Postnatal adaptations of phosphatidylcholine metabolism in extremely preterm infants: implications for choline and PUFA metabolism

BACKGROUND: Lipid metabolism in pregnancy delivers PUFAs from maternal liver to the developing fetus. The transition at birth to diets less enriched in PUFA is especially challenging for immature, extremely preterm infants who are typically supported by total parenteral nutrition. OBJECTIVE: The aim was to characterize phosphatidylcholine (PC) and choline metabolism in preterm infants and demonstrate the molecular specificity of PC synthesis by the immature preterm liver in vivo. METHODS: This MS-based lipidomic study quantified the postnatal adaptations to plasma PC molecular composition in 31 preterm infants <28 weeks' gestational age. Activities of the cytidine diphosphocholine (CDP-choline) and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways for PC synthesis were assessed from incorporations of deuterated methyl-D9-choline chloride. RESULTS: The concentration of plasma PC in these infants increased postnatally from median values of 481 (IQR: 387-798) µM at enrollment to 1046 (IQR: 616-1220) µM 5 d later (P < 0.001). Direct incorporation of methyl-D9-choline demonstrated that this transition was driven by an active CDP-choline pathway that synthesized PC enriched in species containing oleic and linoleic acids. A second infusion of methyl-D9-choline chloride at day 5 clearly indicated continued activity of this pathway. Oxidation of D9-choline through D9-betaine resulted in the transfer of 1 deuterated methyl group to S-adenosylmethionine. A very low subsequent transfer of this labeled methyl group to D3-PC indicated that liver PEMT activity was essentially inactive in these infants. CONCLUSIONS: This study demonstrated that the preterm infant liver soon after birth, and by extension the fetal liver, was metabolically active in lipoprotein metabolism. The low PEMT activity, which is the only pathway for endogenous choline synthesis and is responsible for hormonally regulated export of PUFAs from adult liver, strongly supports increased supplementation of preterm parenteral nutrition with both choline and PUFAs

Hospital treatment -is it affordable? A structured cost analysis of vaginal deliveries and planned caesarean sections

<p>Abstract</p> <p>Introduction</p> <p>The analysis of cost effectiveness in hospitals is as difficult as treating the patients properly. We are yet not able to answer the simple question of what costs are caused by a certain diagnosis and its treatment during an average hospital stay.</p> <p>Methods</p> <p>To answer some issues of the global problem of cost effectiveness during hospitalisation, we analysed the costs and the cost structure of a normal obstetrical hospital stay during an uncomplicated vaginal delivery and a planned caesarean section. Cost data was collected and summarized from the patients file, the hospital's computer system gathering all cost centres, known material expenses and expenses of non obstetrical medical services.</p> <p>Results</p> <p>For vaginal deliveries/planned caesareans we can calculate with a surplus of about 83 €/1432 €. About 45% of the summarized costs are calculated on a reliable database.</p> <p>Discussion</p> <p>The introduction of the DRG based clearing system in Germany has aggravated the discussion on cost effectiveness. Our meticulous work-up of expenses excluded personal precautionary costs and personnel costs of documentation because no tools are described to depict such costs. If we would add these costs to the known expenses of our study, we strongly suspect that hospital treatment of vaginal deliveries or planned caesarean sections is not cost effective.</p

Strongly magnetized pulsars: explosive events and evolution

Well before the radio discovery of pulsars offered the first observational confirmation for their existence (Hewish et al., 1968), it had been suggested that neutron stars might be endowed with very strong magnetic fields of $10^{10}$-$10^{14}$G (Hoyle et al., 1964; Pacini, 1967). It is because of their magnetic fields that these otherwise small ed inert, cooling dead stars emit radio pulses and shine in various part of the electromagnetic spectrum. But the presence of a strong magnetic field has more subtle and sometimes dramatic consequences: In the last decades of observations indeed, evidence mounted that it is likely the magnetic field that makes of an isolated neutron star what it is among the different observational manifestations in which they come. The contribution of the magnetic field to the energy budget of the neutron star can be comparable or even exceed the available kinetic energy. The most magnetised neutron stars in particular, the magnetars, exhibit an amazing assortment of explosive events, underlining the importance of their magnetic field in their lives. In this chapter we review the recent observational and theoretical achievements, which not only confirmed the importance of the magnetic field in the evolution of neutron stars, but also provide a promising unification scheme for the different observational manifestations in which they appear. We focus on the role of their magnetic field as an energy source behind their persistent emission, but also its critical role in explosive events.Comment: Review commissioned for publication in the White Book of "NewCompStar" European COST Action MP1304, 43 pages, 8 figure

Reporting of loss to follow-up information in randomised controlled trials with time-to-event outcomes: a literature survey

<p>Abstract</p> <p>Background</p> <p>To assess the reporting of loss to follow-up (LTFU) information in articles on randomised controlled trials (RCTs) with time-to-event outcomes, and to assess whether discrepancies affect the validity of study results.</p> <p>Methods</p> <p>Literature survey of all issues of the BMJ, Lancet, JAMA, and New England Journal of Medicine published between 2003 and 2005. Eligible articles were reports of RCTs including at least one Kaplan-Meier plot. Articles were classified as "assessable" if sufficient information was available to assess LTFU. In these articles, LTFU information was derived from Kaplan-Meier plots, extracted from the text, and compared. Articles were then classified as "consistent" or "not consistent". Sensitivity analyses were performed to assess the validity of study results.</p> <p>Results</p> <p>319 eligible articles were identified. 187 (59%) were classified as "assessable", as they included sufficient information for evaluation; 140 of 319 (44%) presented consistent LTFU information between the Kaplan-Meier plot and text. 47 of 319 (15%) were classified as "not consistent". These 47 articles were included in sensitivity analyses. When various imputation methods were used, the results of a chi²-test applied to the corresponding 2 × 2 table changed and hence were not robust in about half of the studies.</p> <p>Conclusions</p> <p>Less than half of the articles on RCTs using Kaplan-Meier plots provide assessable and consistent LTFU information, thus questioning the validity of the results and conclusions of many studies presenting survival analyses. Authors should improve the presentation of both Kaplan-Meier plots and LTFU information, and reviewers of study publications and journal editors should critically appraise the validity of the information provided.</p

