| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Nguyen, Thanh N, et al.
(författare)
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Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:4
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Tidskriftsartikel (refereegranskat)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
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| 3. |
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The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
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Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
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| 4. |
- Adamson, Carly, et al.
(författare)
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Dapagliflozin for Heart Failure According to Body Mass Index : The DELIVER Trial.
- 2022
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 43:41, s. 4406-4417
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Obesity is common and associated with unique phenotypic features in heart failure with preserved ejection fraction (HFpEF). Therefore, understanding the efficacy and safety of new therapies in HFpEF patients with obesity is important. The effects of dapagliflozin were examined according to body mass index (BMI) among patients in the Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure trial. METHODS AND RESULTS: Body mass index was analysed by World Health Organization (WHO) categories and as a continuous variable using restricted cubic splines. Body mass index ranged from 15.2 to 50 kg/m2 with a mean value of 29.8 (standard deviation +/- 6.1) kg/m2. The proportions, by WHO category, were: normal weight 1343 (21.5%); overweight 2073 (33.1%); Class I obesity 1574 (25.2%); Class II obesity 798 (12.8%); and Class III obesity 415 (6.6%). Compared with placebo, dapagliflozin reduced the risk of the primary outcome to a similar extent across these categories: hazard ratio (95% confidence interval): 0.89 (0.69-1.15), 0.87 (0.70-1.08), 0.74 (0.58-0.93), 0.78 (0.57-1.08), and 0.72 (0.47-1.08), respectively (P-interaction = 0.82). The placebo-corrected change in Kansas City Cardiomyopathy Questionnaire total symptom score with dapagliflozin at 8 months was: 0.9 (-1.1, 2.8), 2.5 (0.8, 4.1), 1.9 (-0.1, 3.8), 2.7 (-0.5, 5.8), and 8.6 (4.0, 13.2) points, respectively (P-interaction = 0.03). The placebo-corrected change in weight at 12 months was: -0.88 (-1.28, -0.47), -0.65 (-1.04, -0.26), -1.42 (-1.89, -0.94), -1.17 (-1.94, -0.40), and -2.50 (-4.4, -0.64) kg (P-interaction = 0.002). CONCLUSIONS: Obesity is common in patients with HFpEF and is associated with higher rates of heart failure hospitalization and worse health status. Treatment with dapagliflozin improves cardiovascular outcomes across the spectrum of BMI, leads to greater symptom improvement in patients with obesity, compared with those without, and has the additional benefit of causing modest weight loss.
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| 5. |
- Bhatt, Ankeet S., et al.
(författare)
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Operational Challenges and Mitigation Measures during the COVID-19 Pandemic-Lessons from DELIVER.
- 2023
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Ingår i: American heart journal. ; 263, s. 133-140
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Catastrophic disruptions in care delivery threaten the operational efficiency and potentially the validity of clinical research efforts, in particular randomized clinical trials. Most recently, the COVID-19 pandemic affected essentially all aspects of care delivery and clinical research conduct. While consensus statements and clinical guidance documents have detailed potential mitigation measures, few real- world experiences detailing clinical trial adaptations to the COVID-19 pandemic exist, particularly among, large, global registrational cardiovascular trials. METHODS: We outline the operational impact of COVID-19 and resultant mitigation measures in the Dapagliflozin Evaluation to Improve the LIVEs of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial, one of the largest and most globally diverse experiences with COVID-19 of any cardiovascular clinical trial to date. Specifically, we address the needed coordination between academic investigators, trial leadership, clinical sites, and the supporting sponsor to ensure the safety of participants and trial staff, to maintain the fidelity of trial operations, and to prospectively adapt statistical analyses plans to evaluate the impact of COVID-19 and the pandemic at large on trial participants. These discussions included key operational issues such as ensuring delivery of study medications, adaptations to study visits, enhanced COVID-19 related endpoint adjudication, and protocol and analytical plan revisions. CONCLUSION: Our findings may have important implications for establishing consensus on prospective contingency planning in future clinical trials. CLINICALTRIAL: gov: NCT03619213. CLINICALTRIAL: GOV: NCT03619213.
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| 6. |
- Butt, Jawad H., et al.
(författare)
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Atrial Fibrillation and Dapagliflozin Efficacy in Patients With Preserved or Mildly Reduced Ejection Fraction.
