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Prasugrel 5-mg in the very elderly attenuates platelet inhibition but maintains non-inferiority to prasugrel 10-mg in non-elderly patients: The GENERATIONS trial, a pharmacodynamic and pharmacokinetic study in stable coronary artery disease patients.

OBJECTIVES: We assessed pharmacodynamic (PD) response for the reduced prasugrel 5-mg maintenance dose in very elderly (≥75y; VE) patients. BACKGROUND: In TRITON-TIMI 38, prasugrel 10-mg reduced ischemic events versus clopidogrel 75-mg, but increased bleeding in VE patients. METHODS: We examined PD and active-metabolite pharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a three

Towards more flexible enterprise information systems

The aim of this paper is to present the software development techniques used to build the EIS Patterns development framework, which is a testbed for a series of techniques that aim at giving more flexibility to EIS in general. Some of these techniques are customizations or extensions of practices created by the agile software development movement, while others represent new proposals. This paper a

Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in Preeclampsia

Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We furth

The role of RANK-ligand inhibition in cancer : the story of denosumab

The diagnosis of bone metastases is an event with certain consequences for the patient. They often mean pain and can also mean pathological fractures, hypercalcemia, and spinal cord compression, all synonymous with a diminished quality of life and often also hospitalization. Since the advent of the intravenous bisphosphonates, things began to look a bit brighter for patients with bone metastases-b

Transforming trash to treasure Cultural ambiguity in foetal cell research

Background: Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the trans‐ formative cultural, biological and technical processes inv

Inference to the Best Explanation (IBE) and Archaeology: Old Tool, New Model.

The last decades have seen a renewed interest in the study of argumentation in archaeology, particularly in response to the overproduction of weak and unreliable interpretations and explanations. Concurrently, recent appeals for scientific transparency and efficiency in the management of archaeological information in digital form have stressed the necessity of explicitly showing the processes foll

Sodium-glucose co-transporter inhibitors and atrial fibrillation : A systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Sodium-glucose co-transporter (SGLT) inhibitors reduce cardiovascular outcomes including mortality in several populations; however, their effect on atrial fibrillation/flutter (AF) remains unclear. Our objective was to determine whether SGLT inhibitors reduce AF and whether a history of AF modifies the effect of SGLT inhibitors on the composite of heart failure hospitalization or cardi

Meteorological Data Policies Needed to Support Biodiversity Monitoring with Weather Radar

Weather radar networks have great potential for continuous and long-term monitoring of aerial biodiversity of birds, bats, and insects. Biological data from weather radars can support ecological research, inform conservation policy development and implementation, and increase the public’s interest in natural phenomena such as migration. Weather radars are already used to study animal migration, qu

Tobacco smoke exposure in early life and adolescence in relation to lung function

Maternal smoking during pregnancy is associated with impaired lung function among young children, but less is known about long-term effects and the impact of adolescents' own smoking. We investigated the influence of maternal smoking during pregnancy, secondhand smoke exposure and adolescent smoking on lung function at age 16 years.The BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) b

The role of sulphonylurea in combination therapy assessed in a trial of sulphonylurea withdrawal. Scandinavian Insulin-Sulphonylurea Study Group Research Team

AIMS: To evaluate the effect of adding insulin to sulphonylurea (SU) and the effect of SU withdrawal on glycaemic control in Type 2 diabetic patients who failed on treatment with SU alone.METHOD: One hundred and seventy-five patients were included in a placebo-controlled multicentre study. During phase I (4 months), premixed insulin was added to glibenclamide therapy; during phase II (1-4 months,

Syndecan-2 is a novel ligand for the protein tyrosine phosphatase receptor CD148

Syndecan-2 is a heparan sulfate proteoglycan that has a cell adhesion regulatory domain contained within its extracellular core protein. Cell adhesion to the syndecan-2 extracellular domain (S2ED) is β1 integrin dependent; however, syndecan-2 is not an integrin ligand. Here the protein tyrosine phosphatase receptor CD148 is shown to be a key intermediary in cell adhesion to S2ED, with downstream β

JASMINE: Near-infrared astrometry and time-series photometry science

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way's central core structure and formation history from Gaia-lev

Evolving therapies, neurocognitive outcomes, and functional independence in adult survivors of childhood glioma

Background: Treatment of childhood glioma has evolved to reduce radiotherapy exposure with the goal of limiting late toxicity. However, the associations between treatment changes and neurocognition, and the contribution of neurocognition and chronic health conditions to attainment of adult independence, remain unknown. Methods: Adult survivors of childhood glioma diagnosed in 1970-1999 in the Chil

Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer : patient-level meta-analysis of randomised trials

BACKGROUND: The long-term effects of adjuvant polychemotherapy regimens in oestrogen-receptor-poor (ER-poor) breast cancer, and the extent to which these effects are modified by age or tamoxifen use, can be assessed by an updated meta-analysis of individual patient data from randomised trials.METHODS: Collaborative meta-analyses of individual patient data for about 6000 women with ER-poor breast c

Transcriptomic subtyping of malignant peripheral nerve sheath tumours highlights immune signatures, genomic profiles, patient survival and therapeutic targets

Background: Malignant peripheral nerve sheath tumour (MPNST) is an aggressive orphan disease commonly affecting adolescents or young adults. Current knowledge of molecular tumour biology has been insufficient for development of rational treatment strategies. We aimed to discover molecular subtypes of potential clinical relevance. Methods: Fresh frozen samples of MPNSTs (n = 94) and benign neurofib

Impact of the gut microbiome on immunological responses to COVID-19 vaccination in healthy controls and people living with HIV

Although mRNA SARS-CoV-2 vaccines are generally safe and effective, in certain immunocompromised individuals they can elicit poor immunogenic responses. Among these individuals, people living with HIV (PLWH) have poor immunogenicity to several oral and parenteral vaccines. As the gut microbiome is known to affect vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immu

Bivalirudin vs Heparin Anticoagulation in STEMI : Confirmation of the BRIGHT-4 Results

Background: In the BRIGHT-4 (Bivalirudin With Prolonged Full-Dose Infusion During Primary PCI Versus Heparin Trial-4), anticoagulation with bivalirudin plus a 2- to 4-hour high-dose infusion after percutaneous coronary intervention (PCI) reduced all-cause mortality and bleeding without increasing reinfarction or stent thrombosis compared with heparin alone in patients with ST-segment elevation myo

Transcriptomic profiles of myxofibrosarcoma and undifferentiated pleomorphic sarcoma correlate with clinical and genomic features

Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) are two common and aggressive subtypes of soft tissue sarcoma. The aim of this study was to assess potential transcriptomic differences between MFS and UPS tumours and to evaluate the extent to which differences in gene expression profiles were associated with genomic and clinical features. The study included 162 patients with t

Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART) : a single-blind, non-inferiority, registry-based, randomised controlled trial

Background: Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to as