Population genetic structure of serotine bats (Eptesicus serotinus) across Europe and implications for the potential spread of bat rabies (European bat lyssavirus EBLV-1)

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.Understanding of the movements of species at multiple scales is essential to appreciate patterns of population connectivity and in some cases, the potential for pathogen transmission. The serotine bat (Eptesicus serotinus) is a common and widely distributed species in Europe where it frequently harbours European bat lyssavirus type 1 (EBLV-1), a virus causing rabies and transmissible to humans. In the United Kingdom, it is rare, with a distribution restricted to south of the country and so far the virus has never been found there. We investigated the genetic structure and gene flow of E. serotinus across the England and continental Europe. Greater genetic structuring was found in England compared with continental Europe. Nuclear data suggest a single population on the continent, although further work with more intensive sampling is required to confirm this, while mitochondrial sequences indicate an east-west substructure. In contrast, three distinct populations were found in England using microsatellite markers, and mitochondrial diversity was very low. Evidence of nuclear admixture indicated strong male-mediated gene flow among populations. Differences in connectivity could contribute to the high viral prevalence on the continent in contrast with the United Kingdom. Although the English Channel was previously thought to restrict gene flow, our data indicate relatively frequent movement from the continent to England highlighting the potential for movement of EBLV-1 into the United Kingdom.We acknowledge DEFRA and University of Exeter for funding this stud

Combinatorial RNA Design: Designability and Structure-Approximating Algorithm

In this work, we consider the Combinatorial RNA Design problem, a minimal instance of the RNA design problem which aims at finding a sequence that admits a given target as its unique base pair maximizing structure. We provide complete characterizations for the structures that can be designed using restricted alphabets. Under a classic four-letter alphabet, we provide a complete characterization of designable structures without unpaired bases. When unpaired bases are allowed, we provide partial characterizations for classes of designable/undesignable structures, and show that the class of designable structures is closed under the stutter operation. Membership of a given structure to any of the classes can be tested in linear time and, for positive instances, a solution can be found in linear time. Finally, we consider a structure-approximating version of the problem that allows to extend bands (helices) and, assuming that the input structure avoids two motifs, we provide a linear-time algorithm that produces a designable structure with at most twice more base pairs than the input structure.Comment: CPM - 26th Annual Symposium on Combinatorial Pattern Matching, Jun 2015, Ischia Island, Italy. LNCS, 201

Designing a package of sexual and reproductive health and HIV outreach services to meet the heterogeneous preferences of young people in Malawi: results from a discrete choice experiment.

BACKGROUND: This article examines young people's preferences for integrated family planning (FP) and HIV services in rural Malawi. Different hypothetical configurations for outreach services are presented using a Discrete Choice Experiment (DCE). Responses are analysed using Random Parameters Logit and Generalised Mixed Logit (GMXL) models in preference space and a GMXL model parameterised in willingness-to-pay space. Simulations are used to estimate the proportion of respondents expected to choose different service packages as elements are varied individually and in combination. RESULTS: Responses were collected from 537 young people aged 15-24. Results show that when considering attending an outreach service to access family planning young people value confidentiality and the availability of HIV services including HIV counselling and testing (HCT) and HIV treatment, though significant observable and unobservable heterogeneity is present. Female respondents and those aged 20-24 were less concerned with service confidentiality compared to male respondents and those aged 15-19; respondents who were in a relationship at the time of the survey valued confidentiality more than those who reported being single. The addition of sports and recreation for young people may also be an attractive feature of a youth-friendly service; however, preferences for this attribute vary according to respondent gender. Results of the simulation modelling indicate that the most preferred service package is one that offers confidential services, both HCT and HIV treatment and sports for youth, with up to 32% of respondents expected to choose this service over a service where clients may have concerns over confidentiality, only HCT is available and there are no additional activities for young people. Estimates of willingness-to-pay for service attributes indicate that respondents were willing to pay up to USD$1.76 for confidentiality, USD$0.65 for a service offering both HCT and HIV treatment and USD$0.26 for a service including sports for youth. CONCLUSIONS: Young people were able to complete a complex DCE and appeared to trade between the different characteristics used to describe the outreach services. These findings may offer important insight to policy makers designing youth friendly SRH outreach services and providers aiming to improve the acceptability and uptake of FP services

Imaging glial activation in patients with post-treatment Lyme disease symptoms: A pilot study using [ ¹¹ C]DPA-713 PET

The pathophysiology of post-treatment Lyme disease syndrome (PTLDS) may be linked to overactive immunity including aberrant activity of the brain's resident immune cells, microglia. Here we used [ 11 C]DPA-713 and positron emission tomography to quantify the 18 kDa translocator protein, a marker of activated microglia or reactive astrocytes, in the brains of patients with post-treatment Lyme disease symptoms of any duration compared to healthy controls. Genotyping for the TSPO rs6971 polymorphism was completed, and individuals with the rare, low affinity binding genotype were excluded. Data from eight brain regions demonstrated higher [ 11 C]DPA-713 binding in 12 patients relative to 19 controls. [ 11 C]DPA-713 PET is a promising tool to study cerebral glial activation in PTLDS and its link to cognitive symptoms

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Varus distal femoral osteotomy in young adults with valgus knee

<p>Abstract</p> <p>Background</p> <p>Musculoskeletal disorders specially knee osteoarthritis are the most common causes of morbidity in old patients. Disturbance of the mechanical axis of the lower extremity is one of the most important causes in progression of knee osteoarthritis. The purpose of the present study was to analyze the surgical results of distal femoral varus osteotomy in patients with genu valgum.</p> <p>Methods</p> <p>In this study, after recording history and physical examination, appropriate radiographs were taken. We did varus distal femoral osteotomy by standard medial subvastus approach and 90-angle blade plate fixation then followed the patients clinically and radiographically.</p> <p>Results</p> <p>This study was done on 23 knees (16 patients) age 23.3 years (range, 17 to 41 years). The mean duration of following up was 16.3 months (range, 8 to 25 months). Based on paired T test, there were statistically significant difference between pre- and postoperative tibiofemoral and congruence angles (p < 0.001, t = 21.3 and p < 0.001, t = 10.1 respectively). Pearson correlation between the amount of tibiofemoral and congruence angle correction was also statistically significant (p = 0.02 and r = 0.46).</p> <p>Conclusion</p> <p>Distal femoral varus osteotomy with blade plate fixation can be a reliable procedure for the treatment of valgus knee deformity. In this procedure, with more tibiofemoral angle correction, more congruence angle correction can be achieved. Therefore, along with genu valgum correction, the patella should be stabilized simultaneously.</p

Quantification and analysis of icebergs in a tidewater glacier fjord using an object-based approach

Tidewater glaciers are glaciers that terminate in, and calve icebergs into, the ocean. In addition to the influence that tidewater glaciers have on physical and chemical oceanography, floating icebergs serve as habitat for marine animals such as harbor seals (Phoca vitulina richardii). The availability and spatial distribution of glacier ice in the fjords is likely a key environmental variable that influences the abundance and distribution of selected marine mammals; however, the amount of ice and the fine-scale characteristics of ice in fjords have not been systematically quantified. Given the predicted changes in glacier habitat, there is a need for the development of methods that could be broadly applied to quantify changes in available ice habitat in tidewater glacier fjords. We present a case study to describe a novel method that uses object-based image analysis (OBIA) to classify floating glacier ice in a tidewater glacier fjord from high-resolution aerial digital imagery. Our objectives were to (i) develop workflows and rule sets to classify high spatial resolution airborne imagery of floating glacier ice; (ii) quantify the amount and fine-scale characteristics of floating glacier ice; (iii) and develop processes for automating the object-based analysis of floating glacier ice for large number of images from a representative survey day during June 2007 in Johns Hopkins Inlet (JHI), a tidewater glacier fjord in Glacier Bay National Park, southeastern Alaska. On 18 June 2007, JHI was comprised of brash ice ([Formula: see text] = 45.2%, SD = 41.5%), water ([Formula: see text] = 52.7%, SD = 42.3%), and icebergs ([Formula: see text] = 2.1%, SD = 1.4%). Average iceberg size per scene was 5.7 m2 (SD = 2.6 m2). We estimate the total area (± uncertainty) of iceberg habitat in the fjord to be 455,400 ± 123,000 m2. The method works well for classifying icebergs across scenes (classification accuracy of 75.6%); the largest classification errors occur in areas with densely-packed ice, low contrast between neighboring ice cover, or dark or sediment-covered ice, where icebergs may be misclassified as brash ice about 20% of the time. OBIA is a powerful image classification tool, and the method we present could be adapted and applied to other ice habitats, such as sea ice, to assess changes in ice characteristics and availability