- 2022
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 80:18, s. 1705-1717
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Atrial fibrillation (AF) is common in heart failure (HF), is associated with worse outcomes compared with sinus rhythm, and may modify the effects of therapy. OBJECTIVES: This study examined the effects of dapagliflozin according to the presence or not of AF in the DELIVER (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure) trial. METHODS: A total of 6,263 patients with HF with New York Heart Association functional class II-IV, left ventricular ejection fraction $>$40%, evidence of structural heart disease, and elevated N-terminal pro-B-type natriuretic peptide levels were randomized to dapagliflozin or placebo. Clinical outcomes and the effect of dapagliflozin, according to AF status, were examined. The primary outcome was a composite of cardiovascular death or worsening HF. RESULTS: Of the 6,261 patients with data on baseline AF, 43.3% had no AF, 18.0% had paroxysmal AF, and 38.7% had persistent/permanent AF. The risk of the primary endpoint was higher in patients with AF, especially paroxysmal AF, driven by a higher rate of HF hospitalization: no AF, HF hospitalization rate per 100 person-years (4.5 [95% CI: 4.0-5.1]), paroxysmal AF (7.5 [95% CI: 6.4-8.7]), and persistent/permanent AF (6.4 [95% CI: 5.7-7.1]) (P $<$ 0.001). The benefit of dapagliflozin on the primary outcome was consistent across AF types: no AF, HR: 0.89 (95% CI: 0.74-1.08); paroxysmal AF, HR: 0.75 (95% CI: 0.58-0.97); persistent/permanent AF, HR: 0.79 (95% CI: 0.66-0.95) (Pinteraction = 0.49). Consistent effects were observed for HF hospitalization, cardiovascular death, all-cause mortality, and improvement in the KCCQ- TSS. CONCLUSIONS: In DELIVER, the beneficial effects of dapagliflozin compared with placebo on clinical events and symptoms were consistent, irrespective of type of AF at baseline. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure. [DELIVER]; NCT03619213).
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| 7. |
- Butt, Jawad H., et al.
(författare)
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Efficacy and Safety of Dapagliflozin According to Frailty in Patients With Heart Failure : A Prespecified Analysis of the DELIVER Trial.
- 2022
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Ingår i: Circulation. ; 146:16, s. 1210-1224
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Frailty is increasing in prevalence. Because patients with frailty are often perceived to have a less favorable risk/benefit profile, they may be less likely to receive new pharmacologic treatments. We investigated the efficacy and tolerability of dapagliflozin according to frailty status in patients with heart failure with mildly reduced or preserved ejection fraction randomized in DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure). METHODS: Frailty was measured using the Rockwood cumulative deficit approach. The primary end point was time to a first worsening heart failure event or cardiovascular death. RESULTS: Of the 6263 patients randomized, a frailty index (FI) was calculable in 6258. In total, 2354 (37.6%) patients had class 1 frailty (FI $<$/=0.210; ie, not frail), 2413 (38.6%) had class 2 frailty (FI 0.211-0.310; ie, more frail), and 1491 (23.8%) had class 3 frailty (FI $>$/=0.311; ie, most frail). Greater frailty was associated with a higher rate of the primary end point (per 100 person-years): FI class 1, 6.3 (95% CI 5.7-7.1); class 2, 8.3 (7.5-9.1); and class 3, 13.4 (12.1-14.7; P$<$0.001). The effect of dapagliflozin (as a hazard ratio) on the primary end point from FI class 1 to 3 was 0.85 (95% CI, 0.68-1.06), 0.89 (0.74-1.08), and 0.74 (0.61-0.91), respectively (Pinteraction=0.40). Although patients with a greater degree of frailty had worse Kansas City Cardiomyopathy Questionnaire scores at baseline, their improvement with dapagliflozin was greater than it was in patients with less frailty: placebo-corrected improvement in Kansas City Cardiomyopathy Questionnaire Overall Summary Score at 4 months in FI class 1 was 0.3 (95% CI, -0.9 to 1.4); in class 2, 1.5 (0.3-2.7); and in class 3, 3.4 (1.7-5.1; Pinteraction=0.021). Adverse reactions and treatment discontinuation, although more frequent in patients with a greater degree of frailty, were not more common with dapagliflozin than with placebo irrespective of frailty class. CONCLUSIONS: In DELIVER, frailty was common and associated with worse outcomes. The benefit of dapagliflozin was consistent across the range of frailty studied. The improvement in health-related quality of life with dapagliflozin occurred early and was greater in patients with a higher level of frailty. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03619213.
