| 1. |
- Thomas, HS, et al.
(författare)
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- 2019
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swepub:Mat__t
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| 2. |
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| 3. |
- Drake, TM, et al.
(författare)
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Surgical site infection after gastrointestinal surgery in children: an international, multicentre, prospective cohort study
- 2020
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Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:12
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Tidskriftsartikel (refereegranskat)abstract
- Surgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings.MethodsA multicentre, international, prospective, validated cohort study of children aged under 16 years undergoing clean-contaminated, contaminated or dirty gastrointestinal surgery. Any hospital in the world providing paediatric surgery was eligible to contribute data between January and July 2016. The primary outcome was the incidence of SSI by 30 days. Relationships between explanatory variables and SSI were examined using multilevel logistic regression. Countries were stratified into high development, middle development and low development groups using the United Nations Human Development Index (HDI).ResultsOf 1159 children across 181 hospitals in 51 countries, 523 (45·1%) children were from high HDI, 397 (34·2%) from middle HDI and 239 (20·6%) from low HDI countries. The 30-day SSI rate was 6.3% (33/523) in high HDI, 12·8% (51/397) in middle HDI and 24·7% (59/239) in low HDI countries. SSI was associated with higher incidence of 30-day mortality, intervention, organ-space infection and other HAIs, with the highest rates seen in low HDI countries. Median length of stay in patients who had an SSI was longer (7.0 days), compared with 3.0 days in patients who did not have an SSI. Use of laparoscopy was associated with significantly lower SSI rates, even after accounting for HDI.ConclusionThe odds of SSI in children is nearly four times greater in low HDI compared with high HDI countries. Policies to reduce SSI should be prioritised as part of the wider global agenda.
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| 4. |
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| 5. |
- Abdo, A. A., et al.
(författare)
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FERMI/LARGE AREA TELESCOPE BRIGHT GAMMA-RAY SOURCE LIST
- 2009
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 183:1, s. 46-66
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Tidskriftsartikel (refereegranskat)abstract
- Following its launch in 2008 June, the Fermi Gamma-ray Space Telescope (Fermi) began a sky survey in August. The Large Area Telescope (LAT) on Fermi in three months produced a deeper and better resolved map of the gamma-ray sky than any previous space mission. We present here initial results for energies above 100 MeV for the 205 most significant (statistical significance greater than similar to 10 sigma) gamma-ray sources in these data. These are the best characterized and best localized point-like (i.e., spatially unresolved) gamma-ray sources in the early mission data.
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| 6. |
- Abdo, A. A., et al.
(författare)
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A limit on the variation of the speed of light arising from quantum gravity effects
- 2009
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 462:7271, s. 331-334
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Tidskriftsartikel (refereegranskat)abstract
- A cornerstone of Einstein’s special relativity is Lorentz invariance—the postulate that all observers measure exactly the same speed of light in vacuum, independent of photon-energy. While special relativity assumes that there is no fundamental length-scale associated with such invariance, there is a fundamental scale (the Planck scale, lPlanck~1.62×10-33cm or EPlanck = MPlanckc2~1.22×1019GeV), at which quantum effects are expected to strongly affect the nature of space–time. There is great interest in the (not yet validated) idea that Lorentz invariance might break near the Planck scale. A key test of such violation of Lorentz invariance is a possible variation of photon speed with energy. Even a tiny variation in photon speed, when accumulated over cosmological light-travel times, may be revealed by observing sharp features in γ-ray burst (GRB) light-curves. Here we report the detection of emission up to ~31GeV from the distant and short GRB090510. We find no evidence for the violation of Lorentz invariance, and place a lower limit of 1.2EPlanck on the scale of a linear energy dependence (or an inverse wavelength dependence), subject to reasonable assumptions about the emission (equivalently we have an upper limit of lPlanck/1.2 on the length scale of the effect). Our results disfavour quantum-gravity theories in which the quantum nature of space–time on a very small scale linearly alters the speed of light.
