Thick blood film examination for Plasmodium falciparum malaria has reduced sensitivity and underestimates parasite density

BACKGROUND: Thick blood films are routinely used to diagnose Plasmodium falciparum malaria. Here, they were used to diagnose volunteers exposed to experimental malaria challenge. METHODS: The frequency with which blood films were positive at given parasite densities measured by PCR were analysed. The poisson distribution was used to calculate the theoretical likelihood of diagnosis. Further in vitro studies used serial dilutions to prepare thick films from malaria cultures at known parasitaemia. RESULTS: Even in expert hands, thick blood films were considerably less sensitive than might have been expected from the parasite numbers measured by quantitative PCR. In vitro work showed that thick films prepared from malaria cultures at known parasitaemia consistently underestimated parasite densities. CONCLUSION: It appears large numbers of parasites are lost during staining. This limits their sensitivity, and leads to erroneous estimates of parasite density

Fluorescence-based nano-oxygen particles for spatiometric monitoring of cell physiological conditions

Closed-loop artificial pancreas systems have recently been proposed as a solution for treating stage I diabetes by reproducing the function of the pancreas. However, there are many unresolved issues associated with their development, including monitoring and controlling oxygen, immune responses and the optimization of glucose. All of which need to be monitored and controlled to produce an efficient and viable artificial organ, that can become integrated in the patient and maintain homeostasis. This research focused on monitoring oxygen concentration, specifically achieving this kinetically as the oxygen gradient in an artificial pancreas made of alginate spheres containing islet cells. Functional Nanoparticle (NP) for measuring the oxygen gradient in different hydrogel cellular environments using fluorescence-based (F) microscopy were developed and tested. By ester bond, a linker Pluronic F127 was conjugated with a carboxylic acid modified polystyrene Nanoparticle (510 nm). A hydrophilic/ hydrophobic interaction between the commercially available oxygen sensitive fluorophore with F127 results in Fluorescence-based Nano oxygen particle (FNOP). The in-house synthesized FNOP was calibrated inside electro sprayed alginate filled hydrogels and demonstrated a good broad Dynamic Range (2.73-22.23) mg/L as well as a Resolution of -0.01 mg/L with an accuracy of ± 4%. The calibrated FNOP was utilised for continuous measuring of oxygen concentration gradient for cell lines RIN-m5F / HeLa for more than five days in alginate hydrogel spheres in vitro

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

Numerical study on load-bearing capabilities of beam-like lattice structures with three different unit cells

The design and analysis of lattice structures manufactured using Additive Manufacturing (AM) technique is a new approach to create lightweight high-strength components. However, it is difficult for engineers to choose the proper unit cell for a certain function structure and loading case. In this paper, three beam-like lattice structures with triangular prism, square prism and hexagonal prism were designed, manufactured by SLM process using AlSi10Mg and tested. The mechanical performances of lattice structures with equal relative density, equal base area and height, and equal length for all unit cells were conducted by Finite Element Analysis (FEA). It was found that effective Young’s modulus is proportional to relative density, but with different affecting levels. When the lattice structures are designed with the same relative density or the same side lengths, the effective Young’s modulus of lattice structure with triangular prism exhibits the maximum value for both cases. When the lattice structures are designed with the same base areas for all unit cells, the effective Young’s modulus of lattice structures with square prism presents the maximum. FEA results also show that the maximum stress of lattice structures with triangular prisms in each comparison is at the lowest level and the stiffness-to-mass ratio remains at the maximum value, showing the overwhelming advantages in terms of mechanical strength. The excellent agreements between numerical results and experimental tests reveal the validity of FEA methods applied. The results in this work provide an explicit guideline to fabricate beam-like lattice structures with the best tensile and bending capabilities

A knowledge management tool for public health: health-evidence.ca

<p>Abstract</p> <p>Background</p> <p>The ultimate goal of knowledge translation and exchange (KTE) activities is to facilitate incorporation of research knowledge into program and policy development decision making. Evidence-informed decision making involves translation of the best available evidence from a systematically collected, appraised, and analyzed body of knowledge. Knowledge management (KM) is emerging as a key factor contributing to the realization of evidence-informed public health decision making. The goal of health-evidence.ca is to promote evidence-informed public health decision making through facilitation of decision maker access to, retrieval, and use of the best available synthesized research evidence evaluating the effectiveness of public health interventions.</p> <p>Methods</p> <p>The systematic reviews that populate health evidence.ca are identified through an extensive search (1985-present) of 7 electronic databases: MEDLINE, EMBASE, CINAHL, PsycINFO, Sociological Abstracts, BIOSIS, and SportDiscus; handsearching of over 20 journals; and reference list searches of all relevant reviews. Reviews are assessed for relevance and quality by two independent reviewers. Commonly-used public health terms are used to assign key words to each review, and project staff members compose short summaries highlighting results and implications for policy and practice.</p> <p>Results</p> <p>As of June 2010, there are 1913 reviews in the health-evidence.ca registry in 21 public health and health promotion topic areas. Of these, 78% have been assessed as being of strong or moderate methodological quality. Health-evidence.ca receives approximately 35,000 visits per year, 20,596 of which are unique visitors, representing approximately 100 visits per day. Just under half of all visitors return to the site, with the average user spending six minutes and visiting seven pages per visit. Public health nurses, program managers, health promotion workers, researchers, and program coordinators are among the largest groups of registered users, followed by librarians, dieticians, medical officers of health, and nutritionists. The majority of users (67%) access the website from direct traffic (e.g., have the health-evidence.ca webpage bookmarked, or type it directly into their browser).</p> <p>Conclusions</p> <p>Consistent use of health-evidence.ca and particularly the searching for reviews that correspond with current public health priorities illustrates that health-evidence.ca may be playing an important role in achieving evidence-informed public health decision making.</p

