231 research outputs found
EPICA Dome C electronic control system
AbstractA new deep drill has been developed within the framework of the European Programme for Ice Coring in Antarctica (EPICA). Several versions of the EPICA drill exist. The version used at Dome Concordia (75Ë06'1" S, 123Ë23'71" E) was operated with a new electronic control system developed by the Ente per le Nuove tecnologie, l'Energia e l'Ambiente (ENEA) Research Center in Brasimone, Italy. This electronic control system was used for the first time during the 1997/98 Antarctic summer season
Real-world utilization and outcomes of systemic therapy among patients with advanced or recurrent endometrial cancer in the United States
OBJECTIVE: Evaluate systemic therapy utilization patterns and outcomes by line of therapy among patients with advanced/recurrent endometrial cancer (EC) treated in the United States.
METHODS: This retrospective observational study used the Optum Clinformatics Extended Data Mart Date of Death database (1 January 2004-31 December 2019) and included de-identified data from adult patients with advanced/recurrent EC who were treated with first-line (1L) platinum-based chemotherapy and initiated second-line (2L) anti-neoplastic therapy. The index date was the date of 1L therapy initiation. The number and sequence of treatments received and the proportion of patients who received each type of treatment for each line of therapy were evaluated. To account for new drug approvals, patients first treated in 2018 or 2019 were also assessed separately.
RESULTS: Among the 1317 patients who met all eligibility criteria, 520 (39.5%) and 235 (17.8%) patients received 3 or 4+ lines of treatment, respectively, during a median total follow-up time of 25.2 months (range, 2.5-173.3âmonths) following the index date. Chemotherapy, including platinum- and non-platinum-based regimens, was the most common treatment across all lines of therapy: 2L, 80.0%; 3L, 66.2%; 4L+, 80.4%. Overall, 2.5%, 2.3%, and 8.9% of 2L, 3L, and 4Lâ+âpatients, respectively, received anti-program death 1 (anti-PD-1) immunotherapies. In patients first treated in 2018 and 2019 (
CONCLUSIONS: Among patients with advanced/recurrent EC treated with 1L platinum-based therapy in clinical practice, chemotherapy was the most common treatment choice across all lines of therapy. Immunotherapy use was low overall but increased in patients who started treatment in 2018 or 2019. Overall, median TTNT decreased as lines of therapy increased
New insights on the population genetic structure of the great scallop (Pecten maximus) in the English Channel coupling microsatellite data and demogenetic simulations.
International audienceThe great scallop (Pecten maximus) is a commercially important bivalve in Europe, particularly in the English Channel, where fisheries are managed at regional and local scales through the regulation of fishing effort. In the long term, knowledge about larval dispersal and gene flow between populations is essential to ensure proper stock management. Yet, previous population genetic studies have reported contradictory results. In this study, scallop samples collected across the main fishing grounds along the French and English coasts of the English Channel (20 samples with temporal replicates for three sites,n= 1059 individuals), and the population genetic structure was analysed using 13 microsatellite loci. Coupling empirical genetic data with demogenetic modelling based on a biophysical model simulating larval exchanges among scallop beds revealed a subtle genetic differentiation between south-west English populations and the rest of the English Channel, which was consistent with larval dispersal simulations. The present study provides a step forward in the understanding of great scallop population biology in the English Channel, underlining the fact that even in a context of potentially high gene flow and recent divergence times since the end of the last glacial maximum, weak but significant spatial genetic structure can be identified at a regional scale
Availability of Advance Care Planning Documentation for Older Emergency Department Patients: A Cross-Sectional Study
Introduction: Increasing advance care planning (ACP) among older adults is a national priority. Documentation of ACP in the electronic health record (EHR) is particularly important during emergency care
Erectile dysfunction is frequent in systemic sclerosis and associated with severe disease: a study of the EULAR Scleroderma Trial and Research group
Introduction: Erectile dysfunction (ED) is common in men with systemic sclerosis (SSc) but the demographics, risk factors and treatment coverage for ED are not well known.
Method: This study was carried out prospectively in the multinational EULAR Scleroderma Trial and Research database by amending the electronic data-entry system with the International Index of Erectile Function-5 and items related to ED risk factors and treatment. Centres participating in this EULAR Scleroderma Trial and Research substudy were asked to recruit patients consecutively.
Results: Of the 130 men studied, only 23 (17.7%) had a normal International Index of Erectile Function-5 score. Thirty-eight per cent of all participants had severe ED (International Index of Erectile Function-5 score †7). Men with ED were significantly older than subjects without ED (54.8 years vs. 43.3 years, P < 0.001) and more frequently had simultaneous non-SSc-related risk factors such as alcohol consumption. In 82% of SSc patients, the onset of ED was after the manifestation of the first non-Raynaud's symptom (median delay 4.1 years). ED was associated with severe cutaneous, muscular or renal involvement of SSc, elevated pulmonary pressures and restrictive lung disease. ED was treated in only 27.8% of men. The most common treatment was sildenafil, whose efficacy is not established in ED of SSc patients.
