Crystal Structure Analyses of Organic and Organometallic Compounds

The thesis is divided into three parts: the first part is a brief review of the theory and methods of x-ray crystallography, the second part describes a number of computer programmes devised either wholly or partly by the author, and in the third part accounts of three structure analyses are presented. The computer programmes described in Part II are written in ALGOL for the English Electric KDP9 Computer. The molecular functions system is a group of six programmes for interpreting the results of a structure analysis: bond lengths and interbond angles with their standard deviations, intermolecular contacts, and mean plane equations may be calculated and rigid-body vibrational analysis can be carried out. The automatic structure solution (ASS) system allows semi-automatic Fourier refinement to be performed. The minimum residual programme permits crystal structures to be refined in projection by direct calculation of the minimum R-factor. The structure analyses presented in Part III are applications of the x-ray method to organic and organo-metallic structural problems. It has been known for more than twenty years that indene can form a 1:2 adduct with dimethylacetylene-dicarboxylate. Earlier chemical and spectroscopic studies on the adduct did not lead to a successful structure determination. The molecular structure of the adduct has now been definitely established by x-ray analysis of its dibromo-derivative. The structure analyses of phenanthrenechromium tricarbonyl, C14H10Cr(CO)3, and of 9,10-dihydrophenanthrenechromium tricarbonyl, C14H12Cr(CO)3, were undertaken to obtain accurate dimensions for aromatic rings bonded to chromium. In both analyses the standard deviations of the C-C bonds range from 0.006 to 0.010 A. The results suggest that the chromium atom causes a slight increase in the mean bond length of the bonded ring without alteration of the ring symmetry. Structural studies on related arenechromium complexes are discussed

Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Although genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa

Taking the learning beyond the individual:how reflection informs change in practice

OBJECTIVES: The purpose of this research was to explore the value of reflection and its application to practice through the implementation of educational modules within a new Diabetes Care and Education Master Degree Programme in Kuwait, and to realise how this teaching intervention informs changes in practice. METHODS: A small exploratory case study was conducted within the Dasman Diabetes Institute, Kuwait. A qualitative approach using focus group interviews was carried out with seventeen participants all of whom are studying on the Diabetes Care and Education Master Degree Programme in Kuwait. An inductive approach to thematic analysis, which focused on examining themes within data, was performed. RESULTS: The results indicate that participants value the opportunity to study through organised, structured and assessed reflection. The learning provides useful information and support to the participant by highlighting the role which reflection plays to enhance personal and professional development, the value of educational theory, continuing professional development, collaboration and enhancing patient education and practice. CONCLUSIONS: The significance of reflection is often seen in the literature as an important aspect of professional competence. This research has highlighted the value of reflection as a key component within a new educational programme

Basic Salts with »Very Short« Hydrogen Bonds; the Crystal Structure of a-Picoline-N-oxide Hemihydrochloride Sesquihydrate (Dunlop\u27s Salt)

Type A acid salts of many simple carboxylic acids (HX) crystallise with anions, XHx-, which are symmetrical and which contain »very short« OHO-bonds with O . .. 0 less than 250 pm. Such compounds also reveal anomalous IR spectra. The Glasgow work on such crystal structures has benefited from a long collaboration with Hadzi\u27s spectroscopic group at Ljubljana. The importance of such joint studies in helping the understanding of strong hydrogen bonding is discussed. Some organic bases form analogous basic salts, which have similarly anomalous spectra. An example, discovered by Hadzi in 1962, is the hemihydrobromide of a.-picoline-N-oxide, B · 1/2HBr, where B = CoH7NO, for which he predicted the formula BHB+ Br-. Preliminary X-ray work confirmed this and the presence of a »very short« OHO-bond. Hitherto unpublished crystallographic work is summarised. Dunlop\u27s salt is the sesquihydrated hemihydrochloride of the same base. A careful X-ray study has been made (1040 reflexions; R = 3.70/o): B · 1/2HCl · 3/2H20 has a structure corresponding to BHB+ c1- · 3H20; the cation lies across a centre of symmetry, with O ... O = 241.4(3) pm. At one stage the salt was supposed to include a symmetrical ClHc1- anion; but our more precise work shows the anion to be c1- ... H-OH (or HO-H ... en symmetrised by disorder across a twofold axis of the crystal, with c1- ... O = = 297(1) pm. The spectrum of DSALT is almost identical with that of the hemihydrobromide

