| 31. |
- Mitra, M. Tanya, et al.
(author)
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Social, educational and vocational outcomes in patients with childhood-onset and young-adult-onset growth hormone deficiency
- 2017
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In: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 86:4, s. 526-533
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Journal article (peer-reviewed)abstract
- Objective Hypopituitarism diagnosed in childhood, adolescence and young adulthood has the potential to affect growth and somatic development. Less is known about the impact of such a diagnosis on other aspects of development. Design An analysis of the KIMS database (Pfizer International Metabolic Database) was performed to explore social, educational and vocational outcomes of adult patients diagnosed in childhood, adolescence and young adulthood compared with adult-onset controls. Patients A total of 2952 adult patients diagnosed with hypothalamic pituitary conditions before the age of 25 were divided into two groups: childhood-onset [<16 years (CO)] (n = 1782) and young-adult-onset [16 to <25 years (YAO)] (n = 1170). A total of 1617 adult patients diagnosed with a nonfunctioning pituitary adenoma at the age of 25 or older formed the adult-onset control group (AO). Measurements KIMS Patient Life Situation Form which provided information on social, educational and vocational outcomes. Results Compared with the AO control group, CO and YAO patients were between 45 and 80 times more likely to live with their parents in adulthood; CO and YAO patients were also less likely to live in partnership and to have children. The impact on educational and vocational outcomes was less marked than on social outcomes with no significant differences compared with the AO control group. Educational and vocational outcomes showed the lowest level in male and female CO and YAO patients who had been previously diagnosed with a brain tumour. ConclusionsSocial outcomes were more affected than educational and vocational outcomes. Although CO patients are more adversely affected, YAO patients were also failing to achieve social milestones. This has consequences for the delivery of endocrine care in both paediatric and adult services.
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| 32. |
- Ross, A. J., et al.
(author)
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A first-principles based description of the Hf-Ni system supported by high-temperature synchrotron experiments
- 2018
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In: Thermochimica Acta. - : Elsevier B.V.. - 0040-6031 .- 1872-762X. ; 668, s. 142-151
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Journal article (peer-reviewed)abstract
- Hf-Ni is an important binary system for high temperature alloys and shape memory alloys which has been investigated several times in the literature but often using samples of Hf contaminated by Zr. The thermodynamics of this system are remodeled in this work based on first-principles calculations and additional experiments using Hf with relatively low Zr contamination (0.25 wt. %). Diffusion couples in the Ni-rich portion of the Hf-Ni system heat treated at 1173, 1273 and 1373 K are used to measure phase stability and Hf solubility in the fcc phase. The solubility observed in fcc Ni from Ni/Ni50Hf50 (at.%) diffusion couples is larger than that observed in previous experiments. These results are the only source fit to during modeling of the fcc solubility to mitigate effects from Zr contamination. Data in the literature suggests that the high temperature crystal structure of the B33 NiHf phase is, in fact, the B2 structure. High temperature synchrotron measurements provide confirmation of this crystal structure. Modeling of the B2 phase was aided by first-principles calculations using special quasi-random structures (SQS). The present CALPHAD model will prove useful when designing shape memory alloys containing Hf and when modeling the Hf activity in Ni-base high temperature alloys.
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| 33. |
- Ross, A., et al.
(author)
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Tailoring critical Al concentration to form external Al2O3 scale on Ni–Al alloys by computational approach
- 2022
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In: Journal of The American Ceramic Society. - : Wiley. - 0002-7820 .- 1551-2916. ; 105:12, s. 7770-7777
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Journal article (peer-reviewed)abstract
- Nickel (Ni)-based superalloys for high-temperature applications are often designed to form a continuous and slow-growing oxide scale by adding Al and Cr and other beneficial elements. In the present work, the critical Al concentration in Ni–Al alloys needed to establish an α-Al2O3 scale in contrast to internal oxide formation is predicted as a function of temperature by means of the CALPHAD approach coupled with models in the literature, which account for the thermodynamics and kinetics of oxidation. The present thermodynamic remodeling of the Ni–O system results in a better agreement with experimental data of oxygen solubility in Ni at high temperatures. The oxygen solubility is combined with kinetic parameters to determine oxygen permeability in Ni, and the critical Al concentration needed to establish an α-Al2O3 scale at a given exposure temperature. Good agreement is found with available experimental data for both oxygen permeability and critical Al concentration, indicating the capacity of the CALPHAD approach to tailor oxidation resistance for materials of interest using thermodynamic and kinetic knowledge.
