Loss of Müller's cells and photoreceptors in macular telangiectasia type 2

PURPOSE: To correlate postmortem histology from a patient with macular telangiectasia (MacTel) type 2 with previously recorded clinical imaging data. DESIGN: Observational clinicopathologic case report. METHODS: The distribution of retinal blood vessels was used to map the location of serial wax sections in color fundus and optical coherence tomography (OCT) images. Fluorescent immunohistochemistry was used to visualize markers for Müller's cells (vimentin and retinaldehyde-binding protein 1), photoreceptors (L-M opsin, rhodopsin, and cytochrome oxidase 2), and the outer limiting membrane (OLM) (zonula occludens 1 and occludin). MAIN OUTCOME MEASURES: Distribution of specific markers in immunohistochemistry on retinal sections through the fovea in relation to clinical data. RESULTS: The clinically recorded region of macular pigment loss in the macula correlated well with Müller's cell depletion. The OCT data showed a loss of the photoreceptor inner segment/outer segment (IS/OS) junction in the central retina, which correlated well with rod loss but not with cone loss. Markers for the OLM were lost where Müller's cells were lost. CONCLUSIONS: We have confirmed our previous finding of Müller's cell loss in MacTel type 2 and have shown that the area of Müller's cell loss matches the area of macular pigment depletion. In this patient, the IS/OS junction seen by OCT was absent in a region where rods were depleted but cones were still present

Target product profiles for protecting against outdoor malaria transmission.

BACKGROUND\ud \ud Long-lasting insecticidal nets (LLINs) and indoor residual sprays (IRS) have decimated malaria transmission by killing indoor-feeding mosquitoes. However, complete elimination of malaria transmission with these proven methods is confounded by vectors that evade pesticide contact by feeding outdoors.\ud \ud METHODS\ud \ud For any assumed level of indoor coverage and personal protective efficacy with insecticidal products, process-explicit malaria transmission models suggest that insecticides that repel mosquitoes will achieve less impact upon transmission than those that kill them outright. Here such models are extended to explore how outdoor use of products containing either contact toxins or spatial repellents might augment or attenuate impact of high indoor coverage of LLINs relying primarily upon contact toxicity.\ud \ud RESULTS\ud \ud LLIN impact could be dramatically enhanced by high coverage with spatial repellents conferring near-complete personal protection, but only if combined indoor use of both measures can be avoided where vectors persist that prefer feeding indoors upon humans. While very high levels of coverage and efficacy will be required for spatial repellents to substantially augment the impact of LLINs or IRS, these ambitious targets may well be at least as practically achievable as the lower requirements for equivalent impact using contact insecticides.\ud \ud CONCLUSIONS\ud \ud Vapour-phase repellents may be more acceptable, practical and effective than contact insecticides for preventing outdoor malaria transmission because they need not be applied to skin or clothing and may protect multiple occupants of spaces outside of treatable structures such as nets or houses

Techno-economic evaluation of reducing shielding gas consumption in GMAW whilst maintaining weld quality

A new method of supplying shielding gases in an alternating manner has been developed to enhance the efficiency of conventional gas metal arc welding (GMAW). However, the available literature on this advanced joining process is very sparse and no cost evaluation has been reported to date. In simple terms, the new method involves discretely supplying two different shielding gases to the weld pool at predetermined frequencies which creates a dynamic action within the liquid pool. In order to assess the potential benefits of this new method from a technical and cost perspective, a comparison has been drawn between the standard shielding gas composition of Ar/20%CO2, which is commonly used in UK and European shipbuilding industries for carbon steels, and a range of four different frequencies alternating between Ar/20%CO2 and helium. The beneficial effects of supplying the weld shielding gases in an alternating manner were found to provide attractive benefits for the manufacturing community. For example, the present study showed that compared with conventional GMAW, a 17 per cent reduction in total welding cost was achieved in the case of the alternating gas method and savings associated with a reduction in the extent of post-weld straightening following plate distortion were also identified. Also, the mechanical properties of the alternating case highlighted some marginal improvements in strength and Charpy impact toughness which were attributed to a more refined weld microstructure

Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.

OBJECTIVE: Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH). METHODS: Patients with CTD-PAH participating in the ARIES-1 and -2 clinical trials and their long-term extension were evaluated. Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening, and survival were collected at routine study visits. Additional analyses of 6MWD categorical (30 m) breakpoints were conducted to determine any relationship between 6MWD and a prognostic threshold for survival. RESULTS: 124 patients with CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At 3 years, 64% of patients were free from clinical worsening and 76% of patients were still alive (Kaplan-Meier estimates). Identified factors holding prognostic relevance for survival include: baseline functional class, CTD-PAH subgroup, patient sex, improvement in 6MWD ≥30 m over the first 12 weeks of treatment, the most recent 6MWD, and a 6MWD absolute threshold of 222 m. CONCLUSION: These first analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed fewer clinical worsening events and improved survival compared to historical controls. Key exercise parameters were also identified which appear important in guiding treatment

