Reliable microsatellite genotyping of the Eurasian badger (Meles meles) using faecal DNA

The potential link between badgers and bovine tuberculosis has made it vital to develop accurate techniques to census badgers. Here we investigate the potential of using genetic profiles obtained from faecal DNA as a basis for population size estimation. After trialling several methods we obtained a high amplification success rate (89%) by storing faeces in 70% ethanol and using the guanidine thiocyanate/silica method for extraction. Using 70% ethanol as a storage agent had the advantage of it being an antiseptic. In order to obtain reliable genotypes with fewer amplification reactions than the standard multiple-tubes approach, we devised a comparative approach in which genetic profiles were compared and replication directed at similar, but not identical, genotypes. This modified method achieved a reduction in polymerase chain reactions comparable with the maximumlikelihood model when just using reliability criteria, and was slightly better when using reliability criteria with the additional proviso that alleles must be observed twice to be considered reliable. Our comparative approach would be best suited for studies that include multiple faeces from each individual. We utilized our approach in a well-studied population of badgers from which individuals had been sampled and reliable genotypes obtained. In a study of 53 faeces sampled from three social groups over 10 days, we found that direct enumeration could not be used to estimate population size, but that the application of mark–recapture models has the potential to provide more accurate results

Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies

<p>Abstract</p> <p>Background</p> <p>Osteoporosis-related fractures are a significant public health concern. Interventions that increase detection and treatment of osteoporosis, as well as prevention of fractures and falls, are substantially underutilized. This paper outlines the protocol for a pragmatic randomised trial of a multifaceted community-based care program aimed at optimizing the evidence-based management of falls and fractures in patients at risk.</p> <p>Design</p> <p>6-month randomised controlled study.</p> <p>Methods</p> <p>This population-based study was completed in the Algoma District of Ontario, Canada a geographically vast area with Sault Ste Marie (population 78 000) as its main city. Eligible patients were allocated to an immediate intervention protocol (IP) group, or a delayed intervention protocol (DP) group. The DP group received usual care for 6 months and then was crossed over to receive the interventions. Components of the intervention were directed at the physicians and their patients and included patient-specific recommendations for osteoporosis therapy as outlined by the clinical practice guidelines developed by Osteoporosis Canada, and falls risk assessment and treatment. Two primary outcomes were measured including implementation of appropriate osteoporosis and falls risk management. Secondary outcomes included quality of life and the number of falls, fractures, and hospital admissions over a twelve-month period. The patient is the unit of allocation and analysis. Analyses will be performed on an intention to treat basis.</p> <p>Discussion</p> <p>This paper outlines the protocol for a pragmatic randomised trial of a multi-faceted, community-based intervention to optimize the implementation of evidence based management for patients at risk for falls and osteoporosis.</p> <p>Trial Registration</p> <p>This trial has been registered with clinicaltrials.gov (ID: NCT00465387)</p

Site-specific perturbations of alpha-synuclein fibril structure by the Parkinson's disease associated mutations A53T and E46K.

PMCID: PMC3591419This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Parkinson's disease (PD) is pathologically characterized by the presence of Lewy bodies (LBs) in dopaminergic neurons of the substantia nigra. These intracellular inclusions are largely composed of misfolded α-synuclein (AS), a neuronal protein that is abundant in the vertebrate brain. Point mutations in AS are associated with rare, early-onset forms of PD, although aggregation of the wild-type (WT) protein is observed in the more common sporadic forms of the disease. Here, we employed multidimensional solid-state NMR experiments to assess A53T and E46K mutant fibrils, in comparison to our recent description of WT AS fibrils. We made de novo chemical shift assignments for the mutants, and used these chemical shifts to empirically determine secondary structures. We observe significant perturbations in secondary structure throughout the fibril core for the E46K fibril, while the A53T fibril exhibits more localized perturbations near the mutation site. Overall, these results demonstrate that the secondary structure of A53T has some small differences from the WT and the secondary structure of E46K has significant differences, which may alter the overall structural arrangement of the fibrils

Heterostructures produced from nanosheet-based inks.

The new paradigm of heterostructures based on two-dimensional (2D) atomic crystals has already led to the observation of exciting physical phenomena and creation of novel devices. The possibility of combining layers of different 2D materials in one stack allows unprecedented control over the electronic and optical properties of the resulting material. Still, the current method of mechanical transfer of individual 2D crystals, though allowing exceptional control over the quality of such structures and interfaces, is not scalable. Here we show that such heterostructures can be assembled from chemically exfoliated 2D crystals, allowing for low-cost and scalable methods to be used in device fabrication.This work was supported by The Royal Society, U.S. Army, European Science Foundation (ESF) under the EUROCORES Programme EuroGRAPHENE (GOSPEL), European Research Council, and EC under the Graphene Flagship (contract no. CNECT-ICT-604391). Y.-J.K.’s work was supported by the Global Research Laboratory (GRL) Program (2011-0021972) of the Ministry of Education, Science and Technology, Korea. F.W. acknowledges support from the Royal Academy of Engineering; A.F. is a FRS-FNRS Research Fellow

Correction: Internet Tool to Support Self-Assessment and Self-Swabbing of Sore Throat: Development and Feasibility Study.

[This corrects the article DOI: 10.2196/39791.]

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Large tunable valley splitting in edge-free graphene quantum dots on boron nitride

Coherent manipulation of binary degrees of freedom is at the heart of modern quantum technologies. Graphene offers two binary degrees: the electron spin and the valley. Efficient spin control has been demonstrated in many solid state systems, while exploitation of the valley has only recently been started, yet without control on the single electron level. Here, we show that van-der Waals stacking of graphene onto hexagonal boron nitride offers a natural platform for valley control. We use a graphene quantum dot induced by the tip of a scanning tunneling microscope and demonstrate valley splitting that is tunable from -5 to +10 meV (including valley inversion) by sub-10-nm displacements of the quantum dot position. This boosts the range of controlled valley splitting by about one order of magnitude. The tunable inversion of spin and valley states should enable coherent superposition of these degrees of freedom as a first step towards graphene-based qubits

Electron quantum metamaterials in van der Waals heterostructures

In recent decades, scientists have developed the means to engineer synthetic periodic arrays with feature sizes below the wavelength of light. When such features are appropriately structured, electromagnetic radiation can be manipulated in unusual ways, resulting in optical metamaterials whose function is directly controlled through nanoscale structure. Nature, too, has adopted such techniques -- for example in the unique coloring of butterfly wings -- to manipulate photons as they propagate through nanoscale periodic assemblies. In this Perspective, we highlight the intriguing potential of designer sub-electron wavelength (as well as wavelength-scale) structuring of electronic matter, which affords a new range of synthetic quantum metamaterials with unconventional responses. Driven by experimental developments in stacking atomically layered heterostructures -- e.g., mechanical pick-up/transfer assembly -- atomic scale registrations and structures can be readily tuned over distances smaller than characteristic electronic length-scales (such as electron wavelength, screening length, and electron mean free path). Yet electronic metamaterials promise far richer categories of behavior than those found in conventional optical metamaterial technologies. This is because unlike photons that scarcely interact with each other, electrons in subwavelength structured metamaterials are charged, and strongly interact. As a result, an enormous variety of emergent phenomena can be expected, and radically new classes of interacting quantum metamaterials designed

Effects of Acute Ethanol Administration on Neocortical Inhibition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65719/1/j.1530-0277.1986.tb05132.x.pd

Electronic properties of graphene encapsulated with different two-dimensional atomic crystals.

Hexagonal boron nitride is the only substrate that has so far allowed graphene devices exhibiting micrometer-scale ballistic transport. Can other atomically flat crystals be used as substrates for making quality graphene heterostructures? Here we report on our search for alternative substrates. The devices fabricated by encapsulating graphene with molybdenum or tungsten disulfides and hBN are found to exhibit consistently high carrier mobilities of about 60 000 cm(2) V(-1) s(-1). In contrast, encapsulation with atomically flat layered oxides such as mica, bismuth strontium calcium copper oxide, and vanadium pentoxide results in exceptionally low quality of graphene devices with mobilities of ∼1000 cm(2) V(-1) s(-1). We attribute the difference mainly to self-cleansing that takes place at interfaces between graphene, hBN, and transition metal dichalcogenides. Surface contamination assembles into large pockets allowing the rest of the interface to become atomically clean. The cleansing process does not occur for graphene on atomically flat oxide substrates.This work was supported by the European Research Council, Graphene Flagship, Engineering and Physical Sciences Research Council (UK), the Royal Society, US Office of Naval Research, US Air Force Office of Scientific Research, US Army Research Office