6 research outputs found
IGF and IGFBP as an index for discrimination between vitamin D supplementation responders and nonresponders in overweight Saudi subjects
No full textVitamin D deficiency is common in the Kingdom of Saudi Arabia (KSA). Therefore, it is significant to recognize which biochemical markers modulate serum 25 hydroxyvitamin D (25(OH)D) in response to vitamin D supplementation in such a population. Our aim was to study the correlation of insulin-like growth factor (IGF) and insulin growth factor binding protein (IGFBP) with serum 25(OH)D in response to vitamin D supplementation in a Saudi population. A total of 199 (89 males/110 females) vitamin D deficient subjects (25(OH)D level <50 nmol/L), aged 40.4 ± 11.4 years, were given vitamin D supplements (50,000 IU/mL every week) for the first 2 months, then twice a month for 2 months, followed by daily 1000 IU in the last 2 months. Fasting blood samples were taken at baseline and 6 months after the final dose of vitamin D. Serum 25(OH)D, IGF-1 and IGF-2, and IGFBPs 2-5 were measured. Vitamin D response was computed for all subjects as the difference in levels of serum 25(OH)D concentration at the end of 6 months compared to baseline. After intervention, serum 25(OH)D concentration significantly increased from 35.6 nmol/L (26.6-43.5) to 61.8 nmol/L (54.8-73.3) in responder subjects (P < .01) and from 35.1 nmol/L (21.2-58.2) to 38.3 nmol/L (25.5-48.3) in nonresponders (P = .13). Subjects with lower baseline serum IGF-II, IGFBP-2, and IGF-1/IGFBP-3 ratio are more sensitive to acute vitamin D status changes. IGF1 and IGF-1/IGFBP-3 ratio significantly increased in all subjects after 6 months (P = .01). Changes in 25(OH)D was significantly associated with changes in IGFBP-2 and IGF-1/IGFBP-3 ratio in responders only. This study proposes that changes in circulating IGF-I and IGFBP-3 are modulated by vitamin D supplementation and can be taken into consideration in investigations involving vitamin D correction. Moreover, increase in serum 25(OH)D and IGF-I/IGFBP-3 molar ratio are more sensitive markers for the response to vitamin D supplementation in Saudi population.</p
IGF and IGFBP as an index for discrimination between Vitamin D supplementation responders and nonresponders in overweight Saudi subjects
No full textVitamin D deficiency is common in the Kingdom of Saudi Arabia (KSA). Therefore, it is significant to recognize which biochemical markers modulate serum 25 hydroxyvitamin D (25(OH)D) in response to vitamin D supplementation in such a population. Our aim was to study the correlation of insulin-like growth factor (IGF) and insulin growth factor binding protein (IGFBP) with serum 25(OH)D in response to vitamin D supplementation in a Saudi population. A total of 199 (89 males/110 females) vitamin D deficient subjects (25 (OH)D level <50 nmol/L), aged 40.4 ± 11.4 years, were given vitamin D supplements (50,000 IU/mL every week) for the first 2 months, then twice a month for 2 months, followed by daily 1000 IU in the last 2 months. Fasting blood samples were taken at baseline and 6 months after the final dose of vitamin D. Serum 25(OH)D, IGF-1 and IGF-2, and IGFBPs 2-5 were measured. Vitamin D response was computed for all subjects as the difference in levels of serum 25(OH)D concentration at the end of 6 months compared to baseline. After intervention, serum 25(OH)D concentration significantly increased from 35.6 nmol/L (26.6-43.5) to 61.8 nmol/L (54.8-73.3) in responder subjects (P < .01) and from 35.1 nmol/L (21.2-58.2) to 38.3 nmol/L (25.5-48.3) in nonresponders (P = .13). Subjects with lower baseline serum IGF-II, IGFBP-2, and IGF-1/IGFBP-3 ratio are more sensitive to acute vitamin D status changes. IGF1 and IGF-1/IGFBP-3 ratio significantly increased in all subjects after 6 months (P = .01). Changes in 25(OH)D was significantly associated with changes in IGFBP-2 and IGF-1/IGFBP-3 ratio in responders only. This study proposes that changes in circulating IGF-I and IGFBP-3 are modulated by vitamin D supplementation and can be taken into consideration in investigations involving vitamin D correction. Moreover, increase in serum 25(OH)D and IGF-I/IGFBP-3 molar ratio are more sensitive markers for the response to vitamin D supplementation in Saudi population. © 2018 the Author(s). Published by Wolters Kluwer Health, Inc
Proteomics profiling of CLL versus healthy B-cells identifies putative therapeutic targets and a subtype-independent signature of spliceosome dysregulation
