922 research outputs found

    Local versus Global Strategies in Multi-parameter Estimation

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    We consider the problem of estimating multiple phases using a multi-mode interferometer. In this setting we show that while global strategies with multi-mode entanglement can lead to high precision gains, the same precision enhancements can be obtained with mode-separable states and local measurements. The crucial resource for quantum enhancement is shown to be a large number variance in the probe state, which can be obtained without any entanglement between the modes. This has important practical implications because local strategies using separable states have many advantages over global schemes using multi-mode-entangled states. Such advantages include a robustness to local estimation failure, more flexibility in the distribution of resources, and comparatively easier state preparation. We obtain our results by analyzing two different schemes: the first uses a set of interferometers, which can be used as a model for a network of quantum sensors, and the second looks at measuring a number of phases relative to a reference, which is concerned primarily with quantum imaging

    Influence of maternal folate depletion on Art3 DNA methylation in the murine adult brain; potential consequences for brain and neurocognitive health

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    \ua9 The Author(s) 2024. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. The developmental origins of health and disease hypothesis suggest early-life environment impacts health outcomes throughout the life course. In particular, epigenetic marks, including DNA methylation, are thought to be key mechanisms through which environmental exposures pro-gramme later-life health. Adequate maternal folate status before and during pregnancy is essential in the protection against neural tube defects, but data are emerging that suggest early-life folate exposures may also influence neurocognitive outcomes in childhood and, potentially, thereafter. Since folate is key to the supply of methyl donors for DNA methylation, we hypothesize that DNA methylation may be a mediating mechanism through which maternal folate influences neurocognitive outcomes. Using bisulphite sequencing, we measured DNA methylation of five genes (Art3, Rsp16, Tspo, Wnt16, and Pcdhb6) in the brain tissue of adult offspring of dams who were depleted of folate (n = 5, 0.4 mg folic acid/kg diet) during pregnancy (~19-21 days) and lactation (mean 22 days) compared with controls (n = 6, 2 mg folic acid/kg diet). Genes were selected as methylation of their promoters had previously been found to be altered by maternal folate intake in mice and humans across the life course, and because they have potential associations with neurocognitive outcomes. Maternal folate depletion was significantly associated with Art3 gene hypomethylation in subcortical brain tissue of adult mice at 28 weeks of age (mean decrease 6.2%, P = .03). For the other genes, no statistically significant differences were found between folate depleted and control groups. Given its association with neurocognitive outcomes, we suggest Art3 warrants further study in the context of lifecourse brain health. We have uncovered a potential biomarker that, once validated in accessible biospecimens and human context, may be useful to track the impact of early-life folate exposure on later-life neurocognitive health, and potentially be used to develop and monitor the effects of interventions

    Rapid hepatic clearance of full length CCN-2/CTGF: a putative role for LRP1-mediated endocytosis

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    This is the final version. Available on open access from Springer via the DOI in this record.CCN-2 (connective tissue growth factor; CTGF) is a key factor in fibrosis. Plasma CCN-2 has biomarker potential in numerous fibrotic disorders, but it is unknown which pathophysiological factors determine plasma CCN-2 levels. The proteolytic amino-terminal fragment of CCN-2 is primarily eliminated by the kidney. Here, we investigated elimination and distribution profiles of full length CCN-2 by intravenous administration of recombinant CCN-2 to rodents. After bolus injection in mice, we observed a large initial distribution volume (454 mL/kg) and a fast initial clearance (120 mL/kg/min). Immunosorbent assay and immunostaining showed that CCN-2 distributed mainly to the liver and was taken up by hepatocytes. Steady state clearance in rats, determined by continuous infusion of CCN-2, was fast (45 mL/kg/min). Renal CCN-2 clearance, determined by arterial and renal vein sampling, accounted for only 12 % of total clearance. Co-infusion of CCN-2 with receptor-associated protein (RAP), an antagonist of LDL-receptor family proteins, showed that RAP prolonged CCN-2 half-life and completely prevented CCN-2 internalization by hepatocytes. This suggests that hepatic uptake of CCN-2 is mediated by a RAP-sensitive mechanism most likely involving LRP1, a member of the LDL-receptor family involved in hepatic clearance of various plasma proteins. Surface plasmon resonance binding studies confirmed that CCN-2 is an LRP1 ligand. Co-infusion of CCN-2 with an excess of the heparan sulphate-binding protamine lowered the large initial distribution volume of CCN-2 by 88 % and reduced interstitial staining of CCN-2, suggesting binding of CCN-2 to heparan sulphate proteoglycans (HSPGs). Protamine did not affect clearance rate, indicating that RAP-sensitive clearance of CCN-2 is HSPG independent. In conclusion, unlike its amino-terminal fragment which is cleared by the kidney, full length CCN-2 is primarily eliminated by the liver via a fast RAP-sensitive, probably LRP1-dependent pathway.FibroGen, Inc

    Athlete level, sport-type, and gender influences on training, mental health, and sleep during the early COVID-19 lockdown in Malaysia

