Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo drug sensitivity and parasite polymorphisms associated with sensitivity in 459 Plasmodium falciparum samples obtained from subjects enrolled in two clinical trials in Tororo, Uganda, from 2010 to 2013. Sensitivities to chloroquine and monodesethylamodiaquine varied widely; sensitivities to quinine, dihydroartemisinin, lumefantrine, and piperaquine were generally good. Associations between ex vivo drug sensitivity and parasite polymorphisms included decreased chloroquine and monodesethylamodiaquine sensitivity and increased lumefantrine and piperaquine sensitivity with pfcrt 76T, as well as increased lumefantrine sensitivity with pfmdr1 86Y, Y184, and 1246Y. Over time, ex vivo sensitivity decreased for lumefantrine and piperaquine and increased for chloroquine, the prevalences of pfcrt K76 and pfmdr1 N86 and D1246 increased, and the prevalences of pfdhfr and pfdhps polymorphisms associated with antifolate resistance were unchanged. In recurrent infections, recent prior treatment with artemether-lumefantrine was associated with decreased ex vivo lumefantrine sensitivity and increased prevalence of pfcrt K76 and pfmdr1 N86, 184F, and D1246. In children assigned chemoprevention with monthly dihydroartemisinin-piperaquine with documented circulating piperaquine, breakthrough infections had increased the prevalence of pfmdr1 86Y and 1246Y compared to untreated controls. The noted impacts of therapy and chemoprevention on parasite polymorphisms remained significant in multivariate analysis correcting for calendar time. Overall, changes in parasite sensitivity were consistent with altered selective pressures due to changing treatment practices in Uganda. These changes may threaten the antimalarial treatment and preventive efficacies of artemether-lumefantrine and dihydroartemisinin-piperaquine, respectively. M alaria, in particular disease caused by Plasmodium falciparum, remains an overwhelming problem in most of subSaharan Africa (1, 2). Malaria control was greatly limited by resistance to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), leading to adoption of artemisinin-based combination therapy (ACT) as the standard treatment for uncomplicated falciparum malaria in the last decade (3). ACT consists of a rapid-acting artemisinin derivative plus a longer-acting partner drug that clears parasites not eliminated by the artemisinin component and limits selection of artemisinin resistance (4, 5). In nearly all countries in sub-Saharan Africa, either artemether-lumefantrine (AL) or artesunate-amodiaquine (AS-AQ) is recommended to treat uncomplicated malaria (6). Other ACTs are dihydroartemisinin (DHA)-piperaquine (DP), a first-line therapy in some countries in Asia, with particular promise for malaria prevention due to the extended halflife of piperaquine (7), and artesunate-mefloquine (AS-MQ), which is used in some countries in Asia and South America. In Uganda, AL was named the national ma...

Long acquisition times can limit the use of MRI in pediatric patients, and the use of sedation or general anesthesia is frequently necessary to facilitate diagnostic examinations. The use of sedation or anesthesia has disadvantages including increased cost and imaging time and potential risks to the patient. Reductions in imaging time may decrease or eliminate the need for sedation or general anesthesia. Over the past decade, a number of imaging techniques that can decrease imaging time have become commercially available. These products have been used increasingly in clinical practice and include parallel imaging, simultaneous multisection imaging, radial k-space acquisition, compressed sensing MRI reconstruction, and automated protocol selection software. The underlying concepts, supporting data, current clinical applications, and available products for each of these strategies are reviewed in this article. In addition, emerging techniques that are still under investigation may provide further reductions in imaging time, including artificial intelligence-based reconstruction, gradient-controlled aliasing sampling and reconstruction, three-dimensional MR spectroscopy, and prospective motion correction. The preliminary results for these techniques are also discussed.

IN BRIEF Although the number of diabetes treatments has substantially increased in the past two decades, today's therapies are considered far from ideal. Yet, what constitutes an ideal therapy is not readily clear, as diabetes drug therapies are regularly judged both by their effects on glycemia and by a wide variety of nonglycemic metrics. This review describes the characteristics of an ideal diabetes therapy from the perspective of patients, physicians, payors, and financial analysts and examines how well currently available therapies and several late-stage candidates meet these guideposts.