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| 34. |
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| 35. |
- Schwellnus, Martin, et al.
(author)
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How much is too much? (Part 2) International Olympic Committee consensus statement on load in sport and risk of illness
- 2016
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In: British Journal of Sports Medicine. - : BMJ PUBLISHING GROUP. - 0306-3674 .- 1473-0480. ; 50:17, s. 1043-1052
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Journal article (peer-reviewed)abstract
- The modern-day athlete participating in elite sports is exposed to high training loads and increasingly saturated competition calendar. Emerging evidence indicates that inappropriate load management is a significant risk factor for acute illness and the overtraining syndrome. The IOC convened an expert group to review the scientific evidence for the relationship of loadincluding rapid changes in training and competition load, competition calendar congestion, psychological load and traveland health outcomes in sport. This paper summarises the results linking load to risk of illness and overtraining in athletes, and provides athletes, coaches and support staff with practical guidelines for appropriate load management to reduce the risk of illness and overtraining in sport. These include guidelines for prescription of training and competition load, as well as for monitoring of training, competition and psychological load, athlete well-being and illness. In the process, urgent research priorities were identified.
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| 36. |
- Sharma, Rohini, et al.
(author)
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Multicenter Reproducibility of F-18-Fluciclatide PET Imaging in Subjects with Solid Tumors
- 2015
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In: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 56:12, s. 1855-1861
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Journal article (peer-reviewed)abstract
- Integrins are upregulated on both tumor cells and associated vasculature, where they play an important role in angiogenesis and metastasis. Fluciclatide is an arginine-glycine-aspartic acid peptide with high affinity for alpha(v)beta(3)/alpha(v)beta(5) integrin, which can be radio-labeled for PET imaging of angiogenesis. Thus, F-18-fluciclatide is a potential biomarker of therapeutic response to antiangiogenic inhibitors. The aim of this study was to evaluate the reproducibility of F-18-fluciclatide in multiple solid-tumor types. Methods: Thirty-nine patients underwent PET/CT scanning at 40, 65, and 90 min after injection of F-18-fluciclatide (maximum, 370 MBq) on 2 separate days (2-9 d apart). Patients did not receive any therapy between PET/CT scans. F-18-fluciclatide images were reported and quantitative measures of uptake were extracted using the PERCIST methodology. Intrasubject reproducibility of PET uptake in all measurable lesions was evaluated by calculating relative differences in SUV between PET scans for each lesion during the 2 imaging sessions. Results: Thirty-nine measurable lesions were detected in 26 patients. Lesion uptake correlated strongly across imaging sessions (r = 0.92, P < 0.05, at 40 min; r = 0.94, P < 0.05, at 65 min; r = 0.94, P, 0.05, at 90 min) with a mean relative difference and SD of the relative difference of 0.006 +/- 0.18 at 40 min, 0.003 +/- 0.19 at 65 min, and 0.025 +/- 0.20 at 90 min. This reflects 95% limits of repeatability of 35%-39% for the difference between the 2 SUV measurements or a variability of 18%-20% in agreement from that observed in well-calibrated multicenter F-18-FDG studies. Conclusion: The test-retest reproducibility of F-18-fluciclatide across multiple tumor types has been measured and shown to be acceptable. This is an important step in the development of this in vivo biomarker to identify and quantify response to antiangiogenic therapy in cancer patients.
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| 37. |
- Simeon, Saw, et al.
(author)
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Insights into the EGFR SAR of N-phenylquinazolin-4-amine-derivatives using quantum mechanical pairwise-interaction energies.
