| 1. |
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| 2. |
- Geyer, C. E., et al.
(författare)
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Overall survival in the OlympiA phase Ill trial of adjuvant olaparib in patients with germime pathogenic variants in BRCA1/2 and high-risk, early breast cancer
- 2022
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Ingår i: Annals of Oncology. - : Elsevier BV. - 0923-7534. ; 33:12, s. 1250-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods: One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results: With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Delta 3.4%, 95% CI -0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Delta 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Delta 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion: With 35 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDES and DDFS with no new safety signals.
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| 3. |
- Dent, E., et al.
(författare)
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International Clinical Practice Guidelines for Sarcopenia (ICFSR) : Screening, Diagnosis and Management
- 2018
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 22:10, s. 1148-1161
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Sarcopenia, defined as an age-associated loss of skeletal muscle function and muscle mass, occurs in approximately 6 - 22 % of older adults. This paper presents evidence-based clinical practice guidelines for screening, diagnosis and management of sarcopenia from the task force of the International Conference on Sarcopenia and Frailty Research (ICSFR).Methods: To develop the guidelines, we drew upon the best available evidence from two systematic reviews paired with consensus statements by international working groups on sarcopenia. Eight topics were selected for the recommendations: (i) defining sarcopenia; (ii) screening and diagnosis; (iii) physical activity prescription; (iv) protein supplementation; (v) vitamin D supplementation; (vi) anabolic hormone prescription; (vii) medications under development; and (viii) research. The ICSFR task force evaluated the evidence behind each topic including the quality of evidence, the benefit harm balance of treatment, patient preferences/values, and cost-effectiveness. Recommendations were graded as either strong or conditional (weak) as per the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Consensus was achieved via one face-to-face workshop and a modified Delphi process.Recommendations: We make a conditional recommendation for the use of an internationally accepted measurement tool for the diagnosis of sarcopenia including the EWGSOP and FNIH definitions, and advocate for rapid screening using gait speed or the SARC-F. To treat sarcopenia, we strongly recommend the prescription of resistance-based physical activity, and conditionally recommend protein supplementation/a protein-rich diet. No recommendation is given for Vitamin D supplementation or for anabolic hormone prescription. There is a lack of robust evidence to assess the strength of other treatment options.
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| 4. |
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| 5. |
- Manini, T. M., et al.
(författare)
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Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1419-1428
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements. DESIGN Cross-sectional data analyses of pooled data. SETTING University-based research assessment centers. PARTICIPANTS Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed. MEASUREMENTS Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously). RESULTS CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m(2)or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m(2). Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers. CONCLUSION GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements.
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| 6. |
- Cawthon, P. M., et al.
(författare)
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Putative Cut-Points in Sarcopenia Components and Incident Adverse Health Outcomes: AnSDOCAnalysis
- 2020
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Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1429-1437
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES Analyses performed by the Sarcopenia Definitions and Outcomes Consortium (SDOC) identified cut-points in several metrics of grip strength for consideration in a definition of sarcopenia. We describe the associations between the SDOC-identified metrics of low grip strength (absolute or standardized to body size/composition); low dual-energy x-ray absorptiometry (DXA) lean mass as previously defined in the literature (appendicular lean mass [ALM]/ht(2)); and slowness (walking speed <.8 m/s) with subsequent adverse outcomes (falls, hip fractures, mobility limitation, and mortality). DESIGN Individual-level, sex-stratified pooled analysis. We calculated odds ratios (ORs) or hazard ratios (HRs) for incident falls, mobility limitation, hip fractures, and mortality. Follow-up time ranged from 1 year for falls to 8.8 +/- 2.3 years for mortality. SETTING Eight prospective observational cohort studies. PARTICIPANTS A total of 13,421 community-dwelling men and 4,828 community-dwelling women. MEASUREMENTS Grip strength by hand dynamometry, gait speed, and lean mass by DXA. RESULTS Low grip strength (absolute or standardized to body size/composition) was associated with incident outcomes, usually independently of slowness, in both men and women. ORs and HRs generally ranged from 1.2 to 3.0 for those below vs above the cut-point. DXA lean mass was not consistently associated with these outcomes. When considered together, those who had both muscle weakness by absolute grip strength (<35.5 kg in men and <20 kg in women) and slowness were consistently more likely to have a fall, hip fracture, mobility limitation, or die than those without either slowness or muscle weakness. CONCLUSION Older men and women with both muscle weakness and slowness have a higher likelihood of adverse health outcomes. These results support the inclusion of grip strength and walking speed as components in a summary definition of sarcopenia.
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| 7. |
- Cawthon, Peggy M, et al.
(författare)
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What Cut-Point in Gait Speed Best Discriminates Community-Dwelling Older Adults With Mobility Complaints From Those Without? A Pooled Analysis From the Sarcopenia Definitions and Outcomes Consortium.
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1758-535X .- 1079-5006. ; 76:10
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Tidskriftsartikel (refereegranskat)abstract
- Cut-points to define slow walking speed have largely been derived from expert opinion.Study participants (13 589 men and 5043 women aged ≥65years) had walking speed (m/s) measured over 4-6 m (mean ± SD: 1.20 ± 0.27 m/s in men and 0.94 ± 0.24 m/s in women.) Mobility limitation was defined as any self-reported difficulty with walking approximately 1/4 mile (prevalence: 12.6% men, 26.4% women). Sex-stratified classification and regression tree (CART) models with 10-fold cross-validation identified walking speed cut-points that optimally discriminated those who reported mobility limitation from those who did not.Among 5043 women, CART analysis identified 2 cut-points, classifying 4144 (82.2%) with walking speed ≥0.75 m/s, which we labeled as "fast"; 478 (9.5%) as "intermediate" (walking speed ≥0.62 m/s but <0.75 m/s); and 421 (8.3%) as "slow" (walking speed <0.62 m/s). Among 13 589 men, CART analysis identified 3 cut-points, classifying 10 001 (73.6%) with walking speed ≥1.00 m/s ("very fast"); 2901 (21.3%) as "fast" (walking speed ≥0.74 m/s but <1.00 m/s); 497 (3.7%) as "intermediate" (walking speed ≥0.57 m/s but <0.74 m/s); and 190 (1.4%) as "slow" (walking speed <0.57 m/s). Prevalence of self-reported mobility limitation was lowest in the "fast" or "very fast" (11% for men and 19% for women) and highest in the "slow" (60.5% in men and 71.0% in women). Rounding the 2 slower cut-points to 0.60 m/s and 0.75 m/s reclassified very few participants.Cut-points in walking speed of approximately 0.60 m/s and 0.75 m/s discriminate those with self-reported mobility limitation from those without.
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| 8. |
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| 9. |
- Yang, H., et al.
(författare)
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Preliminary Characterization of Submarine Basalt Magnetic Mineralogy Using Amplitude-Dependence of Magnetic Susceptibility
- 2024
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Ingår i: Geochemistry, Geophysics, Geosystems. - 1525-2027. ; 25:2
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Tidskriftsartikel (refereegranskat)abstract
- The past ∼200 million years of Earth's geomagnetic field behavior have been recorded within oceanic basalts, many of which are only accessible via scientific ocean drilling. Obtaining the best possible paleomagnetic measurements from such valuable samples requires an a priori understanding of their magnetic mineralogies when choosing the most appropriate protocol for stepwise demagnetization experiments (either alternating field or thermal). Here, we present a quick, and non-destructive method that utilizes the amplitude-dependence of magnetic susceptibility to screen submarine basalts prior to choosing a demagnetization protocol, whenever conducting a pilot study or other detailed rock-magnetic characterization is not possible. We demonstrate this method using samples acquired during International Ocean Discovery Program Expedition 391. Our approach is rooted in the observation that amplitude-dependent magnetic susceptibility is observed in basalt samples whose dominant magnetic carrier is multidomain titanomagnetite (∼TM60–65, (Ti0.60–0.65Fe0.35–0.40)Fe2O4). Samples with low Ti contents within titanomagnetite or samples that have experienced a high degree of oxidative weathering do not display appreciable amplitude dependence. Due to their low Curie temperatures, basalts that possess amplitude-dependence should ideally be demagnetized either using alternating fields or via finely-spaced thermal demagnetization heating steps below 300°C. Our screening method can enhance the success rate of paleomagnetic studies of oceanic basalt samples.
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| 10. |
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| 11. |
- Thoram, S., et al.
(författare)
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Nature and Origin of Magnetic Lineations Within Valdivia Bank : Ocean Plateau Formation by Complex Seafloor Spreading
- 2023
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Ingår i: Geophysical Research Letters. - 0094-8276. ; 50:13
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Tidskriftsartikel (refereegranskat)abstract
- Valdivia Bank (VB) is a Late Cretaceous oceanic plateau formed by volcanism from the Tristan-Gough hotspot at the Mid-Atlantic Ridge (MAR). To better understand its origin and evolution, magnetic data were used to generate a magnetic anomaly grid, which was inverted to determine crustal magnetization. The magnetization model reveals quasi-linear polarity zones crossing the plateau and following expected MAR paleo-locations, implying formation by seafloor spreading over ∼4 Myr during the formation of anomalies C34n-C33r. Paleomagnetism and biostratigraphy data from International Ocean Discovery Program Expedition 391 confirm the magnetic interpretation. Anomaly C33r is split into two negative bands, likely by a westward ridge jump. One of these negative anomalies coincides with deep rift valleys, indicating their age and mechanism of formation. These findings imply that VB originated by seafloor spreading-type volcanism during a plate reorganization, not from a vertical stack of lava flows as expected for a large volcano.
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| 12. |
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| 13. |
- Fielding, R. A., et al.
(författare)
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Effect of structured physical activity and nutritional supplementation on physical function in mobility-limited older adults : Results from the VIVE2 randomized trial
- 2017
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Ingår i: The Journal of Nutrition, Health & Aging. - : Springer Science and Business Media LLC. - 1279-7707 .- 1760-4788. ; 21:9, s. 936-942
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Tidskriftsartikel (refereegranskat)abstract
- The interactions between nutritional supplementation and physical activity on changes in physical function among older adults remain unclear. The primary objective of this study was to examine the impact of nutritional supplementation plus structured physical activity on 400M walk capacity in mobility-limited older adults across two sites (Boston, USA and Stockholm, Sweden). All subjects participated in a physical activity program (3x/week for 24 weeks), involving walking, strength, balance, and flexibility exercises. Subjects were randomized to a daily nutritional supplement (150kcal, 20g whey protein, 800 IU vitamin D) or placebo (30kcal, non-nutritive). Participants were recruited from urban communities at 2 field centers in Boston MA USA and Stockholm SWE. Mobility-limited (Short Physical Performance Battery (SPPB) ae9) and vitamin D insufficient (serum 25(OH) D 9 - 24 ng/ml) older adults were recruited for this study. Primary outcome was gait speed assessed by the 400M walk. Results: 149 subjects were randomized into the study (mean age=77.5 +/- 5.4; female=46.3%; mean SPPB= 7.9 +/- 1.2; mean 25(OH)D=18.7 +/- 6.4 ng/ml). Adherence across supplement and placebo groups was similar (86% and 88%, respectively), and was also similar across groups for the physical activity intervention (75% and 72%, respectively). Both groups demonstrated an improvement in gait speed with no significant difference between those who received the nutritional supplement compared to the placebo (0.071 and 0.108 m/s, respectively (p=0.06)). Similar effects in physical function were observed using the SPPB. Serum 25(OH)D increased in supplemented group compared to placebo 7.4 ng/ml versus 1.3 ng/ml respectively. Results suggest improved gait speed following physical activity program with no further improvement with added nutritional supplementation.
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| 14. |
- Kaufman, Bella, et al.
(författare)
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Olaparib Monotherapy in Patients With Advanced Cancer and a Germline BRCA1/2 Mutation.
- 2015
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Ingår i: Journal of Clinical Oncology. - 1527-7755. ; 33:3, s. 134-244
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Tidskriftsartikel (refereegranskat)abstract
- Olaparib is an oral poly (ADP-ribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) -associated breast and ovarian cancers. We evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2-associated cancers.
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| 15. |
- Morley, John E., et al.
