Reducing microscopy-based malaria misdiagnosis in a low-resource area of Tanzania

Misdiagnosis of malaria is a major problem in Africa leading not only to incorrect individual level treatment, but potentially the acceleration of the spread of drug resistance in low-transmission areas. In this paper we report on the outcomes of a simple intervention that utilized a social entrepreneurship approach (SEA) to reduce misdiagnosis associated with hospital-based microscopy of malaria in a low-transmission area of rural Tanzania. A pre-post assessment was conducted on patients presenting to the hospital outpatient department with malaria and non-malaria like symptoms in January 2009 (pre-intervention) and June 2009 (post-intervention). All participants were asked a health seeking behavior questionnaire and blood samples were taken for local and quality control microscopy. Multivariate logistic regression was conducted to determine magnitude of misdiagnosis with local microscopy pre- versus- post intervention. Local microscopy pre-intervention specificity was 29.5% (95% CI = 21.6% – 38.4%) whereas the post intervention specificity was 68.6% (95% CI = 60.2% - 76.2%). Both pre and post intervention sensitivity were difficult to determine due to an unexpected low number of true positive cases. The proportion of participants misdiagnosed pre-intervention was 70.2% (95%CI = 61.3%-78.0%) as compared to 30.6% (95%CI = 23.2%–38.8%) post-intervention. This resulted in a 39.6% reduction in misdiagnosis of malaria at the local hospital. The magnitude of misdiagnosis for the pre-intervention participants was 5.3 (95%CI = 3.1–9.3) that of the post-intervention participants. In conclusion, this study provides evidence that a simple intervention can meaningfully reduce the magnitude of microscopy-based misdiagnosis of malaria for those individuals seeking treatment for uncomplicated malaria. We anticipate that this intervention will facilitate a valuable and sustainable change in malaria diagnosis at the local hospital

Diffuse flow environments within basalt- and sediment-based hydrothermal vent ecosystems harbor specialized microbial communities

Hydrothermal vents differ both in surface input and subsurface geochemistry. The effects of these differences on their microbial communities are not clear. Here, we investigated both alpha and beta diversity of diffuse flow-associated microbial communities emanating from vents at a basalt-based hydrothermal system along the East Pacific Rise (EPR) and a sediment-based hydrothermal system, Guaymas Basin. Both Bacteria and Archaea were targeted using high throughput 16S rRNA gene pyrosequencing analyses. A unique aspect of this study was the use of a universal set of 16S rRNA gene primers to characterize total and diffuse flow-specific microbial communities from varied deep-sea hydrothermal environments. Both surrounding seawater and diffuse flow water samples contained large numbers of Marine Group I (MGI) Thaumarchaea and Gammaproteobacteria taxa previously observed in deep-sea systems. However, these taxa were geographically distinct and segregated according to type of spreading center. Diffuse flow microbial community profiles were highly differentiated. In particular, EPR dominant diffuse flow taxa were most closely associated with chemolithoautotrophs, and off axis water was dominated by heterotrophic-related taxa, whereas the opposite was true for Guaymas Basin. The diversity and richness of diffuse flow-specific microbial communities were strongly correlated to the relative abundance of Epsilonproteobacteria, proximity to macrofauna, and hydrothermal system type. Archaeal diversity was higher than or equivalent to bacterial diversity in about one third of the samples. Most diffuse flow-specific communities were dominated by OTUs associated with Epsilonproteobacteria, but many of the Guaymas Basin diffuse flow samples were dominated by either OTUs within the Planctomycetes or hyperthermophilic Archaea. This study emphasizes the unique microbial communities associated with geochemically and geographically distinct hydrothermal diffuse flow environments

Relationship Between Static Mobility of the First Ray and First Ray, Midfoot, and Hindfoot Motion During Gait

