The solution of linear systems of equations with a structural analysis code on the NAS CRAY-2

Two methods for solving linear systems of equations on the NAS Cray-2 are described. One is a direct method; the other is an iterative method. Both methods exploit the architecture of the Cray-2, particularly the vectorization, and are aimed at structural analysis applications. To demonstrate and evaluate the methods, they were installed in a finite element structural analysis code denoted the Computational Structural Mechanics (CSM) Testbed. A description of the techniques used to integrate the two solvers into the Testbed is given. Storage schemes, memory requirements, operation counts, and reformatting procedures are discussed. Finally, results from the new methods are compared with results from the initial Testbed sparse Choleski equation solver for three structural analysis problems. The new direct solvers described achieve the highest computational rates of the methods compared. The new iterative methods are not able to achieve as high computation rates as the vectorized direct solvers but are best for well conditioned problems which require fewer iterations to converge to the solution

Efficient multitasking of Choleski matrix factorization on CRAY supercomputers

A Choleski method is described and used to solve linear systems of equations that arise in large scale structural analysis. The method uses a novel variable-band storage scheme and is structured to exploit fast local memory caches while minimizing data access delays between main memory and vector registers. Several parallel implementations of this method are described for the CRAY-2 and CRAY Y-MP computers demonstrating the use of microtasking and autotasking directives. A portable parallel language, FORCE, is used for comparison with the microtasked and autotasked implementations. Results are presented comparing the matrix factorization times for three representative structural analysis problems from runs made in both dedicated and multi-user modes on both computers. CPU and wall clock timings are given for the parallel implementations and are compared to single processor timings of the same algorithm

Elevated circulating Sclerostin concentrations in individuals with high bone mass, with and without LRP5 mutations.

CONTEXT: The role and importance of circulating sclerostin is poorly understood. High bone mass (HBM) caused by activating LRP5 mutations has been reported to be associated with increased plasma sclerostin concentrations; whether the same applies to HBM due to other causes is unknown. OBJECTIVE: Our objective was to determine circulating sclerostin concentrations in HBM. DESIGN AND PARTICIPANTS: In this case-control study, 406 HBM index cases were identified by screening dual-energy x-ray absorptiometry (DXA) databases from 4 United Kingdom centers (n = 219 088), excluding significant osteoarthritis/artifact. Controls comprised unaffected relatives and spouses. MAIN MEASURES: Plasma sclerostin; lumbar spine L1, total hip, and total body DXA; and radial and tibial peripheral quantitative computed tomography (subgroup only) were evaluated. RESULTS: Sclerostin concentrations were significantly higher in both LRP5 HBM and non-LRP5 HBM cases compared with controls: mean (SD) 130.1 (61.7) and 88.0 (39.3) vs 66.4 (32.3) pmol/L (both P < .001, which persisted after adjustment for a priori confounders). In combined adjusted analyses of cases and controls, sclerostin concentrations were positively related to all bone parameters found to be increased in HBM cases (ie, L1, total hip, and total body DXA bone mineral density and radial/tibial cortical area, cortical bone mineral density, and trabecular density). Although these relationships were broadly equivalent in HBM cases and controls, there was some evidence that associations between sclerostin and trabecular phenotypes were stronger in HBM cases, particularly for radial trabecular density (interaction P < .01). CONCLUSIONS: Circulating plasma sclerostin concentrations are increased in both LRP5 and non-LRP5 HBM compared with controls. In addition to the general positive relationship between sclerostin and DXA/peripheral quantitative computed tomography parameters, genetic factors predisposing to HBM may contribute to increased sclerostin levels.This study was supported by The Wellcome Trust NIHR Clinical Research Network (portfolio number 5163); and the supporting Comprehensive Local Research Networks included Birmingham and the Black Country, North and East Yorkshire and Northern Lincolnshire, South Yorkshire, West Anglia, and Western. C.L.G. was funded through a Wellcome Trust Clinical Research Training Fellowship (080280/Z/06/Z) and is now funded by Arthritis Research UK (Grant 20000). K.E.S.P. acknowledges the support of Cambridge NIHR Biomedical Research Centre and the Medical Research Council Human Nutrition Research Unit, Cambridge.This is the author accepted manuscript. The final version is available from the Endocrine Society via http://dx.doi.org/10.1210/jc.2013-395

Interplay Between Time-Temperature-Transformation and the Liquid-Liquid Phase Transition in Water

We study the TIP5P water model proposed by Mahoney and Jorgensen, which is closer to real water than previously-proposed classical pairwise additive potentials. We simulate the model in a wide range of deeply supercooled states and find (i) the existence of a non-monotonic ``nose-shaped'' temperature of maximum density line and a non-reentrant spinodal, (ii) the presence of a low temperature phase transition, (iii) the free evolution of bulk water to ice, and (iv) the time-temperature-transformation curves at different densities.Comment: RevTeX4, 4 pages, 4 eps figure

Increased development of radiographic hip osteoarthritis in individuals with high bone mass: a prospective cohort study.

