Addressing Barriers to the Development and Adoption of Rapid Diagnostic Tests in Global Health

Immunochromatographic rapid diagnostic tests (RDTs) have demonstrated significant potential for use as point-of-care diagnostic tests in resource-limited settings. Most notably, RDTs for malaria have reached an unparalleled level of technological maturity and market penetration, and are now considered an important complement to standard microscopic methods of malaria diagnosis. However, the technical development of RDTs for other infectious diseases, and their uptake within the global health community as a core diagnostic modality, has been hindered by a number of extant challenges. These range from technical and biological issues, such as the need for better affinity agents and biomarkers of disease, to social, infrastructural, regulatory and economic barriers, which have all served to slow their adoption and diminish their impact. In order for the immunochromatographic RDT format to be successfully adapted to other disease targets, to see widespread distribution, and to improve clinical outcomes for patients on a global scale, these challenges must be identified and addressed, and the global health community must be engaged in championing the broader use of RDTs

Development of the Maypole (Hoop/Column) deployable reflector concept for large space systems applications

The conceptual design, performance projections, and materials development for the maypole (hoop/column) reflector concept are summarized. Factors influencing configuration choices are discussed along with quad aperture/feed characteristics and antenna requirements based on missions

Negative refraction using Raman transitions and chirality

We present a scheme that achieves negative refraction with low absorption in far-off resonant atomic systems. The scheme utilizes Raman resonances and does not require the simultaneous presence of an electric-dipole transition and a magnetic-dipole transition near the same wavelength. We show that two interfering Raman transitions coupled to a magnetic-dipole transition can achieve a negative index of refraction with low absorption through magnetoelectric cross-coupling. We confirm the validity of the analytical results with exact numerical simulations of the density matrix. We also discuss possible experimental implementations of the scheme in rare-earth metal atomic systems. The concept of negative refraction, which was first predicted by Veselago [1] more than four decades ago, has recently emerged as a very exciting field of science. In his seminal paper, Veselago argued that materials with simultaneously negative permittivity and permeability would acquire a negative index of refraction, n < 0 [1]. These materials exhibit many seemingly strange properties such as the electromagnetic vectors forming a left-handed triad (hence the term left-handed materials) and the Poynting vector being antiparallel to the k vector. Although the interest in these materials remained only a scientific curiosity for a long time, it is now understood that negative refraction may have important and far-reaching practical consequences. The key potential application for these materials was discovered in the year 2000 when Pendry predicted that a slab with a negative index of refraction, known as a perfect lens, can image objects with, in principle, unlimited resolution Materials with a negative index of refraction do not exist naturally, and thus they need to be artificially constructed. One approach is to artificially engineer periodic metal-dielectric structures with appropriate electric and magnetic resonances. These structures, termed metamaterials, typically have a characteristic periodicity scale smaller than the wavelength so that a nearly uniform electromagnetic response is obtained. Initial experiments have demonstrated negative refraction in the microwave region of the spectrum using metamaterials constructed from metal wires and split-ring resonators In this paper, we focus on atomic systems that are driven with lasers in their internal states so that negative refraction for a weak probe wave is achieved. The key advantages of using driven atomic systems as opposed to metamaterials are (i) using interference principles, one can obtain a negative index of refraction with negligible absorption; (ii) atomic systems are uniquely suited for achieving negative refraction at shorter and shorter wavelengths, particularly in the visible and ultraviolet regions of the spectrum; (iii) since negative refraction is achieved through manipulation of internal states, the properties of the material can be dynamically modified, opening an array of exciting applications including perfectlens switches. Despite these advantages, achieving negative refraction in atomic systems is a very challenging problem that has not yet been experimentally demonstrated due to several difficulties. All recent proposals require a strong electricdipole transition and a strong magnetic-dipole transition at almost exactly the same wavelength. It is difficult to satisfy this condition in real atomic systems. Furthermore, achieving negative permittivity and permeability simultaneously requires atomic densities greater than 10 18 cm −3 , which is impractical. We have recently suggested an approach that overcomes some of these difficulties 053836-

Nutrient export to groundwater across a land use and historical climate gradient

Groundwater inputs to streams are important to intermittent stream function and can be a source of nutrients such as nitrogen and phosphorus. The amount of nutrients within groundwater are an important factor for downstream processes, including eutrophication far from the groundwater source. We asked whether land use and precipitation affect nutrient export patterns to groundwater. Soil samples were taken from sites across a variable precipitation gradient in Kansas with three land uses: agriculture, native prairie, and restored prairie. By analyzing the relative concentrations of nitrogen and phosphorus in the water after leaching the soil samples in mesocosms, we can tell how water quality is affected by land use and precipitation patterns, especially in intermittent streams

Abiotic and biotic context dependency of perennial crop yield

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Perennial crops in agricultural systems can increase sustainability and the magnitude of ecosystem services, but yield may depend upon biotic context, including soil mutualists, pathogens and cropping diversity. These biotic factors themselves may interact with abiotic factors such as drought. We tested whether perennial crop yield depended on soil microbes, water availability and crop diversity by testing monocultures and mixtures of three perennial crop species: a novel perennial grain (intermediate wheatgrass—Thinopyrum intermedium-- that produces the perennial grain Kernza®), a potential perennial oilseed crop (Silphium intregrifolium), and alfalfa (Medicago sativa). Perennial crop performance depended upon both water regime and the presence of living soil, most likely the arbuscular mycorrhizal (AM) fungi in the whole soil inoculum from a long term perennial monoculture and from an undisturbed native remnant prairie. Specifically, both Silphium and alfalfa strongly benefited from AM fungi. The presence of native prairie AM fungi had a greater benefit to Silphium in dry pots and alfalfa in wet pots than AM fungi present in the perennial monoculture soil. Kernza did not benefit from AM fungi. Crop mixtures that included Kernza overyielded, but overyielding depended upon inoculation. Specifically, mixtures with Kernza overyielded most strongly in sterile soil as Kernza compensated for poor growth of Silphium and alfalfa. This study identifies the importance of soil biota and the context dependence of benefits of native microbes and the overyielding of mixtures in perennial crops.Perennial Agricultural Project sponsored by the Malone Family Land Preservation FoundationNational Science Foundation (DEB-1556664, DEB- 1738041, OIA 1656006

Using Sensors and Generators of H2O2 to Elucidate the Toxicity Mechanism of Piperlongumine and Phenethyl Isothiocyanate

Aims: Chemotherapeutics target vital functions that ensure survival of cancer cells, including their increased reliance on defense mechanisms against oxidative stress compared to normal cells. Many chemotherapeutics exploit this vulnerability to oxidative stress by elevating the levels of intracellular reactive oxygen species (ROS). A quantitative understanding of the oxidants generated and how they induce toxicity will be important for effective implementation and design of future chemotherapeutics. Molecular tools that facilitate measurement and manipulation of individual chemical species within the context of the larger intracellular redox network present a means to develop this understanding. In this work, we demonstrate the use of such tools to elucidate the roles of H[subscript 2]O[subscript 2] and glutathione (GSH) in the toxicity mechanism of two ROS-based chemotherapeutics, piperlongumine and phenethyl isothiocyanate. Results: Depletion of GSH as a result of treatment with these compounds is not an important part of the toxicity mechanisms of these drugs and does not lead to an increase in the intracellular H[subscript 2]O[subscript 2] level. Measuring peroxiredoxin-2 (Prx-2) oxidation as evidence of increased H[subscript 2]O[subscript 2], only piperlongumine treatment shows elevation and it is GSH independent. Using a combination of a sensor (HyPer) along with a generator (D-amino acid oxidase) to monitor and mimic the drug-induced H[subscript 2O[subscript 2] production, it is determined that H[subscript 2]O[subscript 2] produced during piperlongumine treatment acts synergistically with the compound to cause enhanced cysteine oxidation and subsequent toxicity. The importance of H[subscript 2]O[subscript 2] elevation in the mechanism of piperlongumine promotes a hypothesis of why certain cells, such as A549, are more resistant to the drug than others. Innovation and Conclusion: The approach described herein sheds new light on the previously proposed mechanism of these two ROS-based chemotherapeutics and advocates for the use of both sensors and generators of specific oxidants to isolate their effects. Antioxid. Redox Signal. 24, 924–938.National Science Foundation (U.S.). Graduate Research Fellowship ProgramBurroughs Wellcome Fund (Career Award at the Scientific Interface

