Polymorphism in codon 17 of the CTLA-4 gene (+49 A/G) is not associated with susceptibility to rheumatoid arthritis in British Caucasians

The role of the CTLA-4 antigen in the development of autoimmune diseases is well documented, with several autoimmune disorders showing association or linkage with the CTLA-4 locus. Its role in the aetiology of rheumatoid arthritis (RA) however, remains unclear, as the functional studies of the B7-CTLA-4 pathway in mouse models of RA and genetic studies in humans have given contrasting results. We have studied the single nucleotide polymorphism at position +49 (A/G) of the CTLA-4 gene, in a cohort of 421 RA cases and 452 healthy controls from the UK. Despite the high statistical power to detect even a weak susceptibility effect, no significant association was found. We also analysed the distribution of the allele and genotype frequencies with respect to the presence of the shared epitope (a known RA susceptibility factor) and found no statistically significant differences. We conclude that, although the importance of the B7-CTLA-4 interaction in the development of RA can not be excluded, the CTLA-4 gene is unlikely to be a predisposing factor to this disease.

The impact of wall shear stress and pressure drop on the stability of the atherosclerotic plaque

Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The mechanism of blood flow and plaque rupture in stenotic arteries is still not fully understood. A three dimensional rigid wall model was solved under steady state conditions and unsteady conditions by assuming a time-varying inlet velocity profile to investigate the relative importance of axial forces and pressure drops in arteries with asymmetric stenosis. Flow-structure interactions were investigated for the same geometry and the results were compared with those retrieved with the corresponding 2D cross-section structural models. The Navier-Stokes equations were used as the governing equations for the fluid. The tube wall was assumed hyperelastic, homogeneous, isotropic and incompressible. The analysis showed that the three dimensional behavior of velocity, pressure and wall shear stress is in general very different from that predicted by cross-section models. Pressure drop across the stenosis was found to be much higher than shear stress. Therefore, pressure may be the more important mechanical trigger for plaque rupture other than shear stress, although shear stress is closely related to plaque formation and progression.

Osteopenia and rickets in the extremely low birth weight infant: A survey of the incidence and a radiological classification

A review was carried out of the radiographs of twenty-five infants with birth weights under 1000 G, who survived for more than twenty-eight days; eighteen of these had enough suitable films for a survey of the progressive bone changes which occur in these infants, including estimation of humeral cortical cross-sectional area. The incidence of the changes has been assessed and a typical progression of radiographic appearances has been shown, with a suggested system of staging. All infants showed some loss of bone mineral, with frank changes of rickets occurring in forty-four percent. Aetiological factors are mainly concerned with the difficulty of supplying and ensuring absorption of sufficient bone mineral (calcium and phosphate) and vitamin D. Liver immaturity may be another factor. Disease states additional to prematurity accentuate the problem. Rib fractures occurring around 80–90 days post-nataEy commonly draw attention to the bone disorder and are probably the major clinical factor of importance; there is a high incidence of associated lung disease of uncertain pathology. Attention is drawn to possible confusion with other bone disorders in the post-natal period.

The Context-integrity of the global carbon regime: The relevance and impact of the World Trade Organization

In the study of the integrity of the global carbon regime there are a number of institutions that must be considered for their impacts on this system. In particular, the subject matter of this chapter is concerned with the main international institution for trade, the World Trade Organization (the WTO). Otherwise stated, this chapter is concerned with how the institutional integrity of the global carbon regime aligns with the values and policy objectives of the WTO. This is done with a view to consider whether the global carbon regime aligns with these values and objectives in a way demonstrative of context-integrity. This alignment is not a single-sided undertaking and, therefore, it is essential that the underlying values of the WTO themselves align with the global carbon regime. I suggest this is particularly crucial given the importance of the objectives of the climate change regime, and the scientific predictions of the current climate projections.