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    Purpose: We evaluated the extent of changes in training practices, recovery, mental health, and sleep patterns of athletes during the early COVID-19 lockdown in a single country-cohort. Methods: A total of 686 athletes (59% male, 41% female; 9% World Class, 28% International, 29% National, 26% State, 8% Recreational) from 50 sports (45% individual, 55% team) in Malaysia completed an online, survey-based questionnaire study. The questions were related to training practices (including recovery and injury), mental health, and sleep patterns. Results: Relative to pre-lockdown, training intensity (−34%), frequency (−20%, except World-Class), and duration (−24%–59%, especially International/World-Class) were compromised, by the mandated lockdown. During the lockdown, more space/access (69%) and equipment (69%) were available for cardiorespiratory training, than technical and strength; and these resources favoured World-Class athletes. Most athletes trained for general strength/health (88%) and muscular endurance (71%); and some used innovative/digital training tools (World-Class 48% vs. lower classification-levels ≤34%). More World-Class, International, and National athletes performed strength training, plyometrics, and sport-specific technical skills with proper equipment, than State/Recreational athletes. More females (42%) sourced training materials from social media than males (29%). Some athletes (38%) performed injury prevention exercises; 18% had mild injuries (knees 29%, ankles 26%), and 18% received a medical diagnosis (International 31%). Lower-level athletes (e.g., State 44%) disclosed that they were mentally more vulnerable; and felt more anxious (36% vs. higher-levels 14%–21%). Sleep quality and quantity were “normal” (49% for both), “improved” (35% and 27%), and only 16% and 14% (respectively) stated “worsened” sleep. Conclusion: Lockdown compromised training-related practices, especially in lower-level athletes. Athletes are in need of assistance with training, and tools to cope with anxiety that should be tailored to individual country requirements during lockdown situations. In particular, goal-driven (even if it is at home) fitness training, psychological, financial, and lifestyle support can be provided to reduce the difficulties associated with lockdowns. Policies and guidelines that facilitate athletes (of all levels) to train regularly during the lockdown should be developed

    Cost-effectiveness of external cephalic version for term breech presentation

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    <p>Abstract</p> <p>Background</p> <p>External cephalic version (ECV) is recommended by the American College of Obstetricians and Gynecologists to convert a breech fetus to vertex position and reduce the need for cesarean delivery. The goal of this study was to determine the incremental cost-effectiveness ratio, from society's perspective, of ECV compared to scheduled cesarean for term breech presentation.</p> <p>Methods</p> <p>A computer-based decision model (TreeAge Pro 2008, Tree Age Software, Inc.) was developed for a hypothetical base case parturient presenting with a term singleton breech fetus with no contraindications for vaginal delivery. The model incorporated actual hospital costs (e.g., 8,023forcesareanand8,023 for cesarean and 5,581 for vaginal delivery), utilities to quantify health-related quality of life, and probabilities based on analysis of published literature of successful ECV trial, spontaneous reversion, mode of delivery, and need for unanticipated emergency cesarean delivery. The primary endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted year of life gained. A threshold of 50,000perqualityadjustedlifeyears(QALY)wasusedtodeterminecosteffectiveness.</p><p>Results</p><p>TheincrementalcosteffectivenessofECV,assumingabaseline5850,000 per quality-adjusted life-years (QALY) was used to determine cost-effectiveness.</p> <p>Results</p> <p>The incremental cost-effectiveness of ECV, assuming a baseline 58% success rate, equaled 7,900/QALY. If the estimated probability of successful ECV is less than 32%, then ECV costs more to society and has poorer QALYs for the patient. However, as the probability of successful ECV was between 32% and 63%, ECV cost more than cesarean delivery but with greater associated QALY such that the cost-effectiveness ratio was less than $50,000/QALY. If the probability of successful ECV was greater than 63%, the computer modeling indicated that a trial of ECV is less costly and with better QALYs than a scheduled cesarean. The cost-effectiveness of a trial of ECV is most sensitive to its probability of success, and not to the probabilities of a cesarean after ECV, spontaneous reversion to breech, successful second ECV trial, or adverse outcome from emergency cesarean.</p> <p>Conclusions</p> <p>From society's perspective, ECV trial is cost-effective when compared to a scheduled cesarean for breech presentation provided the probability of successful ECV is > 32%. Improved algorithms are needed to more precisely estimate the likelihood that a patient will have a successful ECV.</p

    Exoplanet Atmosphere Measurements from Transmission Spectroscopy and other Planet-Star Combined Light Observations

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    It is possible to learn a great deal about exoplanet atmospheres even when we cannot spatially resolve the planets from their host stars. In this chapter, we overview the basic techniques used to characterize transiting exoplanets - transmission spectroscopy, emission and reflection spectroscopy, and full-orbit phase curve observations. We discuss practical considerations, including current and future observing facilities and best practices for measuring precise spectra. We also highlight major observational results on the chemistry, climate, and cloud properties of exoplanets.Comment: Accepted review chapter; Handbook of Exoplanets, eds. Hans J. Deeg and Juan Antonio Belmonte (Springer-Verlag). 22 pages, 6 figure
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