The novel HLA-C*03:04:01:47 allele sequence identified using Pacific biosciences SMRT sequencing

A novel variant of HLA-C*03:04:01:47 was identified using Pacific Biosciences SMRT sequencing platform

Lessons learned from a subsidised spectacles scheme aiming to improve eye health in Aboriginal people in Victoria, Australia

The Victorian Aboriginal Spectacles Subsidy Scheme (VASSS) aimed to improve access to visual aids and eye care for Aboriginal and Torres Strait Islander Victorians. The VASSS started in July 2010 and has operated continually since. In 2016, we explored the collaborations, planning, adaptations and performance of the VASSS over the first 6 years by reviewing and analysing service data, as well as data from semistructured interviews, focus groups and surveys. An estimated 10 853 VASSS cofunded visual aids were delivered over 6 years, and the mean annual number of comprehensive eye examinations provided within services using VASSS grew 4.6-fold faster compared with the 4 years preceding the VASSS. We estimate that 16% and 19% of recipients presented with distance and near vision impairments respectively, all of which were corrected with visual aids. VASSS achievements were attained through collaborations, flexibility, trust and communication between organisations, all facilitated by funding resulting from evidence-based advocacy. Access to visual aids and eye examinations by Aboriginal Victorians has improved during the operation of the VASSS, with associated direct and indirect benefits to Aboriginal health, productivity and quality of life. The success of the VASSS may be replicable in other jurisdictions and provides lessons that may be applicable in other fields. What is known about the topic?: The 2009 National Indigenous Eye Health Survey estimated that the age-adjusted prevalence of vision impairment was 2.8-fold higher and the prevalence of blindness 6.2-fold higher among adult Aboriginal Australians compared with non-Aboriginal Australians, predominantly due to uncorrected refractive error and cataract. What does this paper add?: Implemented in 2010, the Victorian Aboriginal Spectacles Subsidy Scheme (VASSS) has been supported, designed and well received by stakeholders and, critically, the Aboriginal community. The VASSS has successfully improved access to comprehensive eye examinations and high-quality affordable visual aids (principally spectacles, with cost certainty). What are the implications for practitioners?: The VASSS demonstrates the power of collaborative partnerships and the potential for solutions targeted at specific components of a system to generate wider benefits, including the reduction of the prevalence and burden of vision impairment by correcting refractive error, managing vision-threatening eye disease and increasing awareness of eye health issues

A method for visualizing surface-exposed and internal PfEMP1 adhesion antigens in Plasmodium falciparum infected erythrocytes

<p>Abstract</p> <p>Background</p> <p>The insertion of parasite antigens into the host erythrocyte membrane and the structure and distribution of <it>Plasmodium falciparum </it>adhesion receptors on that membrane are poorly understood. Laser scanning confocal microscopy (LSCM) and a novel labelling and fixation method have been used to obtain high resolution immuno-fluorescent images of erythrocyte surface PfEMP1 and internal antigens which allow analysis of the accumulation of PfEMP1 on the erythrocyte membrane during asexual development.</p> <p>Methods</p> <p>A novel staining technique has been developed which permits distinction between erythrocyte surface PfEMP1 and intracellular PfEMP1, in parasites whose nuclear material is exceptionally well resolved. Primary antibody detection by fluorescence is carried out on the live parasitized erythrocyte. The surface labelled cells are then fixed using paraformaldehyde and permeabilized with a non-ionic detergent to permit access of antibodies to internal parasite antigens. Differentiation between surface and internal antigens is achieved using antibodies labelled with different fluorochromes and confocal microscopy</p> <p>Results</p> <p>Surface exposed PfEMP1 is first detectable by antibodies at the trophozoite stage of intracellular parasite development although the improved detection method indicates that there are differences between different laboratory isolates in the kinetics of accumulation of surface-exposed PfEMP1.</p> <p>Conclusion</p> <p>A sensitive method for labelling surface and internal PfEMP1 with up to three different fluorochromes has been developed for laser scanning confocal optical microscopy and the analysis of the developmental expression of malaria adhesion antigens.</p

The role of tool geometry in process damped milling

The complex interaction between machining structural systems and the cutting process results in machining instability, so called chatter. In some milling scenarios, process damping is a useful phenomenon that can be exploited to mitigate chatter and hence improve productivity. In the present study, experiments are performed to evaluate the performance of process damped milling considering different tool geometries (edge radius, rake and relief angles and variable helix/pitch). The results clearly indicate that variable helix/pitch angles most significantly increase process damping performance. Additionally, increased cutting edge radius moderately improves process damping performance, while rake and relief angles have a smaller and closely coupled effect

Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric aggregates

The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently attracted much attention since it has been associated with neurodegenerative conditions such as Alzheimer's and Parkinson's diseases. We provide a description of a sequence-indepedent mechanism by which polypeptide chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our results illustrate how the formation of ordered arrays of hydrogen bonds drives the formation of beta-sheets within the disordered oligomeric aggregates that form early under the effect of hydrophobic forces. Initially individual beta-sheets form with random orientations, which subsequently tend to align into protofilaments as their lengths increases. Our results suggest that amyloid aggregation represents an example of the Ostwald step rule of first order phase transitions by showing that ordered cross-beta structures emerge preferentially from disordered compact dynamical intermediate assemblies.Comment: 14 pages, 4 figure