- 2019
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In: Journal of Computer-Aided Molecular Design. - : Springer Nature. - 0920-654X .- 1573-4951. ; 33:8, s. 745-757
-
Journal article (peer-reviewed)abstract
- Protein kinases are an important class of enzymes that play an essential role in virtually all major disease areas. In addition, they account for approximately 50% of the current targets pursued in drug discovery research. In this work, we explore the generation of structure-based quantum mechanical (QM) quantitative structure-activity relationship models (QSAR) as a means to facilitate structure-guided optimization of protein kinase inhibitors. We explore whether more accurate, interpretable QSAR models can be generated for a series of 76 N-phenylquinazolin-4-amine inhibitors of epidermal growth factor receptor (EGFR) kinase by comparing and contrasting them to other standard QSAR methodologies. The QM-based method involved molecular docking of inhibitors followed by their QM optimization within a ~ 300 atom cluster model of the EGFR active site at the M062X/6-31G(d,p) level. Pairwise computations of the interaction energies with each active site residue were performed. QSAR models were generated by splitting the datasets 75:25 into a training and test set followed by modelling using partial least squares (PLS). Additional QSAR models were generated using alignment dependent CoMFA and CoMSIA methods as well as alignment independent physicochemical, e-state indices and fingerprint descriptors. The structure-based QM-QSAR model displayed good performance on the training and test sets (r2 ~ 0.7) and was demonstrably more predictive than the QSAR models built using other methods. The descriptor coefficients from the QM-QSAR models allowed for a detailed rationalization of the active site SAR, which has implications for subsequent design iterations.
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| 38. |
- Simeon, Saw, et al.
(author)
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PepBio : predicting the bioactivity of host defense peptides
- 2017
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In: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 7:56, s. 35119-35134
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Journal article (peer-reviewed)abstract
- Host defense peptides (HDPs) represents a class of ubiquitous and rapid responding immune molecules capable of direct inactivation of a wide range of pathogens. Recent research has shown HDPs to be promising candidates for development as a novel class of broad-spectrum chemotherapeutic agent that is effective against both pathogenic microbes and malignant neoplasm. This study aims to quantitatively explore the relationship between easy-to-interpret amino acid composition descriptors of HDPs with their respective bioactivities. Classification models were constructed using the C4.5 decision tree and random forest classifiers. Good predictive performance was achieved as deduced from the accuracy, sensitivity and specificity in excess of 90% and Matthews correlation coefficient in excess of 0.5 for all three evaluated data subsets (e.g. training, 10-fold cross-validation and external validation sets). The source code and data set used for the construction of classification models are available on GitHub at https://github.com/chaninn/pepbio/.
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| 39. |
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| 40. |
- Thompson, C., et al.
(author)
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The Clearance of Serum Human Epididymis Protein 4 Following Primary Cytoreductive Surgery for Ovarian Carcinoma
- 2018
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In: International Journal of Gynecological Cancer. - : BMJ. - 1048-891X. ; 28:6, s. 1066-1072
-
Journal article (peer-reviewed)abstract
- Objective The aim of this study was to examine the clearance of serum human epididymis protein 4 (HE4) in the immediate postoperative period in patients undergoing maximal effort cytoreductive surgery for ovarian carcinoma. Methods The study was performed at a tertiary gynecologic oncology center. The surgery was performed by accredited gynecological oncologists. Results Preoperative and serial postoperative venous blood samples at 4, 8, 24, 48, 72, 96, and 120 hours were taken from 10 sequential patients. Pretreatment HE4 is considered elevated at greater than 70 pmol/L. Human epididymis protein 4 was greater than 70 pmol/L in 7 patients, including all patients with high-grade serous carcinoma. Patients with preoperative elevation of serum HE4 and complete cytoreduction cleared more than 80% of serum HE4 in the first 4 hours and more than 88% within 5 days of surgery. One patient with incomplete cytoreduction of high-grade serous carcinoma had 66% clearance at 4 hours and a plateau thereafter. Conclusions Human epididymis protein 4 derived from ovarian carcinoma had a short half-life of less than 4 hours in the circulation when cytoreductive surgery was complete. Sustained low HE4 following surgery could be a useful indicator of the completeness of cytoreduction. Plateau or rise in serum HE4 could suggest persistent disease. Comparison of values on day 1 and day 4 or 5 might have value in assessing the completeness of cytoreduction.
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