(författare)
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Sarcopenia With Limited Mobility : An International Consensus
- 2011
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier BV. - 1525-8610 .- 1538-9375. ; 12:6, s. 403-409
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Tidskriftsartikel (refereegranskat)abstract
- A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, le, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s.
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| 16. |
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| 17. |
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| 18. |
- Tutt, A. N. J., et al.
(författare)
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Adjuvant Olaparib for Patients with BRCA1- or BRCA2-Mutated Breast Cancer
- 2021
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 384:25, s. 2394-2405
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Poly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. METHODS We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival. RESULTS A total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P<0.001). The 3-year distant disease-free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest. CONCLUSIONS Among patients with high-risk, HER2-negative early breast cancer and germline BRCA1 or BRCA2 pathogenic or likely pathogenic variants, adjuvant olaparib after completion of local treatment and neoadjuvant or adjuvant chemotherapy was associated with significantly longer survival free of invasive or distant disease than was placebo. Olaparib had limited effects on global patient-reported quality of life.
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| 19. |
- Vellas, B., et al.
(författare)
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IMPLICATIONS OF ICD-10 FOR SARCOPENIA CLINICAL PRACTICE AND CLINICAL TRIALS : REPORT BY THE INTERNATIONAL CONFERENCE ON FRAILTY AND SARCOPENIA RESEARCH TASK FORCE
- 2018
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Ingår i: Journal of Frailty & Aging. - : EDITIONS SERDI. - 2260-1341 .- 2273-4309. ; 7:1, s. 2-9
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Tidskriftsartikel (refereegranskat)abstract
- Establishment of an ICD-10-CM code for sarcopenia in 2016 was an important step towards reaching international consensus on the need for a nosological framework of age-related skeletal muscle decline. The International Conference on Frailty and Sarcopenia Research Task Force met in April 2017 to discuss the meaning, significance, and barriers to the implementation of the new code as well as strategies to accelerate development of new therapies. Analyses by the Sarcopenia Definitions and Outcomes Consortium are underway to develop quantitative definitions of sarcopenia. A consensus conference is planned to evaluate this analysis. The Task Force also discussed lessons learned from sarcopenia trials that could be applied to future trials, as well as lessons from the osteoporosis field, a clinical condition with many constructs similar to sarcopenia and for which ad hoc treatments have been developed and approved by regulatory agencies.
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| 20. |
- Westbury, L. D., et al.
(författare)
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Recent sarcopenia definitions-prevalence, agreement and mortality associations among men: Findings from population-based cohorts
- 2023
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Ingår i: Journal of Cachexia Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 14:1, s. 565-575
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) and the Sarcopenia Definitions and Outcomes Consortium (SDOC) have recently proposed sarcopenia definitions. However, comparisons of the performance of these approaches in terms of thresholds employed, concordance in individuals and prediction of important health-related outcomes such as death are limited. We addressed this in a large multinational assembly of cohort studies that included information on lean mass, muscle strength, physical performance and health outcomes. MethodsWhite men from the Health Aging and Body Composition (Health ABC) Study, Osteoporotic Fractures in Men (MrOS) Study cohorts (Sweden, USA), the Hertfordshire Cohort Study (HCS) and the Sarcopenia and Physical impairment with advancing Age (SarcoPhAge) Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over courses of 2.4-6 m. Deaths were recorded and verified. Definitions of sarcopenia were as follows: EWGSOP2 (grip strength <27 kg and ALM index <7.0 kg/m(2)), SDOC (grip strength <35.5 kg and gait speed <0.8 m/s) and Modified SDOC (grip strength <35.5 kg and gait speed <1.0 m/s). Cohen's kappa statistic was used to assess agreement between original definitions (EWGSOP2 and SDOC). Presence versus absence of sarcopenia according to each definition in relation to mortality risk was examined using Cox regression with adjustment for age and weight; estimates were combined across cohorts using random-effects meta-analysis. ResultsMean (SD) age of participants (n = 9170) was 74.3 (4.9) years; 5929 participants died during a mean (SD) follow-up of 12.1 (5.5) years. The proportion with sarcopenia according to each definition was EWGSOP2 (1.1%), SDOC (1.7%) and Modified SDOC (5.3%). Agreement was weak between EWGSOP2 and SDOC (kappa = 0.17). Pooled hazard ratios (95% CI) for mortality for presence versus absence of each definition were EWGSOP2 [1.76 (1.42, 2.18), I-2: 0.0%]; SDOC [2.75 (2.28, 3.31), I-2: 0.0%]; and Modified SDOC [1.93 (1.54, 2.41), I-2: 58.3%]. ConclusionsThere was low prevalence and poor agreement among recent sarcopenia definitions in community-dwelling cohorts of older white men. All indices of sarcopenia were associated with mortality. The strong relationship between sarcopenia and mortality, regardless of the definition, illustrates that identification of appropriate management and lifecourse intervention strategies for this condition is of paramount importance.
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| 21. |
- Bickerton, A. S. T., et al.
(författare)
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Adipose tissue fatty acid metabolism in insulin-resistant men
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:8, s. 1466-1474
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulin-resistant overweight men (BM1 25-35 kg/m(2)). Methods In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n = 124) and in men with fasting insulin below the median (n 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls. Results In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 mu mol/l; controls, 445 2 mu mol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p<0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p=0.02, and 44%, p=0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p=0.03). Conclusions/interpretation Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism. and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.
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| 22. |
- Frank, T.D., et al.
(författare)
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Pace, magnitude, and nature of terrestrial climate change through the end-Permian extinction in southeastern Gondwana
- 2021
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Ingår i: Geology. - : Geological Society of America. - 0091-7613 .- 1943-2682. ; 49:9, s. 1089-1095
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Tidskriftsartikel (refereegranskat)abstract
- Rapid climate change was a major contributor to the end-Permian extinction (EPE). Although well constrained for the marine realm, relatively few records document the pace, nature, and magnitude of climate change across the EPE in terrestrial environments. We generated proxy records for chemical weathering and land surface temperature from continental margin deposits of the high-latitude southeastern margin of Gondwana. Regional climate simulations provide additional context. Results show that Glossopteris forest-mire ecosystems collapsed during a pulse of intense chemical weathering and peak warmth, which capped ∼1 m.y. of gradual warming and intensification of seasonality. Erosion resulting from loss of vegetation was short lived in the low-relief landscape. Earliest Triassic climate was∼10–14 °C warmer than the late Lopingian and landscapes were no longer persistently wet. Aridification, commonly linked to the EPE, developed gradually, facilitating the persistence of refugia for moisture-loving terrestrial groups.
