Paper-based microfluidics for DNA diagnostics of malaria in low resource underserved rural communities

Rapid, low-cost, species-specific diagnosis, based upon DNA testing, is becoming important in the treatment of patients with infectious diseases. Here, we demonstrate an innovation that uses origami to enable multiplexed, sensitive assays that rival polymerase chain reactions (PCR) laboratory assays and provide high-quality, fast precision diagnostics for malaria. The paper-based microfluidic technology proposed here combines vertical flow sample-processing steps, including paper folding for whole-blood sample preparation, with an isothermal amplification and a lateral flow detection, incorporating a simple visualization system. Studies were performed in village schools in Uganda with individual diagnoses being completed in <50 min (faster than the standard laboratory-based PCR). The tests, which enabled the diagnosis of malaria species in patients from a finger prick of whole blood, were both highly sensitive and specific, detecting malaria in 98% of infected individuals in a double-blind first-in-human study. Our method was more sensitive than other field-based, benchmark techniques, including optical microscopy and industry standard rapid immunodiagnostic tests, both performed by experienced local healthcare teams (which detected malaria in 86% and 83% of cases, respectively). All assays were independently validated using a real-time double-blinded reference PCR assay. We not only demonstrate that advanced, low-cost DNA-based sensors can be implemented in underserved communities at the point of need but also highlight the challenges associated with developing and implementing new diagnostic technologies in the field, without access to laboratories or infrastructure

Probing interactions in mesoscopic gold wires

We have measured in gold wires the energy exchange rate between quasiparticles, the phase coherence time of quasiparticles and the resistance vs. temperature, in order to probe the interaction processes which are relevant at low temperatures. We find that the energy exchange rate is higher than expected from the theory of electron-electron interactions, and that it has a different energy dependence. The dephasing time is constant at temperatures between 8 K and 0.5 K, and it increases below 0.5 K. The magnetoresistance is negative at large field scales, and the resistance decreases logarithmically with increasing temperatures, indicating the presence of magnetic impurities, probably Fe. Whereas resistivity and phase coherence measurements can be attributed to magnetic impurities, the question is raised whether these magnetic impurities could also mediate energy exchanges between quasiparticles.Comment: latex pothier.tex, 12 files, 15 pages in: Proceedings of the NATO Advanced Research Workshop on Size Dependent Magnetic Scattering, Pesc, Hungary, May 28 - June 1st, 2000 Chandrasekhar V., Van Haesendonck C. eds (Kluwer, 2001) [SPEC-S00/083

Primordial magnetic fields at preheating

Using lattice techniques we investigate the generation of long range cosmological magnetic fields during a cold electroweak transition. We will show how magnetic fields arise, during bubble collisions, in the form of magnetic strings. We conjecture that these magnetic strings originate from the alignment of magnetic dipoles associated with EW sphaleron-like configurations. We also discuss the early thermalisation of photons and the turbulent behaviour of the scalar fields after tachyonic preheating.Comment: 7 pages. Talk presented at Lattice200

The effect of arm training on thermoregulatory responses and calf volume during upper body exercise

The final publication is available at Springer via https://doi.org/10.1007/s00421-014-2842-9.PURPOSE: The smaller muscle mass of the upper body compared to the lower body may elicit a smaller thermoregulatory stimulus during exercise and thus produce novel training-induced thermoregulatory adaptations. Therefore, the principal aim of the study was to examine the effect of arm training on thermoregulatory responses during submaximal exercise. METHODS: Thirteen healthy male participants (Mean ± SD age 27.8 ± 5.0 years, body mass 74.8 ± 9.5 kg) took part in 8 weeks of arm crank ergometry training. Thermoregulatory and calf blood flow responses were measured during 30 min of arm cranking at 60% peak power (W peak) pre-, and post-training and post-training at the same absolute intensity as pre-training. Core temperature and skin temperatures were measured, along with heat flow at the calf, thigh, upper arm and chest. Calf blood flow using venous occlusion plethysmography was performed pre- and post-exercise and calf volume was determined during exercise. RESULTS: The upper body training reduced aural temperature (0.1 ± 0.3 °C) and heat storage (0.3 ± 0.2 J g(-1)) at a given power output as a result of increased whole body sweating and heat flow. Arm crank training produced a smaller change in calf volume post-training at the same absolute exercise intensity (-1.2 ± 0.8% compared to -2.2 ± 0.9% pre-training; P < 0.05) suggesting reduced leg vasoconstriction. CONCLUSION: Training improved the main markers of aerobic fitness. However, the results of this study suggest arm crank training additionally elicits physiological responses specific to the lower body which may aid thermoregulation.Peer reviewedFinal Accepted Versio