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| 18. |
- Horne, B D, et al.
(författare)
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Pharmacogenetic warfarin dose refinements remain significantly influenced by genetic factors after one week of therapy
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 107:2, s. 232-240
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Tidskriftsartikel (refereegranskat)abstract
- By guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6-11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6-11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that "effective" dose constituted a treatment response index . Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1-1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.
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| 19. |
- Abdo, A. A., et al.
(författare)
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FERMI OBSERVATIONS OF HIGH-ENERGY GAMMA-RAY EMISSION FROM GRB 080825C
- 2009
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 707:1, s. 580-592
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Tidskriftsartikel (refereegranskat)abstract
- The Fermi Gamma-ray Space Telescope has opened a new high-energy window in the study of gamma-ray bursts (GRBs). Here we present a thorough analysis of GRB 080825C, which triggered the Fermi Gamma-ray Burst Monitor (GBM), and was the first firm detection of a GRB by the Fermi Large Area Telescope (LAT). We discuss the LAT event selections, background estimation, significance calculations, and localization for Fermi GRBs in general and GRB 080825C in particular. We show the results of temporal and time-resolved spectral analysis of the GBM and LAT data. We also present some theoretical interpretation of GRB 080825C observations as well as some common features observed in other LAT GRBs.
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| 20. |
- Aoun, M. -C, et al.
(författare)
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Gas Security of Supply in the European Union
- 2017
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Ingår i: Europe's Energy Transition. - : Elsevier. - 9780128098066 - 9780128099032 ; , s. 67-78
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Bokkapitel (refereegranskat)abstract
- The EU remains widely dependent on external gas supplies, with imports representing 70% of its consumption in 2013. Member States have different import profiles with divergent levels of dependency on Russian imports. Several European Member States rely heavily on Russian supplies, which shows that the EU gas supply security needs to be examined both from an internal and international perspective. Since the 2009 crisis between Russia and Ukraine, the EU has adopted several legislative tools to strengthen EU gas security of supply. The third legislative package, the security of supply Regulation (EU) 994/2010 and the Energy Infrastructure package identifying Projects of Common Interest have significantly improved the ability of the EU to face import disruptions. However, several countries remain particularly vulnerable to the occurrence of disruption. When considering national production, storage, and the diversity of suppliers, Bulgaria, Czech Republic, Estonia, Finland, Latvia, and Lithuania seem to be at risk. Romania, Poland, and Hungary also import the bulk of their gas from Russia, but have either domestic production or significant storage capacity.
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| 21. |
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| 25. |
- Ridker, P. M., et al.
(författare)
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Antiinflammatory therapy with canakinumab for atherosclerotic disease
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:12, s. 1119-1131
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. METHODS: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P=0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P=0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P=0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P=0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P=0.31). CONCLUSIONS: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. Copyright © 2017 Massachusetts Medical Society.
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| 26. |
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| 27. |
- Abdo, A. A., et al.
(författare)
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FERMI/LARGE AREA TELESCOPE DISCOVERY OF GAMMA-RAY EMISSION FROM THE FLAT-SPECTRUM RADIO QUASAR PKS 1454-354
- 2009
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 697:1, s. 934-941
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery by the Large Area Telescope (LAT) onboard the Fermi Gamma-Ray Space Telescope of high-energy gamma-ray (GeV) emission from the flat-spectrum radio quasar PKS 1454-354 (z = 1.424). On 2008 September 4, the source rose to a peak flux of (3.5 +/- 0.7) x 10(-6) ph cm(-2) s(-1) (E > 100 MeV) on a timescale of hours and then slowly dropped over the following 2 days. No significant spectral changes occurred during the flare. Fermi/LAT observations also showed that PKS 1454-354 is the most probable counterpart of the unidentified EGRET source 3EG J1500-3509. Multiwavelength measurements performed during the following days (7 September with Swift; 6-7 September with the ground-based optical telescope Automated Telescope for Optical Monitoring; 13 September with the Australia Telescope Compact Array) resulted in radio, optical, UV, and X-ray fluxes greater than archival data, confirming the activity of PKS 1454-354.
