Trends in availability and prices of subsidized ACT over the first year of the AMFm: evidence from remote regions of Tanzania

ABSTRACT: BACKGROUND: The Affordable Medicines Facility for malaria (AMFm) is a pilot supra-national subsidy program that aims to increase access and affordability of artemisinin combination therapy (ACT) in public sector clinics and private retail shops. It is unclear to what extent the AMFm model will translate into wide scale availability and price reductions in ACT, particularly for rural, remote areas where disparities in access to medicines often exist. This study is the first to rigorously examine the availability and price of subsidized ACT during the first year of the AMFm, measured through retail audits in remote regions of Tanzania. METHODS: Periodic retail audits of Accredited Drug Dispensing Outlets (ADDOs) were conducted in two remote regions of Tanzania (Mtwara and Rukwa). Temporal and spatial variation in ACT availability and pricing were explored. A composite measure of ADDO remoteness, using variables, such as distance to suppliers and towns, altitude and population density, was used to explore whether ACT availability and price vary systematically with remoteness. RESULTS: Between February 2011 and January 2012, the fraction of ADDOs stocking AMFm-ACT increased from 25% to 88% in Mtwara and from 3% to 62% in Rukwa. Availability was widespread, though dispersion throughout the region was achieved more quickly in Mtwara. No significant relationship was found between ACT availability and remoteness. Adult doses of AMFm-ACT were much more widely available than any other age/weight band. Average prices fell from 1529 TZS (1.03 USD) to 1272 TZS (0.81 USD) over the study period, with significantly higher prices in Rukwa. The government recommended retail price for AMFm- ACT is 1,000 TZS ($0.64 USD). The median retail ACT price in the final round of data collection was 1,000 TZS. CONCLUSIONS: The AMFm led to large increases in availability of low priced ACT in Tanzania, with no significant variation in availability based on remoteness. Availability did remain lower and prices remained higher in Rukwa, which is a more remote region overall. Low availability of child and adolescent ACT doses could be due in part to lower quantities of non-adult packs imported into Tanzania. Future research will explore whether increased availability and affordability persists and whether it translates into higher ACT use in Tanzania.     

A Multilevel Model for Continuous Time Population Estimation

Summary .  Statistical methods have been developed and applied to estimating populations that are difficult or too costly to enumerate. Known as multilist methods in epidemiological settings, individuals are matched across lists and estimation of population size proceeds by modeling counts in incomplete multidimensional contingency tables (based on patterns of presence/absence on lists). As multilist methods typically assume that lists are compiled instantaneously, there are few options available for estimating the unknown size of a closed population based on continuously (longitudinally) compiled lists. However, in epidemiological settings, continuous time lists are a routine byproduct of administrative functions. Existing methods are based on time-to-event analyses with a second step of estimating population size. We propose an alternative approach to address the twofold epidemiological problem of estimating population size and of identifying patient factors related to duration (in days) between visits to a health care facility. A Bayesian framework is proposed to model interval lengths because, for many patients, the data are sparse; many patients were observed only once or twice. The proposed method is applied to the motivating data to illustrate the methods' applicability. Then, a small simulation study explores the performance of the estimator under a variety of conditions. Finally, a small discussion section suggests opportunities for continued methodological development for continuous time population estimation.     

Grasping the Changes Seen in Older Adults When Reaching for Objects of Varied Texture

Old age is associated with reduced mobility of the hand. To investigate age related decline when reaching-to-lift an object we used sophisticated kinematic apparatus to record reaches carried out by healthy older and younger participants. Three objects of different widths were placed at three different distances, with objects having either a high or low friction surface (i.e. rough or slippery). Older participants showed quantitative differences to their younger counterparts – movements were slower and peak speed did not scale with object distance. There were also qualitative differences with older adults showing a greater propensity to stop the hand and adjust finger position before lifting objects. The older participants particularly struggled to lift wide slippery objects, apparently due to an inability to manipulate their grasp to provide the level of precision necessary to functionally enclose the object. These data shed light on the nature of age related changes in reaching-to-grasp movements and establish a powerful technique for exploring how different product designs will impact on prehensile behavior.     