California Men's Health Study (CMHS): a multiethnic cohort in a managed care setting

BACKGROUND: We established a male, multiethnic cohort primarily to study prostate cancer etiology and secondarily to study the etiologies of other cancer and non-cancer conditions. METHODS/DESIGN: Eligible participants were 45-to-69 year old males who were members of a large, prepaid health plan in California. Participants completed two surveys on-line or on paper in 2002 – 2003. Survey content included demographics; family, medical, and cancer screening history; sexuality and sexual development; lifestyle (diet, physical activity, and smoking); prescription and non-prescription drugs; and herbal supplements. We linked study data with clinical data, including laboratory, hospitalization, and cancer data, from electronic health plan files. We recruited 84,170 participants, approximately 40% from minority populations and over 5,000 who identified themselves as other than heterosexual. We observed a wide range of education (53% completed less than college) and income. PSA testing rates (75% overall) were highest among black participants. Body mass index (BMI) (median 27.2) was highest for blacks and Latinos and lowest for Asians, and showed 80.6% agreement with BMI from clinical data sources. The sensitivity and specificity can be assessed by comparing self-reported data, such as PSA testing, diabetes, and history of cancer, to health plan data. We anticipate that nearly 1,500 prostate cancer diagnoses will occur within five years of cohort inception. DISCUSSION: A wide variety of epidemiologic, health services, and outcomes research utilizing a rich array of electronic, biological, and clinical resources is possible within this multiethnic cohort. The California Men's Health Study and other cohorts nested within comprehensive health delivery systems can make important contributions in the area of men's health

Clinical decision-making to facilitate appropriate patient management in chiropractic practice: 'the 3-questions model'

Background A definitive diagnosis in chiropractic clinical practice is frequently elusive, yet decisions around management are still necessary. Often, a clinical impression is made after the exclusion of serious illness or injury, and care provided within the context of diagnostic uncertainty. Rather than focussing on labelling the condition, the clinician may choose to develop a defendable management plan since the response to treatment often clarifies the diagnosis. Discussion This paper explores the concept and elements of defensive problem-solving practice, with a view to developing a model of agile, pragmatic decision-making amenable to real-world application. A theoretical framework that reflects the elements of this approach will be offered in order to validate the potential of a so called '3-Questions Model'; Summary Clinical decision-making is considered to be a key characteristic of any modern healthcare practitioner. It is, thus, prudent for chiropractors to re-visit the concept of defensible practice with a view to facilitate capable clinical decision-making and competent patient examination skills. In turn, the perception of competence and trustworthiness of chiropractors within the wider healthcare community helps integration of chiropractic services into broader healthcare settings

