An ultrasensitive reverse transcription polymerase chain reaction assay to detect asymptomatic low-density Plasmodium falciparum and Plasmodium vivax infections in small volume blood samples.

BackgroundHighly sensitive, scalable diagnostic methods are needed to guide malaria elimination interventions. While traditional microscopy and rapid diagnostic tests (RDTs) are suitable for the diagnosis of symptomatic malaria infection, more sensitive tests are needed to screen for low-density, asymptomatic infections that are targeted by interventions aiming to eliminate the entire reservoir of malaria infection in humans.MethodsA reverse transcription polymerase chain reaction (RT- PCR) was developed for multiplexed detection of the 18S ribosomal RNA gene and ribosomal RNA of Plasmodium falciparum and Plasmodium vivax. Simulated field samples stored for 14 days with sample preservation buffer were used to assess the analytical sensitivity and specificity. Additionally, 1750 field samples from Southeastern Myanmar were tested both by RDT and ultrasensitive RT-PCR.ResultsLimits of detection (LoD) were determined under simulated field conditions. When 0.3 mL blood samples were stored for 14 days at 28 °C and 80% humidity, the LoD was less than 16 parasites/mL for P. falciparum and 19.7 copies/µL for P. vivax (using a plasmid surrogate), about 10,000-fold lower than RDTs. Of the 1739 samples successfully evaluated by both ultrasensitive RT-PCR and RDT, only two were RDT positive while 24 were positive for P. falciparum, 108 were positive for P. vivax, and 127 were positive for either P. vivax and/or P. falciparum using ultrasensitive RT-PCR.ConclusionsThis ultrasensitive RT-PCR method is a robust, field-tested screening method that is vastly more sensitive than RDTs. Further optimization may result in a truly scalable tool suitable for widespread surveillance of low-level asymptomatic P. falciparum and P. vivax parasitaemia

Switching Mechanism in Single-Layer Molybdenum Disulfide Transistors: an Insight into Current Flow across Schottky Barriers

In this article, we study the properties of metal contacts to single-layer molybdenum disulfide (MoS2) crystals, revealing the nature of switching mechanism in MoS2 transistors. On investigating transistor behavior as contact length changes, we find that the contact resistivity for metal/MoS2 junctions is defined by contact area instead of contact width. The minimum gate dependent transfer length is ~0.63 {\mu}m in the on-state for metal (Ti) contacted single-layer MoS2. These results reveal that MoS2 transistors are Schottky barrier transistors, where the on/off states are switched by the tuning the Schottky barriers at contacts. The effective barrier heights for source and drain barriers are primarily controlled by gate and drain biases, respectively. We discuss the drain induced barrier narrowing effect for short channel devices, which may reduce the influence of large contact resistance for MoS2 Schottky barrier transistors at the channel length scaling limit.Comment: ACS Nano, ASAP (2013

Thermally driven spin injection from a ferromagnet into a non-magnetic metal

Creating, manipulating and detecting spin polarized carriers are the key elements of spin based electronics. Most practical devices use a perpendicular geometry in which the spin currents, describing the transport of spin angular momentum, are accompanied by charge currents. In recent years, new sources of pure spin currents, i.e., without charge currents, have been demonstrated and applied. In this paper, we demonstrate a conceptually new source of pure spin current driven by the flow of heat across a ferromagnetic/non-magnetic metal (FM/NM) interface. This spin current is generated because the Seebeck coefficient, which describes the generation of a voltage as a result of a temperature gradient, is spin dependent in a ferromagnet. For a detailed study of this new source of spins, it is measured in a non-local lateral geometry. We developed a 3D model that describes the heat, charge and spin transport in this geometry which allows us to quantify this process. We obtain a spin Seebeck coefficient for Permalloy of -3.8 microvolt/Kelvin demonstrating that thermally driven spin injection is a feasible alternative for electrical spin injection in, for example, spin transfer torque experiments