Influence of oxygen content of the certain types of biodiesels on particulate oxidative potential

Oxidative potential (OP) is related to the organic phase, specifically to its oxygenated organic fraction (OOA). Furthermore, the oxygen content of fuel molecules has significant influence on particulate OP. Thus, this study aimed to explore the actual dependency of the OOA and ROS to the oxygen content of the fuel. In order to reach the goal, different biodiesels blends, with various ranges of oxygen content; have been employed. The compact time of flight aerosol mass spectrometer (c-ToF AMS) enabled better identification of OOA. ROS monitored by using two assays: DTT and BPEA-nit. Despite emitting lower mass, both assays agreed that oxygen content of a biodiesel is directly correlated with its OOA, and highly related to its OP. Hence, the more oxygen included in the considered biodiesels, the higher the OP of PM emissions. This highlights the importance of taking oxygen content into account while assessing emissions from new fuel types, which is relevant from a health effects standpoint.

Procurement-related critical factors for briefing in public-private partnership projects: Case of Hong Kong

Public private partnerships (PPP) are widely used for construction project procurement. However, the briefing stage of PPP projects has been largely overlooked, although it has a far-reaching influence throughout the project life cycle. In response, we rectify this by exploring the critical factors involved. A set of 15 procurement-related factors are first identified from the existing literature. Then the effects of four background variables on the factors are tested with Hong Kong government data by an exploratory factor analysis extracting four major dimensions. The relationships between these dimensions and background variables indicate the need to take the background variables into account when ranking the factors. The ranking of the factors is then obtained by considering their weighted importance. Finally, the final practical value of the results is discussed.

A heterogeneous computing approach to simulation of the Heston Stochastic Volatility Model

Stochastic volatility models are of fundamental importance to the pricing of derivatives. One of the most commonly used models of stochastic volatility is the Heston Model in which the price and volatility of an asset evolve as a pair of coupled stochastic differential equations. The computation of asset prices and volatilities involves the simulation of many sample trajectories with conditioning. The problem is treated using the method of particle filtering. While the simulation of a shower of particles is computationally expensive, each particle behaves independently making such simulations ideal for massively parallel heterogeneous computing platforms. In this paper, we present our portable Opencl implementation of the Heston model and discuss its performance and efficiency characteristics on a range of architectures including Intel cpus, Nvidia gpus, and Intel Many-Integrated-Core (mic) accelerators.

Computational methods for the prediction of the structure and interactions of coiled-coil peptides

The past several years have seen significant advances in the development of computational methods for the prediction of the structure and interactions of coiled-coil peptides. These methods are generally based on pairwise correlations of amino acids, helical propensity, thermal melts and the energetics of sidechain interactions, as well as statistical patterns based on Hidden Markov Model (HMM) and Support Vector Machine (SVM) techniques. These methods are complemented by a number of public databases that contain sequences, motifs, domains and other details of coiled-coil structures identified by various algorithms. Some of these computational methods have been developed to make predictions of coiled-coil structure on the basis of sequence information; however, structural predictions of the oligomerisation state of these peptides still remains largely an open question due to the dynamic behaviour of these molecules. This review focuses on existing in silico methods for the prediction of coiled-coil peptides of functional importance using sequence and/or three-dimensional structural data.

Towards an understanding of the information dynamics of the handover process in aged care settings: A prerequisite for the safe and effective use of ICT

Background Poor clinical handover has been associated with inaccurate clinical assessment and diagnosis, delays in diagnosis and test ordering, medication errors and decreased patient satisfaction in the acute care setting. Research on the handover process in the residential aged care sector is very limited. Purpose The aims of this study were to: (i) Develop an in-depth understanding of the handover process in aged care by mapping all the key activities and their information dynamics, (ii) Identify gaps in information exchange in the handover process and analyze implications for resident safety, (iii) Develop practical recommendations on how information communication technology (ICT) can improve the process and resident safety. Methods The study was undertaken at a large metropolitan facility in NSW with more than 300 residents and a staff including 55 registered nurses (RNs) and 146 assistants in nursing (AINs). A total of 3 focus groups, 12 interviews and 3 observation sessions were conducted over a period from July to October 2010. Process mapping was undertaken by translating the qualitative data via a five-category code book that was developed prior to the analysis. Results Three major sub-processes were identified and mapped. The three major stages are Handover process (HOP) I “Information gathering by RN”, HOP II “Preparation of preliminary handover sheet” and HOP III “Execution of handover meeting”. Inefficient processes were identified in relation to the handover including duplication of information, utilization of multiple communication modes and information sources, and lack of standardization. Conclusion By providing a robust process model of handover this study has made two critical contributions to research in aged care: (i) a means to identify important, possibly suboptimal practices; and (ii) valuable evidence to plan and improve ICT implementation in residential aged care. The mapping of this process enabled analysis of gaps in information flow and potential impacts on resident safety. In addition it offers the basis for further studies into a process that, despite its importance for securing resident safety and continuity of care, lacks research.