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| 23. |
- Harvey, N. C., et al.
(författare)
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Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX(R), Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study: A Meta-Analysis
- 2021
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:7, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height(2) (ALM/ht(2)) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX(R)) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht(2) only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht(2)), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated +/- fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. (c) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..
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| 24. |
- Reid, Derryck T., et al.
(författare)
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Roadmap on ultrafast optics
- 2016
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Ingår i: Journal of Optics. - : IOP Publishing. - 2040-8978 .- 2040-8986. ; 18:9
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Tidskriftsartikel (refereegranskat)abstract
- The year 2015 marked the 25th anniversary of modern ultrafast optics, since the demonstration of the first Kerr lens modelocked Ti:sapphire laser in 1990 (Spence et al 1990 Conf. on Lasers and Electro-Optics, CLEO, pp 619-20) heralded an explosion of scientific and engineering innovation. The impact of this disruptive technology extended well beyond the previous discipline boundaries of lasers, reaching into biology labs, manufacturing facilities, and even consumer healthcare and electronics. In recognition of such a milestone, this roadmap on Ultrafast Optics draws together articles from some of the key opinion leaders in the field to provide a freeze-frame of the state-of-the-art, while also attempting to forecast the technical and scientific paradigms which will define the field over the next 25 years. While no roadmap can be fully comprehensive, the thirteen articles here reflect the most exciting technical opportunities presented at the current time in Ultrafast Optics. Several articles examine the future landscape for ultrafast light sources, from practical solid-state/fiber lasers and Raman microresonators to exotic attosecond extreme ultraviolet and possibly even zeptosecond x-ray pulses. Others address the control and measurement challenges, requiring radical approaches to harness nonlinear effects such as filamentation and parametric generation, coupled with the question of how to most accurately characterise the field of ultrafast pulses simultaneously in space and time. Applications of ultrafast sources in materials processing, spectroscopy and time-resolved chemistry are also discussed, highlighting the improvements in performance possible by using lasers of higher peak power and repetition rate, or by exploiting the phase stability of emerging new frequency comb sources.
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| 25. |
- Roosli, M, et al.
(författare)
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Brain and Salivary Gland Tumors and Mobile Phone Use: Evaluating the Evidence from Various Epidemiological Study Designs
- 2019
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Ingår i: Annual review of public health. - : Annual Reviews. - 1545-2093 .- 0163-7525. ; 40, s. 221-238
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Tidskriftsartikel (refereegranskat)abstract
- Mobile phones (MPs) are the most relevant source of radiofrequency electromagnetic field (RF-EMF) exposure to the brain and the salivary gland. Whether this exposure implies a cancer risk has been addressed in several case-control and few cohort studies. A meta-analysis of these studies does not show increased risks for meningioma, pituitary, and salivary gland tumors. For glioma and acoustic neuroma, the results are heterogeneous, with few case-control studies reporting substantially increased risks. However, these elevated risks are not coherent with observed incidence time trends, which are considered informative for this specific topic owing to the steep increase in MP use, the availability of virtually complete cancer registry data from many countries, and the limited number of known competing environmental risk factors. In conclusion, epidemiological studies do not suggest increased brain or salivary gland tumor risk with MP use, although some uncertainty remains regarding long latency periods (>15 years), rare brain tumor subtypes, and MP usage during childhood.
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| 26. |
- Sevastianova, K., et al.
(författare)
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Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans
- 2012
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165. ; 96:4, s. 727-734
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease (NAFLD). Objective: We examined whether overfeeding overweight subjects with simple sugars increases liver fat and de novo lipogenesis (DNL) and whether this is reversible by weight loss. Design: Sixteen subjects [BMI (kg/m(2)): 30.6 +/- 1.2] were placed on a hypercaloric diet (>1000 kcal simple carbohydrates/d) for 3 wk and, thereafter, on a hypocaloric diet for 6 mo. The subjects were genotyped for rs739409 in the PNPLA3 gene. Before and after overfeeding and after hypocaloric diet, metabolic variables and liver fat (measured by proton magnetic resonance spectroscopy) were measured. The ratio of palmitate (16:0) to linoleate (18:2n-6) in serum and VLDL triglycerides was used as an index of DNL. Results: Carbohydrate overfeeding increased weight (+/- SEM) by 2% (1.8 +/- 0.3 kg; P < 0.0001) and liver fat by 27% from 9.2 +/- 1.9% to 11.7 +/- 1.9% (P = 0.005). DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3-148II but not PNPLA3-148MM. During the hypocaloric diet, the subjects lost 4% of their weight (3.2 +/- 0.6 kg; P < 0.0001) and 25% of their liver fat content (from 11.7 +/- 1.9% to 8.8 +/- 1.8%; P < 0.05). Conclusions: Carbohydrate overfeeding for 3 wk induced a >10-fold greater relative change in liver fat (27%) than in body weight (2%). The increase in liver fat was proportional to that in DNL. Weight loss restores liver fat to normal. These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD. This trial was registered at www.hus.fi as 235780. Am J Clin Nutr 2012;96:727-34.
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| 27. |
- Westbury, Leo D., et al.
(författare)
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Predictive value of sarcopenia components for all-cause mortality: findings from population-based cohorts
- 2024
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Ingår i: AGING CLINICAL AND EXPERIMENTAL RESEARCH. - : Springer. - 1594-0667 .- 1720-8319. ; 36:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.Aim We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.Methods Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).Results Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.Conclusions Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.
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| 28. |
- BAX, G., SEARLE, M., HEMMLEB, J. & FIELDING, E.J.
(författare)
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3D visualization of earth science data over Mount Everest
- 2003
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Ingår i: 18th Himalaya-Karakorum-Tibet Workshop, 2-4 April 2003, Ascona, Switzerland. ; , s. 24-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 29. |
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| 30. |
- Cawthon, Peggy M., et al.