Conclusions: Severe ED is a common and early problem in men with SSc. Physicians should address modifiable risk factors actively. More research into the pathophysiology, longitudinal development, treatment and psychosocial impact of ED is needed
APOBEC3G/3A Expression in Human Immunodeficiency Virus Type 1-Infected Individuals Following Initiation of Antiretroviral Therapy Containing Cenicriviroc or Efavirenz
Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3) family members are cytidine deaminases that play crucial roles in innate responses to retrovirus infection. The mechanisms by which some of these enzymes restrict human immunodeficiency virus type 1 (HIV-1) replication have been extensively investigated in vitro. However, little is known regarding how APOBEC3 proteins affect the pathogenesis of HIV-1 infection in vivo and how antiretroviral therapy influences their expression. In this work, a longitudinal analysis was performed to evaluate APOBEC3G/3A expression in peripheral blood mononuclear cells of antiretroviral-naive HIV-1-infected individuals treated with cenicriviroc (CVC) or efavirenz (EFV) at baseline and 4, 12, 24, and 48âweeks post-treatment follow-up. While APOBEC3G expression was unaffected by therapy, APOBEC3A levels increased in CVC but not EFV arm at week 48 of treatment. APOBEC3G expression correlated directly with CD4+ cell count and CD4+/CD8+ cell ratio, whereas APOBEC3A levels inversely correlated with plasma soluble CD14. These findings suggest that higher APOBEC3G/3A levels may be associated with protective effects against HIV-1 disease progression and chronic inflammation and warrant further studies
Electrically driven thermal light emission from individual single-walled carbon nanotubes
Light emission from nanostructures exhibits rich quantum effects and has
broad applications. Single-walled carbon nanotubes (SWNTs) are one-dimensional
(1D) metals or semiconductors, in which large number of electronic states in a
narrow range of energies, known as van Hove singularities, can lead to strong
spectral transitions. Photoluminescence and electroluminescence involving
interband transitions and excitons have been observed in semiconducting SWNTs,
but are not expected in metallic tubes due to non-radiative relaxations. Here,
we show that in the negative differential conductance regime, a suspended
quasi-metallic SWNT (QM-SWNT) emits light due to joule-heating, displaying
strong peaks in the visible and infrared corresponding to interband
transitions. This is a result of thermal light emission in 1D, in stark
contrast with featureless blackbody-like emission observed in large bundles of
SWNTs or multi-walled nanotubes. This allows for probing of the electronic
temperature and non-equilibrium hot optical phonons in joule-heated QM-SWNTs
The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions
Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the âŒ120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella
Relevance of large litter bag burial for the study of leaf breakdown in the hyporheic zone
Particulate organic matter is the major source of energy for most low-order streams, but a large part of this litter is buried within bed sediment during floods and thus become poorly available for benthic food webs. The fate of this buried litter is little studied. In most cases, measures of breakdown rates consist of burying a known mass of litter within the stream sediment and following its breakdown over time. We tested this method using large litter bags (15 x 15 cm) and two field experiments. First, we used litter large bags filled with Alnus glutinosa leaves (buried at 20 cm depth with a shovel) in six stations within different land-use contexts and with different sediment grain sizes. Breakdown rates were surprisingly high (0.0011â0.0188 day-1) and neither correlate with most of the physico-chemical characteristics measured in the interstitial habitats nor with the land-use around the stream. In contrast, the rates were negatively correlated with a decrease in oxygen concentrations between surface and buried bags and positively correlated with both the percentage of coarse particles (20â40 mm) in the sediment and benthic macro-invertebrate richness. These results suggest that the vertical exchanges with surface water in the hyporheic zone play a crucial role in litter breakdown. Second, an experimental modification of local sediment (removing fine particles with a shovel to increase vertical exchanges) highlighted the influence of grain size on water and oxygen exchanges, but had no effect on hyporheic breakdown rates. Burying large litter bags within sediments may thus not be a relevant method, especially in clogged conditions, due to changes induced through the burial process in the vertical connectivity between surface and interstitial habitats that modify organic matter processing
Antifibrotic Effects of the Dual CCR2/CCR5 Antagonist Cenicriviroc in Animal Models of Liver and Kidney Fibrosis
Background & Aims
Interactions between C-C chemokine receptor types 2 (CCR2) and 5 (CCR5) and their ligands, including CCL2 and CCL5, mediate fibrogenesis by promoting monocyte/macrophage recruitment and tissue infiltration, as well as hepatic stellate cell activation. Cenicriviroc (CVC) is an oral, dual CCR2/CCR5 antagonist with nanomolar potency against both receptors. CVCâs anti-inflammatory and antifibrotic effects were evaluated in a range of preclinical models of inflammation and fibrosis.
Methods
Monocyte/macrophage recruitment was assessed in vivo in a mouse model of thioglycollate-induced peritonitis. CCL2-induced chemotaxis was evaluated ex vivo on mouse monocytes. CVCâs antifibrotic effects were evaluated in a thioacetamide-induced rat model of liver fibrosis and mouse models of diet-induced non-alcoholic steatohepatitis (NASH) and renal fibrosis. Study assessments included body and liver/kidney weight, liver function test, liver/kidney morphology and collagen deposition, fibrogenic gene and protein expression, and pharmacokinetic analyses.
Results
CVC significantly reduced monocyte/macrophage recruitment in vivo at doses â„20 mg/kg/day (p < 0.05). At these doses, CVC showed antifibrotic effects, with significant reductions in collagen deposition (p < 0.05), and collagen type 1 protein and mRNA expression across the three animal models of fibrosis. In the NASH model, CVC significantly reduced the non-alcoholic fatty liver disease activity score (p < 0.05 vs. controls). CVC treatment had no notable effect on body or liver/kidney weight.
Conclusions
CVC displayed potent anti-inflammatory and antifibrotic activity in a range of animal fibrosis models, supporting human testing for fibrotic diseases. Further experimental studies are needed to clarify the underlying mechanisms of CVCâs antifibrotic effects. A Phase 2b study in adults with NASH and liver fibrosis is fully enrolled (CENTAUR Study 652-2-203; NCT02217475)
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