Molecular phylogeny of Oreochromis (Cichlidae: Oreochromini) reveals mito-nuclear discordance and multiple colonisation of adverse aquatic environments

Although the majority of cichlid diversity occurs in the African Great Lakes, these fish have also diversified across the African continent. Such continental radiations, occurring in both rivers and lakes have received far less attention than lacustrine radiations despite some members, such as the oreochromine cichlids (commonly referred to as ‘tilapia’), having significant scientific and socioeconomic importance both within and beyond their native range. Unique among cichlids, several species of the genus Oreochromis exhibit adaptation to soda conditions (including tolerance of elevated temperatures and salinity), which are of interest from evolutionary biology research and aquaculture perspectives. Questions remain regarding the factors facilitating the diversification of this group, which to date have not been addressed within a phylogenetic framework. Here we present the first comprehensive (32/37 described species) multi-marker molecular phylogeny of Oreochromis and closely related Alcolapia, based on mitochondrial (1583 bp) and nuclear (3092 bp) sequence data. We show widespread discordance between nuclear DNA and mitochondrial DNA trees. This could be the result of incomplete lineage sorting and/or introgression in mitochondrial loci, although we didn’t find a strong signal for the latter. Based on our nuclear phylogeny we demonstrate that adaptation to adverse conditions (elevated salinity, temperature, or alkalinity) has occurred multiple times within Oreochromis, but that adaptation to extreme (soda) conditions (high salinity, temperature, and alkalinity) has likely arisen once in the lineage leading to O. amphimelas and Alcolapia. We also show Alcolapia is nested within Oreochromis, which is in agreement with previous studies, and here revise the taxonomy to synonymise the genus in Oreochromis, retaining the designation as subgenus Oreochromis (Alcolapia)

Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

Background: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. Methods: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. Results: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain. Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). Conclusion: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain

X-ray Absorption and Reflection in Active Galactic Nuclei

X-ray spectroscopy offers an opportunity to study the complex mixture of emitting and absorbing components in the circumnuclear regions of active galactic nuclei, and to learn about the accretion process that fuels AGN and the feedback of material to their host galaxies. We describe the spectral signatures that may be studied and review the X-ray spectra and spectral variability of active galaxies, concentrating on progress from recent Chandra, XMM-Newton and Suzaku data for local type 1 AGN. We describe the evidence for absorption covering a wide range of column densities, ionization and dynamics, and discuss the growing evidence for partial-covering absorption from data at energies > 10 keV. Such absorption can also explain the observed X-ray spectral curvature and variability in AGN at lower energies and is likely an important factor in shaping the observed properties of this class of source. Consideration of self-consistent models for local AGN indicates that X-ray spectra likely comprise a combination of absorption and reflection effects from material originating within a few light days of the black hole as well as on larger scales. It is likely that AGN X-ray spectra may be strongly affected by the presence of disk-wind outflows that are expected in systems with high accretion rates, and we describe models that attempt to predict the effects of radiative transfer through such winds, and discuss the prospects for new data to test and address these ideas.Comment: Accepted for publication in the Astronomy and Astrophysics Review. 58 pages, 9 figures. V2 has fixed an error in footnote

Darkness’s Descent on the American Anthropological Association: A Cautionary Tale

In September 2000, the self-styled “anthropological journalist” Patrick Tierney began to make public his work claiming that the Yanomamö people of South America had been actively—indeed brutally—harmed by the sociobiological anthropologist Napoleon Chagnon and the geneticist-physician James Neel. Following a florid summary of Tierney’s claims by the anthropologists Terence Turner and Leslie Sponsel, the American Anthropological Association (AAA) saw fit to take Tierney’s claims seriously by conducting a major investigation into the matter. This paper focuses on the AAA’s problematic actions in this case but also provides previously unpublished information on Tierney’s falsehoods. The work presented is based on a year of research by a historian of medicine and science. The author intends the work to function as a cautionary tale to scholarly associations, which have the challenging duty of protecting scholarship and scholars from baseless and sensationalistic charges in the era of the Internet and twenty-four-hour news cycles

Modelling and simulating change in reforesting mountain landscapes using a social-ecological framework

Natural reforestation of European mountain landscapes raises major environmental and societal issues. With local stakeholders in the Pyrenees National Park area (France), we studied agricultural landscape colonisation by ash (Fraxinus excelsior) to enlighten its impacts on biodiversity and other landscape functions of importance for the valley socio-economics. The study comprised an integrated assessment of land-use and land-cover change (LUCC) since the 1950s, and a scenario analysis of alternative future policy. We combined knowledge and methods from landscape ecology, land change and agricultural sciences, and a set of coordinated field studies to capture interactions and feedback in the local landscape/land-use system. Our results elicited the hierarchically-nested relationships between social and ecological processes. Agricultural change played a preeminent role in the spatial and temporal patterns of LUCC. Landscape colonisation by ash at the parcel level of organisation was merely controlled by grassland management, and in fact depended on the farmer's land management at the whole-farm level. LUCC patterns at the landscape level depended to a great extent on interactions between farm household behaviours and the spatial arrangement of landholdings within the landscape mosaic. Our results stressed the need to represent the local SES function at a fine scale to adequately capture scenarios of change in landscape functions. These findings orientated our modelling choices in the building an agent-based model for LUCC simulation (SMASH - Spatialized Multi-Agent System of landscape colonization by ASH). We discuss our method and results with reference to topical issues in interdisciplinary research into the sustainability of multifunctional landscapes