355 research outputs found

    Effect of timed dosing of usual antihypertensives according to patient chronotype on cardiovascular outcomes:the Chronotype sub-study cohort of the Treatment in Morning versus Evening (TIME) study

    Get PDF
    Background: Timing drug administration to endogenous circadian rhythms may enhance treatment efficacy. In the Chronotype sub-study of the Treatment in Morning versus Evening (TIME) clinical trial we examined whether timing of usual antihypertensive medications according to patient chronotype (a behavioural marker of personal circadian rhythm) may influence clinical cardiovascular outcomes.Methods: This was a cohort sub-study of TIME, a prospective, randomised, open-label, blinded-endpoint, UK clinical trial of morning versus evening dosing of usual antihypertensive medications and cardiovascular outcomes. On August 3rd, 2020, all active TIME participants were invited to complete a validated chronotype questionnaire. Chronotype was quantitatively assessed as the mid sleep time on free days corrected for sleep debt on workdays (MSFsc). We analysed associations between chronotype and antihypertensive dosing time and explored their combined effect on cardiovascular outcomes (a composite endpoint of hospitalisation for non-fatal myocardial infarction (MI) or non-fatal stroke, and single components) using proportional hazard time-to-event models adjusted for baseline covariates. These were used to specifically test for interactions between dosing time and chronotype.Findings: Between August 3, 2020, and March 31, 2021, 5358 TIME participants completed the online questionnaire. 2778 were previously randomised to morning dosing and 2580 to evening dosing of their usual antihypertensives. Chronotype was symmetrically distributed around a median MSFsc of 3:07 am. The composite endpoint increased for later MSFsc (later chronotype) dosed in the morning but not in those dosed in the evening (hazard ratios 1.46 [95% CI 1.14-1.86] and 0.96 [95% CI 0.70-1.30] per hour of MSFsc, respectively; interaction p = 0.036). Later chronotype was associated with increased risk of hospitalisation for non-fatal MI in the morning dosing group, and reduced risk in the evening dosing group (hazard ratios 1.62 [95% CI 1.18-2.22] and 0.66 [95% CI 0.44-1.00] per hour of MSFsc, respectively; interaction p &lt; 0.001). No interaction between chronotype and antihypertensive dosing time was observed for stroke events.Interpretation: Alignment of dosing time of usual antihypertensives with personal chronotype could lower the incidence of non-fatal MI compared to a 'misaligned' dosing time regimen. Future studies are warranted to establish whether synchronizing administration time of antihypertensive therapy with individual chronotype reduces risk of MI.</p

    Linkages between mineralogy, fluid chemistry, and microbial communities within hydrothermal chimneys from the Endeavor Segment, Juan de Fuca Ridge

    Get PDF
    Rock and fluid samples were collected from three hydrothermal chimneys at the Endeavour Segment, Juan de Fuca Ridge to evaluate linkages among mineralogy, fluid chemistry, and microbial community composition within the chimneys. Mössbauer, midinfrared thermal emission, and visible-near infrared spectroscopies were utilized for the first time to characterize vent mineralogy, in addition to thin-section petrography, X-ray diffraction, and elemental analyses. A 282°C venting chimney from the Bastille edifice was composed primarily of sulfide minerals such as chalcopyrite, marcasite, and sphalerite. In contrast, samples from a 300°C venting chimney from the Dante edifice and a 321°C venting chimney from the Hot Harold edifice contained a high abundance of the sulfate mineral anhydrite. Geochemical modeling of mixed vent fluids suggested the oxic-anoxic transition zone was above 100°C at all three vents, and that the thermodynamic energy available for autotrophic microbial redox reactions favored aerobic sulfide and methane oxidation. As predicted, microbes within the Dante and Hot Harold chimneys were most closely related to mesophilic and thermophilic aerobes of the Betaproteobacteria and Gammaproteobacteria and sulfide-oxidizing autotrophic Epsilonproteobacteria. However, most of the microbes within the Bastille chimney were most closely related to mesophilic and thermophilic anaerobes of the Deltaproteobacteria, especially sulfate reducers, and anaerobic hyperthermophilic archaea. The predominance of anaerobes in the Bastille chimney indicated that other environmental factors promote anoxic conditions. Possibilities include the maturity or fluid flow characteristics of the chimney, abiotic Fe2+ and S2− oxidation in the vent fluids, or O2 depletion by aerobic respiration on the chimney outer wall

    A national quality incentive scheme to reduce antibiotic overuse in hospitals; evaluation of perceptions and impact