ViennaRNA Package 2.0

<p>Abstract</p> <p>Background</p> <p>Secondary structure forms an important intermediate level of description of nucleic acids that encapsulates the dominating part of the folding energy, is often well conserved in evolution, and is routinely used as a basis to explain experimental findings. Based on carefully measured thermodynamic parameters, exact dynamic programming algorithms can be used to compute ground states, base pairing probabilities, as well as thermodynamic properties.</p> <p>Results</p> <p>The <monospace>ViennaRNA</monospace> Package has been a widely used compilation of RNA secondary structure related computer programs for nearly two decades. Major changes in the structure of the standard energy model, the <it>Turner 2004 </it>parameters, the pervasive use of multi-core CPUs, and an increasing number of algorithmic variants prompted a major technical overhaul of both the underlying <monospace>RNAlib</monospace> and the interactive user programs. New features include an expanded repertoire of tools to assess RNA-RNA interactions and restricted ensembles of structures, additional output information such as <it>centroid </it>structures and <it>maximum expected accuracy </it>structures derived from base pairing probabilities, or <it>z</it>-<it>scores </it>for locally stable secondary structures, and support for input in <monospace>fasta</monospace> format. Updates were implemented without compromising the computational efficiency of the core algorithms and ensuring compatibility with earlier versions.</p> <p>Conclusions</p> <p>The <monospace>ViennaRNA Package 2.0</monospace>, supporting concurrent computations <monospace>via OpenMP</monospace>, can be downloaded from <url>http://www.tbi.univie.ac.at/RNA</url>.</p

Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1

Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune activation. Defensins are also important for wound healing and anti-microbial activities. Therefore, we tested whether sNAG nanofibers induce defensin expression resulting in bacterial clearance.The role of sNAG in defensin expression was examined using immunofluoresence microscopy, pharmacological inhibition, and shRNA knockdown in vitro. The ability of sNAG treatment to induce defensin expression and bacterial clearance in WT and AKT1-/- mice was carried out using immunofluoresent microscopy and tissue gram staining. Neutralization, using an antibody directed against β-defensin 3, was utilized to determine if the antimicrobial properties of sNAG are dependent on the induction of defensin expression.sNAG treatment causes increased expression of both α- and β-type defensins in endothelial cells and β-type defensins in keratinocytes. Pharmacological inhibition and shRNA knockdown implicates Akt1 in sNAG-dependent defensin expression in vitro, an activity also shown in an in vivo wound healing model. Importantly, sNAG treatment results in increased kinetics of wound closure in wild type animals. sNAG treatment decreases bacterial infection of cutaneous wounds infected with Staphylococcus aureus in wild type control animals but not in similarly treated Akt1 null animals. Furthermore, sNAG treatment of S. aureus infected wounds show an increased expression of β-defensin 3 which is required for sNAG-dependent bacterial clearance. Our findings suggest that Akt1 is involved in the regulation of defensin expression and the innate immune response important for bacterial clearance. Moreover, these findings support the use of sNAG nanofibers as a novel method for enhancing wound closure while simultaneously decreasing wound infection