| 1. |
- Ruilope, LM, et al.
(författare)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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Ingår i: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 2. |
- Uy, G. L., et al.
(författare)
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Contribution of chemotherapy mobilization to disease control in multiple myeloma treated with autologous hematopoietic cell transplantation
- 2015
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 50:12, s. 1513-1518
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Tidskriftsartikel (refereegranskat)abstract
- In patients with multiple myeloma (MM) undergoing autologous hematopoietic cell transplantation (auto-HCT), peripheral blood progenitor cells may be collected following mobilization with growth factor alone (GF) or cytotoxic chemotherapy plus GF (CC+GF). It is uncertain whether the method of mobilization affects post-transplant outcomes. We compared these mobilization strategies in a retrospective analysis of 968 patients with MM from the Center for International Blood and Marrow Transplant Research database who received an auto-Ha in the US and Canada between 2007 and 2012. The kinetics of neutrophil engraftment (>= 0.5 x 10(9)/L) was similar between groups (13 vs 13 days, P=0.69) while platelet engraftment (>= 20 x 10(9)/L) was slightly faster with CC+GF (19 vs 18 days, P=0.006). Adjusted 3-year PFS was 43% (95% confidence interval (CI) 38-48) in GF and 40% (95% CI 35-45) in CC+GF, P=0.33. Adjusted 3-year OS was 82% (95% CI 78-86) vs 80% (95% CI 75-84), P=0.43 and adjusted 5-year OS was 62% (95% CI 54-68) vs 60% (95% CI 52-67), P=0.76, for GF and CC+GF, respectively. We conclude that MM patients undergoing auto-Ha have similar outcomes irrespective of the method of mobilization and found no evidence that the addition of chemotherapy to mobilization contributes to disease control.
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| 3. |
- D'Souza, Anita, et al.
(författare)
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Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis : A Center for International Blood and Marrow Transplant Research Study
- 2015
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Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 33:32, s. 3741-
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m(2) or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.
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| 4. |
- Kumar, M., et al.
(författare)
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Arsenic and trace elements in groundwater, vegetables and selected food grains from middle gangetic plain—human health perspective
- 2016
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Ingår i: Arsenic Research and Global Sustainability - Proceedings of the 6th International Congress on Arsenic in the Environment, AS 2016. - : CRC Press/Balkema. - 9781138029415 ; , s. 320-321
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Konferensbidrag (refereegranskat)abstract
- Very limited efforts have been directed to determine the degree of Arsenic (As) and other trace elements contamination in food grains and understanding the associated risk to human through consumption of food in middle Gangetic plain of Bihar, India. Arsenic concentration in groundwater (>80%) samples found above BIS and WHO permissible limit, while 28% samples exceeded the previous WHO drinking water guideline (400 μg/L) for manganese (Mn). In dietary food grains As followed the sequence as rice > wheat > maize. The estimated daily intake by individual of As, Mn, Ni, Cd, Co, Pb, Zn and Cr from drinking water and dietary food grains were 169,14582, 474, 19, 26, 1449, 12955 and 882 μg/ kg. The Health Risk Index (HRI) were >1 for As in drinking water, vegetables and rice indicated the potential health risk to the residents of the study area. However, HRI <1 for wheat and maize indicate a relative absence of health risks associated with their ingestion.
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| 5. |
- Pistone, Kristina, et al.
