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- Sallee, J. B., et al.
(författare)
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Southern ocean carbon and heat impact on climate
- 2023
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Ingår i: Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences. - 1364-503X .- 1471-2962. ; 381:2249
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Tidskriftsartikel (refereegranskat)abstract
- The Southern Ocean greatly contributes to the regulation of the global climate by controlling important heat and carbon exchanges between the atmosphere and the ocean. Rates of climate change on decadal timescales are therefore impacted by oceanic processes taking place in the Southern Ocean, yet too little is known about these processes. Limitations come both from the lack of observations in this extreme environment and its inherent sensitivity to intermittent processes at scales that are not well captured in current Earth system models. The Southern Ocean Carbon and Heat Impact on Climate programme was launched to address this knowledge gap, with the overall objective to understand and quantify variability of heat and carbon budgets in the Southern Ocean through an investigation of the key physical processes controlling exchanges between the atmosphere, ocean and sea ice using a combination of observational and modelling approaches. Here, we provide a brief overview of the programme, as well as a summary of some of the scientific progress achieved during its first half. Advances range from new evidence of the importance of specific processes in Southern Ocean ventilation rate (e.g. storm-induced turbulence, sea-ice meltwater fronts, wind-induced gyre circulation, dense shelf water formation and abyssal mixing) to refined descriptions of the physical changes currently ongoing in the Southern Ocean and of their link with global climate.This article is part of a discussion meeting issue 'Heat and carbon uptake in the Southern Ocean: the state of the art and future priorities'.
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- Stray-Pedersen, Asbjorg, et al.
(författare)
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Primary immunodeficiency diseases : Genomic approaches delineate heterogeneous Mendelian disorders
- 2017
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Ingår i: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions. Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs. Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping. Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/ 110) and management was directly altered in nearly a quarter (26/ 110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays. Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes.
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- Chotiyarnwong, P., et al.
(författare)
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Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group
- 2022
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Ingår i: Archives of Osteoporosis. - : Springer Science and Business Media LLC. - 1862-3522 .- 1862-3514. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- A Summary The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. Introduction The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. Methods The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. Results and Conclusion The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.
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- Buchan, K. L., et al.
(författare)
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Comparing the drift of Laurentia and baltica in the Proterozoic : the importance of key palaeomagnetic poles
- 2000
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Ingår i: Tectonophysics. - 0040-1951 .- 1879-3266. ; 319:3, s. 167-198
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Tidskriftsartikel (refereegranskat)abstract
- Key palaeomagnetic poles are defined as those which pass basic reliability criteria and are precisely and accurately dated. They allow a more rigorous analysis of Precambrian continental drift and continental reconstructions than the traditional apparent polar wander path (APWP) approach using mostly non-key poles. Between ca. 2.45 and 2.00 Ga in the early Palaeoproterozoic, key poles define the drift of the Archaean Superior craton of Laurentia, yielding a result that is quite unlike the drift interpreted in earlier studies using the APWP method. There are no early Palaeoproterozoic key poles for the other Archaean cratons that amalgamated to form Laurentia and Baltica prior to 1.8 Ga, so that a rigorous test of early Palaeoproterozoic reconstruction models is not possible. Key poles from Laurentia between ca. 1.46 and 1.267 Ga and Baltica between 1.63 and 1.265 Ga help to define, in a preliminary fashion, the early Mesoproterozoic drift of the two shields. The key pole age match at ca. 1.265 Ga is consistent with Baltica located adjacent to eastern Greenland, and geological considerations suggest that the most reasonable fit aligns the Labradorian belt of Laurentia with the Gothian belt of Baltica. Although there is limited support from non-key poles and key poles that are not matched in age for such a fit as early as ca. 1.8 Ga, no rigorous assessment will be possible until a match in key pole ages is achieved. In the late Mesoproterozoic to Neoproterozoic, Laurentia's drift is reasonably well documented by seven key poles between 1.235 and 0.73 Ga. There are no key poles in this period from Baltica, however, so that a ≈90° clockwise rotation of Baltica relative to Laurentia between 1.265 and 1.0 Ga, widely used in the literature, cannot be confirmed.