The relationship between a static measure of dorsal first ray mobility and dynamic motion of the first ray, midfoot, and hindfoot during the stance phase of walking was investigated in healthy, asymptomatic subjects who represented the spectrum of static flexibility. Static first ray mobility of 15 subjects was measured by a load cell device and ranged from stiff (3.1 mm) to lax (8.0 mm). Using three-dimensional motion analysis, mean first ray dorsiflexion/eversion and mid-/hindfoot eversion peak motion, time-to-peak, and eversion excursion were evaluated. Subjects with greater static dorsal mobility of the first ray demonstrated significantly greater time-topeak hindfoot eversion and eversion excursion (p \u3c .01), and midfoot peak eversion and eversion excursion (p \u3c .01). No significant association was found between static first ray mobility and first ray motion during gait. This research provides evidence that the dynamic response of the foot may modulate the consequences of first ray mobility and that compensory strategies are most effective when static measures of dorsal mobility are most extreme

Strategies for selection of subjects for sequencing after detection of a linkage peak

Linkage analysis has the potential to localize disease genes of interest, but the choice of which subjects to select for follow-up sequencing after identifying a linkage peak might influence the ability to find a disease gene. We compare nine different strategies for selection of subjects for follow-up sequencing using sequence data from the Genetic Analysis Workshop 17. We found that our more selective strategies, which included methods to identify case subjects more likely to be affected by genetic causes, out-performed sequencing all case and control subjects in linked pedigrees and required sequencing fewer individuals. We found that using genotype data from population control subjects had a higher benefit-cost ratio than sequencing control subjects selected as being the opposite extreme of the case subjects. We conclude that choosing case subjects for sequencing based on more selective strategies can be reliable and cost-effective

Academic Institutions and One Health: Building Capacity for Transdisciplinary Research Approaches to Address Complex Health Issues at the Animal–Human–Ecosystem Interface

To improve health at the human, animal, and ecosystem interface, defined as One Health, training of researchers must transcend individual disciplines to develop a new process of collaboration. The transdisciplinary research approach integrates frameworks and methodologies beyond academic disciplines and includes involvement of and input from policy makers and members of the community. The authors argue that there should be a significant shift in academic institutions' research capacity to achieve the added value of a transdisciplinary approach for addressing One Health problems. This Perspective is a call to action for academic institutions to provide the foundations for this salient shift. The authors begin by describing the transdisciplinary approach, propose methods for building transdisciplinary research capacity, and highlight three value propositions that support the case. Examples are provided to illustrate how the transdisciplinary approach to research adds value through improved sustainability of impact, increased cost-effectiveness, and enhanced abilities to mitigate potentially harmful unintended consequences. The authors conclude with three key recommendations for academic institutions: (1) a focus on creating enabling environments for One Health and transdisciplinary research, (2) the development of novel funding structures for transdisciplinary research, and (3) training of "transmitters" using real-world-oriented educational programs that break down research silos through collaboration across disciplines

Reducing malaria misdiagnosis: the importance of correctly interpreting Paracheck Pf® "faint test bands" in a low transmission area of Tanzania