(författare)
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Observed correlations between aerosol and cloud properties in an Indian Ocean trade cumulus regime
- 2016
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:8, s. 5203-5227
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Tidskriftsartikel (refereegranskat)abstract
- There are many contributing factors which determine the micro- and macrophysical properties of clouds, including atmospheric vertical structure, dominant meteorological conditions, and aerosol concentration, all of which may be coupled to one another. In the quest to determine aerosol effects on clouds, these potential relationships must be understood. Here we describe several observed correlations between aerosol conditions and cloud and atmospheric properties in the Indian Ocean winter monsoon season. In the CARDEX (Cloud, Aerosol, Radiative forcing, Dynamics EXperiment) field campaign conducted in February and March 2012 in the northern Indian Ocean, continuous measurements were made of atmospheric precipitable water vapor (PWV) and the liquid water path (LWP) of trade cumulus clouds, concurrent with measurements of water vapor flux, cloud and aerosol vertical profiles, meteorological data, and surface and total-column aerosol from instrumentation at a ground observatory and on small unmanned aircraft. We present observations which indicate a positive correlation between aerosol and cloud LWP only when considering cases with low atmospheric water vapor (PWV < 40aEuro-kg m(-2)), a criterion which acts to filter the data to control for the natural meteorological variability in the region. We then use the aircraft and ground-based measurements to explore possible mechanisms behind this observed aerosol-LWP correlation. The increase in cloud liquid water is found to coincide with a lowering of the cloud base, which is itself attributable to increased boundary layer humidity in polluted conditions. High pollution is found to correlate with both higher temperatures and higher humidity measured throughout the boundary layer. A large-scale analysis, using satellite observations and meteorological reanalysis, corroborates these covariations: high-pollution cases are shown to originate as a highly polluted boundary layer air mass approaching the observatory from a northwesterly direction. The source air mass exhibits both higher temperatures and higher humidity in the polluted cases. While the warmer temperatures may be attributable to aerosol absorption of solar radiation over the subcontinent, the factors responsible for the coincident high humidity are less evident: the high-aerosol conditions are observed to disperse with air mass evolution, along with a weakening of the high-temperature anomaly, while the high-humidity condition is observed to strengthen in magnitude as the polluted air mass moves over the ocean toward the site of the CARDEX observations. Potential causal mechanisms of the observed correlations, including meteorological or aerosol-induced factors, are explored, though future research will be needed for a more complete and quantitative understanding of the aerosol-humidity relationship.
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| 6. |
- Steffen, Will, et al.
(författare)
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Planetary boundaries : Guiding human development on a changing planet
- 2015
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 347:6223
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Tidskriftsartikel (refereegranskat)abstract
- The planetary boundaries framework defines a safe operating space for humanity based on the intrinsic biophysical processes that regulate the stability of the Earth system. Here, we revise and update the planetary boundary framework, with a focus on the underpinning biophysical science, based on targeted input from expert research communities and on more general scientific advances over the past 5 years. Several of the boundaries now have a two-tier approach, reflecting the importance of cross-scale interactions and the regional-level heterogeneity of the processes that underpin the boundaries. Two core boundaries-climate change and biosphere integrity-have been identified, each of which has the potential on its own to drive the Earth system into a new state should they be substantially and persistently transgressed.
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| 7. |
- Wilcox, Eric M., et al.
(författare)
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Black carbon solar absorption suppresses turbulence in the atmospheric boundary layer
- 2016
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 113:42, s. 11794-11799
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Tidskriftsartikel (refereegranskat)abstract
- The introduction of cloud condensation nuclei and radiative heating by sunlight-absorbing aerosols can modify the thickness and coverage of low clouds, yielding significant radiative forcing of climate. The magnitude and sign of changes in cloud coverage and depth in response to changing aerosols are impacted by turbulent dynamics of the cloudy atmosphere, but integrated measurements of aerosol solar absorption and turbulent fluxes have not been reported thus far. Here we report such integrated measurements made from unmanned aerial vehicles (UAVs) during the CARDEX (Cloud Aerosol Radiative Forcing and Dynamics Experiment) investigation conducted over the northern Indian Ocean. The UAV and surface data reveal a reduction in turbulent kinetic energy in the surface mixed layer at the base of the atmosphere concurrent with an increase in absorbing black carbon aerosols. Polluted conditions coincide with a warmer and shallower surface mixed layer because of aerosol radiative heating and reduced turbulence. The polluted surface mixed layer was also observed to be more humid with higher relative humidity. Greater humidity enhances cloud development, as evidenced by polluted clouds that penetrate higher above the top of the surface mixed layer. Reduced entrainment of dry air into the surface layer from above the inversion capping the surface mixed layer, due to weaker turbulence, may contribute to higher relative humidity in the surface layer during polluted conditions. Measurements of turbulence are important for studies of aerosol effects on clouds. Moreover, reduced turbulence can exacerbate both the human health impacts of high concentrations of fine particles and conditions favorable for low-visibility fog events.