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| 28. |
- Abdo, A. A., et al.
(författare)
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FERMI LARGE AREA TELESCOPE OBSERVATIONS OF THE VELA PULSAR
- 2009
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 696:2, s. 1084-1093
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Tidskriftsartikel (refereegranskat)abstract
- The Vela pulsar is the brightest persistent source in the GeV sky and thus is the traditional first target for new gamma-ray observatories. We report here on initial Fermi Large Area Telescope observations during verification phase pointed exposure and early sky survey scanning. We have used the Vela signal to verify Fermi timing and angular resolution. The high-quality pulse profile, with some 32,400 pulsed photons at E >= 0.03 GeV, shows new features, including pulse structure as fine as 0.3 ms and a distinct third peak, which shifts in phase with energy. We examine the high-energy behavior of the pulsed emission; initial spectra suggest a phase-averaged power-law index of Gamma = 1.51(-0.04)(+0.05) with an exponential cutoff at E-c = 2.9 +/- 0.1 GeV. Spectral fits with generalized cutoffs of the form e(-(E/Ec)b) require b <= 1, which is inconsistent with magnetic pair attenuation, and thus favor outer-magnetosphere emission models. Finally, we report on upper limits to any unpulsed component, as might be associated with a surrounding pulsar wind nebula.
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| 29. |
- Abdo, A. A., et al.
(författare)
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MULTIWAVELENGTH MONITORING OF THE ENIGMATIC NARROW-LINE SEYFERT 1 PMN J0948+0022 IN 2009 MARCH-JULY
- 2009
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 707:1, s. 727-737
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Tidskriftsartikel (refereegranskat)abstract
- Following the recent discovery of gamma rays from the radio-loud narrow-line Seyfert 1 galaxy PMN J0948+0022 (z = 0.5846), we started a multiwavelength campaign from radio to gamma rays, which was carried out between the end of 2009 March and the beginning of July. The source displayed activity at all the observed wavelengths: a general decreasing trend from optical to gamma-ray frequencies was followed by an increase of radio emission after less than two months from the peak of the gamma-ray emission. The largest flux change, about a factor of about 4, occurred in the X-ray band. The smallest was at ultraviolet and near-infrared frequencies, where the rate of the detected photons dropped by a factor 1.6-1.9. At optical wavelengths, where the sampling rate was the highest, it was possible to observe day scale variability, with flux variations up to a factor of about 3. The behavior of PMN J0948+0022 observed in this campaign and the calculated power carried out by its jet in the form of protons, electrons, radiation, and magnetic field are quite similar to that of blazars, specifically of flat-spectrum radio quasars. These results confirm the idea that radio-loud narrow-line Seyfert 1 galaxies host relativistic jets with power similar to that of average blazars.
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| 30. |
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| 31. |
- Augustsson, Anna, et al.
