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- Mann, G. W., et al.
(författare)
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Intercomparison and evaluation of global aerosol microphysical properties among AeroCom models of a range of complexity
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 14:9, s. 4679-4713
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Tidskriftsartikel (refereegranskat)abstract
- Many of the next generation of global climate models will include aerosol schemes which explicitly simulate the microphysical processes that determine the particle size distribution. These models enable aerosol optical properties and cloud condensation nuclei (CCN) concentrations to be determined by fundamental aerosol processes, which should lead to a more physically based simulation of aerosol direct and indirect radiative forcings. This study examines the global variation in particle size distribution simulated by 12 global aerosol microphysics models to quantify model diversity and to identify any common biases against observations. Evaluation against size distribution measurements from a new European network of aerosol supersites shows that the mean model agrees quite well with the observations at many sites on the annual mean, but there are some seasonal biases common to many sites. In particular, at many of these European sites, the accumulation mode number concentration is biased low during winter and Aitken mode concentrations tend to be overestimated in winter and underestimated in summer. At high northern latitudes, the models strongly underpredict Aitken and accumulation particle concentrations compared to the measurements, consistent with previous studies that have highlighted the poor performance of global aerosol models in the Arctic. In the marine boundary layer, the models capture the observed meridional variation in the size distribution, which is dominated by the Aitken mode at high latitudes, with an increasing concentration of accumulation particles with decreasing latitude. Considering vertical profiles, the models reproduce the observed peak in total particle concentrations in the upper troposphere due to new particle formation, although modelled peak concentrations tend to be biased high over Europe. Overall, the multimodel-mean data set simulates the global variation of the particle size distribution with a good degree of skill, suggesting that most of the individual global aerosol microphysics models are performing well, although the large model diversity indicates that some models are in poor agreement with the observations. Further work is required to better constrain size-resolved primary and secondary particle number sources, and an improved understanding of nucleation and growth (e. g. the role of nitrate and secondary organics) will improve the fidelity of simulated particle size distributions.
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- Borchgrevink, Petter C., et al.
(författare)
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A Clinical Description of Chronic Pain in a General Population Using ICD-10 and ICD-11 (The HUNT Pain Examination Study)
- 2022
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Ingår i: Journal of Pain. - : Elsevier. - 1526-5900 .- 1528-8447. ; 23:2, s. 337-348
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Tidskriftsartikel (refereegranskat)abstract
- The purpose was to present a total description, distribution, and ranking of chronic pain conditions in the general population. This was based on structured clinical examinations of a random sample from a population-based survey (HUNT3) with a calculated oversampling of participants with chronic pain. Supplemented with access to hospital reports, the examination was performed by experienced physicians and psychologists using a consistent definition of chronic pain as well as ICD-10- and the new ICD-11-classification. The main findings were that a higher proportion of the 551 participants had chronic pain assessed by clinical examination (399) than by self-report in a survey the same day (337). Among those with examination-verified chronic pain estimated from HUNT3 to represent 27.9% of the general population, 63% had chronic primary pain, 81% musculoskeletal pain, and 77% more than one chronic pain condition. When separating chronic primary from chronic secondary pain according to ICD-11, the weighted prevalence was 17.7% for chronic pain conditions of unknown and 10.2% of known cause. When all the participants’ conditions were accounted for, the most prevalent was nonspecific low back (10.8%) and neck pain (7.6%). Participants with chronic primary pain did not have significantly more psychopathology than those with chronic secondary pain: 14.5% versus 12.5%.
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- Dent, E., et al.
(författare)
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Physical Frailty : ICFSR International Clinical Practice Guidelines for Identification and Management
- 2019
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Ingår i: The Journal of Nutrition, Health & Aging. - : SPRINGER FRANCE. - 1279-7707 .- 1760-4788. ; 23:9, s. 771-787
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults.Methods: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care.Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation).Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.
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- Glette, Mari, et al.
(författare)
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Catastrophizing, Solicitous Responses From Significant Others, and Function in Individuals With Neuropathic Pain, Osteoarthritis, or Spinal Pain in the General Population
- 2018
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 19:9, s. 983-995
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Tidskriftsartikel (refereegranskat)abstract
- That certain psychological factors are negatively associated with function in patients with chronic pain is well established. However, few studies have evaluated these factors in individuals with chronic pain from the general population. The aims of this study were to: 1) evaluate the unique associations between catastrophizing and perceived solicitous responses and psychological function, physical function, and insomnia severity in individuals with neuropathic pain, osteoarthritis, or spinal pain in the general population; and 2) determine if diagnosis moderates the associations found. Five hundred fifty-one individuals from the general population underwent examinations with a physician and physiotherapist, and a total of 334 individuals were diagnosed with either neuropathic pain (n = 34), osteoarthritis (n = 78), or spinal pain (n = 222). Results showed that catastrophizing was significantly associated with reduced psychological and physical function, explaining 24% and 2% of the variance respectively, whereas catastrophizing as well as perceived solicitous responding were significantly and uniquely associated with insomnia severity, explaining 8% of the variance. Perceived solicitous responding was significantly negatively associated with insomnia severity. Moderator analyses indicated that: 1) the association between catastrophizing and psychological function was greater among individuals with spinal pain and neuropathic pain than those with osteoarthritis, and 2) the association between catastrophizing and insomnia was greater among individuals with spinal pain and osteoarthritis than those with neuropathic pain. No statistically significant interactions including perceived solicitous responses were found. The findings support earlier findings of an association between catastrophizing and function among individuals with chronic pain in the general population, and suggest that diagnosis may serve a moderating role in some of these associations. Perspective: When examining persons with pain in the general population, catastrophizing is associated with several aspects of function, and diagnosis serves as a moderator for these associations. The replication of these associations in the general population support their reliability and generalizability.