Chondrocalcinosis is common in the absence of knee involvement

Introduction: We aimed to describe the distribution of radiographic chondrocalcinosis (CC) and to examine whether metacarpophalangeal joint (MCPJ) calcification and CC at other joints occurs in the absence of knee involvement. Methods: This was a cross-sectional study embedded in the Genetics of Osteoarthritis and Lifestyle study (GOAL). All participants (n = 3,170) had radiographs of the knees, hands, and pelvis. These were scored for radiographic changes of osteoarthritis (OA), for CC at knees, hips, symphysis pubis, and wrists, and for MCPJ calcification. The prevalence of MCPJ calcification and CC overall, at each joint, and in the presence or absence of knee involvement, was calculated. Results: The knee was the commonest site of CC, followed by wrists, hips, and symphysis pubis. CC was more likely to be bilateral at knees and wrists but unilateral at hips. MCPJ calcification was usually bilateral, and less common than CC at knees, hips, wrists, and symphysis pubis. Unlike that previously reported, CC commonly occurred without any knee involvement; 44.4% of wrist CC, 45.9% of hip CC, 45.5% of symphysis pubis CC, and 31.3% of MCPJ calcification occurred in patients without knee CC. Those with meniscal or hyaline articular cartilage CC had comparable ages (P = 0.21), and neither preferentially associated with fibrocartilage CC at distant joints. Conclusions: CC visualized on a plain radiograph commonly occurs at other joints in the absence of radiographic knee CC. Therefore, knee radiographs alone are an insufficient screening test for CC. This has significant implications for clinical practice, for epidemiologic and genetic studies of CC, and for the definition of OA patients with coexistent crystal deposition

Provably stable numerical method for the anisotropic diffusion equation in toroidally confined magnetic fields

We present a novel numerical method for solving the anisotropic diffusion equation in toroidally confined magnetic fields which is efficient, accurate and provably stable. The continuous problem is written in terms of a derivative operator for the perpendicular transport and a linear operator, obtained through field line tracing, for the parallel transport. We derive energy estimates of the solution of the continuous initial boundary value problem. A discrete formulation is presented using operator splitting in time with the summation by parts finite difference approximation of spatial derivatives for the perpendicular diffusion operator. Weak penalty procedures are derived for implementing both boundary conditions and parallel diffusion operator obtained by field line tracing. We prove that the fully-discrete approximation is unconditionally stable and asymptotic preserving. Discrete energy estimates are shown to match the continuous energy estimate given the correct choice of penalty parameters. Convergence tests are shown for the perpendicular operator by itself, and the ``NIMROD benchmark" problem is used as a manufactured solution to show the full scheme converges even in the case where the perpendicular diffusion is zero. Finally, we present a magnetic field with chaotic regions and islands and show the contours of the anisotropic diffusion equation reproduce key features in the field.Comment: 33 pages, 8 figure

Mild acetabular dysplasia and risk of osteoarthritis of the hip : a case-control study

Objective To determine whether mild variation in acetabular depth (AD) and shape is a risk factor for osteoarthritis (OA) of the hip. Methods The unaffected contralateral hip of patients with unilateral hip OA was compared with hips of asymptomatic controls without hip OA, derived from the Nottingham Genetics Osteoarthritis and Lifestyle case–control study. Standardised anteroposterior x-rays of the pelvis were used to measure centre edge (CE) angle and AD. Cut-off points for narrow CE angle and shallow AD were calculated from the control group (mean −1.96×SD). The relative risk of hip OA associated with each feature was estimated using OR and 95% CI and adjusted risks were calculated by logistic regression. Results In controls, both the CE angle and the AD were lower in the left hip than in the right hip. The CE angle related to age in both hips, and AD of the right hip was lower in men than in women. The contralateral unaffected hip in patients with unilateral hip OA had a decreased CE angle and AD compared with controls, irrespective of side. The lowest tertile of the CE angle in contralateral hips was associated with an eightfold risk of OA (aOR 8.06, 95% CI 4.87 to 13.35) and the lowest tertile of AD was associated with a 2.5-fold risk of OA (aOR 2.53, 95% CI 1.28 to 5.00). Significant increases in the risk of OA were also found as the CE angle and AD decreased

Crystal Structure of the Phosphinyl-stabilised Ylide Me3NNP(=O)Ph2 ⋅ H2O

Crystals of trimethylammonio-P,P-diphenylphosphinamidate hydrate, Me3NNP(=O)Ph2 ⋅ H2O, are held together by hydrogen bonds which link two Me3NNP(=O)Ph2 and two water molecules to form a centrosymmetric O4H4 ring belonging to graph set R2 4(8). Each P=O oxygen atom can thereby act as acceptor to two hydrogen bonds, rather than to only one, as in the two-fold symmetric P=O⋅⋅⋅H–O–H⋅⋅⋅O=P motif commonly found in phosphine oxide hemihydrates. The unusual P–N bond in Me3NNP(=O)Ph2 is short enough 1.614(3) Å to indicate some multiple character