Evaluating the sensitivity of hybridization-based epigenotyping using a methyl binding domain protein

Hypermethylation of CpG islands in gene promoter regions has been shown to be a predictive biomarker for certain diseases. Most current methods for methylation profiling are not well-suited for clinical analysis. Here, we report the development of an inexpensive device and an epigenotyping assay with a format conducive to multiplexed analysis.David H. Koch Institute for Integrative Cancer Research at MIT (First-year Graduate Fellowship)National Science Foundation (U.S.). Graduate Research FellowshipBurroughs Wellcome Fund (Career Award at the Scientific Interface)National Institute of Environmental Health Sciences (Grant P30-ES002109)Massachusetts Institute of Technology. James H. Ferry Fund for Innovation in Research Educatio

Vibrational Enhancement of the Effective Donor - Acceptor Coupling

The paper deals with a simple three sites model for charge transfer phenomena in an one-dimensional donor (D) - bridge (B) - acceptor (A) system coupled with vibrational dynamics of the B site. It is found that in a certain range of parameters the vibrational coupling leads to an enhancement of the effective donor - acceptor electronic coupling as a result of the formation of the polaron on the B site. This enhancement of the charge transfer efficiency is maximum at the resonance, where the effective energy of the fluctuating B site coincides with the donor (acceptor) energy.Comment: 5 pages, 3 figure

Root pathogen diversity and composition varies with climate in undisturbed grasslands, but less so in anthropogenically disturbed grasslands

Soil-borne pathogens structure plant communities, shaping their diversity, and through these effects may mediate plant responses to climate change and disturbance. Little is known, however, about the environmental determinants of plant pathogen communities. Therefore, we explored the impact of climate gradients and anthropogenic disturbance on root-associated pathogens in grasslands. We examined the community structure of two pathogenic groups—fungal pathogens and oomycetes—in undisturbed and anthropogenically disturbed grasslands across a natural precipitation and temperature gradient in the Midwestern USA. In undisturbed grasslands, precipitation and temperature gradients were important predictors of pathogen community richness and composition. Oomycete richness increased with precipitation, while fungal pathogen richness depended on an interaction of precipitation and temperature, with precipitation increasing richness most with higher temperatures. Disturbance altered plant pathogen composition and precipitation and temperature had a reduced effect on pathogen richness and composition in disturbed grasslands. Because pathogens can mediate plant community diversity and structure, the sensitivity of pathogens to disturbance and climate suggests that degradation of the pathogen community may mediate loss, or limit restoration of, native plant diversity in disturbed grasslands, and may modify plant community response to climate change

"It was then that I thought 'whaat? This is not my Dad”: the implications of the ‘still the same person’ narrative for children and young people who have a parent with dementia

This research used auto/biographical interviews to explore the experiences of 19, 8 to 31 year olds who had a parent with dementia. Thematic analysis revealed challenges occasioned by the master narrative that people with dementia are ‘still’ the same person they were prior to the onset of their condition. While this notion is – rightly – at the heart of person-centered care in dementia services, the ‘still’ discourse conflicts with the experiences of young people. Their accounts suggest that the construction of their parent as the same person is not helpful and that, furthermore, expectations that they will behave and feel towards that parent as they did before are a source of distress in what is already a challenging situation. This paper highlights the need to equip young people with support that acknowledges that their parent may well be drastically different to the Mum or Dad they previously ‘knew