Disease transmission models for public health decision making: toward an approach for designing intervention strategies for Schistosomiasis japonica.

Mathematical models of disease transmission processes can serve as platforms for integration of diverse data, including site-specific information, for the purpose of designing strategies for minimizing transmission. A model describing the transmission of schistosomiasis is adapted to incorporate field data typically developed in disease control efforts in the mountainous regions of Sichuan Province in China, with the object of exploring the feasibility of model-based control strategies. The model is studied using computer simulation methods. Mechanistically based models of this sort typically have a large number of parameters that pose challenges in reducing parametric uncertainty to levels that will produce predictions sufficiently precise to discriminate among competing control options. We describe here an approach to parameter estimation that uses a recently developed statistical procedure called Bayesian melding to sequentially reduce parametric uncertainty as field data are accumulated over several seasons. Preliminary results of applying the approach to a historical data set in southwestern Sichuan are promising. Moreover, technologic advances using the global positioning system, remote sensing, and geographic information systems promise cost-effective improvements in the nature and quality of field data. This, in turn, suggests that the utility of the modeling approach will increase over time

Testing density-functional approximations on a lattice and the applicability of the related Hohenberg-Kohn-like theorem

We present a metric-space approach to quantify the performance of approximations in lattice density-functional theory for interacting many-body systems and to explore the regimes where the Hohenberg-Kohn-type theorem on fermionic lattices is applicable. This theorem demonstrates the existence of one-to-one mappings between particle densities, wave functions and external potentials. We then focus on these quantities, and quantify how far apart in metric space the approximated and exact ones are. We apply our method to the one-dimensional Hubbard model for different types of external potentials, and assess the regimes where it is applicable to one of the most used approximations in density-functional theory, the local density approximation (LDA). We find that the potential distance may have a very different behaviour from the density and wave function distances, in some cases even providing the wrong assessments of the LDA performance trends. We attribute this to the systems reaching behaviours which are borderline for the applicability of the one-to-one correspondence between density and external potential. On the contrary the wave function and density distances behave similarly and are always sensitive to system variations. Our metric-based method correctly predicts the regimes where the LDA performs fairly well and the regimes where it fails. This suggests that our method could be a practical tool for testing the efficiency of density-functional approximations

Impact of specific functional groups in flavonoids on the modulation of platelet activation

Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4th carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationships of flavonoids upon the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents

How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRR’s Rehabilitation Engineering Research Centers

Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a “total approach to rehabilitation”, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970’s, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program

Ecological Implications of Extreme Events: Footprints of the 2010 Earthquake along the Chilean Coast

Deciphering ecological effects of major catastrophic events such as earthquakes, tsunamis, volcanic eruptions, storms and fires, requires rapid interdisciplinary efforts often hampered by a lack of pre-event data. Using results of intertidal surveys conducted shortly before and immediately after Chile's 2010 Mw 8.8 earthquake along the entire rupture zone (ca. 34–38°S), we provide the first quantification of earthquake and tsunami effects on sandy beach ecosystems. Our study incorporated anthropogenic coastal development as a key design factor. Ecological responses of beach ecosystems were strongly affected by the magnitude of land-level change. Subsidence along the northern rupture segment combined with tsunami-associated disturbance and drowned beaches. In contrast, along the co-seismically uplifted southern rupture, beaches widened and flattened increasing habitat availability. Post-event changes in abundance and distribution of mobile intertidal invertebrates were not uniform, varying with land-level change, tsunami height and coastal development. On beaches where subsidence occurred, intertidal zones and their associated species disappeared. On some beaches, uplift of rocky sub-tidal substrate eliminated low intertidal sand beach habitat for ecologically important species. On others, unexpected interactions of uplift with man-made coastal armouring included restoration of upper and mid-intertidal habitat seaward of armouring followed by rapid colonization of mobile crustaceans typical of these zones formerly excluded by constraints imposed by the armouring structures. Responses of coastal ecosystems to major earthquakes appear to vary strongly with land-level change, the mobility of the biota and shore type. Our results show that interactions of extreme events with human-altered shorelines can produce surprising ecological outcomes, and suggest these complex responses to landscape alteration can leave lasting footprints in coastal ecosystems

Roles of Major Facilitator Superfamily Transporters in Phosphate Response in Drosophila

The major facilitator superfamily (MFS) transporter Pho84 and the type III transporter Pho89 are responsible for metabolic effects of inorganic phosphate in yeast. While the Pho89 ortholog Pit1 was also shown to be involved in phosphate-activated MAPK in mammalian cells, it is currently unknown, whether orthologs of Pho84 have a role in phosphate-sensing in metazoan species. We show here that the activation of MAPK by phosphate observed in mammals is conserved in Drosophila cells, and used this assay to characterize the roles of putative phosphate transporters. Surprisingly, while we found that RNAi-mediated knockdown of the fly Pho89 ortholog dPit had little effect on the activation of MAPK in Drosophila S2R+ cells by phosphate, two Pho84/SLC17A1–9 MFS orthologs (MFS10 and MFS13) specifically inhibited this response. Further, using a Xenopus oocyte assay, we show that MSF13 mediates uptake of [³³P]-orthophosphate in a sodium-dependent fashion. Consistent with a role in phosphate physiology, MSF13 is expressed highest in the Drosophila crop, midgut, Malpighian tubule, and hindgut. Altogether, our findings provide the first evidence that Pho84 orthologs mediate cellular effects of phosphate in metazoan cells. Finally, while phosphate is essential for Drosophila larval development, loss of MFS13 activity is compatible with viability indicating redundancy at the levels of the transporters.National Institutes of Health (U.S.) (NIDDK 5K08DK078361)Harvard Catalys

Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Disease: Changes in Lung Function

Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a ≥5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27–53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an “idiopathic” interstitial pneumonia

Practice-Driven Evaluation of a Multi-layered Psychosocial Care Package for Children in Areas of Armed Conflict

Psychosocial and mental health service delivery frameworks for children in low-income countries are scarce. This paper presents a practice-driven evaluation of a multi-layered community-based care package in Burundi, Indonesia, Sri Lanka and Sudan, through a set of indicators; (a) perceived treatment gains; (b) treatment satisfaction; (c) therapist burden; (d) access to care; (e) care package costs. Across four settings (n = 29,292 children), beneficiaries reported high levels of client satisfaction and moderate post-treatment problem reductions. Service providers reported significant levels of distress related to service delivery. Cost analyses demonstrated mean cost per service user to vary from 3.46 to 17.32 € depending on country and specification of costs. The results suggest a multi-layered psychosocial care package appears feasible and satisfactory in reaching out to substantial populations of distressed children through different levels of care. Future replication should address therapist burden, cost reductions to increase sustainability and increase evidence for treatment efficacy

A cross-sectional study of the prevalence of intensity of infection with Schistosoma japonicum in 50 irrigated and rain-fed villages in Samar Province, the Philippines

BACKGROUND: Few studies have described heterogeneity in Schistosoma japonicum infection intensity, and none were done in Philippines. The purpose of this report is to describe the village-to-village variation in the prevalence of two levels of infection intensity across 50 villages of Samar Province, the Philippines. METHODS: This cross-sectional study was conducted in 25 rain-fed and 25 irrigated villages endemic for S. japonicum between August 2003 and November 2004. Villages were selected based on irrigation and farming criteria. A maximum of 35 eligible households were selected per village. Each participant was asked to provide stool samples on three consecutive days. All those who provided at least one stool sample were included in the analysis. A Bayesian three category outcome hierarchical cumulative logit regression model with adjustment for age, sex, occupation and measurement error of the Kato-Katz technique was used for analysis. RESULTS: A total of 1427 households and 6917 individuals agreed to participate in the study. A total of 5624 (81.3%) participants provided at least one stool sample. The prevalences of those lightly and at least moderately infected varied from 0% (95% Bayesian credible interval (BCI): 0%–3.1%) to 45.2% (95% BCI: 36.5%–53.9%) and 0% to 23.0% (95% BCI: 16.4%–31.2%) from village-to-village, respectively. Using the 0–7 year old group as a reference category, the highest odds ratio (OR) among males and females were that of being aged 17–40-year old (OR = 8.76; 95% BCI: 6.03–12.47) and 11–16-year old (OR = 8.59; 95% BCI: 4.74–14.28), respectively. People who did not work on a rice farm had a lower prevalence of infection than those working full time on a rice farm. The OR for irrigated villages compared to rain-fed villages was 1.41 (95% BCI: 0.50–3.21). DISCUSSION: We found very important village-to-village variation in prevalence of infection intensity. This variation is probably due to village-level variables other than that explained by a crude classification of villages into the irrigated and non-irrigated categories. We are planning to capture this spatial heterogeneity by updating our initial transmission dynamics model with the data reported here combined with 1-year post-treatment follow-up of study participants

Impacts of Sediments on Coral Energetics: Partitioning the Effects of Turbidity and Settling Particles

Sediment loads have long been known to be deleterious to corals, but the effects of turbidity and settling particles have not previously been partitioned. This study provides a novel approach using inert silicon carbide powder to partition and quantify the mechanical effects of sediment settling versus reduced light under a chronically high sedimentary regime on two turbid water corals commonly found in Singapore (Galaxea fascicularis and Goniopora somaliensis). Coral fragmentswere evenly distributed among three treatments: an open control (30% ambient PAR), a shaded control (15% ambient PAR) and sediment treatment (15% ambient PAR; 26.4 mg cm22 day21). The rate of photosynthesis and respiration, and the dark-adapted quantum yield were measured once a week for four weeks. By week four, the photosynthesis to respiration ratio (P/R ratio) and the photosynthetic yield (Fv/Fm) had fallen by 14% and 3–17% respectively in the shaded control,contrasting with corals exposed to sediments whose P/R ratio and yield had declined by 21% and 18–34% respectively. The differences in rates between the shaded control and the sediment treatment were attributed to the mechanical effects of sediment deposition. The physiological response to sediment stress differed between species with G. fascicularis experiencing a greater decline in the net photosynthetic yield (13%) than G. somaliensis (9.5%), but a smaller increase in the respiration rates (G. fascicularis = 9.9%, G. somaliensis = 14.2%). These different physiological responses were attributed, in part, to coral morphology and highlighted key physiological processes that drive species distribution along high to low turbidity and depositional gradients