Improving the Accuracy of UK Regulatory Cost Estimates

UK Government departments are required to undertake a Regulatory Impact Assessment (RIA) when introducing any policy change that places a burden on businesses, charities, the voluntary sector or individuals. Part of this assessment involves the appraisal of the costs (and benefits) associated with complying with all the available options, as well as the wider economic costs. Recent evidence has suggested that the compliance costs, when assessed ex post, tend to be lower than the ex ante assessment made beforehand (see e.g. Harrington et al 1999). Accurate cost estimates are important as errors can lead to under or over regulation. This, in turn, can result in growth and innovation being hindered or, in the case of under regulation, growth being achieved at the expense of the natural resource base (including human health and well being). In order to shed more light on the validity of RIA cost estimates and identify ways of improving their accuracy, Defra decided to commission a study comparing the ex ante and ex post costs of complying with regulatory changes. A total of eight case studies were carried out for this study, covering a range of recent environmental, agricultural and food-related regulations in the UK. Preliminary findings of this study indicate that while ex ante costs are often overestimated, there can also be significant underestimates. Reasons for errors in cost estimation are discussed and strategies for improving their accuracy suggested.Public Economics,

Macro-B12 masking B12 deficiency

In clinical practice, the finding of an elevated serum B(12) concentration is often the consequence of supplementation with B(12) in either oral form or injections. Also, elevated serum B(12) may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequence of complex formation of B(12)-vitamin binding proteins with immunoglobulins, the so-called macro-B(12). We describe a young woman who previously was diagnosed with B(12) deficiency, and in whom, after cessation of B(12) injection treatment, neurologic symptoms re-appeared, and despite this, repeatedly elevated serum B(12) concentrations above the upper limit of the assay were found. We demonstrated that this was caused by the presence of macro-B(12), which not only resulted in erroneous and longstanding elevated serum B(12), but also masked her underlying B(12) deficiency

Metal-coordination: using one of nature's tricks to control soft material mechanics

Growing evidence supports a critical role of dynamic metal-coordination crosslinking in soft biological material properties such as self-healing and underwater adhesion. Using bio-inspired metal-coordinating polymers, initial efforts to mimic these properties have shown promise. Here we demonstrate how bio-inspired aqueous polymer network mechanics can be easily controlled via metal-coordination crosslink dynamics; metal ion-based crosslink stability control allows aqueous polymer network relaxation times to be finely tuned over several orders of magnitude. In addition to further biological material insights, our demonstration of this compositional scaling mechanism should provide inspiration for new polymer material property-control designs.National Science Foundation (U.S.). Materials Research Science and Engineering Centers (Program) (DMR-0820054)Danish Council for Independent Research (Natural Sciences for a Post-Doctoral Fellowship 272-08-0087)University of Chicago. Materials Research Science and Engineering Center (DMR 0820054

The Effects of Parenteral K1 Administration in Pseudoxanthoma Elasticum Patients Versus Controls. A Pilot Study

Introduction: Pseudoxanthoma elasticum (PXE) is a rare disease caused by mutations in the ABCC6 gene. Vitamin K1 is involved in the posttranslational carboxylation of some proteins related to inhibition of the calcification process. Our aim was to investigate, in patients affected by PXE, baseline levels of vitamin K1-dependent proteins and -metabolites and whether parenteral administration of phytomenadione was effective in modulating their levels. Methods: We included eight PXE patients with typical clinical symptoms (skin, retina, and vascular calcification) and two ABCC6 causative mutations; 13 clinically unaffected first-degree patients' relatives (9 carrying one ABCC6 mutation and 4 non-carriers). We assessed urinary vitamin K1 metabolites and serum Glu- and Gla-OC, Gas6 and undercaboxylated prothrombin (PIVKA-II), at baseline and after 1 and 6\u2009weeks after a single intramuscular injection of 10\u2009mg vitamin K1. Results: Comparison of PXE patients, heterozygous, and non-carriers revealed differences in baseline levels of serum MK-4 and of urinary vitamin K metabolites. The response to phytomenadione administration on vitamin K-dependent proteins was similar in all groups. Conclusion: The physiological axis between vitamin K1 and vitamin K-dependent proteins is preserved; however, differences in the concentration of vitamin K metabolites and of MK-4 suggest that vitamin K1 metabolism/catabolism could be altered in PXE patients

Exclusively breastmilk‐fed preterm infants are at high risk of developing subclinical vitamin K deficiency despite intramuscular prophylaxis at birth

Background: There is near-global consensus that all newborns be given parenteral vitamin K1 (VK1) at birth as prophylaxis against VK deficiency bleeding (VKDB). Breastmilk has a low VK content and cases of late VKDB are reported in exclusively breastmilk-fed preterm infants despite VK prophylaxis at birth. Objectives: To assess the prevalence of functional VK insufficiency in preterm infants based on elevated under-γ-carboxylated (Glu) species of Gla-proteins, factor II (PIVKA-II) and osteocalcin (GluOC), synthesized by liver and bone respectively. Patients/Methods: Prospective, multi-center, observational study in preterm infants born <33 weeks’ gestation. Blood samples and dietary history were collected before hospital discharge, and post discharge at 2-3 months corrected age. Outcome measures were serum VK1, PIVKA-II, and %GluOC (GluOC as a percentage of the sum of GluOC plus GlaOC) compared between exclusively breastmilk-fed and formula/mixed-fed infants post-discharge. Results: Post discharge, breastmilk-fed babies had significantly lower serum VK1 (0.15 vs. 1.81 μg/L), higher PIVKA-II (0.10 vs. 0.02 AU/mL) and higher %GluOC (63.6% vs. 8.1%) than those receiving a formula/mixed-feed diet. Pre-discharge (based on elevated PIVKA-II), only 1 (2%) of 45 breastmilk-fed infants was VK insufficient. Post-discharge, 8 (67%) of 12 exclusively breastmilk-fed babies were VK insufficient versus only 1 (4%) of 25 formula/mixed-fed babies. Conclusions: Preterm infants who remain exclusively or predominantly human breastmilk-fed post neonatal unit discharge are at high risk of developing subclinical VK deficiency in early infancy. Routine post-discharge VK1 supplementation of breastfed infants to provide intakes comparable to those from formula milks should prevent this deficiency

Cross-sectional characterization of HIV-1 env compartmentalization in cerebrospinal fluid over the full disease course

To characterize HIV-1 env compartmentalization between cerebrospinal fluid (CSF) and peripheral blood plasma over all stages of the HIV-1 disease course, and to determine the relationship between the extent of CSF HIV-1 env compartmentalization and clinical neurologic disease status

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Fifteenth Data Release of the Sloan Digital Sky Surveys: First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library

Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July–2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA—we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020–2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data