(författare)
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Consumption of freshwater fish : A variable but significant risk factor for PFOS exposure
- 2021
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Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 192, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- PFOS, PFOA, PFNA and PFHxS are the PFAS substances that currently contribute most to human exposure, and in 2020 the European Food Safety Authority (EFSA) presented a draft opinion on a tolerable intake of 8 ng/kg/week for the sum of these four substances (equaling 0.42 mu g/kg if expressed as an annual dose). Diet is usually the dominating exposure pathway, and in particular the intake of PFOS has been shown to be strongly related to the consumption of fish and seafood. Those who eat freshwater fish may be especially at risk since freshwater and its biota typically display higher PFOS concentrations than marine systems. In this study, we estimated the range in PFOS intake among average Swedish "normal" and "high" consumers of freshwater fish. By average we mean persons of average weight who eat average-sized portions. The "normal consumers" were assumed to eat freshwater fish 3 times per year, and the "high consumers" once a week. Under these assumptions, the yearly tolerable intake for "normal" and "high" consumers is reached when the PFOS concentrations in fish equals 59 and 3.4 mu g per kg fish meat. For this study, PFOS concentrations in the muscle tissue of edible-sized perch, pike and pikeperch were retrieved from three different Swedish datasets, covering both rural and urban regions and a total of 78 different inland waters. Mean PFOS concentrations in fish from these sites varied from 0.3 to 750 mu g/kg. From the available data, the annual min-max dietary PFOS intake for male "normal consumers" was found to be in the range 0.0021-5.4 mu g/kg/yr for the evaluated scenarios, with median values of 0.02-0.16 mu g/kg/yr. For male "high consumers", the total intake range was estimated to be 0.04-93 mu g/kg/yr, with median values being 0.27-1.6 mu g/kg/yr. For women, the exposure estimates were slightly lower, about 79% of the exposure in men. Despite highly variable PFOS concentrations in fish from different sites, we conclude that the three most commonly consumed freshwater species in Sweden constitute an important source for the total annual intake even for people who eat this kind of fish only a few times per year. The analyses of PFOA, PFNA and PFHxS showed values which were all below detection limit, and their contribution to the total PFAS intake via freshwater fish consumption is negligible in comparison to PFOS.
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| 32. |
- Bergkvist, C., et al.
(författare)
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Dietary exposure to polychlorinated biphenyls is associated with increased risk of stroke in women
- 2014
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Ingår i: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 276:3, s. 248-259
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Tidskriftsartikel (refereegranskat)abstract
- Objective. The potentially beneficial effects of fish consumption on stroke may be modified by major food contaminants in fish. Polychlorinated biphenyls (PCBs) in particular are proposed to play a role in the aetiology of stroke. The aim of this study was to assess the association between dietary PCB exposure and stroke risk with the intake of long-chain omega-3 fish fatty acids and fish consumption. Design. The prospective population-based Swedish Mammography Cohort was examined. It was comprised of 34 591 women free of cardiovascular diseases and cancer at baseline in 1997 and followed up for 12 years. Validated estimates of dietary PCB exposure were obtained via a food frequency questionnaire at baseline. Incident cases of stroke were ascertained through register linkage. Results. During 12 years of follow-up (397 309 person-years), there were 2015 incident cases of total stroke (1532 ischaemic strokes, 216 intracerebral haemorrhages, 94 subarachnoid haemorrhages and 173 unspecified strokes). Multivariable-adjusted relative risks (RR), controlled for known stroke risk factors and fish consumption, were 1.67 [95% confidence interval (CI), 1.29-2.17] for total stroke, 1.61 (95% CI, 1.19-2.17) for ischaemic stroke and 2.80 (95% CI, 1.42-5.55) for haemorrhagic stroke for women in the highest quartile of dietary PCB exposure (median 288 ng day(-1)) compared with women in the lowest quartile (median 101 ng day(-1)). Conclusion. Dietary exposure to PCBs was associated with an increased stroke risk in women, especially haemorrhagic stroke. The results provide important information regarding the risk-benefit analysis of fish consumption, particularly for cerebrovascular disease prevention.
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| 36. |
- Hedelin, Beatrice, 1974-, et al.
(författare)
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What's left before participatory modeling can fully support real-world environmental planning processes : A case study review
- 2021
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152 .- 1873-6726. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- In environmental participatory modeling (PM), both computer and non-computer-based modeling techniques are used to aid participatory problem description, solution, and decision-making actions in environmental contexts. Although many PM case studies have been published, few efforts have sought to systematically describe and understand dominant PM processes or establish best practices for PM. As a first step, we have reviewed a random sample of environmental PM case study articles (n = 60) using a novel PM process evaluation instrument. We found that significant work likely remains for PM to fully support participatory and integrated planning processes. While PM reports systematically address knowledge integration and learning, they often neglect the facilitation of a multi-value perspective within a democratic process, and the integration across organizations within a governance system. If not reported, we suspect these aspects are also neglected in practice. We conclude with key research and practice issues for improving PM as an approach for real-world participatory planning and governance.
