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

Vitamin D metabolism in critically ill patients with acute kidney injury:a prospective observational study

BackgroundVitamin D deficiency in critically ill patients is associated with poor outcomes, and vitamin D supplementation is recommended for patients with chronic kidney disease. Whether acute kidney injury (AKI) is associated with altered Vitamin D metabolism is unknown. We aimed to compare the longitudinal profiles of serum 25(OH)D and 1,25(OH)2D concentrations in critically ill patients with and without moderate to severe AKI and explore the impact of renal recovery and parathyroid hormone (PTH).MethodsIn this prospective, observational study in two centres in the UK, critically ill patients with and without AKI underwent serial measurement of serum 25(OH)D and 1,25(OH)2D and plasma PTH concentrations for 5 days. Linear mixed model analysis and sensitivity analyses were performed.ResultsSerial data of 137 patients were analysed. Seventy-one patients had AKI stage II/III of whom 23 recovered kidney function during the 5-day study period; 66 patients did not have AKI at enrolment of whom 14 developed new AKI. On day of enrolment, patients’ serum 25(OH)D concentrations were low (median 18 nmol/L) but there was no significant difference between patients with and without AKI. Median serum 1,25(OH)2D levels were significantly lower in patients with AKI II/III (41 pmol/L [IQR 26, 58]) compared to similarly unwell patients without AKI (54 pmol/L [IQR 33, 69]) during the 5-day period. Recovery of kidney function in patients with AKI was associated with a rise in 1,25(OH)2D concentrations. Plasma PTH results were impacted by serum calcium and magnesium levels but not associated with 1,25(OH)2D levels.ConclusionsCritically ill patients with moderate-to-severe AKI have significantly lower serum 1,25(OH)2D concentrations than similarly sick patients without AKI but there was no difference in serum 25(OH)D concentrations. Recovery of AKI was associated with a rise in serum 1,25(OH)2D concentrations. More research is needed to investigate the health benefits and safety of supplementation with active vitamin D in critically ill patients with moderate-to-severe AKI.Trial registration Clinicaltrials.gov (NCT02869919), registered on 16 May 2016.<br/

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

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

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