Although malaria rapid diagnostic tests (RDTs) have been extensively evaluated since their introduction in the early 1990's, sensitivity and specificity vary widely limiting successful integration into clinical practice. This paper reviews specific issues surrounding RDT use in field settings and presents results of research investigating how to interpret "faint test bands" on ParaCheck Pf® in areas of low transmission in order to reduce malaria misdiagnosis.\ud A multi-phase cross-sectional study was conducted at a remote hospital in the northern Tanzanian highlands. Capillary blood samples were taken from consenting participants (n = 319) for blood smear and ParaCheck Pf® testing. Primary outcome variables were sensitivity, specificity and proportion misdiagnosed by ParaCheck Pf® and local microscopy. ParaCheck Pf® "faint bands" were classified as both true positives or true negatives during evaluation to determine appropriate clinical interpretation. Multivariate logistic regression adjusted for age and gender was conducted to determine odds of misdiagnosis for local microscopy and ParaCheck Pf®. Overall, 23.71% of all ParaCheck Pf® tests resulted in a "faint band" and 94.20% corresponded with true negatives. When ParaCheck Pf® "faint bands" were classified as positive, specificity was 75.5% (95% CI = 70.3%-80.6%) as compared to 98.9% (95% CI = 97.0%-99.8%) when classified as negative. The odds of misdiagnosis by local microscopy for those > 5 years as compared to those ≤ 5 years are 0.370 (95% CI = 0.1733-0.7915, p = 0.010). In contrast, even when ParaCheck Pf® faint bands are considered positive, the odds of misdiagnosis by ParaCheck Pf® for those > 5 years as compared to those ≤ 5 years are 0.837 (95% CI = 0.459-1.547, p = 0.5383). We provide compelling evidence that in areas of low transmission, "faint bands" should be considered a negative test when used to inform clinical decision-making. Correct interpretation of RDT test bands in a clinical setting plays a central role in successful malaria surveillance, appropriate patient management and most importantly reducing misdiagnosis

Cache Impacts of Datatype Acceleration

Hardware acceleration is a widely accepted solution for performance and energy efficient computation because it removes unnecessary hardware for general computation while delivering exceptional performance via specialized control paths and execution units. The spectrum of accelerators available today ranges from coarse-grain off-load engines such as GPUs to fine-grain instruction set extensions such as SSE. This research explores the benefits and challenges of managing memory at the data-structure level and exposing those operations directly to the ISA. We call these instructions. Abstract Datatype Instructions (ADIs). This paper quantifies the performance and energy impact of ADIs on the instruction and data cache hierarchies. For instruction fetch, our measurements indicate that ADIs can result in 21-48% and 16-27% reductions in instruction fetch time and energy respectively. For data delivery, we observe a 22-40% reduction in total data read/write time and 9-30% in total data read/write energy

A Comparison Of Crassostrea Virginica And C. Ariakensis In Chesapeake Bay: Does Oyster Species Affect Habitat Function?

We examined the possibility that a nonnative oyster species would provide an ecologically functional equivalent of the native oyster species if introduced into the Chesapeake Bay. Habitat complexity and associated benthic communities of experimental triploid Crassostrea virginica and Crassostrea ariakensis reefs were investigated at 4 sites of varying salinity, tidal regime, water depth, predation intensity, and disease pressure in the Chesapeake Bay region (Maryland and Virginia). Four experimental treatments were established at each site: C. virginica, C. ariakensis, 50:50 of C. virginica and C. ariakensis, and shell only. Abundance, biomass, species richness, evenness, dominance, and diversity of reef-associated fauna were evaluated in relation to habitat location and oyster species. Although habitat complexity varied with location, no differences among complexity were associated with oyster species. Similarly, differences in faunal assemblages were more pronounced between sites than within sites. Our results show functional equivalency between oyster species with respect to habitat at the intertidal site and the low-salinity subtidal location. At subtidal sites of higher salinity, however, the numbers of organisms associated with C. virginica reefs per unit of oyster biomass were significantly greater than the numbers of organisms associated with C. ariakensis reefs. Multivariate analyses of data from subtidal high-salinity sites revealed unique communities associated with C. virginica treatments, whereas mixed-oyster species assemblages were functionally equivalent to monospecific C. ariakensis experimental treatments. Our study represents the first effort to quantify the potential habitat function of C. ariakensis, which has been proposed for an intentional introduction into Chesapeake Bay, and provides evidence of species-specific similarities and differences in reef-associated communities

Centre variation in home dialysis uptake: A survey of kidney centre practice in relation to home dialysis organisation and delivery in England