Expression profiling of lymph nodes in tuberculosis patients reveal inflammatory milieu at site of infection

Extrapulmonary manifestations constitute 15 to 20% of tuberculosis cases, with lymph node tuberculosis (LNTB) as the most common form of infection. However, diagnosis and treatment advances are hindered by lack of understanding of LNTB biology. To identify host response, Mycobacterium tuberculosis infected lymph nodes from LNTB patients were studied by means of transcriptomics and quantitative proteomics analyses. The selected targets obtained by comparative analyses were validated by quantitative PCR and immunohistochemistry. This approach provided expression data for 8,728 transcripts and 102 proteins, differentially regulated in the infected human lymph node. Enhanced inflammation with upregulation of T-helper1-related genes, combined with marked dysregulation of matrix metalloproteinases, indicates tissue damage due to high immunoactivity at infected niche. This expression signature was accompanied by significant upregulation of an immunoregulatory gene, leukotriene A4 hydrolase, at both transcript and protein levels. Comparative transcriptional analyses revealed LNTB-specific perturbations. In contrast to pulmonary TB-associated increase in lipid metabolism, genes involved in fatty-acid metabolism were found to be downregulated in LNTB suggesting differential lipid metabolic signature. This study investigates the tissue molecular signature of LNTB patients for the first time and presents findings that indicate the possible mechanism of disease pathology through dysregulation of inflammatory and tissue-repair processes.

Mutational analysis of the insulin‑like growth factor 1 receptor tyrosine kinase domain in non-small cell lung cancer patients

The insulin‑like growth factor 1 receptor (IGF1R) pathway plays an important role in the pathogenesis of non‑small cell lung cancer (NSCLC) and also provides a mechanism of resistance to targeted therapies. IGF1R is therefore an ideal therapeutic target and several inhibitors have entered clinical trials. However, thus far the response to these inhibitors has been poor, highlighting the importance of predictive biomarkers to identify patient cohorts who will benefit from these targeted agents. It is well‑documented that mutations and/or deletions in the epidermal growth factor receptor (EGFR) tyrosine kinase (TK) domain predict sensitivity of NSCLC patients to EGFR TK inhibitors. Single‑nucleotide polymorphisms (SNPs) in the IGF pathway have been associated with disease, including breast and prostate cancer. The aim of the present study was to elucidate whether the IGF1R TK domain harbours SNPs, somatic mutations or deletions in NSCLC patients and correlates the mutation status to patient clinicopathological data and prognosis. Initially 100 NSCLC patients were screened for mutations/deletions in the IGF1R TK domain (exons 16‑21) by sequencing analysis. Following the identification of SNP rs2229765, a further 98 NSCLC patients and 866 healthy disease‑free control patients were genotyped using an SNP assay. The synonymous SNP (rs2229765) was the only aberrant base change identified in the IGF1R TK domain of 100 NSCLC patients initially analysed. SNP rs2229765 was detected in exon 16 and was found to have no significant association between IGF1R expression and survival. The GA genotype was identified in 53.5 and 49.4% of NSCLC patients and control individuals, respectively. No significant difference was found in the genotype (P=0.5487) or allele (P=0.9082) frequencies between the case and control group. The present findings indicate that in contrast to the EGFR TK domain, the IGF1R TK domain is not frequently mutated in NSCLC patients. The synonymous SNP (rs2229765) had no significant association between IGF1R expression and survival in the cohort of NSCLC patients.