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Sökning: WFRF:(O'Riordan A.)

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1.
  • Glasbey, JC, et al. (författare)
  • 2021
  • swepub:Mat__t
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  • Pöntinen, M., et al. (författare)
  • Euclid: Identification of asteroid streaks in simulated images using deep learning
  • 2023
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 679
  • Tidskriftsartikel (refereegranskat)abstract
    • The material composition of asteroids is an essential piece of knowledge in the quest to understand the formation and evolution of the Solar System. Visual to near-infrared spectra or multiband photometry is required to constrain the material composition of asteroids, but we currently have such data, especially in the near-infrared wavelengths, for only a limited number of asteroids. This is a significant limitation considering the complex orbital structures of the asteroid populations. Up to 150 000 asteroids will be visible in the images of the upcoming ESA Euclid space telescope, and the instruments of Euclid will offer multiband visual to near-infrared photometry and slitless near-infrared spectra of these objects. Most of the asteroids will appear as streaks in the images. Due to the large number of images and asteroids, automated detection methods are needed. A non-machine-learning approach based on the Streak Det software was previously tested, but the results were not optimal for short and/or faint streaks. We set out to improve the capability to detect asteroid streaks in Euclid images by using deep learning. We built, trained, and tested a three-step machine-learning pipeline with simulated Euclid images. First, a convolutional neural network (CNN) detected streaks and their coordinates in full images, aiming to maximize the completeness (recall) of detections. Then, a recurrent neural network (RNN) merged snippets of long streaks detected in several parts by the CNN. Lastly, gradient-boosted trees (XGBoost) linked detected streaks between different Euclid exposures to reduce the number of false positives and improve the purity (precision) of the sample. The deep-learning pipeline surpasses the completeness and reaches a similar level of purity of a non-machine-learning pipeline based on the StreakDet software. Additionally, the deep-learning pipeline can detect asteroids 0.25–0.5 magnitudes fainter than StreakDet. The deep-learning pipeline could result in a 50% increase in the number of detected asteroids compared to the StreakDet software. There is still scope for further refinement, particularly in improving the accuracy of streak coordinates and enhancing the completeness of the final stage of the pipeline, which involves linking detections across multiple exposures.
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  • Adams, D., et al. (författare)
  • Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis
  • 2018
  • Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:1, s. 11-21
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters] x albumin level in grams per liter; lower values indicated worse nutritional status).RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (+/- SD) mNIS+7 at baseline was 80.9 +/- 41.5 in the patisiran group and 74.6 +/- 37.0 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.0 +/- 1.7 versus 28.0 +/- 2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (+/- SD) baseline Norfolk QOL-DN score was 59.6 +/- 28.2 in the patisiran group and 55.5 +/- 24.3 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.7 +/- 1.8 versus 14.4 +/- 2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08 +/- 0.02 m per second with patisiran versus -0.24 +/- 0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7 +/- 9.6 versus -119.4 +/- 14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups.CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis.
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  • Rabe, Patrick, et al. (författare)
  • X-ray free-electron laser studies reveal correlated motion during isopenicillin N synthase catalysis
  • 2021
  • Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:34
  • Tidskriftsartikel (refereegranskat)abstract
    • Isopenicillin N synthase (IPNS) catalyzes the unique reaction of L-delta-(alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV) with dioxygen giving isopenicillin N (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.