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| 8. |
- Höpner, Friederike, et al.
(författare)
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Vertical profiles of optical and microphysical particle properties above the northern Indian Ocean during CARDEX 2012
- 2016
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:2, s. 1045-1064
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Tidskriftsartikel (refereegranskat)abstract
- A detailed analysis of optical and microphysical properties of aerosol particles during the dry winter monsoon season above the northern Indian Ocean is presented. The Cloud Aerosol Radiative Forcing Experiment (CARDEX), conducted from 16 February to 30 March 2012 at the Maldives Climate Observatory on Hanimaadhoo island (MCOH) in the Republic of the Maldives, used autonomous unmanned aerial vehicles (AUAV) to perform vertical in situ measurements of particle number concentration, particle number size distribution as well as particle absorption coefficients. These measurements were used together with surface-based Mini Micro Pulse Lidar (MiniMPL) observations and aerosol in situ and off-line measurements to investigate the vertical distribution of aerosol particles. Air masses were mainly advected over the Indian subcontinent and the Arabian Peninsula. The mean surface aerosol number concentration was 1717 +/- 604cm(-3) and the highest values were found in air masses from the Bay of Bengal and Indo-Gangetic Plain (2247 +/- 370cm(-3)). Investigations of the free tropospheric air showed that elevated aerosol layers with up to 3 times higher aerosol number concentrations than at the surface occurred mainly during periods with air masses originating from the Bay of Bengal and the Indo-Gangetic Plain. This feature is different compared to what was observed during the Indian Ocean Experiment (INDOEX) conducted in winter 1999, where aerosol number concentrations generally decreased with height. In contrast, lower particle absorption at the surface (sigma(abs)(520nm) = 8.5 + 4.2Wm(-1)) was found during CARDEX compared to INDOEX 1999. Layers with source region specific single-scattering albedo (SSA) values were derived by combining vertical in situ particle absorption coefficients and scattering coefficients calculated with Mie theory. These SSA layers were utilized to calculate vertical particle absorption profiles from MiniMPL profiles. SSA surface values for 550 nm for dry conditions were found to be 0 : 94 +/- 0 : 02 and 0 : 91 +/- 0 : 02 for air masses from the Arabian Sea (and Middle East countries) and India (and Bay of Bengal), respectively. Lidar-derived particle absorption coefficient profiles showed both a similar magnitude and structure as the in situ profiles measured with the AUAV. However, primarily due to insufficient accuracy in the SSA estimates, the lidar-derived absorption coefficient profiles have large uncertainties and are generally weakly correlated to vertically in situ measured particle absorption coefficients. Furthermore, the mass absorption efficiency (MAE) for the northern Indian Ocean during the dry monsoon season was calculated to determine equivalent black carbon (EBC) concentrations from particle absorption coefficient measurements. A mean MAE of 11.6 and 6.9m(2) g(-1) for 520 and 880 nm, respectively, was found, likely representing internally mixed BC containing particles. Lower MAE values for 880 and 520 nm were found for air masses originating from dust regions such as the Arabian Peninsula and western Asia (MAE(880 nm) = 5.6m(2) g(-1), MAE(520 nm) = 9.5m(2) g(-1)) or from closer source regions as southern India (MAE(880 nm) = 4.3m(2) g(-1), MAE(520 nm) = 7. 3m(2) g(-1)).
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| 9. |
- Kumar, M., et al.