(författare)
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Defining terms commonly used in sarcopenia research : a glossary proposed by the Global Leadership in Sarcopenia (GLIS) Steering Committee
- 2022
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Ingår i: European Geriatric Medicine. - : Springer. - 1878-7649 .- 1878-7657. ; 13:6, s. 1239-1244
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Tidskriftsartikel (refereegranskat)abstract
- MethodsThe aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings. The Global Leadership Initiative in Sarcopenia (GLIS) aims to bring together leading investigators in sarcopenia research to develop a single definition that can be utilized worldwide; work on a global definition of sarcopenia is ongoing. The first step of GLIS is to develop the common terminology, or a glossary, that will facilitate agreement on a global definition of sarcopenia as well as interpretation of clinical and research findings.ResultsSeveral terms that are commonly used in sarcopenia research are defined, including self-reported measures of function and ability; objective physical performance tests; and measures related to muscle function and size.ConclusionAs new methods and technologies are developed, these definitions may be expanded or refined over time. Our goal is to promote this common language to describe sarcopenia and its components in clinical and research settings in order to increase clinical awareness and research interest in this important condition. We hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.Key summary pointsAimThe aim of this paper is to define terms commonly related to sarcopenia to enable standardization of these terms in research and clinical settings.FindingsThis paper provides definitions for commonly used terminology in sarcopenia in both clinical and research settings. As new methods and technologies are developed, this terminology may be expanded or refined over time.MessageWe hope that the use of common terminology in sarcopenia research will increase understanding of the concept and improve communication around this important age-related condition.
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| 31. |
- Costa, Sara I. R., et al.
(författare)
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Surface engineering strategy using urea to improve the rate performance of Na2Ti3O7 in Na-ion batteries
- 2021
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Ingår i: Chemistry - A European Journal. - : John Wiley & Sons. - 0947-6539 .- 1521-3765. ; 27:11, s. 3875-3886
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Tidskriftsartikel (refereegranskat)abstract
- Na2Ti3O7 (NTO) is considered a promising anode material for Na-ion batteries due to its layered structure with an open framework and low and safe average operating voltage of 0.3 V vs. Na+/Na. However, its poor electronic conductivity needs to be addressed to make this material attractive for practical applications among other anode choices. Here, we report a safe, controllable and affordable method using urea that significantly improves the rate performance of NTO by producing surface defects such as oxygen vacancies and hydroxyl groups, and the secondary phase Na2Ti6O13. The enhanced electrochemical performance agrees with the higher Na+ ion diffusion coefficient, higher charge carrier density and reduced bandgap observed in these samples, without the need of nanosizing and/or complex synthetic strategies. A comprehensive study using a combination of diffraction, microscopic, spectroscopic and electrochemical techniques supported by computational studies based on DFT calculations, was carried out to understand the effects of this treatment on the surface, chemistry and electronic and charge storage properties of NTO. This study underscores the benefits of using urea as a strategy for enhancing the charge storage properties of NTO and thus, unfolding the potential of this material in practical energy storage applications.
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| 32. |
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| 33. |
- Cruz-Jentoft, Alfonso J, et al.
(författare)
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Prevalence of and interventions for sarcopenia in ageing adults : a systematic review : Report of the International Sarcopenia Initiative (EWGSOP and IWGS)
- 2014
-
Ingår i: Age and Ageing. - : Oxford University Press (OUP). - 0002-0729 .- 1468-2834. ; 43:6, s. 748-759
-
Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: to examine the clinical evidence reporting the prevalence of sarcopenia and the effect of nutrition and exercise interventions from studies using the consensus definition of sarcopenia proposed by the European Working Group on Sarcopenia in Older People (EWGSOP).METHODS: PubMed and Dialog databases were searched (January 2000-October 2013) using pre-defined search terms. Prevalence studies and intervention studies investigating muscle mass plus strength or function outcome measures using the EWGSOP definition of sarcopenia, in well-defined populations of adults aged ≥50 years were selected.RESULTS: prevalence of sarcopenia was, with regional and age-related variations, 1-29% in community-dwelling populations, 14-33% in long-term care populations and 10% in the only acute hospital-care population examined. Moderate quality evidence suggests that exercise interventions improve muscle strength and physical performance. The results of nutrition interventions are equivocal due to the low number of studies and heterogeneous study design. Essential amino acid (EAA) supplements, including ∼2.5 g of leucine, and β-hydroxy β-methylbutyric acid (HMB) supplements, show some effects in improving muscle mass and function parameters. Protein supplements have not shown consistent benefits on muscle mass and function.CONCLUSION: prevalence of sarcopenia is substantial in most geriatric settings. Well-designed, standardised studies evaluating exercise or nutrition interventions are needed before treatment guidelines can be developed. Physicians should screen for sarcopenia in both community and geriatric settings, with diagnosis based on muscle mass and function. Supervised resistance exercise is recommended for individuals with sarcopenia. EAA (with leucine) and HMB may improve muscle outcomes.
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| 34. |
- de Souto Barreto, P., et al.
(författare)
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Appetite Loss and Anorexia of Aging in Clinical Care : An ICFSR Task Force Report
- 2022
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Ingår i: Journal of Frailty & Aging. - : Springer. - 2260-1341 .- 2273-4309. ; 11:2, s. 129-134
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Tidskriftsartikel (refereegranskat)abstract
- Appetite lossianorexia of aging is a highly prevalent and burdensome geriatric syndrome that strongly impairs the quality of life of older adults. Loss of appetite is associated with several clinical conditions, including comorbidities and other geriatric syndromes, such as frailty. Despite its importance, appetite loss has been under-evaluated and, consequently, under-diagnosed and under-treated in routine clinical care. The International Conference on Frailty and Sarcopenia Research (ICFSR) Task Force met virtually on September 27th 2021 to debate issues related to appetite loss/anorexia of aging. In particular, topics related to the implementation and management of appetite loss in at-risk older adult populations, energy balance during aging, and the design of future clinical trials on this topic were discussed. Future actions in this field should focus on the systematic assessment of appetite in the care pathway of older people, such as the Integrated Care for Older People (ICOPE) program recommended by the World Health Organization. Moreover, clinical care should move from the assessment to the treatment of appetite loss/anorexia. Researchers continue to pursue their efforts to find out effective pharmacologic and non-pharmacologic interventions with a favorable risk/benefit ratio.
