The practical implications of using standardized estimation equations in calculating the prevalence of chronic kidney disease

BACKGROUND: Kidney Disease Outcomes Quality Initiative (KDOQI) chronic kidney disease (CKD) guidelines have focused on the utility of using the modified four-variable MDRD equation (now traceable by isotope dilution mass spectrometry IDMS) in calculating estimated glomerular filtration rates (eGFRs). This study assesses the practical implications of eGFR correction equations on the range of creatinine assays currently used in the UK and further investigates the effect of these equations on the calculated prevalence of CKD in one UK regionMETHODS: Using simulation, a range of creatinine data (30-300 micromol/l) was generated for male and female patients aged 20-100 years. The maximum differences between the IDMS and MDRD equations for all 14 UK laboratory techniques for serum creatinine measurement were explored with an average of individual eGFRs calculated according to MDRD and IDMS &lt; 60 ml/min/1.73 m(2) and 30 ml/min/1.73 m(2). Similar procedures were applied to 712,540 samples from patients &gt; or = 18 years (reflecting the five methods for serum creatinine measurement utilized in Northern Ireland) to explore, graphically, maximum differences in assays. CKD prevalence using both estimation equations was compared using an existing cohort of observed data.RESULTS: Simulated data indicates that the majority of laboratories in the UK have small differences between the IDMS and MDRD methods of eGFR measurement for stages 4 and 5 CKD (where the averaged maximum difference for all laboratory methods was 1.27 ml/min/1.73 m(2) for females and 1.59 ml/min/1.73 m(2) for males). MDRD deviated furthest from the IDMS results for the Endpoint Jaffe method: the maximum difference of 9.93 ml/min/1.73 m(2) for females and 5.42 ml/min/1.73 m(2) for males occurred at extreme ages and in those with eGFR &gt; 30 ml/min/1.73 m(2). Observed data for 93,870 patients yielded a first MDRD eGFR &lt; 60 ml/min/1.73 m(2) in 2001. 66,429 (71%) had a second test &gt; 3 months later of which 47,093 (71%) continued to have an eGFR &lt; 60 ml/min/1.73 m(2). Estimated crude prevalence was 3.97% for laboratory detected CKD in adults using the MDRD equation which fell to 3.69% when applying the IDMS equation. Over 95% of this difference in prevalence was explained by older females with stage 3 CKD (eGFR 30-59 ml/min/1.73 m(2)) close to the stage 2 CKD (eGFR 60-90 ml/min/1.73 m(2)) interface.CONCLUSIONS: Improved accuracy of eGFR is obtainable by using IDMS correction especially in the earlier stages of CKD 1-3. Our data indicates that this improved accuracy could lead to reduced prevalence estimates and potentially a decreased likelihood of onward referral to nephrology services particularly in older females.</p

The fourteenth-century poll tax returns and the study of English surname distribution

The modern-day distributions of English surnames have been considered in genealogical, historical, and philological research as possible indicators of their origins. However, many centuries have passed since hereditary surnames were first used, and so their distribution today does not necessarily reflect their original spread, misrepresenting their origins. Previously, medieval data with national coverage have not been available for a study of surname distribution, but with the recent publication of the fourteenth-century poll tax returns, this has changed. By presenting discrepancies in medieval and nineteenth-century distributions, it is shown that more recent surname data may not be a suitable guide to surname origins and can be usefully supplemented by medieval data in order to arrive at more accurate conclusions

Local structure, pseudosymmetry, and phase transitions in Na1/2Bi1/2TiO3-K1/2Bi1/2TiO3 ceramics

The structural behavior of ceramic solid solutions (1 - x)Na1/2Bi1/2TiO3-xK(1/2)Bi(1/2)TiO(3) (NBT-KBT) was studied using high-resolution powder diffraction and transmission electron microscopy. A temperature-independent morphotropic phase boundary (MPB) separating NBT-like pseudorhombohedral (R) and KBT-like pseudotetragonal (T) phases was observed at x approximate to 0.2. For x 0.2 exhibit a tetragonal-like distortion; however, complex splitting of reflections in XRD patterns suggests that the actual symmetry is lower than tetragonal. For 0.2 0.5 the structure becomes untilted. In-phase tilting evolves above the ferroelectric transition and occurs around a nonpolar (a or b) axis of the average T structure. The onset of polar order has no significant effect on the coherence length of in-phase tilting, which suggests only weak coupling between the two phenomena. The average symmetry of the T phase is determined by the effective symmetry (Imm2) of assemblages of coherent in-phase tilted nanodomains. Near the MPB, the coexistence of extended R-and T-like regions is observed, but lattice distortions within each phase are small, yielding narrow peaks with a pseudocubic appearance in XRD. The temperature of the FE phase transition exhibits a minimum at the MPB. The structured diffuse scattering observed in electron diffraction patterns for all the compositions suggests that polar order in NBT-KBT solid solutions is modulated away from the average displacements refined using powder diffraction data.open13