Field Application of a Subunit Vaccine against an Enteric Protozoan Disease

Background: Coccidiosis is a major global veterinary health problem in intensively reared chickens. It is caused by apicomplexan parasites of the genus Eimeria. Principal Findings: A subunit vaccine composed of purified antigens from the gametocytes of Eimeria maxima was used to stimulate the production and transfer of maternal antibodies between breeding hens and their hatchlings. The vaccine was injected into hens twice before they began laying eggs. Immunization had no adverse affects on egg laying or health of the hens and resulted in high antibody levels throughout the life of the hens. Progeny of immunized hens excreted significantly less oocysts of various species of Eimeria in their faeces than chicks from unvaccinated hens. Furthermore, the offspring of vaccinated hens developed stronger natural immunity to Eimeria, so that they were resistant to challenge infection even at 8 weeks of age, well after all maternal antibodies had left their circulation. Field trials were conducted in South Africa, Brazil and Thailand, involving at least 1 million progeny of vaccinated hens and at least 1 million positive control birds (raised on feed containing anticoccidial drugs or immunized with a live vaccine) in each country. Additionally, trials were carried out in Israel involving 60 million progeny of vaccinated hens and 112 million positive control birds. There were no significant differences in growth rate, feed conversion ratios or mortality in the offspring of vaccinated hens compared with the positive control chickens in any of these countries regardless of different management practices, different breeds of chickens or climate. Conclusions: These results demonstrate that a vaccine composed of antigens purified from the gametocytes of Eimeria can be used safely and effectively to prevent the deleterious effects of coccidiosis. It is the first subunit vaccine against any protozoan parasite to be successfully applied on a commercial scale. © 2008 Wallach et al

Understanding health and social challenges for aging and long-term care in China

The second King’s College London Symposium on Ageing and Long-term Care in China was convened from 4 to 5th July 2019 at King’s College London in London. The aim of the Symposium was to have a better understanding of health and social challenges for aging and long-term care in China. This symposium draws research insights from a wide range of disciplines, including economics, public policy, demography, gerontology, public health and sociology. A total of 20 participants from eight countries, seek to identify the key issues and research priorities in the area of aging and long-term care in China. The results published here are a synthesis of the top four research areas that represent the perspectives from some of the leading researchers in the field. © The Author(s) 2020

No Evidence of Association between HIV-1 and Malaria in Populations with Low HIV-1 Prevalence

The geographic overlap between HIV-1 and malaria has generated much interest in their potential interactions. A variety of studies have evidenced a complex HIV-malaria interaction within individuals and populations that may have dramatic effects, but the causes and implications of this co-infection at the population level are still unclear. In a previous publication, we showed that the prevalence of malaria caused by the parasite Plasmodium falciparum is associated with HIV infection in eastern sub-Saharan Africa. To complement our knowledge of the HIV-malaria co-infection, the objective of this work was to assess the relationship between malaria and HIV prevalence in the western region of sub-Saharan Africa.Population-based cross-sectional data were obtained from the HIV/AIDS Demographic and Health Surveys conducted in Burkina Faso, Ghana, Guinea, Mali, Liberia and Cameroon, and the malaria atlas project. Using generalized linear mixed models, we assessed the relationship between HIV-1 and Plasmodium falciparum parasite rate (PfPR) adjusting for important socio-economic and biological cofactors. We found no evidence that individuals living in areas with stable malaria transmission (PfPR>0.46) have higher odds of being HIV-positive than individuals who live in areas with PfPR≤0.46 in western sub-Saharan Africa (estimated odds ratio 1.14, 95% confidence interval 0.86-1.50). In contrast, the results suggested that PfPR was associated with being infected with HIV in Cameroon (estimated odds ratio 1.56, 95% confidence interval 1.23-2.00).Contrary to our previous research on eastern sub-Saharan Africa, this study did not identify an association between PfPR and infection with HIV in western sub-Saharan Africa, which suggests that malaria might not play an important role in the spread of HIV in populations where the HIV prevalence is low. Our work highlights the importance of understanding the epidemiologic effect of co-infection and the relevant factors involved in this relationship for the implementation of effective control strategies

Characterization of BNL and HPK AC-LGAD sensors with a 120 GeV proton beam

We present measurements of AC-LGADs performed at the Fermilab's test beam facility using 120 GeV protons. We studied the performance of various strip and pad AC-LGAD sensors that were produced by BNL and HPK. The measurements are performed with our upgraded test beam setup that utilizes a high precision telescope tracker, and a simultaneous readout of up to 7 channels per sensor, which allows detailed studies of signal sharing characteristics. These measurements allow us to assess the differences in designs between different manufacturers, and optimize them based on experimental performance. We then study several reconstruction algorithms to optimize position and time resolutions that utilize the signal sharing properties of each sensor. We present a world's first demonstration of silicon sensors in a test beam that simultaneously achieve better than 6-10 micron position and 30 ps time resolution. This represents a substantial improvement to the spatial resolution than would be obtained with binary readout of sensors with similar pitch

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

<div><p>Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway <i>i</i>.<i>e</i>., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3–38 times <i>vs</i>. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation.</p></div