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| 37. |
- Lignell, S., et al.
(författare)
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Environmental organic pollutants in human milk before and after weight loss
- 2016
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 159, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Elsevier Ltd.Many persistent organic pollutants (POPs) are banned because they accumulate in organisms and are toxic. Lipophilic POPs are stored in maternal adipose tissue and concentrations in human milk (HM) may increase during weight loss. Our aim was to examine associations between weight loss and concentrations of chlorinated POPs in HM in lactating women participating in a weight loss study. We analysed POPs (PCB 28, PCB 153, HCB, DDE) in HM at 12 and 24 weeks postpartum from 32 women who participated in a randomized, 2 × 2 factorial trial of diet and exercise for postpartum weight loss. Participants donated milk before and after the intervention period. We examined associations between weight loss and change in POP concentrations and estimated the intake of POPs by their breastfed infants. Most (n = 27) women lost weight during intervention, 0.45 ± 0.30 kg/week (mean ± SD). Among these women, the concentration of PCB 153 in HM was significantly (p = 0.04) higher at follow-up than at baseline. Weight loss was significantly positively associated with changes in concentrations of all studied POPs (2.0-2.4% increase per percent weight loss). Estimated mean intakes of POPs (ng/day) remained stable because infant milk consumption decreased during the study period. As infants gained weight, estimated mean intakes per kg body weight decreased 17-22%. Changes in concentrations of POPs in HM correlated positively with maternal weight loss, but it is unlikely that the balance between the benefits and risks of breastfeeding will change if the weight loss is restricted to 0.5 kg per week.
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| 40. |
- Ridker, Paul M, et al.
(författare)
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Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial.
- 2018
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Ingår i: Lancet (London, England). - 1474-547X. ; 391:10118, s. 319-328
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Tidskriftsartikel (refereegranskat)abstract
- Canakinumab, a monoclonal antibody targeting interleukin-1β, reduces inflammation and cardiovascular event rates with no effect on lipid concentrations. However, it is uncertain which patient groups benefit the most from treatment and whether reductions in the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) correlate with clinical benefits for individual patients.The Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) used computer-generated codes to randomly allocate 10061 men and women with a history of myocardial infarction to placebo or one of three doses of canakinumab (50 mg, 150 mg, or 300 mg) given subcutaneously once every 3 months. In a prespecified secondary analysis designed to address the relationship of hsCRP reduction to event reduction in CANTOS, we evaluated the effects of canakinumab on rates of major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality according to on-treatment concentrations of hsCRP. We used multivariable modelling to adjust for baseline factors associated with achieved hsCRP and multiple sensitivity analyses to address the magnitude of residual confounding. The median follow-up was 3·7 years. The trial is registered with ClinicalTrials.gov, number NCT01327846.Baseline clinical characteristics did not define patient groups with greater or lesser cardiovascular benefits when treated with canakinumab. However, trial participants allocated to canakinumab who achieved hsCRP concentrations less than 2 mg/L had a 25% reduction in major adverse cardiovascular events (multivariable adjusted hazard ratio [HRadj]=0·75, 95% CI 0·66-0·85, p<0·0001), whereas no significant benefit was observed among those with on-treatment hsCRP concentrations of 2 mg/L or above (HRadj=0·90, 0·79-1·02, p=0·11). For those treated with canakinumab who achieved on-treatment hsCRP concentrations less than 2 mg/L, cardiovascular mortality (HRadj=0·69, 95% CI 0·56-0·85, p=0·0004) and all-cause mortality (HRadj=0·69, 0·58-0·81, p<0·0001) were both reduced by 31%, whereas no significant reduction in these endpoints was observed among those treated with canakinumab who achieved hsCRP concentrations of 2 mg/L or above. Similar differential effects were found in analyses of the trial prespecified secondary cardiovascular endpoint (which additionally included hospitalisation for unstable angina requiring unplanned revascularisation) and in sensitivity analyses alternatively based on median reductions in hsCRP, on 50% or greater reductions in hsCRP, on the median percent reduction in hsCRP, in dose-specific analyses, and in analyses using a causal inference approach to estimate the effect of treatment among individuals who would achieve a targeted hsCRP concentration.The magnitude of hsCRP reduction following a single dose of canakinumab might provide a simple clinical method to identify individuals most likely to accrue the largest benefit from continued treatment. These data further suggest that lower is better for inflammation reduction with canakinumab.Novartis Pharmaceuticals.