Comparing and Evaluating Real Time Character Engines for Virtual Environments

As animated characters increasingly become vital parts of virtual environments, then the engines that drive these characters increasingly become vital parts of virtual environment software. This paper gives an overview of the state of the art in character engines, and proposes a taxonomy of the features that are commonly found in them. This taxonomy can be used as a tool for comparison and evaluation of different engines. In order to demonstrate this we use it to compare three engines. The first is Cal3D, the most commonly used open source engine. We also introduce two engines created by the authors, Piavca and HALCA. The paper ends with a brief discussion of some other popular engines

Dielectric multilayer waveguides for TE and TM mode matching

We analyse theoretically for the first time to our knowledge the perfect phase matching of guided TE and TM modes with a multilayer waveguide composed of linear isotropic dielectric materials. Alongside strict investigation into dispersion relations for multilayer systems, we give an explicit qualitative explanation for the phenomenon of mode matching on the basis of the standard one-dimensional homogenization technique, and discuss the minimum number of layers and the refractive index profile for the proposed device scheme. Direct applications of the scheme include polarization-insensitive, intermodal dispersion-free planar propagation, efficient fibre-to-planar waveguide coupling and, potentially, mode filtering. As a self-sufficient result, we present compact analytical expressions for the mode dispersion in a finite, N-period, three-layer dielectric superlattice.Comment: 13 pages with figure

Standard and derived Planck quantities: selected analysis and derivations

We provide an overview of the fundamental units of physical quantities determined naturally by the values of fundamental constants of nature. We discuss a comparison between the 'Planck units', now widely used in theoretical physics and the pre-quantum 'Stoney units' in which, instead of the Planck constant, the charge of the electron is used with very similar quantitative results. We discuss some of the physical motivation for these special units, attributed much after they were introduced, and also put forth a summary of the arguments supporting various cases for making specific physical interpretations of the meanings of some of these units. The new aspects we discuss are a possible physical basis for the Stoney units, their link to the Planck units, and also the importance of Planck units for thermodynamical quantities in the context of quantum gravity.Comment: 22 pages, 1 tabl

The Influence of Physiological Status on age Prediction of Anopheles Arabiensis Using Near Infra-red spectroscopy

Determining the age of malaria vectors is essential for evaluating the impact of interventions that reduce the survival of wild mosquito populations and for estimating changes in vectorial capacity. Near infra-red spectroscopy (NIRS) is a simple and non-destructive method that has been used to determine the age and species of Anopheles gambiae s.l. by analyzing differences in absorption spectra. The spectra are affected by biochemical changes that occur during the life of a mosquito and could be influenced by senescence and also the life history of the mosquito, i.e., mating, blood feeding and egg-laying events. To better understand these changes, we evaluated the influence of mosquito physiological status on NIR energy absorption spectra. Mosquitoes were kept in individual cups to permit record keeping of each individual insect’s life history. Mosquitoes of the same chronological age, but at different physiological stages, were scanned and compared using cross-validations. We observed a slight trend within some physiological stages that suggest older insects tend to be predicted as being physiologically more mature. It was advantageous to include mosquitoes of different chronological ages and physiological stages in calibrations, as it increases the robustness of the model resulting in better age predictions. Progression through different physiological statuses of An. arabiensis influences the chronological age prediction by the NIRS. Entomologists that wish to use NIR technology to predict the age of field-caught An. gambiae s.l from their study area should use a calibration developed from their field strain using mosquitoes of diverse chronological ages and physiological stages to increase the robustness and accuracy of the predictions.\u

A study protocol of qualitative data sharing practices in clinical trials in the UK and Ireland: towards the production of good practice guidance [version 2; peer review: 2 approved]

BACKGROUND: Data sharing enables researchers to conduct novel research with previously collected data sets, thus maximising scientific findings and cost effectiveness, and reducing research waste. The value of sharing anonymised data from clinical trials is well recognised with a moderated access approach recommended. While substantial challenges to data sharing remain, there are additional challenges for qualitative data. Qualitative data including videos, interviews, and observations are often more readily identifiable than quantitative data. Existing guidance from UK Economic and Social Research Council applies to sharing qualitative data but does not address the additional challenges related to sharing qualitative data collected within trials, including the need to incorporate the necessary information and consent into already complex recruitment processes, with the additional sensitive nature of health-related data. METHODS: Work package 1 will involve separate focus group interviews with members of each stakeholder group: trial managers, clinical trialists, qualitative researchers, members of research funding bodies and trial participants who have been involved in qualitative research. Data will be analysed using thematic analysis and managed within QSR NVivo to enhance transparency. Work package 2 will involve a documentary analysis of current consent procedures for qualitative data collected as part of the conduct of clinical trials. We will include documents such as participant information leaflets and consent forms for the qualitative components in trials. We will extract data such as whether specific clauses for data sharing are included in the consent form. Content analysis will be used to analyse whether and how consent is being obtained for qualitative data sharing. CONCLUSIONS: This study will provide insight into the existing practice of sharing of qualitative data in clinical trials and the current issues and opportunities, to help shape future research and development of guidance to encourage maximum learning to be gained from this valuable dat