BACKGROUND: Individuals with high bone mass (HBM) have a greater odds of prevalent radiographic hip osteoarthritis (OA), reflecting an association with bone-forming OA sub-phenotypes (e.g. osteophytosis, subchondral sclerosis). As the role of bone mineral density (BMD) in hip OA progression is unclear, we aimed to determine if individuals with HBM have increased incidence and/or progression of bone-forming OA sub-phenotypes. METHODS: We analysed an adult cohort with and without HBM (L1 and/or total hip BMD Z-score > + 3.2) with pelvic radiographs collected at baseline and 8-year follow-up. Sub-phenotypes were graded using the OARSI atlas. Superior/inferior acetabular/femoral osteophyte and medial/superior joint space narrowing (JSN) grades were summed and Δosteophyte and ΔJSN derived. Pain and functional limitations were quantified using the WOMAC questionnaire. Associations between HBM status and change in OA sub-phenotypes were determined using multivariable linear/logistic regression, adjusting for age, sex, height, total body fat mass, follow-up time and baseline sub-phenotype grade. Generalised estimating equations accounted for individual-level clustering. RESULTS: Of 136 individuals, 62% had HBM at baseline, 72% were female and mean (SD) age was 59 (10) years. HBM was positively associated with both Δosteophytes and ΔJSN (adjusted mean grade differences between individuals with and without HBM βosteophyte = 0.30 [0.01, 0.58], p = 0.019 and βJSN = 0.10 [0.01, 0.18], p = 0.019). Incident subchondral sclerosis was rare. HBM individuals had higher WOMAC hip functional limitation scores (β = 8.3 [0.7, 15.98], p = 0.032). CONCLUSIONS: HBM is associated with the worsening of hip osteophytes and JSN over an average of 8 years, as well as increased hip pain and functional limitation

Configurational Entropy and Diffusivity of Supercooled Water

We calculate the configurational entropy S_conf for the SPC/E model of water for state points covering a large region of the (T,rho) plane. We find that (i) the (T,rho) dependence of S_conf correlates with the diffusion constant and (ii) that the line of maxima in S_conf tracks the line of density maxima. Our simulation data indicate that the dynamics are strongly influenced by S_conf even above the mode-coupling temperature T_MCT(rho).Comment: Significant update of reference

UK clinical guideline for the prevention and treatment of osteoporosis

The National Osteoporosis Guideline Group (NOGG) has revised the UK guideline for the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. Accredited by NICE, this guideline is relevant for all healthcare professionals involved in osteoporosis management. INTRODUCTION The UK National Osteoporosis Guideline Group (NOGG) first produced a guideline on the prevention and treatment of osteoporosis in 2008, with updates in 2013 and 2017. This paper presents a major update of the guideline, the scope of which is to review the assessment and management of osteoporosis and the prevention of fragility fractures in postmenopausal women, and men age 50 years and older. METHODS Where available, systematic reviews, meta-analyses and randomised controlled trials were used to provide the evidence base. Conclusions and recommendations were systematically graded according to the strength of the available evidence. RESULTS Review of the evidence and recommendations are provided for the diagnosis of osteoporosis, fracture-risk assessment and intervention thresholds, management of vertebral fractures, non-pharmacological and pharmacological treatments, including duration and monitoring of anti-resorptive therapy, glucocorticoid-induced osteoporosis, and models of care for fracture prevention. Recommendations are made for training; service leads and commissioners of healthcare; and for review criteria for audit and quality improvement. CONCLUSION The guideline, which has received accreditation from the National Institute of Health and Care Excellence (NICE), provides a comprehensive overview of the assessment and management of osteoporosis for all healthcare professionals involved in its management. This position paper has been endorsed by the International Osteoporosis Foundation and by the European Society for the Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases

Mutations in Known Monogenic High Bone Mass Loci Only Explain a Small Proportion of High Bone Mass Cases.