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| 42. |
- Akinkuolie, Akintunde O, et al.
(författare)
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Group IIA Secretory Phospholipase A2, Vascular Inflammation, and Incident Cardiovascular Disease.
- 2019
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636. ; 39:6, s. 1182-1190
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Tidskriftsartikel (refereegranskat)abstract
- Objective- Inflammation is a causal risk factor for cardiovascular disease (CVD). sPLA2-IIA (group IIA secretory phospholipase A2) plays an integral role in regulating vascular inflammation. Although studies investigated sPLA2-IIA in secondary prevention, we prospectively evaluated sPLA2-IIA mass and genetic variants with CVD events in a primary prevention population with chronic inflammation. Approach and Results- The JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) randomized participants with LDL (low-density lipoprotein) <130 mg/dL and hsCRP (high-sensitivity C-reactive protein) ≥2 mg/L to high-intensity rosuvastatin versus placebo. Baseline and 1-year plasma sPLA2-IIA mass was measured (N=11269 baseline; N=9620 1 year). We also identified genetic variants influencing sPLA2-IIA using genome-wide association and examined them with CVD. Three hundred thirteen incident CVD events occurred during follow-up. Baseline sPLA2-IIA mass (median, 25th-75th percentile: 3.81, 2.49-6.03 ng/mL) was associated with increased risk of CVD: risk factor-adjusted hazard ratio (95% CI; P) per SD increment: 1.22 (1.08-1.38; P=0.002). This remained significant (1.18; 1.04-1.35; P=0.01) after incrementally adjusting for hsCRP. Similar estimates were observed in rosuvastatin and placebo groups ( P treatment interaction>0.05). The rs11573156C variant in PLA2G2A (encoding sPLA2-IIA) had the strongest effect on sPLA2-II: median (25th-75th percentile, ng/mL) for CC and GG genotypes: 2.79 (1.97-4.01) and 7.38 (5.38-10.19), respectively; and had nonsignificant trend for higher CVD risk (hazard ratio, 1.11; 95% CI, 0.89-1.38; P=0.34). Conclusions- In the JUPITER population recruited on chronic inflammation, sPLA2-IIA mass was associated with CVD risk relating to vascular inflammation not fully reflected by hsCRP. Additional studies, including larger functional genetic and clinical studies, are needed to determine whether sPLA2-IIA may be a potential pharmacological target for primary prevention of CVD. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT00239681.
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| 44. |
- Arrington, N. A.N.C.Y., et al.
(författare)
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Constitutional Reform and the Gender Diversification of Peak Courts
- 2021
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Ingår i: American Political Science Review. - 0003-0554 .- 1537-5943. ; 115:3, s. 851-868
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Tidskriftsartikel (refereegranskat)abstract
- Do the processes states use to select judges for peak courts influence gender diversity? Scholars have debated whether concentrating appointment power in a single individual or diffusing appointment power across many individuals best promotes gender diversification. Others have claimed that the precise structure of the process matters less than fundamental changes in the process. We clarify these theoretical mechanisms, derive testable implications concerning the appointment of the first woman to a state's highest court, and then develop a matched-pair research design within a Rosenbaum permutation approach to observational studies. Using a global sample beginning in 1970, we find that constitutional change to the judicial selection process decreases the time until the appointment of the first woman justice. These results reflect claims that point to institutional disruptions as critical drivers of gender diversity on important political posts.
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