Electron diffraction studies of thin films, deposited in particular at liquid helium temperatures

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A low dilution fusion technique for the determination of major, minor and trace elements in Lamproite and Kimberlite samples by X-ray fluorescence spectrometry

Bibliography: pages 200-204.A low dilution fusion technique using a 2:1 flux:sample ratio has been developed for the accurate determination of major, minor and trace elements by x-ray fluorescence spectrometry (XRFS). This method has been used to analyze geological samples of widely varying and unusual composition such as lamproites and kimberlites. The results are shown to be of comparable if not better accuracy than other methods of sample preparation for XRFS. Analytical conditions, including corrections for spectral line interferences are reported for all the elements determined. For major element analysis three methods of calculating appropriate alpha coefficients were investigated, namely (1) multiple regression analysis, (2) Norrish and Hutton method and (3) a computer program, NBSGSC, involving fundamental parameters and the COLA equation. Methods (1) and (2) gave poor results for rock types of widely varying composition. The third method requires that the variation of alpha coefficients with varying weight fraction of the analyte element be taken into account when calculating alpha coefficients if accurate values for major and minor elements are to be obtained on low dilution fusion discs. For trace element analysis the average relative error was less than 5% and there was a decrease in sensitivity by about a factor of 2 compared with XRFS determinations on powder pellets. The elimination of particle size effects in the homogeneous glass fusion discs is a major advantage over the use of powder pellets, especially for the determination of elements such as Ba, Cr and the REEs. A loss on fusion technique has been employed to ensure complete loss of volatiles from the rock samples. Data presented highlight the problems encountered in the determination of the volatile content in geological samples. The oxidation and retention of sulphur in the discs was also investigated

Investigation of metabolic bone disease by in vivo neutron activation analysis

A technique for measuring total body calcium (TBCa) by in vivo neutron activation analysis (IVNAA) was described. It had a precision of 1.8% for a dose of 13 mSv. TBCa was measured in 40 healthy volunteers and the mean value (SD) for 20 men was 1143g (134g) and for 20 wcmen it was 821 g (124g). A formula for predicting TBCa (TBCap) from height in men and from span and years postmenopause in wcmen was derived. The results from patient groups were expressed as a ratio of TBCa to TBCap, the calcium ratio (CaR). The mean CaR in eight wcmen with wrist fracture was 1.00 (0.10, SD) and in 14 wcmen with vertebral fractures was 0.87 (0.06, SD). The latter group had a significantly lower CaR than the female controls of 1 .00 (0.07, SD, P<0.001). The TBCa was normalized for span alone to obtain an index reflecting the bone lost since the menopause, the osteopaenia index. Patients with vertebral fractures all had values below 0.78 and so this was considered the fracture threshold. A low mean value for CaR was found in 14 patients with primary hyperparathyroidism. Significant increases in TBCa were found in four out of seven patients followed for up to 34 months postoperatively. The initial mean CaR was 0.85 (P<0.001 ). Seven wcmen with osteomalacia due to malabsorption had a low mean TBCa and osteopaenia index (P<0.001). One patient who was remeasured after eight months of vitamin D therapy had an 18% increase in TBCa, the largest increase found in any patient in the present study. Twelve patients were measured prior to, or shortly after, renal transplantation. The eight men had a mean CaR of 0.93 (P<0.05) and the four wcmen a mean value of 0.82. There was no significant change following renal transplantation over an average of 17 months. This result was attributed to a balance between the healing of renal osteodystrophy and the osteopaenic effect of steroid therapy. Forty-one men studied after peptic ulcer surgery had a low mean CaR of 0.94 (0.07, SD, P<0.01 ). The reduction in bone mass was similar for patients after partial gastrectomy and for those after vagotomy and drainage procedures. The hypothesis was proposed that bone disease after peptic ulcer surgery was due to secondary hyperparathyroidism caused by calcium malabsorption and not by subclinical osteomalacia. This was supported by the following findings. Plasma 25-hydroxycalciferol was normal when compared with season-matched controls. However, there were low plasma calcium and high parathyroid hormone levels compared with age-matched controls. Dietary calcium was normal but 7-day calcium retention was increased when the calcium was given as a solution

Mifepristone reduces insulin resistance in patient volunteers with adrenal incidentalomas that secrete low levels of cortisol : a pilot study