Celastrol inhibits aminoglycoside-induced ototoxicity via heat shock protein 32

Hearing loss is often caused by death of the mechanosensory hair cells of the inner ear. Hair cells are susceptible to death caused by aging, noise trauma, and ototoxic drugs, including the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Ototoxic drugs result in permanent hearing loss for over 500 000 Americans annually. We showed previously that induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. In order to begin to translate these findings into a clinical therapy aimed at inhibiting ototoxic drug-induced hearing loss, we have now examined a pharmacological HSP inducer, celastrol. Celastrol induced upregulation of HSPs in utricles, and it provided significant protection against aminoglycoside-induced hair cell death in vitro and in vivo. Moreover, celastrol inhibited hearing loss in mice receiving systemic aminoglycoside treatment. Our data indicate that the major heat shock transcription factor HSF-1 is not required for celastrol-mediated protection. HSP32 (also called heme oxygenase-1, HO-1) is the primary mediator of the protective effect of celastrol. HSP32/HO-1 inhibits pro-apoptotic c-Jun N-terminal kinase (JNK) activation and hair cell death. Taken together, our data indicate that celastrol inhibits aminoglycoside ototoxicity via HSP32/HO-1 induction

Financial wellbeing of Asian Americans

The Asian American population in the United States has been increasing. Research on the economic wellbeing of this minority group is far from being adequate. It is generally found that Asian Americans are more highly educated and have more wealth. Although the homeownership rate of this population is lower than the national average rate, the gap is gradually narrowing. Asian Americans are found to have more confidence in their financial future and have better management in their financial lives. In addition, Asian-owned businesses have been an important part of the U.S. economy and, as such, the self-employment status of Asian Americans has stimulated great interest for research. Large differences in financial behaviors exist among different groups in Asian Americans. This chapter serves the purpose to summarize past research on Asian American consumer finances and provide directions for future research.Includes bibliographical references

Inversion of the balance between hydrophobic and hydrogen bonding interactions in protein folding and aggregation.

Identifying the forces that drive proteins to misfold and aggregate, rather than to fold into their functional states, is fundamental to our understanding of living systems and to our ability to combat protein deposition disorders such as Alzheimer's disease and the spongiform encephalopathies. We report here the finding that the balance between hydrophobic and hydrogen bonding interactions is different for proteins in the processes of folding to their native states and misfolding to the alternative amyloid structures. We find that the minima of the protein free energy landscape for folding and misfolding tend to be respectively dominated by hydrophobic and by hydrogen bonding interactions. These results characterise the nature of the interactions that determine the competition between folding and misfolding of proteins by revealing that the stability of native proteins is primarily determined by hydrophobic interactions between side-chains, while the stability of amyloid fibrils depends more on backbone intermolecular hydrogen bonding interactions

Polymorphism in a lincRNA Associates with a Doubled Risk of Pneumococcal Bacteremia in Kenyan Children.

Bacteremia (bacterial bloodstream infection) is a major cause of illness and death in sub-Saharan Africa but little is known about the role of human genetics in susceptibility. We conducted a genome-wide association study of bacteremia susceptibility in more than 5,000 Kenyan children as part of the Wellcome Trust Case Control Consortium 2 (WTCCC2). Both the blood-culture-proven bacteremia case subjects and healthy infants as controls were recruited from Kilifi, on the east coast of Kenya. Streptococcus pneumoniae is the most common cause of bacteremia in Kilifi and was thus the focus of this study. We identified an association between polymorphisms in a long intergenic non-coding RNA (lincRNA) gene (AC011288.2) and pneumococcal bacteremia and replicated the results in the same population (p combined = 1.69 × 10(-9); OR = 2.47, 95% CI = 1.84-3.31). The susceptibility allele is African specific, derived rather than ancestral, and occurs at low frequency (2.7% in control subjects and 6.4% in case subjects). Our further studies showed AC011288.2 expression only in neutrophils, a cell type that is known to play a major role in pneumococcal clearance. Identification of this novel association will further focus research on the role of lincRNAs in human infectious disease.Wellcome Trust (Grant ID: 084716/Z/08/Z)This is the final version of the article. It first appeared from Cell Press/Elsevier via http://dx.doi.org/10.1016/j.ajhg.2016.03.02