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| 35. |
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| 36. |
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| 37. |
- FIELDING, E.J., BAX, G. & SEARLE, M.
(författare)
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How steep is Mount Everest? And why?
- 2003
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Ingår i: 18th Himalaya-Karakorum-Tibet Workshop, 2-4 April 2003, Ascona, Switzerland. ; , s. 41-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 38. |
- Flores, H., et al.
(författare)
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Impact of climate change on Antarctic krill
- 2012
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Ingår i: Marine Ecology-Progress Series. - : Inter-Research Science Center. - 0171-8630 .- 1616-1599. ; 458, s. 1-19
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Tidskriftsartikel (refereegranskat)abstract
- Antarctic krill Euphausia superba (hereafter 'krill') occur in regions undergoing rapid environmental change, particularly loss of winter sea ice. During recent years, harvesting of krill has in creased, possibly enhancing stress on krill and Antarctic ecosystems. Here we review the overall impact of climate change on krill and Antarctic ecosystems, discuss implications for an ecosystem-based fisheries management approach and identify critical knowledge gaps. Sea ice decline, ocean warming and other environmental stressors act in concert to modify the abundance, distribution and life cycle of krill. Although some of these changes can have positive effects on krill, their cumulative impact is most likely negative. Recruitment, driven largely by the winter survival of larval krill, is probably the population parameter most susceptible to climate change. Predicting changes to krill populations is urgent, because they will seriously impact Antarctic ecosystems. Such predictions, however, are complicated by an intense inter-annual variability in recruitment success and krill abundance. To improve the responsiveness of the ecosystem-based management approach adopted by the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR), critical knowledge gaps need to be filled. In addition to a better understanding of the factors influencing recruitment, management will require a better understanding of the resilience and the genetic plasticity of krill life stages, and a quantitative understanding of under-ice and benthic habitat use. Current precautionary management measures of CCAMLR should be maintained until a better understanding of these processes has been achieved. [GRAPHICS] .
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| 39. |
- Harvey, Nicholas C., et al.
(författare)
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Sarcopenia Definitions as Predictors of Fracture Risk Independent of FRAX®, Falls, and BMD in the Osteoporotic Fractures in Men (MrOS) Study : A Meta-Analysis
- 2021
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Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 36:7, s. 1235-1244
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Tidskriftsartikel (refereegranskat)abstract
- Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX®) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2), and Sarcopenia Definitions and Outcomes Consortium (gait speed and grip strength). Associations were adjusted for age and time since baseline and reported as hazard ratio (HR) for first incident fracture, here major osteoporotic fracture (MOF; clinical vertebral, hip, distal forearm, proximal humerus). Further analyses adjusted additionally for FRAX-MOF probability (n = 7531; calculated ± fnBMD), prior falls (y/n), or fnBMD T-score. Results were synthesized by meta-analysis. In 5660 men in USA, 2764 Sweden and 1987 Hong Kong (mean ages 73.5, 75.4, and 72.4 years, respectively), sarcopenia prevalence ranged from 0.5% to 35%. Sarcopenia status, by all definitions except those of FNIH, was associated with incident MOF (HR = 1.39 to 2.07). Associations were robust to adjustment for prior falls or FRAX probability (without fnBMD); adjustment for fnBMD T-score attenuated associations. EWGSOP2 severe sarcopenia (incorporating chair stand time, gait speed, and grip strength plus ALM) was most predictive, albeit at low prevalence, and appeared only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures.
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| 40. |
- Hodson, L., et al.
(författare)
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Menopausal Status and Abdominal Obesity Are Significant Determinants of Hepatic Lipid Metabolism in Women
- 2015
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- Background-Android fat distribution (abdominal obesity) is associated with insulin resistance, hepatic steatosis, and greater secretion of large very low-density lipoprotein (VLDL) particles in men. Since abdominal obesity is becoming increasingly prevalent in women, we aimed to investigate the relationship between android fat and hepatic lipid metabolism in pre-and postmenopausal women. Methods and Results-We used a combination of stable isotope tracer techniques to investigate intrahepatic fatty acid synthesis and partitioning in 29 lean and 29 abdominally obese women (android fat/total fat 0.065 [0.02 to 0.08] and 0.095 [0.08 to 0.11], respectively). Thirty women were premenopausal aged 35 to 45 and they were matched for abdominal obesity with 28 postmenopausal women aged 55 to 65. As anticipated, abdominal obese women were more insulin resistant with enhanced hepatic secretion of large (404 +/- 30 versus 268 +/- 26 mg/kg lean mass, P<0.001) but not small VLDL (160 +/- 11 versus 142 +/- 13). However, postmenopausal status had a pronounced effect on the characteristics of small VLDL particles, which were considerably triglyceride-enriched (production ratio of VLDL2-triglyceride: apolipoprotein B 30 +/- 5.3 versus 19 +/- 1.6, P<0.05). In contrast to postmenopausal women, there was a tight control of hepatic fatty acid metabolism and triglyceride production in premenopausal women, whereby oxidation (r(s)=-0.49, P=0.006), de novo lipogenesis (r(s)=0.55, P=0.003), and desaturation (r(s)=0.48, P=0.012) were closely correlated with abdominal obesity-driven large VLDL-triglyceride secretion rate. Conclusions-In women, abdominal obesity is a major driver of hepatic large VLDL particle secretion, whereas postmenopausal status was characterized by increased small VLDL particle size. These data provide a mechanistic basis for the hyperlipidemia observed in postmenopausal obesity.
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| 41. |
- Karat, Aaron S., et al.