Background: Incidental adrenal masses are commonly detected during imaging for other pathologies. 10% of the elderly population has an ‘adrenal incidentaloma’, up to 20% of these show low-grade autonomous cortisol secretion and 60% of patients with autonomous cortisol secretion have insulin resistance. Cortisol excess is known to cause insulin resistance, an independent cardiovascular risk marker, however in patients with adrenal incidentalomas it is unknown whether their insulin resistance is secondary to the excess cortisol and therefore potentially reversible. In a proof of concept study we examined the short-term effects of glucocorticoid receptor (GR) antagonism in patients with an adrenal incidentaloma to determine whether their insulin resistance was reversible. Methodology/Principal Findings: In a prospective open-label pilot study, six individuals with adrenal incidentalomas and autonomous cortisol secretion were treated with mifepristone (a GR antagonist) 200 mg twice daily and studied for 4 weeks on a Clinical Research Facility. Insulin resistance at four weeks was assessed by insulin resistance indices, lnHOMA-IR and lnMatsuda, and AUC insulin during a 2-hour glucose tolerance test. Biochemical evidence of GR blockade was shown in all individuals and across the group there was a significant reduction in insulin resistance: lnHOMA-IR (1.0vs0.6; p = 0.03), lnHOMA-%beta (4.8vs4.3; p = 0.03) and lnMatsuda (1.2vs1.6; p = 0.03). Five out of six individuals showed a reduction in insulin AUC .7237 pmol/l.min, and in two patients this showed a clinically significant cardiovascular benefit (as defined by the Helsinki heart study). Conclusions: Short-term GR antagonism is sufficient to reduce insulin resistance in some individuals with adrenal incidentalomas and mild cortisol excess. Further assessment is required to assess if the responses may be used to stratify therapy as adrenal incidentalomas may be a common remediable cause of increased cardiovascular risk

Reference interval for albumin‐adjusted calcium based on a large UK population

Context: Primary hyperparathyroidism is a common condition and results in hypercalcaemia, especially in older women. Thus, it is critical to obtain a robust estimate for the upper limit of the reference interval for albumin‐adjusted serum calcium in the general population. The current reference interval in use in the UK (Pathology Harmony range, 2.20 to 2.60 mmol/L) was based on a consensus. Objectives: To establish a reference interval for albumin‐adjusted serum calcium in men and women. Design: Cross‐sectional study of men and women who did not have chronic kidney disease or vitamin D deficiency; outliers were identified statistically and then rejected and then a 99% reference interval was calculated. Patients: 502 524 men and women aged 40 to 69 years from the UK Biobank Study. Measurements: Serum total calcium, albumin, 25‐hydroxyvitamin D, estimated glomerular function (eGFR). Results: We developed an equation for albumin‐adjusted serum calcium and applied it to 178 377 men and women who did not have chronic kidney disease or vitamin D deficiency. We identified 2962 (1.7%) as outliers, and when excluded, we report a 99% reference interval of 2.19 to 2.56 mmol/L (8.76 to 10.24 mg/dL). We found that for older (55‐69 years) and younger women (40‐55 years) the upper limits were 2.59 mmol/L and 2.57 mmol/L and that for all men, the upper limit was 2.55 mmol/L. Conclusions: We have established an upper limit of the reference range for older women that would identify all high outliers (2.60 mmol/L and above). The upper limit for young women and for men is lower, at 2.57 and 2.55 mmol/L respectively. The current reference interval in use has to be updated and improved based on these findings. These upper limits may prove helpful for identifying hypercalcaemic disorders like primary hyperparathyroidism in clinical practice

Experimental Validation of DXA-based Finite Element models for prediction of femoral strength

Osteoporotic fractures are a major clinical problem and current diagnostic tools have an accuracy of only 50%. The aim of this study was to validate dual energy x-rays absorptiometry (DXA)-based Finite Element (FE) models to predict femoral strength in two loading configurations. Thirty-six pairs of fresh frozen human proximal femora were scanned with DXA and quantitative computed tomography (QCT). For each pair one femur was tested until failure in a one-legged standing configuration (STANCE) and one by replicating the positon of the femur in a fall onto the greater trochanter (SIDE). Subject-specific 2D DXA-based linear FE models and 3D QCT-based nonlinear FE models were generated for each specimen and used to predict the measured femoral strength. The outcomes of the models were compared to standard DXA-based areal bone mineral density (aBMD) measurements. For the STANCE configuration the DXA-based FE models (R²=0.74, SEE=1473N) outperformed the best densitometric predictor (Neck_aBMD, R²=0.66, SEE=1687N) but not the QCT-based FE models (R²=0.80, SEE=1314N). For the SIDE configuration both QCT-based FE models (R²=0.85, SEE=455N) and DXA neck aBMD (R²=0.80, SEE=502N) outperformed DXA-based FE models (R²=0.77, SEE=529N). In both configurations the DXA-based FE model provided a good 1:1 agreement with the experimental data (CC=0.87 for SIDE and CC=0.86 for STANCE), with proper optimization of the failure criteria. In conclusion we found that the DXA-based FE models are a good predictor of femoral strength as compared with experimental data ex vivo. However, it remains to be investigated whether this novel approach can provide good predictions of the risk of fracture in vivo