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- von Rundstedt, F. -C., et al.
(författare)
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Patients' acceptance of urinary diversion. The pouch of Sisyphus
- 2012
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Ingår i: Der Urologe. - : Springer Science and Business Media LLC. - 0340-2592 .- 1433-0563. ; 51:4, s. 515-521
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Tidskriftsartikel (refereegranskat)abstract
- It is important that any patient with a urinary diversion can accept the psychological impact alongside the surgical and physical aspects. However, there are currently no validated methods or instruments available to allow direct measurement of this phenomenon in these patients. Health-related quality of life (HRQoL) is often high following different types of urinary diversion - this may suggest a high acceptance level and thus may act as a secondary end point. Such an assessment is a retrospective validation of successful patient selection, allowing us to redirect the nihilistic misinterpretation that urologists should return to offering ileal conduits as a standard. In modern urinary diversion, high patient acceptance develops from comprehensive counselling providing a realistic expectation, careful patient-to-method-matching, strict adherence to surgical detail during the procedure and a meticulous lifelong follow-up. Coping strategies, disease-related social support and confidence in the success of treatment are among other factors which contribute to acceptance of urinary reconstruction as either independent or combined factors. Significant experience is required in every respect, as misjudgement and mistakes in any of these issues may be detrimental to the patients' health. It should be acknowledged that there is no 'best' urinary diversion in general terms. A reconstructive surgeon must have all techniques available and choices need to be tailored to the individual patient.
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- Haim-Vilmovsky, Liora, et al.
(författare)
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Mapping Rora expression in resting and activated CD4+ T cells
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:5
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4 + T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment. Copyright: © 2021 Haim-Vilmovsky et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 19. |
- Ulloa, Jose L, et al.
(författare)
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Assessment of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter inhibition
- 2013
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Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 26:10, s. 1258-1270
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury (DILI) is a clinically important adverse drug reaction, which prevents the development of many otherwise safe and effective new drugs. Currently, there is a lack of sensitive and specific biomarkers that can be used to predict, assess and manage this toxicity. The aim of this work was to evaluate gadoxetate-enhanced MRI as a potential novel biomarker of hepatobiliary transporter inhibition in the rat. Initially, the volume fraction of extracellular space in the liver was determined using gadopentetate to enable an estimation of the gadoxetate concentration in hepatocytes. Using this information, a compartmental model was developed to characterise the pharmacokinetics of hepatic uptake and biliary excretion of gadoxetate. Subsequently, we explored the impact of an investigational hepatobiliary transporter inhibitor on the parameters of the model in vivo in rats. The investigational hepatobiliary transporter inhibitor reduced both the rate of uptake of gadoxetate into the hepatocyte, k 1 , and the Michaelis-Menten constant, V max , characterising its excretion into bile, whereas K M values for biliary efflux were increased. These effects were dose dependent and correlated with effects on plasma chemistry markers of liver dysfunction, in particular bilirubin and bile acids. These results indicate that gadoxetate-enhanced MRI provides a novel functional biomarker of inhibition of transporter-mediated hepatic uptake and clearance in the rat. Since gadoxetate is used clinically, the technology has the potential to provide a translatable biomarker of drug-induced perturbation of hepatic transporters that may also be useful in humans to explore deleterious functional alterations caused by transporter inhibition. © 2013 John Wiley & Sons, Ltd.
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| 20. |
- Vickman, R. E., et al.
(författare)
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Deconstructing tumor heterogeneity : The stromal perspective
- 2020
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Ingår i: Oncotarget. - : Impact Journals LLC. - 1949-2553. ; 11:40, s. 3621-3632
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Tidskriftsartikel (refereegranskat)abstract
- Significant advances have been made towards understanding the role of immune cell-tumor interplay in either suppressing or promoting tumor growth, progression, and recurrence, however, the roles of additional stromal elements, cell types and/or cell states remain ill-defined. The overarching goal of this NCI-sponsored workshop was to highlight and integrate the critical functions of non-immune stromal components in regulating tumor heterogeneity and its impact on tumor initiation, progression, and resistance to therapy. The workshop explored the opposing roles of tumor supportive versus suppressive stroma and how cellular composition and function may be altered during disease progression. It also highlighted microenvironment-centered mechanisms dictating indolence or aggressiveness of early lesions and how spatial geography impacts stromal attributes and function. The prognostic and therapeutic implications as well as potential vulnerabilities within the heterogeneous tumor microenvironment were also discussed. These broad topics were included in this workshop as an effort to identify current challenges and knowledge gaps in the field. Copyright:
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