(författare)
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Performance of verbal autopsy methods in estimating HIV-associated mortality among adults in South Africa
- 2018
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Verbal autopsy (VA) can be integrated into civil registration and vital statistics systems, but its accuracy in determining HIV-associated causes of death (CoD) is uncertain. We assessed the sensitivity and specificity of VA questions in determining HIV status and antiretroviral therapy (ART) initiation and compared HIV-associated mortality fractions assigned by different VA interpretation methods.Methods: Using the WHO 2012 instrument with added ART questions, VA was conducted for deaths among adults with known HIV status (356 HIV positive and 103 HIV negative) in South Africa. CoD were assigned using physician-certified VA (PCVA) and computer-coded VA (CCVA) methods and compared with documented HIV status.Results: The sensitivity of VA questions in detecting HIV status and ART initiation was 84.3% (95% CI 80 to 88) and 91.0% (95% CI 86 to 95); 283/356 (79.5%) HIV-positive individuals were assigned HIV-associated CoD by PCVA, 166 (46.6%) by InterVA-4.03, 201 (56.5%) by InterVA-5, and 80 (22.5%) and 289 (81.2%) by SmartVA-Analyze V.1.1.1 and V.1.2.1. Agreement between PCVA and older CCVA methods was poor (chance-corrected concordance [CCC] <0; cause-specific mortality fraction [CSMF] accuracy <= 56%) but better between PCVA and updated methods (CCC 0.21-0.75; CSMF accuracy 65%-98%). All methods were specific (specificity 87% to 96%) in assigning HIV-associated CoD.Conclusion: All CCVA interpretation methods underestimated the HIV-associated mortality fraction compared with PCVA; InterVA-5 and SmartVA-Analyze V. 1.2.1 performed better than earlier versions. Changes to VA methods and classification systems are needed to track progress towards targets for reducing HIV-associated mortality.
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| 42. |
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| 43. |
- Kirk, Ben, et al.
(författare)
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The Conceptual Definition of Sarcopenia : Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS)
- 2024
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Ingår i: Age and Ageing. - : Oxford University Press. - 0002-0729 .- 1468-2834. ; 53:3
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Tidskriftsartikel (refereegranskat)abstract
- Importance Sarcopenia, the age-related loss of muscle mass and strength/function, is an important clinical condition. However, no international consensus on the definition exists. Objective The Global Leadership Initiative in Sarcopenia (GLIS) aimed to address this by establishing the global conceptual definition of sarcopenia. Design The GLIS steering committee was formed in 2019-21 with representatives from all relevant scientific societies worldwide. During this time, the steering committee developed a set of statements on the topic and invited members from these societies to participate in a two-phase International Delphi Study. Between 2022 and 2023, participants ranked their agreement with a set of statements using an online survey tool (SurveyMonkey). Statements were categorised based on predefined thresholds: strong agreement (>80%), moderate agreement (70-80%) and low agreement (<70%). Statements with strong agreement were accepted, statements with low agreement were rejected and those with moderate agreement were reintroduced until consensus was reached. Results 107 participants (mean age: 54 +/- 12 years [1 missing age], 64% men) from 29 countries across 7 continents/regions completed the Delphi survey. Twenty statements were found to have a strong agreement. These included; 6 statements on 'general aspects of sarcopenia' (strongest agreement: the prevalence of sarcopenia increases with age (98.3%)), 3 statements on 'components of sarcopenia' (muscle mass (89.4%), muscle strength (93.1%) and muscle-specific strength (80.8%) should all be a part of the conceptual definition of sarcopenia)) and 11 statements on 'outcomes of sarcopenia' (strongest agreement: sarcopenia increases the risk of impaired physical performance (97.9%)). A key finding of the Delphi survey was that muscle mass, muscle strength and muscle-specific strength were all accepted as 'components of sarcopenia', whereas impaired physical performance was accepted as an 'outcome' rather than a 'component' of sarcopenia. Conclusion and relevance The GLIS has created the first global conceptual definition of sarcopenia, which will now serve to develop an operational definition for clinical and research settings.
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| 44. |
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| 45. |
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| 46. |
- Lienhardt, C, et al.
(författare)
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Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo
- 2002
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Ingår i: European Journal of Immunology. - 1521-4141. ; 32:6, s. 1605-1613
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Tidskriftsartikel (refereegranskat)abstract
- Activation of Th1 lymphocytes, IFN-gamma production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL-4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)-3] and Th2 (IgE, soluble CD30, and CCL22/macrophage-derived chemokine) activity were measured in 414 HIV-negative tuberculosis patients from The Gambia and Guinee and in 414 healthy household and community controls. Measurements were repeated during treatment to assess the effect of therapy on Th1/Th2 ratio. At diagnosis, sLAG-3 levels were lower in patients than in community controls (p<0.0001), but were higher in household controls exposed to contact with patients than in community controls (p<0.0001). In comparison with community controls, patients had consistently higher levels of IgE, sCD30, and CCL22 (p<0.0001), whereas household controls had lower levels of indicators of Th2 activity (P<0.0001). After treatment, cured patients had higher levels of Th1 (p<0.0001) and lower levels of Th2 (p<0.0001) activity than patients who were not successfully treated or interrupted therapy. In Africa, tuberculosis is associated with low Th1 and high Th2 activity in vivo, whereas close exposure to tuberculosis is associated with a high Th1/Th2 ratio. Patients with favorable outcome after treatment exhibit a higher Th1/Th2 ratio compared to patients with poor clinical outcome.
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| 47. |
- Mays, Chris, 1983-, et al.
(författare)
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Lethal microbial blooms delayed freshwater ecosystem recovery following the end-Permian extinction
- 2021
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Ingår i: Nature Communications. - London : Nature Publishing Group. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Harmful algal and bacterial blooms linked to deforestation, soil loss and global warming are increasingly frequent in lakes and rivers. We demonstrate that climate changes and deforestation can drive recurrent microbial blooms, inhibiting the recovery of freshwater ecosystems for hundreds of millennia. From the stratigraphic successions of the Sydney Basin, Australia, our fossil, sedimentary and geochemical data reveal bloom events following forest ecosystem collapse during the most severe mass extinction in Earth’s history, the end-Permian event (EPE; c. 252.2 Ma). Microbial communities proliferated in lowland fresh and brackish waterbodies, with algal concentrations typical of modern blooms. These initiated before any trace of post-extinction recovery vegetation but recurred episodically for >100 kyrs. During the following 3 Myrs, algae and bacteria thrived within short-lived, poorly-oxygenated, and likely toxic lakes and rivers. Comparisons to global deep-time records indicate that microbial blooms are persistent freshwater ecological stressors during warming driven extinction events.