Effect of age and gender on serum periostin: Relationship to cortical measures, bone turnover and hormones

Periostin is an extracellular matrix protein, and in bone is expressed most highly in the periosteum. It increases bone formation through osteoblast differentiation, cell adhesion, Wnt signalling and collagen cross-linking. We hypothesised that serum periostin would be high at times of life when cortical modeling is active, in early adulthood and in older age, and that it would correlate with cortical bone measures, bone turnover and hormones that regulate cortical modeling. We conducted a cross-sectional observational study of 166 healthy men and women at three skeletal stages; the end of longitudinal growth (16–18 years), peak bone mass (30–32 years) and older age (over 70 years). We measured serum periostin with a new ELISA optimised for human serum and plasma which recognises all known splice variants (Biomedica). We measured the distal radius and distal tibia with HR-pQCT, and measured serum PINP, CTX, sclerostin, PTH, IGF-1, estradiol and testosterone. Periostin was higher at age 16–18 than age 30–32 (1253 vs 842 pmol/l, p < 0.001), but not different between age 30–32 and over age 70. Periostin was inversely correlated with tibia cortical thickness and density (R − 0.229, − 0.233, both p = 0.003). It was positively correlated with PINP (R 0.529, p < 0.001), CTX (R 0.427, p < 0.001) and IGF-1 (R 0.440, p < 0.001). When assessed within each age group these correlations were only significant at age 16–18, except for PINP which was also significant over age 70. We conclude that periostin may have a role in IGF-1 driven cortical modeling and consolidation in young adults, but it may not be an important mediator in older adults

The continuing religious education of the clergy within the Church of England with specific reference to the Diocese of London.

The basic questions addressed by the thesis are\ud concerned with the nature of the ordained ministry of the\ud Church of England as it approaches the twenty first century\ud and what educational provisions are required to prepare and\ud sustain that ministry. Following an introduction, which\ud outlines in detail the methodology of the thesis and the\ud specific terms of reference for the study, the various\ud strands which suggest the constants of ministerial being and\ud function are traced from the New Testament evidence through\ud Church History.\ud The exploration identifies the influences which\ud shaped the ordained ministry and provided it with variable\ud roles and identity within its changing historical context.\ud The specific terms of its being and the functions of\ud oversight, pastoralia and teaching were retained as\ud traditional constants within ministerial formation.\ud The New Testament evidence gives attention to the\ud relationship between discipleship and the Rabbinical\ud teaching tradition as the basis for Apostolic ministry. The\ud emerging structure of ministerial forms is identified by\ud comparing the earliest with the latest of the New Testament\ud documents. The investigation into Church History isolates\ud three periods which are considered to be germane to the\ud study. The first is the rise of Christianity within the\ud multi-racial, cultural and religious Roman world. The second\ud period looks at the medieval Church in England and how it\ud educationally managed its resources in terms of its\ud personnel and parochial provision. Thirdly, the study looks\ud at the Victorian Church as an example of how ministerial\ud change was organised and as the Church which left the\ud present Church of England its immediate legacy.\ud The thesis then examines the current provision of\ud theological preparation for the ordained ministry which is\ud offered in the residential theological colleges and\ud non-residential training courses. A critique of this\ud provision is offered along with an analysis of the\ud educational features which can be found within it. The\ud investigation continues with an examination of\ud post-ordination training and continuing ministerial\ud education.\ud In the concluding chapter, a summary is provided\ud about the main findings of the thesis and the principles of\ud educational reform are identified. This leads to the\ud construction of a new pattern of educational training for\ud and within ministry based upon a continuum principle and\ud one that is related closely to the changing parochial\ud context