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| 8. |
- Bytyci, Ibadete, et al.
(författare)
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Prevalence of statin intolerance : a meta-analysis
- 2022
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:34, s. 3213-3223
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI. METHODS AND RESULTS: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI. CONCLUSION: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI.
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| 9. |
- Cunningham, Jonathan W., et al.
(författare)
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Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction.
- 2022
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 80:14, s. 1302-1310
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients recently hospitalized for heart failure (HF) are at high risk for rehospitalization and death. OBJECTIVES: The purpose of this study was to investigate clinical outcomes and response to dapagliflozin in patients with HF with mildly reduced or preserved left ventricular ejection fraction (LVEF) who were enrolled during or following hospitalization. METHODS: The DELIVER (Dapagliflozin Evaluation to Improve the LIVES of Patients With PReserved Ejection Fraction Heart Failure) trial randomized patients with HF and LVEF $>$40% to dapagliflozin or placebo. DELIVER permitted randomization during or shortly after hospitalization for HF in clinically stable patients off intravenous HF therapies. This prespecified analysis investigated whether recent HF hospitalization modified risk of clinical events or response to dapagliflozin. The primary outcome was worsening HF event or cardiovascular death. RESULTS: Of 6,263 patients in DELIVER, 654 (10.4%) were randomized during HF hospitalization or within 30 days of discharge. Recent HF hospitalization was associated with greater risk of the primary outcome after multivariable adjustment (HR: 1.88; 95% CI: 1.60-2.21; P $<$ 0.001). Dapagliflozin reduced the primary outcome by 22% in recently hospitalized patients (HR: 0.78; 95% CI: 0.60-1.03) and 18% in patients without recent hospitalization (HR: 0.82; 95% CI: 0.72-0.94; Pinteraction = 0.71). Rates of adverse events, including volume depletion, diabetic ketoacidosis, or renal events, were similar with dapagliflozin and placebo in recently hospitalized patients. CONCLUSIONS: Dapagliflozin safely reduced risk of worsening HF or cardiovascular death similarly in patients with and without history of recent HF hospitalization. Starting dapagliflozin during or shortly after HF hospitalization in patients with mildly reduced or preserved LVEF appears safe and effective. (Dapagliflozin Evaluation to Improve the LIVEs of Patients With PReserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).
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| 10. |
- Hasselquist, Sten, et al.
(författare)
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APOGEE Chemical Abundance Patterns of the Massive Milky Way Satellites
- 2021
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 923:2
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Tidskriftsartikel (refereegranskat)abstract
- The SDSS-IV Apache Point Observatory Galactic Evolution Experiment (APOGEE) survey has obtained high-resolution spectra for thousands of red giant stars distributed among the massive satellite galaxies of the Milky Way (MW): the Large and Small Magellanic Clouds (LMC/SMC), the Sagittarius Dwarf Galaxy (Sgr), Fornax (Fnx), and the now fully disrupted Gaia Sausage/Enceladus (GSE) system. We present and analyze the APOGEE chemical abundance patterns of each galaxy to draw robust conclusions about their star formation histories, by quantifying the relative abundance trends of multiple elements (C, N, O, Mg, Al, Si, Ca, Fe, Ni, and Ce), as well as by fitting chemical evolution models to the [α/Fe]-[Fe/H] abundance plane for each galaxy. Results show that the chemical signatures of the starburst in the Magellanic Clouds (MCs) observed by Nidever et al. in the α-element abundances extend to C+N, Al, and Ni, with the major burst in the SMC occurring some 3-4 Gyr before the burst in the LMC. We find that Sgr and Fnx also exhibit chemical abundance patterns suggestive of secondary star formation epochs, but these events were weaker and earlier (∼5-7 Gyr ago) than those observed in the MCs. There is no chemical evidence of a second starburst in GSE, but this galaxy shows the strongest initial star formation as compared to the other four galaxies. All dwarf galaxies had greater relative contributions of AGB stars to their enrichment than the MW. Comparing and contrasting these chemical patterns highlight the importance of galaxy environment on its chemical evolution.
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