
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Ingår i: Campbell Systematic Reviews. - : Wiley. - 1891-1803. ; 17:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: By 2030, the global population of people older than 60 years is expected to be higher than the number of children under 10 years, resulting in major health and social care system implications worldwide. Without a supportive environment, whether social or built, diminished functional ability may arise in older people. Functional ability comprises an individual's intrinsic capacity and people's interaction with their environment enabling them to be and do what they value. Objectives: This evidence and gap map aims to identify primary studies and systematic reviews of health and social support services as well as assistive devices designed to support functional ability among older adults living at home or in other places of residence. Search Methods: We systematically searched from inception to August 2018 in: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, CINAHL, PsycINFO, AgeLine, Campbell Library, ASSIA, Social Science Citation Index and Social Policy & Practice. We conducted a focused search for grey literature and protocols of studies (e.g., ProQuest Theses and Dissertation Global, conference abstract databases, Help Age, PROSPERO, Cochrane and Campbell libraries and ClinicalTrials.gov). Selection Criteria: Screening and data extraction were performed independently in duplicate according to our intervention and outcome framework. We included completed and on-going systematic reviews and randomized controlled trials of effectiveness on health and social support services provided at home, assistive products and technology for personal indoor and outdoor mobility and transportation as well as design, construction and building products and technology of buildings for private use such as wheelchairs, and ramps. Data Collection and Analysis: We coded interventions and outcomes, and the number of studies that assessed health inequities across equity factors. We mapped outcomes based on the International Classification of Function, Disability and Health (ICF) adapted categories: intrinsic capacities (body function and structures) and functional abilities (activities). We assessed methodological quality of systematic reviews using the AMSTAR II checklist. Main Results: After de-duplication, 10,783 records were screened. The map includes 548 studies (120 systematic reviews and 428 randomized controlled trials). Interventions and outcomes were classified using domains from the International Classification of Function, Disability and Health (ICF) framework. Most systematic reviews (n = 71, 59%) were rated low or critically low for methodological quality. The most common interventions were home-based rehabilitation for older adults (n = 276) and home-based health services for disease prevention (n = 233), mostly delivered by visiting healthcare professionals (n = 474). There was a relative paucity of studies on personal mobility, building adaptations, family support, personal support and befriending or friendly visits. The most measured intrinsic capacity domains were mental function (n = 269) and neuromusculoskeletal function (n = 164). The most measured outcomes for functional ability were basic needs (n = 277) and mobility (n = 160). There were few studies which evaluated outcome domains of social participation, financial security, ability to maintain relationships and communication. There was a lack of studies in low- and middle-income countries (LMICs) and a gap in the assessment of health equity issues. Authors' Conclusions: There is substantial evidence for interventions to promote functional ability in older adults at home including mostly home-based rehabilitation for older adults and home-based health services for disease prevention. Remotely delivered home-based services are of greater importance to policy-makers and practitioners in the context of the COVID-19 pandemic. This map of studies published prior to the pandemic provides an initial resource to identify relevant home-based services which may be of interest for policy-makers and practitioners, such as home-based rehabilitation and social support, although these interventions would likely require further adaptation for online delivery during the COVID-19 pandemic. There is a need to strengthen assessment of social support and mobility interventions and outcomes related to making decisions, building relationships, financial security, and communication in future studies. More studies are needed to assess LMIC contexts and health equity issues.
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