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  • Denoncourt, R. N., et al. (författare)
  • Burden of Illness for Patients with Hereditary Attr Amyloidosis with Polyneuropathy Begins with Symptom Onset and Increases with Disease Progression
  • 2016
  • Ingår i: Value in Health. - : Elsevier. - 1098-3015 .- 1524-4733. ; 19:7, s. A436-A436
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Hereditary ATTR amyloidosis with polyneuropathy (hATTR-PN), also known as familial amyloidotic polyneuropathy (FAP), is an inherited, progressive disease leading to death within 5-15 years. hATTR-PN is due to a mutation in the transthyretin (TTR) gene. Patisiran is an investigational, RNA interference (RNAi) therapeutic targeting TTR. This abstract aims to further characterize hATTR-PN burden of illness.Methods: The ongoing, patisiran Phase 3 APOLLO trial was utilized to collect patient-reported EQ-5D, Norfolk-DN, Rasch-built Overall Disability Scale (R-ODS), and healthcare resource utilization from hATTR-PN patients with symptomatic disease.Results: APOLLO included 225 patients; median age of 62 years (range: 24-82), median neurological impairment score (NIS) of 6-141.6 and representative of the global patient population (19 countries) with a broad range of mutations and disease severities. At baseline, 57 patients had a Polyneuropathy Disability (PND) Score I and 168 patients had a PND Score ≥ II. By FAP Stage, 104 were FAP Stage 1 and 121 were FAP Stage 2. 41 patients (PND Score ≥ II) reported ≥1 hospitalization of ≥3 nights in duration due to hATTR-PN in the 12 months prior to enrollment. Mean EQ-5D scores were 0.76 (PND Score I) and 0.59 (PND Score ≥ II). Patients reported perceived health status on the EQ-VAS with mean scores of 66.9 (PND Score I) and 51.3 (PND Score ≥ II). Mean Norfolk-QoL-DN scores were 35.5 (PND Score I) and 66.0 (PND Score ≥ II). 145 patients (131 PND Score ≥ II) reported they cannot work because of hATTR-PN. Mean R-ODS scores were 40.9 and 25.9 for PND Score I and PND Score ≥ II, respectively.Conclusions: These data, from the largest controlled study of patients with hATTR-PN to date, further demonstrate that patients experience considerable burden of illness early in the course of disease and this burden increases with disease progression.
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  • Ljungman, P., et al. (författare)
  • Long-term follow-up of HCV-infected hematopoietic SCT patients and effects of antiviral therapy
  • 2012
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 47:9, s. 1217-1221
  • Tidskriftsartikel (refereegranskat)abstract
    • This prospective study was initiated in 1993 with the aim to study late effects and responses to antiviral therapy in a cohort of hepatitis C virus (HCV)-infected patients. A total of 195 patients were included from 12 centers. In all, 134 patients had undergone allogeneic and 61 autologous hematopoietic SCT (HSCT). The median follow-up from HSCT is currently 16.8 years and the maximum 27.2 years. Overall 33 of 195 patients have died of which 6 died from liver complications. The survival probability was 81.6% and the cumulative incidence for death in liver complications was 6.1% at 20 years after HSCT. The cumulative incidence of severe liver complications (death from liver failure, cirrhosis and liver transplantation) was 11.7% at 20 years after HSCT. In all, 85 patients have been treated with IFN; 42 in combination with ribavirin. The sustained response rate was 40%. The rates of severe side effects were comparable to other patient populations and no patient developed significant exacerbations of GVHD. Patients receiving antiviral therapy had a trend toward a decreased risk of severe liver complications (odds ratio=0.33; P=0.058). HCV infection is associated with morbidity and mortality in long-term survivors after HSCT. Antiviral therapy can be given safely and might reduce the risk for severe complications.
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  • Martin, W. P., et al. (författare)
  • Obesity is common in chronic kidney disease and associates with greater antihypertensive usage and proteinuria: evidence from a cross-sectional study in atertiary nephrology centre
  • 2020
  • Ingår i: Clinical Obesity. - : Wiley. - 1758-8103 .- 1758-8111. ; 10:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is a treatable risk factor for chronic kidney disease progression. We audited the reporting of body-mass index in nephrology outpatient clinics to establish the characteristics of individuals with obesity in nephrology practice. Body-mass index, clinical information and biochemical measures were recorded for patients attending clinics between 3(rd)August, 2018 and 18(th)January, 2019. Inferential statistics and Pearson correlations were used to investigate relationships between body-mass index, type 2 diabetes, hypertension and proteinuria. Mean +/- SD BMI was 28.6 +/- 5.8 kg/m(2)(n = 374). Overweight and obesity class 1 were more common in males (P= .02). Amongst n = 123 individuals with obesity and chronic kidney disease, mean +/- SD age, n (%) female and median[IQR] eGFR were 64.1 +/- 14.2 years, 52 (42.3%) and 29.0[20.5] mL/min/BSA, respectively. A positive correlation between increasing body-mass index and proteinuria was observed in such patients (r= 0.21,P= .03), which was stronger in males and those with CKD stages 4 and 5. Mean body-mass index was 2.3 kg/m(2)higher in those treated with 4-5 versus 0-1 antihypertensives (P= .03). Amongst n = 59 patients with obesity, chronic kidney disease and type 2 diabetes, 2 (3.5%) and 0 (0%) were prescribed a GLP-1 receptor analogue and SGLT2-inhibitor, respectively. Our data provides a strong rationale not only for measuring body-mass index but also for acting on the information in nephrology practice, although prospective studies are required to guide treatment decisions in people with obesity and chronic kidney disease.