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- Ferrari, S. L., et al.
(författare)
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Diagnosis and management of bone fragility in diabetes : an emerging challenge
- 2018
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 29:12, s. 2585-2596
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Tidskriftsartikel (refereegranskat)abstract
- Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.
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| 9. |
- Kanis, J. A., et al.
(författare)
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Primary hyperparathyroidism and fracture probability
- 2023
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 34, s. 489-499
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Tidskriftsartikel (refereegranskat)abstract
- The incidence of hip and major osteoporotic fracture was increased in patients with primary hyperparathyroidism even in patients not referred for parathyroidectomy. The risk of death was also increased which attenuated an effect on fracture probabilities. The findings argue for widening the indications for parathyroidectomy in mild primary hyperparathyroidism.Introduction Primary hyperparathyroidism (PHPT) is associated with an increase in the risk of fracture. In FRAX, the increase in risk is assumed to be mediated by low bone mineral density (BMD). However, the risk of death is also increased and its effect on fracture probability is not known.Objective The aim of this study was to determine whether PHPT affects hip fracture and major osteoporotic fracture risk independently of bone mineral density (BMD) and whether this and any increase in mortality affects the assessment of fracture probability.Methods A register-based survey of patients with PHPT and matched controls in Denmark were identified from hospital registers. The incidence of death, hip fracture, and major osteoporotic fracture were determined for computing fracture probabilities excluding time after parathyroidectomy. The gradient of risk for fracture for differences in BMD was determined in a subset of patients and in BMD controls. The severity of disease was based on serum calcium and parathyroid hormone levels.Results We identified 6884 patients with biochemically confirmed PHPT and 68,665 matched population controls. On follow-up, excluding time after parathyroidectomy in those undergoing surgery, patients with PHPT had a higher risk of death (+52%), hip fracture (+48%), and major osteoporotic fracture (+36%) than population controls. At any given age, average 10-year probabilities of fracture were higher in patients with PHPT than population controls. The gradient of fracture risk with differences in BMD was similar in cases and controls. Results were similar when confined to patients not undergoing parathyroidectomy. Fracture probability decreased with the severity of disease due to an increase in mortality rather than fracture risk.Conclusion The risk of hip and other major osteoporotic fracture is increased in PHPT irrespective of the disease severity. Fracture probability was attenuated due to the competing effect of mortality. The increased fracture risk in patients treated conservatively argues for widening the indications for parathyroidectomy in mild PHPT.
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| 10. |
- Lagerström, Malin C., et al.
(författare)
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A sensory subpopulation depends on vesicular glutamate transporter 2 for mechanical pain, and together with substance P, inflammatory pain
- 2011
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 108:14, s. 5789-5794
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Tidskriftsartikel (refereegranskat)abstract
- Ablating or functionally compromising sets of sensory neurons has provided important insights into peripheral modality-specific wiring in the somatosensory system. Inflammatory hyperalgesia, cold pain, and noxious mechanosensation have all been shown to depend upon Na(v)1.8-positive sensory neurons. The release of fast-acting neurotransmitters, such as glutamate, and more slowly released neuropeptides, such as substance P (SP), contribute to the diversified responses to external stimuli. Here we show that deleting Vglut2 in Na(v)1.8(Cre)-positive neurons compromised mechanical pain and NGF-induced thermal hyperalgesia, whereas tactile-evoked sensation, thermal, formalin-evoked, and chronic neuropathic pain were normal. However, when Vglut2(f/f); Na(v)1.8(Cre) mice were injected with a SP antagonist before the formalin test, the second phase pain response was nearly completely abolished, whereas in control mice, the pain response was unaffected. Our results suggest that VGLUT2-dependent signaling originating from Na(v)1.8-positive neurons is a principal sensing mechanism for mechanical pain and, together with SP, inflammatory pain. These data define sets of primary afferents associated with specific modalities and provide useful genetic tools with which to analyze the pathways that are activated by functionally distinct neuronal populations and transmitters.
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