Setting priorities in global child health research investments: assessment of principles and practice

This article reviews theoretical and practical approaches for setting priorities in global child health research investments. It also provides an overview of previous attempts to develop appropriate tools and methodologies to define priorities in health research investments. A brief review of the most important theoretical concepts that should govern priority setting processes is undertaken, showing how different perspectives, such as medical, economical, legal, ethical, social, political, rational, philosophical, stakeholder driven, and others will necessarily conflict each other in determining priorities. We specially address present research agenda in global child health today and how it relates to United Nation's (UN) Millennium Development Goal 4, which is to reduce child mortality by two-thirds between 1990 and 2015. The outcomes of these former approaches are evaluated and their benefits and shortcomings presented. The case for a new methodology for setting priorities in health research investments is presented, as proposed by Child Health and Nutrition Research Initiative, and a need for its implementation in global child health is outlined. A transdisciplinary approach is needed to address all the perspectives from which investments into health research can be seen as priorities. This prioritization requires a process that is transparent, systematic, and that would take into account many perspectives and build on advantages of previous approaches.     

Distinguishability for magnetic resonance-electrical impedance tomography (MR-EIT)

A distinguishability measure is defined for magnetic resonance-electrical impedance tomography (MR-EIT) based on magnetic flux density measurements. This general definition is valid for 2D and 3D structures of any shape. As a specific case, a 2D cylindrical body with concentric inhomogeneity is considered and a bound of the distinguishability is analytically formulated. Distinguishabilities obtained with potential and magnetic flux density measurements are compared.     

Development and validation of UPLC-PDA method for concurrent analysis of bergenin and menisdaurin in aerial parts of Flueggea virosa (Roxb. ex Willd.)

Bergenin and menisdaurin are biologically active components which are found in plant Flueggea virosa (Phyllanthaceae). Bergenin has pharmacological actions such as chemopreventive and antihepatotoxic while menisdaurin has an anti-viral activity which needs its evaluation by an analytical method (UPLC-PDA method) that can be applied to the quality control of pharmaceutical preparations. The developed UPLC-PDA method was applied for identification and quantification of standards bergenin and menisdaurin in the methanol extract of F. virosa (FVME). The analysis was carried out using Eclipse C18 (4.6?×?100?mm, 3.5?µm) UPLC column. The optimized chromatographic condition was achieved at 0.16?mL/min flow rate using gradient system with acetonitrile and water as mobile phase. Both biomarkers were measured at λ_max 235?nm in PDA detector at ambient temperature. The developed method furnished sharp and intense peaks of menisdaurin and bergenin at Rt?=?2.723 and 3.068?min, respectively along with r2?>?0.99 for both. The recoveries of bergenin and menisdaurin were found in the range of 99.37–101.49% and 98.20–100.08%, respectively. With other validation data, including precision, specificity, accuracy, and robustness, this method demonstrated excellent reliability and sensitivity. The separation parameters i.e. retention, separation, and resolution factors for resolved standards (bergenin and menisdaurin) were >1, which showed good separation. The quantity of bergenin and menisdaurin in the FVME sample was found as 15.16 and 3.28% w/w, respectively. The developed UPLC-PDA method could be conveniently adopted for the routine quality control analysis.     

Lower vitamin D level is associated with poor coronary collateral circulation

Objectives. Vitamin D regulates calcium and bone homeostasis, and parathyroid hormone (PTH) secretion. Cross-sectional associations between lower vitamin D levels and cardiovascular diseases have been reported, but the relationship between vitamin D levels and collateral arteries in stable coronary artery disease (CAD) has not been reported before. Design. Two hundred and fourteen patients with above 95% stenosis in at least one epicardial coronary artery were consecutively recruited after coronary angiography (CAG) during the winter season. The coronary collateral circulation (CCC) was graded using Rentrop classification. Poor CCC group included patients with Rentrop Grade 0–1 CCC and control group included patients with Rentrop Grade 2–3 CCC. Vitamin D and PTH levels were measured on the day of CAG. Results. In the poor CCC group, vitamin D levels were lower (34 ± 25 pmol/L vs. 49 ± 33 pmol/L; p = 0.01) and the prevalence of vitamin D deficiency (< 37 pmol/L) was higher (67% vs. 43%; p = 0.01) compared to the controls. PTH levels, calcium, and phosphate levels were not significantly different between the groups. Female gender, lower HDL cholesterol, and lower vitamin D levels were independently correlated with poor CCC in the study population. Conclusion. Lower vitamin D levels may be associated with poor collateral development in patients with stable CAD.     

Characterization of reactive intermediates formation in dacomitinib metabolism and bioactivation pathways elucidation by LC-MS/MS: in vitro phase I metabolic investigation

Dacomitinib (DCB) is a second generation irreversible tyrosine kinase inhibitor (TKI) that is claimed to overcome the disadvantages of the resistance developed by the first line epidermal growth factor receptor (EGFR) TKIs. In the current study, metabolites of phase I for DCB were systematically explored. DCB reactive metabolites were also investigated in rat liver microsomes in presence of potassium cyanide or methoxylamine that were employed as capturing agents for iminium reactive intermediates and aldehyde, respectively, to form stable complexes which can be detected by LC-MS/MS. As a result, four in vitro phase I metabolites were observed with major pathway of piperidine ring hydroxylation. Additionally, two potentially reactive intermediates, one aldehyde and one iminium ions were characterized. Two different pathways of bioactivation were ultimately proposed.

Dacomitinib (DCB) is a second generation irreversible tyrosine kinase inhibitor (TKI) that is claimed to overcome the disadvantages of the resistance developed by the first line epidermal growth factor receptor (EGFR) TKIs.