Optimizing 2D gas chromatography mass spectrometry for robust tissue, serum and urine metabolite profiling.

Two-dimensional gas chromatography mass spectrometry (GCxGC-MS) is utilized to an increasing extent in biomedical metabolomics. Here, we established and adapted metabolite extraction and derivatization protocols for cell/tissue biopsy, serum and urine samples according to their individual properties. GCxGC-MS analysis revealed detection of ~600 molecular features from which 165 were characterized representing different classes such as amino acids, fatty acids, lipids, carbohydrates, nucleotides and small polar components of glycolysis and the Krebs cycle using electron impact (EI) spectrum matching and validation using external standard compounds. Advantages of two-dimensional gas chromatography based resolution were demonstrated by optimizing gradient length and separation through modulation between the first and second column, leading to a marked increase in metabolite identification due to improved separation as exemplified for lactate versus pyruvate, talopyranose versus methyl palmitate and inosine versus docosahexaenoic acid. Our results demonstrate that GCxGC-MS represents a robust metabolomics platform for discovery and targeted studies that can be used with samples derived from the clinic.

Should new antimalarial drugs be subsidized?

Malaria kills over a million people each year. The loss of chloroquine due to the spread of parasite resistance is largely responsible for the resurgence of malaria. A new class of antimalarial drugs called artemisinins are available, but are unaffordable to most people in malaria-endemic countries and may quickly face the same fate as chloroquine unless they are combined with a partner drug. Subsidies for artemisinin combination treatments may be warranted on second-best grounds as they deter use of single-ingredient drugs, for which externalities from the risk of resistance evolution are larger. Furthermore, by expanding total effective drug use, subsidies reduce infection transmission externalities among individuals. However, use of combination treatments could still lead to drug resistance and the subsidies themselves entail welfare consequences. This paper develops a conceptual and numerical framework for understanding the conditions under which subsidies for artemisinin combinations can be justified on economic efficiency grounds.

Comparing the welfare effects of public and private health care subsidies in the United Kingdom.

We use a calibrated analytical model to compare the welfare costs (gross of externalities) of increasing subsidies for public and private health care in the UK. The model incorporates wait costs for rationed public care, burdens that subsidies impose on the tax system, and distributional weights for different households. Welfare costs are significantly higher for expanding public health care over a range of parameter scenarios. Both policies reduce average wait times, but for public health care this is offset by new waiting costs incurred on extra treatments. And the burden on the tax system is much larger for expanding public health care.