Flavor Violating Higgs Decays

We study a class of nonstandard interactions of the newly discovered 125 GeV Higgs-like resonance that are especially interesting probes of new physics: flavor violating Higgs couplings to leptons and quarks. These interaction can arise in many frameworks of new physics at the electroweak scale such as two Higgs doublet models, extra dimensions, or models of compositeness. We rederive constraints on flavor violating Higgs couplings using data on rare decays, electric and magnetic dipole moments, and meson oscillations. We confirm that flavor violating Higgs boson decays to leptons can be sizeable with, e.g., h -> tau mu and h -> tau e branching ratios of order 10% perfectly allowed by low energy constraints. We estimate the current LHC limits on h -> tau mu and h -> tau e decays by recasting existing searches for the SM Higgs in the tau-tau channel and find that these bounds are already stronger than those from rare tau decays. We also show that these limits can be improved significantly with dedicated searches and we outline a possible search strategy. Flavor violating Higgs decays therefore present an opportunity for discovery of new physics which in some cases may be easier to access experimentally than flavor conserving deviations from the Standard Model Higgs framework.Comment: 39 pages, 12 figures, 3 tables; v2: Improved referencing, updated mu -> 3e bounds to include large loop contributions, corrected single top constraints; conclusions unchanged; matches version to be published in JHEP; v3: included 2-loop contributions in mu -> e conversion, improved discussion of tau -> 3 mu and of EDM constraints on FV top-Higgs couplings; conclusions unchange

Potential of gene drives with genome editing to increase genetic gain in livestock breeding programs

Abstract Background This paper uses simulation to explore how gene drives can increase genetic gain in livestock breeding programs. Gene drives are naturally occurring phenomena that cause a mutation on one chromosome to copy itself onto its homologous chromosome. Methods We simulated nine different breeding and editing scenarios with a common overall structure. Each scenario began with 21 generations of selection, followed by 20 generations of selection based on true breeding values where the breeder used selection alone, selection in combination with genome editing, or selection with genome editing and gene drives. In the scenarios that used gene drives, we varied the probability of successfully incorporating the gene drive. For each scenario, we evaluated genetic gain, genetic variance ( \u3c3 A 2 ) , rate of change in inbreeding ( \u394 F ), number of distinct quantitative trait nucleotides (QTN) edited, rate of increase in favourable allele frequencies of edited QTN and the time to fix favourable alleles. Results Gene drives enhanced the benefits of genome editing in seven ways: (1) they amplified the increase in genetic gain brought about by genome editing; (2) they amplified the rate of increase in the frequency of favourable alleles and reduced the time it took to fix them; (3) they enabled more rapid targeting of QTN with lesser effect for genome editing; (4) they distributed fixed editing resources across a larger number of distinct QTN across generations; (5) they focussed editing on a smaller number of QTN within a given generation; (6) they reduced the level of inbreeding when editing a subset of the sires; and (7) they increased the efficiency of converting genetic variation into genetic gain. Conclusions Genome editing in livestock breeding results in short-, medium- and long-term increases in genetic gain. The increase in genetic gain occurs because editing increases the frequency of favourable alleles in the population. Gene drives accelerate the increase in allele frequency caused by editing, which results in even higher genetic gain over a shorter period of time with no impact on inbreeding

Developmental morphology of cover crop species exhibit contrasting behaviour to changes in soil bulk density, revealed by X-ray computed tomography

Plant roots growing through soil typically encounter considerable structural heterogeneity, and local variations in soil dry bulk density. The way the in situ architecture of root systems of different species respond to such heterogeneity is poorly understood due to challenges in visualising roots growing in soil. The objective of this study was to visualise and quantify the impact of abrupt changes in soil bulk density on the roots of three cover crop species with contrasting inherent root morphologies, viz. tillage radish (Raphanus sativus), vetch (Vicia sativa) and black oat (Avena strigosa). The species were grown in soil columns containing a two-layer compaction treatment featuring a 1.2 g cm-3 (uncompacted) zone overlaying a 1.4 g cm-3 (compacted) zone. Three-dimensional visualisations of the root architecture were generated via X-ray computed tomography, and an automated root-segmentation imaging algorithm. Three classes of behaviour were manifest as a result of roots encountering the compacted interface, directly related to the species. For radish, there was switch from a single tap-root to multiple perpendicular roots which penetrated the compacted zone, whilst for vetch primary roots were diverted more horizontally with limited lateral growth at less acute angles. Black oat roots penetrated the compacted zone with no apparent deviation. Smaller root volume, surface area and lateral growth were consistently observed in the compacted zone in comparison to the uncompacted zone across all species. The rapid transition in soil bulk density had a large effect on root morphology that differed greatly between species, with major implications for how these cover crops will modify and interact with soil structure