Expression profiling of potato germplasm differentiated in quality traits leads to the identification of candidate flavour and texture genes

Quality traits such as flavour and texture are assuming a greater importance in crop breeding programmes. This study takes advantage of potato germplasm differentiated in tuber flavour and texture traits. A recently developed 44,000-element potato microarray was used to identify tuber gene expression profiles that correspond to differences in tuber flavour and texture as well as carotenoid content and dormancy characteristics. Gene expression was compared in two Solanum tuberosum group Phureja cultivars and two S. tuberosum group Tuberosum cultivars; 309 genes were significantly and consistently up-regulated in Phureja, whereas 555 genes were down-regulated. Approximately 46% of the genes in these lists can be identified from their annotation and amongst these are candidates that may underpin the Phureja/Tuberosum trait differences. For example, a clear difference in the cooked tuber volatile profile is the higher level of the sesquiterpene alpha-copaene in Phureja compared with Tuberosum. A sesquiterpene synthase gene was identified as being more highly expressed in Phureja tubers and its corresponding full-length cDNA was demonstrated to encode alpha-copaene synthase. Other potential 'flavour genes', identified from their differential expression profiles, include those encoding branched-chain amino acid aminotransferase and a ribonuclease suggesting a mechanism for 5'-ribonucleotide formation in potato tubers on cooking. Major differences in the expression levels of genes involved in cell wall biosynthesis (and potentially texture) were also identified, including genes encoding pectin acetylesterase, xyloglucan endotransglycosylase and pectin methylesterase. Other gene expression differences that may impact tuber carotenoid content and tuber life-cycle phenotypes are discussed.     

Carbon flow in an upland grassland: effect of liming on the flux of recently photosynthesized carbon to rhizosphere soil

The effect of liming on the flow of recently photosynthesized carbon to rhizosphere soil was studied using ¹³CO₂ pulse labelling, in an upland grassland ecosystem in Scotland. The use of ¹³C enabled detection, in the field, of the effect of a 4‐year liming period of selected soil plots on C allocation from plant biomass to soil, in comparison with unlimed plots. Photosynthetic rates and carbon turnover were higher in plants grown in limed soils than in those from unlimed plots. Higher δ¹³C‰ values were detected in shoots from limed plants than in those from unlimed plants in samples clipped within 15 days of the end of pulse labelling. Analysis of the aboveground plant production corresponding to the 4‐year period of liming indicated that the standing biomass was higher in plots that received lime. Lower δ¹³C‰ values in limed roots compared with unlimed roots were found, whereas no significant difference was detected between soil samples. Extrapolation of our results indicated that more C has been lost through the soil than has been gained via photosynthetic assimilation because of pasture liming in Scotland during the period 1990–1998. However, the uncertainty associated with such extrapolation based on this single study is high and these estimates are provided only to set our findings in the broader context of national soil carbon emissions.     

Training multi-parameter gaits to reduce the knee adduction moment with data-driven models and haptic feedback

The purpose of this study was to evaluate gait retraining for reducing the knee adduction moment. Our primary objective was to determine whether subject-specific altered gaits aimed at reducing the knee adduction moment by 30% or more could be identified and adopted in a single session through haptic (touch) feedback training on multiple kinematic gait parameters. Nine healthy subjects performed gait retraining, in which data-driven models specific to each subject were determined through experimental trials and were used to train novel gaits involving a combination of kinematic changes to the tibia angle, foot progression and trunk sway angles. Wearable haptic devices were used on the back, knee and foot for real-time feedback. All subjects were able to adopt altered gaits requiring simultaneous changes to multiple kinematic parameters and reduced their knee adduction moments by 29-48%. Analysis of single parameter gait training showed that moving the knee medially by increasing tibia angle, increasing trunk sway and toeing in all reduced the first peak of the knee adduction moment with tibia angle changes having the most dramatic effect. These results suggest that individualized data-driven gait retraining may be a viable option for reducing the knee adduction moment as a treatment method for early-stage knee osteoarthritis patients with sufficient sensation, endurance and motor learning capabilities.     

Simultaneous analysis of circulating human cytokines using a high-sensitivity cytokine biochip array

Biochip array technology allows the simultaneous measurement of multiple analytes per sample using a single analytical device. This study shows its applicability to the simultaneous measurement of 12 circulating human cytokines with high-sensitivity detection. This application increases their real-time detectability, maintaining a broad concentration range and without compromising the precision. This methodology represents a very applicable tool in cytokine research when simultaneous determination of minute concentrations can be of interest.     

The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors

The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.