463 research outputs found

    Scaling laws in bacterial genomes: A side-effect of selection of mutational robustness?

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    In the past few years, numerous research projects have focused on identifying and understanding scaling properties in the gene content of prokaryote genomes and the intricacy of their regulation networks. Yet, and despite the increasing amount of data available, the origins of these scalings remain an open question. The RAevol model, a digital genetics model, provides us with an insight into the mechanisms involved in an evolutionary process. The results we present here show that (i) our model reproduces qualitatively these scaling laws and that (ii) these laws are not due to differences in lifestyles but to differences in the spontaneous rates of mutations and rearrangements. We argue that this is due to an indirect selective pressure for robustness that constrains the genome size

    Pioneer Venus polarimetry and haze optical thickness

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    The Pioneer Venus mission provided us with high-resolution measurements at four wavelengths of the linear polarization of sunlight reflected by the Venus atmosphere. These measurements span the complete phase angle range and cover a period of more than a decade. A first analysis of these data by Kawabata et al. confirmed earlier suggestions of a haze layer above and partially mixed with the cloud layer. They found that the haze exhibits large spatial and temporal variations. The haze optical thickness at a wavelength of 365 nm was about 0.06 at low latitudes, but approximately 0.8 at latitudes from 55 deg poleward. Differences between morning and evening terminator have also been reported by the same authors. Using an existing cloud/haze model of Venus, we study the relationship between the haze optical thickness and the degree of linear polarization. Variations over the visible disk and phase angle dependence are investigated. For that purpose, exact multiple scattering computations are compared with Pioneer Venus measurements. To get an impression of the variations over the visible disk, we have first studied scans of the polarization parallel to the intensity equator. After investigating a small subset of the available data we have the following results. Adopting the haze particle characteristics given by Kawabata et al., we find a thickening of the haze at increasing latitudes. Further, we see a difference in haze optical thickness between the northern and southern hemispheres that is of the same order of magnitude as the longitudinal variation of haze thickness along a scan line. These effects are most pronounced at a wavelength of 935 nm. We must emphasize the tentative nature of the results, because there is still an enormous amount of data to be analyzed. We intend to combine further polarimetric research of Venus with constraints on the haze parameters imposed by physical and chemical processes in the atmosphere

    Individual and organisational determinants of use of ergonomic devices in healthcare

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    (CS/IPC): 0.4%/2.7%, day 4 (2.1%/6.1%), day 7 (2.5%/7.9%), day 14 (4.7%/7.3%), and day 90 (1.0%/3.3%) from baseline (preoperative situation). On days 1, 4, and 7 there was a significant difference in leg circumference between the two treatment groups. Conclusions: Edema following femoropopliteal bypass surgery occurs in all patients. For the prevention and treatment of that edema the use of a class I CS proved superior to treatment with IPC. The use of CS remains the recommended practice following femoropopliteal bypass surgery

    Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

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    Vancomycin is an effective but potentially nephrotoxic antibiotic commonly used for severe infections. Dosing guidelines for vancomycin in obese children and adolescents with or without renal impairment are currently lacking. This study describes the pharmacokinetics of vancomycin in a large pediatric cohort with varying degrees of obesity and renal function to design practical dosing guidelines for this population. A multi-center retrospective population pharmacokinetic study was conducted using data from patients aged 1−18 years who received \u3e1 dose of vancomycin and had ≥1 vancomycin concentration measured between January 2006 and December 2012. Besides pharmacokinetic data, age, gender, body weight, creatinine clearance (CLcr, bedside Schwartz equation), ward, race, and neutropenic status were collected. Population pharmacokinetic analysis and simulations were performed using NONMEM7.4. A total of 1892 patients (5524 samples) were included, with total body weight (TBW) ranging 6−188 kg (1344 normal weight, 247 overweight, and 301 obese patients) and CLcr down to 8.6 mL/min/1.73 m2. The two-compartment model, with clearance (CL) significantly increasing with TBW and CLcr, central and peripheral volume of distribution and inter-compartmental clearance increasing with TBW, performed well for all age, weight, and renal function ranges. A dosing guideline is proposed that integrates body weight and CLcr resulting in effective and safe exposures across all ages, body weight, and renal functions in the pediatric population. We have characterized the full pharmacokinetic profile of vancomycin in obese children and adolescents aged 1−18 years and propose a practical dosing guideline that integrates both body weight and renal function

    Photometric Light Curves and Polarization of Close-in Extrasolar Giant Planets

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    The close-in extrasolar giant planets [CEGPs], \ltorder 0.05 AU from their parent stars, may have a large component of optically reflected light. We present theoretical optical photometric light curves and polarization curves for the CEGP systems, from reflected planetary light. Different particle sizes of three condensates are considered. In the most reflective case, the variability is 100\approx 100 micromagnitudes, which will be easily detectable by the upcoming satellite missions MOST, COROT, and MONS, and possibly from the ground in the near future. The least reflective case is caused by small, highly absorbing grains such as solid Fe, with variation of much less than one micromagnitude. Polarization for all cases is lower than current detectability limits. We also discuss the temperature-pressure profiles and resulting emergent spectra of the CEGP atmospheres. We discuss the observational results of Tau Boo b by Cameron et al. (1999) and Charbonneau et al. (1999) in context of our model results. The predictions - the shape and magnitude of the light curves and polarization curves - are highly dependent on the size and type of condensates present in the planetary atmosphere.Comment: 33 pages, accepted by Ap

    Making sense of risk. Donor risk communication in families considering living liverdonation to a child

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    This paper contributes to the growing line of thought in bioethics that respect for autonomy should not be equated to the facilitation of individualistic self determination through standard requirements of informed consent in all healthcare contexts. The paper describes how in the context of donation for living related liver transplantation (LRLT) meaningful, responsible decision making is often embedded within family processes and its negotiation. We suggest that good donor risk communication in families promote “conscientious autonomy” and “reflective trust”. From this, the paper offers the suggestion that transplant teams and other relevant professionals have to broaden their role and responsibility for risk communication beyond proper disclosure by addressing the impact of varied psychosocial conditions on risk interpretation and assessment for potential donors and family stakeholders. In conclusion, we suggest further research questions on how professional responsibility and role-taking in risk communication should be morally understood

    Estimation of ontogeny functions for renal transporters using a combined population pharmacokinetic and physiology-based pharmacokinetic approach : application to OAT1,3

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    To date, information on the ontogeny of renal transporters is limited. Here, we propose to estimate the in vivo functional ontogeny of transporters using a combined population pharmacokinetic (popPK) and physiology-based pharmacokinetic (PBPK) modeling approach called popPBPK. Clavulanic acid and amoxicillin were used as probes for glomerular filtration, combined glomerular filtration, and active secretion through OAT1,3, respectively. The predictive value of the estimated OAT1,3 ontogeny function was assessed by PBPK predictions of renal clearance (CLR) of other OAT1,3 substrates: cefazolin and piperacillin. Individual CL(R)post-hoc values, obtained from a published popPK model on the concomitant use of clavulanic acid and amoxicillin in critically ill children between 1 month and 15 years, were used as dependent variables in the popPBPK analysis. CLR was re-parameterized according to PBPK principles, resulting in the estimation of OAT1,3-mediated intrinsic clearance (CLint,OAT1,3,invivo) and its ontogeny. CLint,OAT1,3,invivo ontogeny was described by a sigmoidal function, reaching half of adult level around 7 months of age, comparable to findings based on renal transporter-specific protein expression data. PBPK-based CLR predictions including this ontogeny function were reasonably accurate for piperacillin in a similar age range (2.5 months-15 years) as well as for cefazolin in neonates as compared to published data (%RMSPE of 21.2 and 22.8%, respectively and %PE within +/- 50%). Using this novel approach, we estimated an in vivo functional ontogeny profile for CLint,OAT1,3,invivo that yields accurate CLR predictions for different OAT1,3 substrates across different ages. This approach deserves further study on functional ontogeny of other transporters

    Особливості розвитку освітнього потенціалу України в умовах глобалізації

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    BACKGROUND: Recommended screening to identify children at risk for diabetes and its precursors impaired glucose tolerance (IGT) and insulin resistance (IR) is fasted plasma glucose (FPG). This study evaluates the added value of fasted plasma insulin (FPI). METHODS: This study analyzed routinely collected data of an oral glucose tolerance test (OGTT) of 311 obese children (age 10.8 ± 3.2 years). Diabetes and IGT were defined according to the American Diabetes Association criteria, IR as homeostasis model assessment (HOMA)-IR ≥3.4. RESULTS: Cases diagnosed with an OGTT if FPG ≥5.6 mmol/L, compared with an OGTT performed if FPG ≥5.6 mmol/L or HOMA-IR ≥3.4, were, respectively, 4 (80%) versus 5 (100%) with diabetes, 7 (28%) versus 16 (64%) with IGT, and 0 (0%) versus 93 (100%) with IR. CONCLUSIONS: Screening with FPG and FPI has equal burden compared with screening with FPG alone, identifies all patients with diabetes, and identifies more patients with precursors of diabetes
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