High bone mass (HBM) can be an incidental clinical finding; however, monogenic HBM disorders (eg, LRP5 or SOST mutations) are rare. We aimed to determine to what extent HBM is explained by mutations in known HBM genes. A total of 258 unrelated HBM cases were identified from a review of 335,115 DXA scans from 13 UK centers. Cases were assessed clinically and underwent sequencing of known anabolic HBM loci: LRP5 (exons 2, 3, 4), LRP4 (exons 25, 26), SOST (exons 1, 2, and the van Buchem's disease [VBD] 52-kb intronic deletion 3'). Family members were assessed for HBM segregation with identified variants. Three-dimensional protein models were constructed for identified variants. Two novel missense LRP5 HBM mutations ([c.518C>T; p.Thr173Met], [c.796C>T; p.Arg266Cys]) were identified, plus three previously reported missense LRP5 mutations ([c.593A>G; p.Asn198Ser], [c.724G>A; p.Ala242Thr], [c.266A>G; p.Gln89Arg]), associated with HBM in 11 adults from seven families. Individuals with LRP5 HBM (∼prevalence 5/100,000) displayed a variable phenotype of skeletal dysplasia with increased trabecular BMD and cortical thickness on HRpQCT, and gynoid fat mass accumulation on DXA, compared with both non-LRP5 HBM and controls. One mostly asymptomatic woman carried a novel heterozygous nonsense SOST mutation (c.530C>A; p.Ser177X) predicted to prematurely truncate sclerostin. Protein modeling suggests the severity of the LRP5-HBM phenotype corresponds to the degree of protein disruption and the consequent effect on SOST-LRP5 binding. We predict p.Asn198Ser and p.Ala242Thr directly disrupt SOST binding; both correspond to severe HBM phenotypes (BMD Z-scores +3.1 to +12.2, inability to float). Less disruptive structural alterations predicted from p.Arg266Cys, p.Thr173Met, and p.Gln89Arg were associated with less severe phenotypes (Z-scores +2.4 to +6.2, ability to float). In conclusion, although mutations in known HBM loci may be asymptomatic, they only account for a very small proportion (∼3%) of HBM individuals, suggesting the great majority are explained by either unknown monogenic causes or polygenic inheritance.This study was supported by The Wellcome Trust and NIHR CRN (portfolio number 5163). CLG was funded by a Wellcome Trust Clinical Research Training Fellowship (080280/Z/06/Z), the EU 7th Framework Programme under grant agreement number 247642 (GEoCoDE), a British Geriatric Society travel grant, and is now funded by Arthritis Research UK (grant ref 20000). SH acknowledges Arthritis Research UK support (grant ref 19580). KESP acknowledges the support of Cambridge NIHR Biomedical Research Centre. KAW is supported by the core programme of the MRC Nutrition and Bone Health group at MRC Human Nutrition Research, funded by the UK Medical Research Council (Grant code U10590371). EM acknowledges support of the Sheffield Teaching Hospitals Foundation Trust Clinical Research Facility. The SGC is a registered charity (no. 1097737) that receives funds from AbbVie, Bayer, Boehringer Ingelheim, Genome Canada (Ontario Genomics Institute OGI- 055), GlaxoSmithKline, Janssen, Lilly Canada, Novartis Research Foundation, Ontario Ministry of Economic Development & Innovation, Pfizer, Takeda, and Wellcome Trust (092809/Z/10/Z).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/jbmr.270

Exploring service providers’ perspectives on the prevention and management of fetal alcohol spectrum disorders in South Africa: a qualitative study

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is among the leading causes of developmental and intellectual disabilities in individuals. Although efforts are being made toward the prevention and management of FASD in South Africa, the prevalence remains high. The sustained high prevalence could be attributed to several factors, including the lack of policy for a coordinated effort to prevent, diagnose and manage FASD nationally. In this study, our aim was to explore the perspectives of service providers (health and allied professionals, teachers, social workers) on the prevention and management of FASD towards developing a guideline to inform policy. METHOD: Guided by the exploratory qualitative research design, we purposively sampled relevant service providers in the field of FASD prevention and management for focus group discussions. Nine of these discussions were conducted with to eight participants per discussion session. The discussants were asked various questions on the current and required interventions and practices for the prevention and management of FASD. Following the Framework Method, data were transcribed verbatim and analysed using the thematic content analysis approach. RESULTS: Our findings show that aspects of the prevention and management of alcohol-related conditions are present in various policies. However, there is no clear focus on coordinated, multi-sectoral efforts for a more comprehensive approach to the prevention and management of FASD. The participants recognized the need for specific requirements on broad-based preventive awareness programs, training and support for parents and caregivers, inclusive education in mainstream schools and training of relevant professionals. CONCLUSION: Comprehensive and coordinated prevention and management programs guided by a specific policy could improve the prevention and management of FASD. Policy formulation demonstrates commitment from the government, highlights the importance of the condition, and elaborates on context-specific prevention and management protocols.IS