    Get PDF
    In 2016/2017, a financially-linked antibiotic prescribing quality improvement initiative (AMR-CQUIN) was introduced across acute hospitals in England. This aimed for >1% reductions in Defined Daily Doses / 1000 admissions of total antibiotics, piperacillin/tazobactam and carbapenems compared with 2013/2014 and improved review of empiric antibiotic prescriptions

    Mineralogy

    Get PDF
    The power of mineralogical analysis as a descriptive or predictive technique stems from the fact that only a few thousand minerals are known to occur in nature as compared to several hundred thousand inorganic compounds. Further, all of the known minerals have specific stability ranges in pressure, temperature, an composition. A specific knowledge of the mineralogy of a planets surface or interior therefore allows one to characterize the present or past conditions under which the minerals were formed or have existed. For the purposes of this paper, a slightly broader definition of mineralogy was adopted by including not only crystalline materials found on planetary surfaces, but also ices and classes that can benefit from in situ types of analyses. Both visual examination and the various spectroscopies available for robotic probes to planetary surfaces are discussed

    Igneous mineralogy at Bradbury Rise: The first ChemCam campaign at Gale crater

    Get PDF
    Textural and compositional analyses using Chemistry Camera (ChemCam) remote microimager and laser-induced breakdown spectroscopy (LIBS) have been performed on five float rocks and coarse gravels along the first 100 m of the Curiosity traverse at Bradbury Rise. ChemCam, the first LIBS instrument sent to another planet, offers the opportunity to assess mineralogic diversity at grain-size scales (~ 100 µm) and, from this, lithologic diversity. Depth profiling indicates that targets are relatively free of surface coatings. One type of igneous rock is volcanic and includes both aphanitic (Coronation) and porphyritic (Mara) samples. The porphyritic sample shows dark grains that are likely pyroxene megacrysts in a fine-grained mesostasis containing andesine needles. Both types have magnesium-poor basaltic compositions and in this respect are similar to the evolved Jake Matijevic rock analyzed further along the Curiosity traverse both with Alpha-Particle X-ray Spectrometer and ChemCam instruments. The second rock type encountered is a coarse-grained intrusive rock (Thor Lake) showing equigranular texture with millimeter size crystals of feldspars and Fe-Ti oxides. Such a rock is not unique at Gale as the surrounding coarse gravels (such as Beaulieu) and the conglomerate Link are dominated by feldspathic (andesine-bytownite) clasts. Finally, alkali feldspar compositions associated with a silica polymorph have been analyzed in fractured filling material of Preble rock and in Stark, a putative pumice or an impact melt. These observations document magmatic diversity at Gale and describe the first fragments of feldspar-rich lithologies (possibly an anorthosite) that may be ancient crust transported from the crater rim and now forming float rocks, coarse gravel, or conglomerate clasts

    Character and spatial distribution of OH/H<SUB>2</SUB>O on the surface of the moon seen by M<SUP>3</SUP> on Chandrayaan-1

    Get PDF
    The search for water on the surface of the anhydrous Moon had remained an unfulfilled quest for 40 years. However, the Moon Mineralogy Mapper (M3) on Chandrayaan-1 has recently detected absorption features near 2.8 to 3.0 micrometers on the surface of the Moon. For silicate bodies, such features are typically attributed to hydroxyl- and/or water-bearing materials. On the Moon, the feature is seen as a widely distributed absorption that appears strongest at cooler high latitudes and at several fresh feldspathic craters. The general lack of correlation of this feature in sunlit M3 data with neutron spectrometer hydrogen abundance data suggests that the formation and retention of hydroxyl and water are ongoing surficial processes. Hydroxyl/water production processes may feed polar cold traps and make the lunar regolith a candidate source of volatiles for human exploration

    Constraining Solar System Bombardment Using In Situ Radiometric Dating

    Get PDF
    The leading, but contentious, model for lunar impact history includes a pronounced increase in impact events at around 3.9 Ga. This late heavy bombardment would have scarred Mars and the terrestrial planets, influenced the course of biologic evolution on the early Earth, and rearranged the very architecture of our Solar System. But what if it's not true? In the last decade, new observations and sample analyses have reinterpreted basin ages and "pulled the pin" on the cataclysm - we may only have the age of one large basin (Imbrium). The Curie mission would constrain the onset of the cataclysm by determining the age of a major pre-Imbrium lunar basin (Nectaris or Crisium), characterize new lunar lithologies far from the Apollo and Luna landing sites, including the basalts in the basin-filling maria and olivine-rich lithologies in the basin margins, and provide a unique vantage point to assess volatiles in the lunar regolith from dawn to dusk
    corecore