The effect of ambient temperature on gross-efficiency in cycling

Time-trial performance deteriorates in the heat. This might potentially be the result of a temperature-induced decrease in gross-efficiency (GE). The effect of high ambient temperature on GE during cycling will be studied, with the intent of determining if a heat-induced change in GE could account for the performance decrements in time trial exercise found in literature. Ten well-trained male cyclists performed 20-min cycle ergometer exercise at 60% \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$P_{V{\text{O}}_{{\text{2max}}} }$$\end{document} (power output at which VO2max was attained) in a thermo-neutral climate (N) of 15.6 ± 0.3°C, 20.0 ± 10.3% RH and a hot climate (H) of 35.5 ± 0.5°C, 15.5 ± 3.2% RH. GE was calculated based on VO2 and RER. Skin temperature (Tsk), rectal temperature (Tre) and muscle temperature (Tm) (only in H) were measured. GE was 0.9% lower in H compared to N (19.6 ± 1.1% vs. 20.5 ± 1.4%) (P < 0.05). Tsk (33.4 ± 0.6°C vs. 27.7 ± 0.7°C) and Tre (37.4 ± 0.6°C vs. 37.0 ± 0.6°C) were significantly higher in H. Tm was 38.7 ± 1.1°C in H. GE was lower in heat. Tm was not high enough to make mitochondrial leakage a likely explanation for the observed reduced GE. Neither was the increased Tre. Increased skin blood flow might have had a stealing effect on muscular blood flow, and thus impacted GE. Cycling model simulations showed, that the decrease in GE could account for half of the performance decrement. GE decreased in heat to a degree that could explain at least part of the well-established performance decrements in the heat

Vocal Communications and the Maintenance of Population Specific Songs in a Contact Zone

Bird song has been hypothesized to play a role in several important aspects of the biology of songbirds, including the generation of taxonomic diversity by speciation; however, the role that song plays in speciation within this group may be dependent upon the ability of populations to maintain population specific songs or calls in the face of gene flow and external cultural influences. Here, in an exploratory study, we construct a spatially explicit model of population movement to examine the consequences of secondary contact of populations singing distinct songs. We concentrate on two broad questions: 1) will population specific songs be maintained in a contact zone or will they be replaced by shared song, and 2) what spatial patterns in the distribution of songs may result from contact? We examine the effects of multiple factors including song-based mating preferences and movement probabilities, oblique versus paternal learning of song, and both cultural and genetic mutations. We find a variety of conditions under which population specific songs can be maintained, particularly when females have preferences for their population specific songs, and we document many distinct patterns of song distribution within the contact zone, including clines, banding, and mosaics

Chronic Nicotine Modifies Skeletal Muscle Na,K-ATPase Activity through Its Interaction with the Nicotinic Acetylcholine Receptor and Phospholemman

Our previous finding that the muscle nicotinic acetylcholine receptor (nAChR) and the Na,K-ATPase interact as a regulatory complex to modulate Na,K-ATPase activity suggested that chronic, circulating nicotine may alter this interaction, with long-term changes in the membrane potential. To test this hypothesis, we chronically exposed rats to nicotine delivered orally for 21–31 days. Chronic nicotine produced a steady membrane depolarization of ∼3 mV in the diaphragm muscle, which resulted from a net change in electrogenic transport by the Na,K-ATPase α2 and α1 isoforms. Electrogenic transport by the α2 isoform increased (+1.8 mV) while the activity of the α1 isoform decreased (−4.4 mV). Protein expression of Na,K-ATPase α1 or α2 isoforms and the nAChR did not change; however, the content of α2 subunit in the plasma membrane decreased by 25%, indicating that its stimulated electrogenic transport is due to an increase in specific activity. The physical association between the nAChR, the Na,K-ATPase α1 or α2 subunits, and the regulatory subunit of the Na,K-ATPase, phospholemman (PLM), measured by co-immuno precipitation, was stable and unchanged. Chronic nicotine treatment activated PKCα/β2 and PKCδ and was accompanied by parallel increases in PLM phosphorylation at Ser63 and Ser68. Collectively, these results demonstrate that nicotine at chronic doses, acting through the nAChR-Na,K-ATPase complex, is able to modulate Na,K-ATPase activity in an isoform-specific manner and that the regulatory range includes both stimulation and inhibition of enzyme activity. Cholinergic modulation of Na,K-ATPase activity is achieved, in part, through activation of PKC and phosphorylation of PLM