(författare)
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Groundwater evolution and its utility in upper Ganges-Yamuna Alluvial plain of Northern India, India : Evidence from solute chemistry and stable isotopes
- 2018
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Ingår i: Groundwater for Sustainable Development. - : Elsevier BV. - 2352-801X. ; 7, s. 400-409
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Tidskriftsartikel (refereegranskat)abstract
- The current study was focused on the characterization of recharge, weathering processes and to check the aptness of groundwater for household and agriculture utility in the Chhaprola industrial area located in Gautam Buddha Nagar district of Uttar Pradesh, India. Groundwater samples (n = 33) were analyzed for major cations and anions from which (n = 22) were analyzed for stable isotopic records (δ2H and δ18O). Solute chemistry revealed neutral to moderately basic nature (pH ranged 6.4–8.8) and showed a higher (ranged 552–3130 µS/cm) of electrical conductivity. Isotopic signals ranged from − 8.7 to − 3.3‰ for δ18O and − 60.1 to − 37‰ for δ2H. Bivariate plot of stable isotopes (δ18O and δ2H) showed that majority of the samples fell below the global meteoric water line (GMWL) and local meteoric water line (LMWL) of New Delhi, indicating enrichment of heavier isotopes in the aquifers, which explain that recharging water, has undergone evaporation before recharging the aquifer. Monsoonal precipitation was observed as the major source of aquifer recharge in the surveyed area. Vertical hydraulic connectivity of the aquifer layers was traced with the help of isotopic record which exhibited a more negative intercept for shallow depth tube well than the middle depth tube well. About 76% of the samples exhibited negative Schoeller index thereby indicated cation-anion exchange reactions while the remaining samples depicted the Base Exchange Reactions. Sodium-normalized Ca versus Na-normalized Mg and HCO3, indicated an equal contribution of silicate and carbonate type weathering on global-average weathering system. About 52% of the groundwater samples fell into the Ca-HCO3 - water type while remaining samples fell into 33% and 15% of Na-HCO3 and Mg-HCO3 type, respectively. Water quality indices (viz. residual sodium carbonate, Kelly index, permeability index, magnesium hazard, and Chloroalkaline indices) revealed unsuitability of the groundwater for drinking and irrigation purpose at few locations.
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| 10. |
- Landgren, Ola, et al.
(författare)
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Association of Immune Marker Changes with Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma
- 2019
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Ingår i: JAMA Oncology. - : American Medical Association (AMA). - 2374-2437 .- 2374-2445.
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Multiple myeloma is consistently preceded by monoclonal gammopathy of undetermined significance (MGUS). Risk models that estimate the risk of progression from MGUS to multiple myeloma use data from a single time point, usually the initial workup. Objective: To longitudinally investigate the alterations of serum immune markers with stable vs progressive MGUS. Design, Setting, and Participants: This prospective cross-sectional cohort study included 77469 adult participants aged 55 to 74 years in the screening arm of the National Cancer Institute Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnosis of progressing MGUS (n = 187) or stable MGUS (n = 498), including light-chain subtype, from November 1993, through December 2011. For each participant, all available serially stored prediagnostic serum samples (N = 3266) were obtained. Data analysis was performed from April 2018, to December 2018. Main Outcomes and Measures: Serum protein and monoclonal immunoglobulin levels, serum free light chains, and serum light chains within each immunoglobulin class were measured. Results: Of 685 individuals included in the study, 461 (67.3%) were men; the mean (SD) age was 69.1 (5.6) years. In cross-sectional modeling, risk factors associated with progressive MGUS were IgA isotype (adjusted odds ratio [OR], 1.80; 95% CI, 1.03-3.13; P =.04), 15 g/L or more monoclonal spike (adjusted OR, 23.5; 95% CI, 8.9-61.9; P <.001), skewed (<0.1 or >10) serum free light chains ratio (adjusted OR, 46.4; 95% CI, 18.4-117.0; P <.001), and severe immunoparesis (≥2 suppressed uninvolved immunoglobulins) (adjusted OR, 19.1; 95% Cl, 7.5-48.3; P <.001). Risk factors associated with progressive light-chain MGUS were skewed serum free light chains ratio (adjusted OR, 44.0; 95% CI, 14.2-136.3; P <.001) and severe immunoparesis (adjusted OR, 48.6; 95% CI, 9.5-248.2; P <.001). In longitudinal analysis of participants with serial samples prior to progression, 23 of 43 participants (53%) had high-risk MGUS before progression; 16 of these 23 (70%) experienced conversion from low-risk or intermediate-risk MGUS within 5 years. Similar results were found for light-chain MGUS. Conclusions and Relevance: The findings of evolving risk patterns support annual blood testing and risk assessment for patients with MGUS or light-chain MGUS.
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