Temperature dependent dielectric and Raman spectra and microwave dielectric properties of gehlenite‐typed Ca2Al2SiO7 ceramics

Gehlenite‐typed Ca2Al2SiO7 ceramics were prepared by the conventional solid‐state reaction. Two anomalies were found in the plot of dielectric constant vs. temperature, which was associated to space charge polarization. Pure phase crystal structure and no phase transition were observed in the temperature dependent XRD patterns and Raman spectra from room temperature to 900°C. There was relevant relation between Q× f and τƒ with the stretching vibrations of Ca‐O bond and O‐Ca‐O bending in CaO8 polyhedron. Excellent microwave dielectric properties (εr = 8.86, Q × f = 22,457GHz, and τf = −51.06 ppm/°C) were obtained for Ca2Al2SiO7 sintered at 1440°C in air, which had the potential application to use in microwave and millimeter‐wave devices such as capacitors and substrates

Historic landscape character and sense of place

This is an Author's Accepted Manuscript of an article published in Landscape Research, 2013, Vol. 38, Issue 2 pp.179-202, copyright Taylor & Francis, available online at: http://www.tandfonline.com/10.1080/01426397.2012.672642.Most studies of landscape character within archaeology and historical geography have focused on morphological features such as whether settlement patterns were nucleated or dispersed, but this paper discusses how adding depth to this, for example by studying place-names, vernacular architecture, and the territorial structures within which a landscape was managed in the past, gives us a far greater understanding of its texture and meaning to local communities. In two case-studies in southern Essex, for example, it is shown how the connections that once existed between inland and coastal communities can be used today to promote public access to the countryside. A further case study, in southwest England, shows how field-/place-names and vernacular architecture also make an important contribution to our appreciation of the time depth and complexity of landscape character.Arts and Humanities Research Council (AHRC)Southend-on-Sea Borough Counci

Disease-Toxicant Interactions in Manganese Exposed Huntington Disease Mice: Early Changes in Striatal Neuron Morphology and Dopamine Metabolism

YAC128 Huntington's disease (HD) transgenic mice accumulate less manganese (Mn) in the striatum relative to wild-type (WT) littermates. We hypothesized that Mn and mutant Huntingtin (HTT) would exhibit gene-environment interactions at the level of neurochemistry and neuronal morphology. Twelve-week-old WT and YAC128 mice were exposed to MnCl2-4H2O (50 mg/kg) on days 0, 3 and 6. Striatal medium spiny neuron (MSN) morphology, as well as levels of dopamine (DA) and its metabolites (which are known to be sensitive to Mn-exposure), were analyzed at 13 weeks (7 days from initial exposure) and 16 weeks (28 days from initial exposure). No genotype-dependent differences in MSN morphology were apparent at 13 weeks. But at 16 weeks, a genotype effect was observed in YAC128 mice, manifested by an absence of the wild-type age-dependent increase in dendritic length and branching complexity. In addition, genotype-exposure interaction effects were observed for dendritic complexity measures as a function of distance from the soma, where only YAC128 mice were sensitive to Mn exposure. Furthermore, striatal DA levels were unaltered at 13 weeks by genotype or Mn exposure, but at 16 weeks, both Mn exposure and the HD genotype were associated with quantitatively similar reductions in DA and its metabolites. Interestingly, Mn exposure of YAC128 mice did not further decrease DA or its metabolites versus YAC128 vehicle exposed or Mn exposed WT mice. Taken together, these results demonstrate Mn-HD disease-toxicant interactions at the onset of striatal dendritic neuropathology in YAC128 mice. Our results identify the earliest pathological change in striatum of YAC128 mice as being between 13 to 16 weeks. Finally, we show that mutant HTT suppresses some Mn-dependent changes, such as decreased DA levels, while it exacerbates others, such as dendritic pathology

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies