At the present time, IEEE 64-bit floating-point arithmetic is sufficiently accurate for most scientific applications. However, for a rapidly growing body of important scientific computing ...applications, a higher level of numeric precision is required. Such calculations are facilitated by high-precision software packages that include high-level language translation modules to minimize the conversion effort. This paper presents an overview of recent applications of these techniques and provides some analysis of their numerical requirements. We conclude that high-precision arithmetic facilities are now an indispensable component of a modern large-scale scientific computing environment.
•Improving jointly health and welfare of farm animals raises new research questions.•An integrated measure of animal health through their lifespan has to be developed.•Synergies and tensions between ...health, welfare and production need to be investigated.•Improving animal health and welfare challenges in industrial and territorial dimensions.•Livestock farmer and citizen expectations towards animal condition need consideration.
The need to integrate more clearly societal expectations on livestock farming has led the authors of this article to consider that livestock farming systems must be redesigned to position health and welfare at the heart of their objectives. This article proposes a vision of the advances in knowledge required at different scales to contribute to this transformation. After defining health and welfare of animals, the article emphasises the need to consider health in a broader perspective, to deepen the question of positive emotional experiences regarding welfare, and raises the question of how to assess these two elements on farms. The positive interactions between health and welfare are presented. Some possible tensions between them are also discussed, in particular when improving welfare by providing a more stimulating and richer environment such as access to outdoor increases the risk of infectious diseases. Jointly improving health and welfare of animals poses a number of questions at various scales, from the animal level to the production chain. At the animal level, the authors highlight the need to explore: the long-term links between better welfare and physiological balance, the role of microbiota, the psycho-neuro-endocrine mechanisms linking positive mental state and health, and the trade-off between the physiological functions of production, reproduction and immunity. At the farm level, in addition to studying the relationships at the group level between welfare, health and production, the paper supports the idea of co-constructing innovative systems with livestock farmers, as well as analysing the cost, acceptability and impact of improved systems on their working conditions and well-being. At the production chain or territory levels, various questions are raised. These include studying the best strategies to improve animal health and welfare while preserving economic viability, the labelling of products and the consumers’ willingness to pay, the consequences of heterogeneity in animal traits on the processing of animal products, and the spatial distribution of livestock farming and the organisation of the production and value chain. At the level of the citizen and consumer, one of the challenges is to better inter-relate sanitary and health perspectives on the one hand, and welfare concerns on the other hand. There is also a need to improve citizens' knowledge on livestock farming, and to develop more intense and constructive exchanges between livestock farmers, the livestock industry and citizens. These difficult issues plead for interdisciplinary and transdisciplinary research involving various scientific disciplines and the different stakeholders, including public policy makers through participatory research.
Essentials
Vitamin K‐dependent coagulant factor deficiency (VKCFD) is a rare autosomal recessive disorder.
We describe a case of inherited VKCFD due to uniparental disomy.
The homozygous mutation ...caused the absence of GGCX isoform 1 and overexpression of Δ2GGCX.
Hepatic and non‐hepatic vitamin K‐dependent proteins must be assayed to monitor VKCFD treatment.
Summary
Background
Inherited deficiency of all vitamin K‐dependent coagulant factors (VKCFD) is a rare autosomal recessive disorder caused by mutations in the γ‐glutamyl carboxylase gene (GGCX) or the vitamin K epoxide reductase gene (VKORC1), with great heterogeneity in terms of both clinical presentation and response to treatment.
Objective
To characterize the molecular basis of VKCFD in a Spanish family.
Methods and Results
Sequencing of candidate genes, comparative genomic hybridization and massive sequencing identified a new mechanism causing VKCFD in the proband. Uniparental disomy (UPD) of chromosome 2 caused homozygosity of a mutation (c.44‐1G>A) resulting in aberrant GGCX splicing. This change contributed to absent expression of the mRNA coding for the full‐length protein, and to four‐fold overexpression of the smaller mRNA isoform lacking exon 2 (Δ2GGCX). Δ2GGCX might be responsible for two unexpected clinical observations in the patient: (i) increased plasma osteocalcin levels following vitamin K1 supplementation; and (ii) a mild non‐bleeding phenotype.
Conclusions
Our study identifies a new autosomal disease, VKCFD1, caused by UPD. These data suggest that the Δ2GGCX isoform may retain enzymatic activity, and strongly encourage the evaluation of both hepatic and non‐hepatic vitamin K‐dependent proteins to assess differing responses to vitamin K supplementation in VKCFD patients.