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| 48. |
- Ooi, E. M., et al.
(författare)
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Triglyceride-rich lipoprotein metabolism in women: roles of apoC-II and apoC-III
- 2016
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 46:8, s. 730-736
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Tidskriftsartikel (refereegranskat)abstract
- Background: Experimental data suggest that apolipoprotein (apo) C-II and C-III regulate triglyceride-rich lipoprotein (TRL) metabolism, but there are limited studies in humans. We investigated the metabolic associations of TRLs with apoC-II and apoC-III concentrations and kinetics in women. Material and methods: The kinetics of plasma apoC-II, apoC-III and very low-density lipoprotein (VLDL) apoB-100 and triglycerides were measured in the postabsorptive state using stable isotopic techniques and compartmental modelling in 60 women with wide-ranging body mass index (19·5–32·9kg/m2). Results: Plasma apoC-II and apoC-III concentrations were positively associated with the concentrations of plasma triglycerides, VLDL1- and VLDL2-apoB-100 and triglyceride (all P<0·05). ApoC-II production rate (PR) was positively associated with VLDL1-apoB-100 concentration, VLDL1 triglyceride concentration and VLDL1 triglyceride PR, while apoC-II fractional catabolic rate (FCR) was positively associated with VLDL1 triglyceride FCR (all P<0·05). No significant associations were observed between apoC-II and VLDL2 apoB-100 or triglyceride kinetics. ApoC-III PR, but not FCR, was positively associated with VLDL1 triglyceride, and VLDL2-apoB-100 and triglyceride concentrations (all P<0·05). No significant associations were observed between apoC-III and VLDL-apoB-100 and triglyceride kinetics. In multivariable analysis, including homoeostasis model assessment score, menopausal status and obesity, apoC-II concentration was significantly associated with plasma triglyceride, VLDL1-apoB-100 and VLDL1 triglyceride concentrations and PR. Using the same multivariable analysis, apoC-III was significantly associated with plasma triglyceride and VLDL1- and VLDL2-apoB-100 and triglyceride concentrations and FCR. Conclusions: In women, plasma apoC-II and apoC-III concentrations are regulated by their respective PR and are significant, independent determinants of the kinetics and plasma concentrations of TRLs. © 2016 Stichting European Society for Clinical Investigation Journal Foundation
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| 49. |
- Risérus, Ulf, et al.
(författare)
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Activation of peroxisome proliferator-activated receptor (PPAR)delta promotes reversal of multiple metabolic abnormalities, reduces oxidative stress, and increases fatty acid oxidation in moderately obese men
- 2008
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 57:2, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIEVE-Pharmacological use of peroxisome proliferator-activated receptor (PPAR)delta agonists and transgenic overexpression of PPAR delta in mice suggest amelioration of features of the metabolic syndrome through enhanced fat oxidation in skeletal muscle. We hypothesize a similar mechanism operates in humans. RESEARCH DESIGN AND METHODS-The PPAR delta agonist (10 mg o.d. GW501516), a comparator PPAR alpha agonist (20 mu g o.d. GW590735)), and placebo were given in a double-blind, randomized, three-parallel group, 2-week study to six healthy moderately overweight subjects in each group. Metabolic evaluation was made before and after treatment including liver fat quantification, fasting blood samples, a 6-h meal tolerance test with stable isotope fatty acids, skeletal muscle biopsy for gene expression, and urinary isoprostanes for global oxidative stress. RESULTS-Treatment with GW501516 showed statistically significant reductions in fasting plasma triglycerides (-30%), apolipoprotein B (-26%), LDL cholesterol (-23%), and insulin (-11%), whereas HDL cholesterol was unchanged. A 20% reduction in liver fat content (P < 0.05) and 30% reduction in urinary isoprostanes (P = 0.01) were also observed. Except for a lowering of triglycerides (-30%, P < 0.05), none of these changes were observed in response to GW590735. The relative proportion of exhaled CO, directly originating from the fat content of the meal was increased (P < 0.05) in response to GW501516, and skeletal muscle expression of carnitine palmitoyl-transferase 1b (CPT1b) was also significantly increased. CONCLUSIONS-The PPAR delta agonist GW501516 reverses multiple abnormalities associated with the metabolic syndrome without increasing oxidative stress. The effect is probably caused by increased fat oxidation in skeletal muscle.
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- Ruge, Toralph, et al.
(författare)
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Fasted to fed trafficking of fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X.
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Tidskriftsartikel (refereegranskat)abstract
- Context: Absence or excess of adipose tissue are both associated with metabolic complications implying the importance of well-functioning adipose tissue present in normal amounts. Adipose tissue sequesters dietary fat and thus protects other tissues from excess fat exposure, especially following meals. Objective: Use of an integrative physiological technique to quantify trafficking of fatty acids (FA) in adipose tissue over a 24-h period. Methods: Adipose tissue FA handling was studied in response to three meals in eight healthy men by the combination of arterio-venous blood sampling, tissue blood flow, and specific labelling of FA tracing of exogenous and endogenous fat by stable isotope methodology. Results: The efficiency of adipose tissue FA uptake increased robustly with each meal. Chylomicron-triglyceride (TG) was the dominating source of FA. Adipose tissue fractional extraction of chylomicron-TG increased from 21+/-4 to 47+/-8% (p=0.03) between the first and last meal. Although adipose tissue lipoprotein lipase (LPL) action increased with time (2-fold), there was an even greater increase in FA re-esterification (3-fold), which led to a reduced spillover of chylomicron-derived FA, from 77+/-15 to 34+/-7% (p=0.04) comparing the end of the first and the third meal period. Increased uptake of VLDL-derived FA was observed, but spillover of VLDL-derived FA was only seen in the fasting state. Conclusion: Human adipose tissue has a significant potential to up-regulate fat storage during a normal day that goes beyond increased LPL activation. The adaptation towards increasing fat storage may provide an explanation for the beneficial properties of normal amounts of adipose tissue.
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