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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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- Abdel-Aal, Arwa, et al.
(författare)
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Prioritising primary care respiratory research needs : results from the 2020 International Primary Care Respiratory Group (IPCRG) global e-Delphi exercise
- 2022
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Ingår i: npj Primary Care Respiratory Medicine. - : Springer Nature. - 2055-1010. ; 32:1
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.
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- Adamo, Christin S., et al.
(författare)
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EMILIN1 deficiency causes arterial tortuosity with osteopenia and connects impaired elastogenesis with defective collagen fibrillogenesis
- 2022
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 109:12, s. 2230-2252
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Tidskriftsartikel (refereegranskat)abstract
- EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1-/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis.
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| 8. |
- 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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| 9. |
- Gauckler, Philipp, et al.
(författare)
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Rituximab in Membranous Nephropathy
- 2021
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 6:4, s. 881-893
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Forskningsöversikt (refereegranskat)abstract
- Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome among adults. The identification of phospholipase A2 receptor (PLA2R) as target antigen in most patients changed the management of MN dramatically, and provided a rationale for B-cell depleting agents such as rituximab. The efficacy of rituximab in inducing remission has been investigated in several studies, including 3 randomized controlled trials, in which complete and partial remission of proteinuria was achieved in approximately two-thirds of treated patients. Due to its favorable safety profile, rituximab is now considered a first-line treatment option for MN, especially in patients at moderate and high risk of deterioration in kidney function. However, questions remain about how to best use rituximab, including the optimal dosing regimen, a potential need for maintenance therapy, and assessment of long-term safety and efficacy outcomes. In this review, we provide an overview of the current literature and discuss both strengths and limitations of “the new standard.”
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- Ward, James P.J., et al.
(författare)
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Stable silicon isotopes uncover a mineralogical control on the benthic silicon cycle in the Arctic Barents Sea
- 2022
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Ingår i: Geochimica et Cosmochimica Acta. - : Elsevier BV. - 0016-7037. ; 329, s. 206-230
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Tidskriftsartikel (refereegranskat)abstract
- Biogeochemical cycling of silicon (Si) in the Barents Sea is under considerable pressure from physical and chemical changes, including dramatic warming and sea ice retreat, together with a decline in dissolved silicic acid (DSi) concentrations of Atlantic inflow waters since 1990. Associated changes in the community composition of phytoplankton blooms will alter the material comprising the depositional flux, which will subsequently influence recycling processes at and within the seafloor. In this study we assess the predominant controls on the early diagenetic cycling of Si, a key nutrient in marine ecosystems, by combining stable isotopic analysis (δ30Si) of pore water DSi and of operationally defined reactive pools of the solid phase. We show that low biogenic silica (BSi) contents (0.26–0.52 wt% or 92–185 μmol g dry wt−1) drive correspondingly low asymptotic concentrations of pore water DSi of ∼100 μM, relative to biosiliceous sediments (>20 wt% BSi) wherein DSi can reach ∼900 μM. While Barents Sea surface sediments appear almost devoid of BSi, we present evidence for the rapid recycling of bloom derived BSi that generates striking transient peaks in sediment pore water [DSi] of up to 300 μM, which is a feature that is subject to future shifts in phytoplankton community compositions. Using a simple isotopic mass balance calculation we show that at two of three stations the pore water DSi pool at 0.5 cm below the seafloor (+0.96 to +1.36 ‰) is sourced from the mixing of core top waters (+1.46 to +1.69 ‰) with the dissolution of BSi (+0.82 to +1.50 ‰), supplemented with a lithogenic Si source (LSi) (−0.89 ±0.16‰). Further, our sediment pore water δ30Si profiles uncover a coupling of the Si cycle with the redox cycling of metal oxides associated with isotopically light Si (−2.88 ±0.17‰). We suggest that a high LSi:BSi ratio and apparent metal oxide influence could lead to a degree of stability in the annual background benthic flux of DSi, despite current pressures on pelagic phytoplankton communities. Coupled with supporting isotopic evidence for the precipitation of authigenic clays in Barents Sea sediment cores, our observations have implications for the regional Si budget.
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