At small coverages of ceria on TiO{sub 2}(110), the CeO{sub x} nanoparticles have an unusual coordination mode. Scanning tunneling microscopy and density-functional calculations point to the presence ...of Ce{sub 2}O{sub 3} dimers, which form diagonal arrays that have specific orientations of 0, 24, and 42{sup o} with respect to the 1 -1 0 direction of the titania substrate. At high coverages of ceria on TiO{sub 2}(110), the surface exhibits two types of terraces. In one type, the morphology is not very different from that observed at low ceria coverage. However, in the second type of terrace, there is a compact array of ceria particles with structures that do not match the structures of CeO{sub 2}(111) or CeO{sub 2}(110). The titania substrate imposes on the ceria nanoparticles nontypical coordination modes, enhancing their chemical reactivity. This phenomenon leads to a larger dispersion of supported metal nanoparticles (M = Au, Cu, Pt) and makes possible the direct participation of the oxide in catalytic reactions. The M/CeO{sub x}/TiO{sub 2}(110) surfaces display an extremely high catalytic activity for the water-gas shift reaction that follows the sequence Au/CeO{sub x}/TiO{sub 2}(110) < Cu/CeO{sub x}/TiO{sub 2}(110) < Pt/CeO{sub x}/TiO{sub 2}(110). For low coverages of Cu and CeO{sub x}, Cu/CeO{sub x}/TiO{sub 2}(110) is 8-12 times more active than Cu(111) or Cu/ZnO industrial catalysts. In the M/CeO{sub x}/TiO{sub 2}(110) systems, there is a strong coupling of the chemical properties of the admetal and the mixed-metal oxide: The adsorption and dissociation of water probably take place on the oxide, CO adsorbs on the admetal nanoparticles, and all subsequent reaction steps occur at the oxide-admetal interface. The high catalytic activity of the M/CeO{sub x}/TiO{sub 2}(110) surfaces reflects the unique properties of the mixed-metal oxide at the nanometer level.
Recent genome-wide association studies have revealed that variations near the gene locus encoding the transcription factor Krüppel-like factor 14 (KLF14) are strongly associated with HDL cholesterol ...(HDL-C) levels, metabolic syndrome, and coronary heart disease. However, the precise mechanisms by which KLF14 regulates lipid metabolism and affects atherosclerosis remain largely unexplored. Here, we report that KLF14 is dysregulated in the liver of 2 dyslipidemia mouse models. We evaluated the effects of both KLF14 overexpression and genetic inactivation and determined that KLF14 regulates plasma HDL-C levels and cholesterol efflux capacity by modulating hepatic ApoA-I production. Hepatic-specific Klf14 deletion in mice resulted in decreased circulating HDL-C levels. In an attempt to pharmacologically target KLF14 as an experimental therapeutic approach, we identified perhexiline, an approved therapeutic small molecule presently in clinical use to treat angina and heart failure, as a KLF14 activator. Indeed, in WT mice, treatment with perhexiline increased HDL-C levels and cholesterol efflux capacity via KLF14-mediated upregulation of ApoA-I expression. Moreover, perhexiline administration reduced atherosclerotic lesion development in apolipoprotein E-deficient mice. Together, these results provide comprehensive insight into the KLF14-dependent regulation of HDL-C and subsequent atherosclerosis and indicate that interventions that target the KLF14 pathway should be further explored for the treatment of atherosclerosis.
Ductal carcinoma in situ (DCIS) accounts for 20% of all newly diagnosed breast cancers. Mastectomy was once the gold standard for the treatment of DCIS; however, breast-conserving surgery (BCS) has ...been adopted as the treatment of choice for patients with small, screen-detected lesions. Both adjuvant radiation and hormonal therapy following BCS have been demonstrated in randomized trials to reduce the risk of both invasive and DCIS recurrence, but neither affects survival. With the variety of surgical and adjuvant treatment options available, there has been great interest in tailoring the treatment to the individual, with the goal of optimizing the balance of risks and benefits according to the values and priorities of the woman herself. Prospective studies of women with "low-risk" DCIS treated with BCS alone have successfully identified women at lower than average risk but have not achieved the goal of identifying a subset of women with DCIS at minimal risk of recurrence after surgical excision alone. No studies have evaluated the safety of medical management alone.
An objective categorization of respiratory infections based on outcomes is an unmet clinical need. Ventilator-associated pneumonia and tracheobronchitis remain used in clinical practice, whereas ...ventilator-associated events (VAE) are limited to surveillance purposes.
This was a secondary analysis from a multicentre observational prospective cohort study. VAE were defined as a sustained increase in minimum Oxygen inspired fraction (FiO2) and/or Positive end-expiratory pressures (PEEP) of ≥ 0.2/2 cm H2O respectively, or an increase of 0.15 FiO2 + 1 cm H20 positive end-expiratory pressures for ≥ 1 calendar-day.
15 Paediatric Intensive Care Units.
Mechanical ventilation duration, intensive care and hospital length of stay; (LOS) and mortality.
A cohort of 391 ventilated children with an age (median, Interquartile Ranges) of 1 year0.2–5.3 and 7 days5–10 of mechanical ventilation were included. Intensive care and hospital stays were 11 7–19 and 21 14–39 days, respectively. Mortality was 5.9 %. Fifty-eight ventilator-associated respiratory infections were documented among 57 patients: Seventeen (29.3 %) qualified as ventilator-associated pneumonia (VAP) and 41 (70.7 %) as ventilator-associated tracheobronchitis (VAT). Eight pneumonias and 16 tracheobronchitis (47 % vs 39 %,P = 0.571) required positive end-expiratory pressure or oxygen increases consistent with ventilator-associated criteria. Pneumonias did not significantly impact on outcomes when compared to tracheobronchitis. In contrast, infections (pneumonia or tracheobronchitis) following VAEs criteria were associated with > 6, 8 and 15 extra-days of ventilation (16 vs 9.5, P = 0.001), intensive care stay (23.5 vs 15; P = 0.004) and hospital stay (39 vs 24; P = 0.015), respectively.
When assessing ventilated children with respiratory infections, VAE apparently is associated with higher ventilator-dependency and LOS compared with pneumonia or tracheobronchitis.
Incorporating the modification of ventilatory settings for further categorization of the respiratory infections may facilitate therapeutic management among ventilated patients.
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