No full textChronic lymphocytic leukaemia (CLL) is a heterogeneous B-cell cancer exhibiting a wide spectrum of disease courses and treatment responses. Molecular characterisation of RNA and DNA from CLL cases has led to the identification of important driver mutations and disease sub-types, but the precise mechanisms of disease progression remain elusive. To further our understanding of CLL biology we performed isobaric labelling and mass spectrometry proteomics on 14 CLL samples, comparing them with B-cells from healthy donors (HDB). Of 8694 identified proteins, ~6000 were relatively quantitated between all samples (q<0.01). A clear CLL signature, independent of subtype, of 544 significantly overexpressed proteins relative to HDB was identified, highlighting establishedhallmarks of CLL (eg. CD5, BCL2, ROR1 and CD23 overexpression). Previously unrecognised surface markers demonstrated overexpression (eg. CKAP4, PIGR, TMCC3 and CD75) and three of these (LAX1, CLEC17A and ATP2B4) were implicated in B-cell receptor signalling, which plays an important role in CLL pathogenesis. Several other proteins (eg. Wee1, HMOX1/2, HDAC7 and INPP5F) were identified with significant overexpression that also represent potential targets. Western blotting confirmed overexpression of a selection of these proteins in an independent cohort. mRNA processing machinery were broadly upregulated across the CLL samples. Spliceosome components demonstrated consistent overexpression (p=1.3x10-21) suggesting dysregulation in CLL, independent of SF3B1 mutations. This study highlights the potential of proteomics in the identification of putative CLL therapeutic targets and reveals a subtype-independent protein expression signature in CLL
Distributed situation awareness: Advances in theory, measurement and application to team work
No full textThis thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.Situation Awareness (SA) is critical commodity for teams working in complex sociotechnical systems and is thus a fundamental consideration in collaborative system design and evaluation. Despite this, SA remains predominantly an individual construct, with the majority of models and measures focused on SA from an individual perspective. In comparison, team SA has received much less attention and this thesis argues that further work is required in the area both in relation to the development of theoretical perspectives and of valid measures, and to the development of guidelines for system, training and procedure design. This thesis advances team SA theory and measurement by further investigating a recently proposed model of SA in complex collaborative environments, the Distributed Situation Awareness (DSA) approach, and by testing a new methodology for representing and analysing DSA during real world collaborative activities. A review of SA theory and SA measurement approaches is presented. Following this, the DSA theory and propositional network assessment methodology are outlined and a series of case studies on DSA during real world collaborative activities in the military and civil domains are presented. The findings are subsequently used to explore the concept of DSA and the sub-concepts of compatible and transactive SA. In conclusion, a model of DSA in complex collaborative systems is presented, and a series of system design guidelines for supporting DSA are outlined
Integrating legacy mainframe systems: architectural issues and solutions
No full textFor more than 30 years, mainframe computers have been the backbone of computing systems throughout the world. Even today it is estimated that some 80% of the worlds' data is held on such machines. However, new business requirements and pressure from evolving technologies, such as the Internet is pushing these existing systems to their limits and they are reaching breaking point. The Banking and Financial Sectors in particular have been relying on mainframes for the longest time to do their business and as a result it is they that feel these pressures the most.
In recent years there have been various solutions for enabling a re-engineering of these legacy systems. It quickly became clear that to completely rewrite them was not possible so various integration strategies emerged.
Out of these new integration strategies, the CORBA standard by the Object Management Group emerged as the strongest, providing a standards based solution that enabled the mainframe applications become a peer in a distributed computing environment.
However, the requirements did not stop there. The mainframe systems were reliable, secure, scalable and fast, so any integration strategy had to ensure that the new distributed systems did not lose any of these benefits. Various patterns or general solutions to the problem of meeting these requirements have arisen and this research looks at applying some of these patterns to mainframe based CORBA applications.
The purpose of this research is to examine some of the issues involved with making mainframebased legacy applications inter-operate with newer Object Oriented Technologies