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  • Benedetto, Chiara, et al. (författare)
  • FIGO Preconception Checklist: Preconception care for mother and baby.
  • 2024
  • Ingår i: International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics. - 1879-3479.
  • Tidskriftsartikel (refereegranskat)abstract
    • The preconception period is a unique and opportunistic time in a woman's life when she is motivated to adopt healthy behaviors that will benefit her and her child, making this time period a critical "window of opportunity" to improve short- and long-term health. Improving preconception health can ultimately improve both fetal and maternal outcomes. Promoting health before conception has several beneficial effects, including an increase in seeking antenatal care and a reduction in neonatal mortality. Preconception health is a broad concept that encompasses the management of chronic diseases, including optimal nutrition, adequate consumption of folic acid, control of body weight, adoption of healthy lifestyles, and receipt of appropriate vaccinations. Use of the FIGO Preconception Checklist, which includes the key elements of optimal preconception care, will empower women and their healthcare providers to better prepare women and their families for pregnancy.
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  • Green, Jonathan M. H., et al. (författare)
  • Research priorities for managing the impacts and dependencies of business upon food, energy, water and the environment
  • 2017
  • Ingår i: Sustainability Science. - : Springer Science and Business Media LLC. - 1862-4065 .- 1862-4057. ; 12:2, s. 319-331
  • Tidskriftsartikel (refereegranskat)abstract
    • Delivering access to sufficient food, energy and water resources to ensure human wellbeing is a major concern for governments worldwide. However, it is crucial to account for the 'nexus' of interactions between these natural resources and the consequent implications for human wellbeing. The private sector has a critical role in driving positive change towards more sustainable nexus management and could reap considerable benefits from collaboration with researchers to devise solutions to some of the foremost sustainability challenges of today. Yet opportunities are missed because the private sector is rarely involved in the formulation of deliverable research priorities. We convened senior research scientists and influential business leaders to collaboratively identify the top forty questions that, if answered, would best help companies understand and manage their food-energy-water-environment nexus dependencies and impacts. Codification of the top order nexus themes highlighted research priorities around development of pragmatic yet credible tools that allow businesses to incorporate nexus interactions into their decision-making; demonstration of the business case for more sustainable nexus management; identification of the most effective levers for behaviour change; and understanding incentives or circumstances that allow individuals and businesses to take a leadership stance. Greater investment in the complex but productive relations between the private sector and research community will create deeper and more meaningful collaboration and cooperation.
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  • Vogelsong, Melissa A., et al. (författare)
  • Influence of sex on survival, neurologic outcomes, and neurodiagnostic testing after out-of-hospital cardiac arrest
  • 2021
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572. ; 167, s. 66-75
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim: Previous studies evaluating the relationship between sex and post-resuscitation care and outcomes following out-of-hospital cardiac arrest (OHCA) are conflicting. We investigated the association between sex and outcomes as well as neurodiagnostic testing in a prospective multicenter international registry of patients admitted to intensive care units following OHCA. Methods: OHCA survivors enrolled in the International Cardiac Arrest Registry (INTCAR) from 2012 to 2017 were included. We assessed the independent association between sex and survival to hospital discharge, good neurologic outcome (Cerebral Performance Category 1 or 2), neurodiagnostic testing, and withdrawal of life-sustaining therapy (WLST). Results: Of 2407 eligible patients, 809 (33.6%) were women. Baseline characteristics differed by sex, with less bystander CPR and initial shockable rhythms among women. Women were less likely to survive to hospital discharge, however significance abated following adjusted analysis (30.1% vs 42.7%, adjusted OR 0.85, 95% CI 0.67–1.08). Women were less likely to have good neurologic outcome at discharge (21.4% vs 34.0%, adjusted OR 0.74, 95% CI 0.57–0.96) and at six months post-arrest (16.7% vs 29.4%, adjusted OR 0.73, 95% CI 0.54–0.98) that persisted after adjustment. Neuroimaging (75.5% vs 74.3%, p = 0.54) and other neurophysiologic testing (78.8% vs 78.6%, p = 0.91) was similar across sex. Women were more likely to undergo WLST (55.6% vs 42.8%, adjusted OR 1.35, 95% CI 1.09–1.66). Conclusions: Women with cardiac arrest have lower odds of good neurologic outcomes and higher odds of WLST, despite comparable rates of neurodiagnostic testing and after controlling for baseline differences in clinical characteristics and cardiac arrest features.
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