Background: Disparities in home dialysis uptake across England suggest inequity and unexplained variation in access. We surveyed staff at all English kidney centres to identify patterns in service organisation/delivery and explore correlations with home therapy uptake, as part of a larger study (‘Inter-CEPt’), which aims to identify potentially modifiable factors to address observed variations. Methods: Between June and September 2022, staff working at English kidney centres were surveyed and individual responses combined into one centre-level response per question using predetermined data aggregation rules. Descriptive analysis described centre practices and their correlation with home dialysis uptake (proportion of new home dialysis starters) using 2019 UK Renal Registry 12-month home dialysis incidence data. Results: In total, 180 responses were received (50/51 centres, 98.0%). Despite varied organisation of home dialysis services, most components of service delivery and practice had minimal or weak correlations with home dialysis uptake apart from offering assisted peritoneal dialysis and ‘promoting flexible decision-making about dialysis modality’. Moderate to strong correlations were identified between home dialysis uptake and centres reporting supportive clinical leadership (correlation 0.32, 95% Confidence Interval (CI): 0.05–0.55), an organisational culture that values trying new initiatives (0.57, 95% CI: 0.34–0.73); support for reflective practice (0.38, 95% CI: 0.11–0.60), facilitating research engagement (0.39, 95% CI: 0.13–0.61) and promoting continuous quality improvement (0.29, 95% CI: 0.01–0.53). Conclusions: Uptake of home dialysis is likely to be driven by organisational culture, leadership and staff attitudes, which provide a supportive clinical environment within which specific components of service organisation and delivery can be effective

Survival And Growth Of Triploid Crassostrea Virginica (Gmelin, 1791) And C-Ariakensis (Fujita, 1913) In Bottom Environments Of Chesapeake Bay: Implications For An Introduction

Survival and growth of triploid Crassostrea virginica and triploid C. ariakensis were investigated at four sites Surrounding Chesapeake Bay, United States, that varied tried in salinity, tidal regime, water depth, predation intensity and disease pressure. Four experimental treatments were established at each site: C. virginica; C. ariakensis; 50:50 of C. virginica: C. ariakensis: and shell only. Oysters were deployed at mean shell heights of 12.80 min and 13.85 mm (C. virginica and C. ariakensis, respectively), at an overall density of 347.5 oysters m(-2). Oyster survival and growth varied significantly, with site and species. Survival was significantly higher in C. virginica than C. ariakensis at the intertidal site, and significantly higher in C. ariakensis than C. virginica at the highest salinity, subtidal site. Survival did not differ significantly between species at the mid and low salinity, subticial sites. For both Species. survival differed significantly between sites, with lowest survival in both species Occurring Lit the intertidal site. Among the subtidal sites. C. virginica survival varied inversely with salinity, whereas C. ariakensis had the lowest Survival at the mid salinity site. Eight months after deployment C. ariakensis were significantly, larger than C. virginica at all sites. This difference generally persisted throughout the experiment, though the size differences between oyster species at the lowest salinity site were small (\u3c 10%). Shell heights within single-species treatments differed significantly between sites; highest growth rates were observed at the high salinity, subtidal site, whereas lowest growth rates were observed at the high salinity, intertidal site. At low and mid salinity subtidal sites, C. ariakensis shell heights were significantly greater in the single-species treatment compared with the mixed-species treatment. Perkinsus marinus infections occurred in both species at all sites, with prevalences varying between sites. In C. virginica, moderate and high intensity infections were only common at the two higher salinity sites, whereas infections in C. ariakensis were generally low, to rare. Haplosporidium nelsoni infections in C. virginica were only observed at the two higher salinity sites and prevalences were generally low. Two out of 53 C. ariakensis tested at the high salinity, subtidal site had rare H. nelsoni infections. Bonamia spp. infections were never observed. Our study supports previous laboratory findings and observations from its native range that C. ariakensis Survives poorly in intertidal habitats. In subtidal habitats, however, C. ariakensis displayed broad environmental tolerances, often exceeding native oyster Survival and growth rates. Post-introduction C. ariakensis Populations would be shaped by the survival and growth patterns described here, but also by their reproductive success, larval Survival, predator-prey interactions and prevailing disease dynamics