Medical management of diabetic retinopathy:fenofibrate and ACCORD eye studies

The approach of all ophthalmologists, diabetologists and general practitioners seeing patients with diabetic retinopathy should be that good control of blood glucose, blood pressure and plasma lipids are all essential components of modern medical management. The more recent data on the use of fenofibrate in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) and The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye studies is reviewed. In FIELD, fenofibrate (200 mg/day) reduced the requirements for laser therapy and prevented disease progression in patients with pre-existing diabetic retinopathy. In ACCORD Eye, fenofibrate (160 mg daily) with simvastatin resulted in a 40% reduction in the odds of retinopathy progressing over 4 years, compared with simvastatin alone. This occurred with an increase in HDL-cholesterol and a decrease in the serum triglyceride level in the fenofibrate group, as compared with the placebo group, and was independent of glycaemic control. We believe fenofibrate is effective in preventing progression of established diabetic retinopathy in type 2 diabetes and should be considered for patients with pre-proliferative diabetic retinopathy and/or diabetic maculopathy, particularly in those with macular oedema requiring laser. © 2011 Macmillan Publishers Limited All rights reserved.

Rib-cage-movement measurements as a potential new trigger signal in non-invasive mechanical ventilation

Non-invasive ventilation performed through an oronasal mask is a standard in clinical and homecare mechanical ventilation. Besides all its advantages, inevitable leaks through the mask cause errors in the feedback information provided by the airflow sensor and, hence, patient-ventilator asynchrony with multiple negative consequences. Here we investigate a new way to provide a trigger to the ventilator. The method is based on the measurement of rib cage movement at the onset of inspiration and during breathing by fibre-optic sensors. In a series of simultaneous measurements by a long-period fibre grating sensor and pneumotachograph we provide the statistical evidence of the 200 ms lag of the pneumo with respect the fibre-optic signal. The lag is registered consistently across three independent delay metrics. Further, we discuss exceptions from this trend and identify the needed improvements to the proposed fibre-sensing scheme.

Student Independent Projects Environmental Studies 2011: A Values Profile for a Healthy, Sustainable Corner Brook Community

We now live in a world where urbanization has become the norm. Approximately half the world now lives in cities(O'brien, 2008). In recent years for a province like Newfoundland and Labrador which has relied heavily on one industry, the fishery, this statistic holds a lot of meaning. For well over a century there has been a continuing movement from Newfoundland to other parts of Canada and the US. Between 1971 and 1998 alone, net out-migration amounted 20% of the provinces population. This exodus has become a significant part of Newfoundland culture (Bowering Delisle, 2008). Communities have declining populations because families can no longer afford to live in their communities. For places like Corner Brook though citizens do not feel the urge to move to bigger urban centers like St. John's or places on the mainland. The purpose of this paper is to outline values which maybe keeping Corner Brook residents from uprooting their families to move to bigger urban centers such as St. John's, in order to be able to support ther families, get experience in their fields or to just acquire a job like many other people around the province.

Exploring business models to provide a foundation for enhanced eye care services in high street optometric practice

High street optometric practices are for-profit businesses. They mostly provide sight testing and eye examination services and sell optical products, such as spectacles and contact lenses. The sight testing services are often sold at a vastly reduced price and profits are generated primarily through high margin spectacle sales, in a loss leading strategy. Published literature highlights weaknesses in this strategy as it forms a barrier to widening the scope of services provided within optometric practices. This includes specialist non-refraction based services, such as shared care. In addition this business strategy discourages investment in advanced diagnostic equipment and higher professional qualifications. The aim of this thesis was to develop a greater understanding of the traditional loss-leading strategy. The thesis also aimed to assess the plausibility of alternative business models to support the development of specialist non-refraction services within high street optometric practice. This research was based on a single independent optometric practice that specialises in advanced retinal imaging and offers a broad range of shared care services. Specialist non-refraction based services were found to be poor generators of spectacle sales likely due to patient needs and presenting concerns. Alternative business strategies to support these services included charging more realistic professional fees via cost-based pricing and monthly payment plans. These strategies enabled specialist services to be more self-sustainable with less reliance on cross-subsidy from spectacle sales. Furthermore, improving operational efficiency can increase stand-alone profits for specialist services.Practice managers may be reluctant to increase professional fees due to market pressures and confidence. However, this thesis found that patients were accepting of increased professional fees. Practice managers can implement alternative business models to enhance eye care provision in high street optometric practices. These alternative business models also improve revenues and profits generated via clinical services and improve patient loyalty.

Radiation Dose to the Lens of the Eye from Computed Tomography Scans of the Head

While it is well known that exposure to radiation can result in cataract formation, questions still remain about the presence of a dose threshold in radiation cataractogenesis. Since the exposure history from diagnostic CT exams is well documented in a patient’s medical record, the population of patients chronically exposed to radiation from head CT exams may be an interesting area to explore for further research in this area. However, there are some challenges in estimating lens dose from head CT exams. An accurate lens dosimetry model would have to account for differences in imaging protocols, differences in head size, and the use of any dose reduction methods.

The overall objective of this dissertation was to develop a comprehensive method to estimate radiation dose to the lens of the eye for patients receiving CT scans of the head. This research is comprised of a physics component, in which a lens dosimetry model was derived for head CT, and a clinical component, which involved the application of that dosimetry model to patient data.

The physics component includes experiments related to the physical measurement of the radiation dose to the lens by various types of dosimeters placed within anthropomorphic phantoms. These dosimeters include high-sensitivity MOSFETs, TLDs, and radiochromic film. The six anthropomorphic phantoms used in these experiments range in age from newborn to adult.

First, the lens dose from five clinically relevant head CT protocols was measured in the anthropomorphic phantoms with MOSFET dosimeters on two state-of-the-art CT scanners. The volume CT dose index (CTDIvol), which is a standard CT output index, was compared to the measured lens doses. Phantom age-specific CTDIvol-to-lens dose conversion factors were derived using linear regression analysis. Since head size can vary among individuals of the same age, a method was derived to estimate the CTDIvol-to-lens dose conversion factor using the effective head diameter. These conversion factors were derived for each scanner individually, but also were derived with the combined data from the two scanners as a means to investigate the feasibility of a scanner-independent method. Using the scanner-independent method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter, most of the fitted lens dose values fell within 10-15% of the measured values from the phantom study, suggesting that this is a fairly accurate method of estimating lens dose from the CTDIvol with knowledge of the patient’s head size.

Second, the dose reduction potential of organ-based tube current modulation (OB-TCM) and its effect on the CTDIvol-to-lens dose estimation method was investigated. The lens dose was measured with MOSFET dosimeters placed within the same six anthropomorphic phantoms. The phantoms were scanned with the five clinical head CT protocols with OB-TCM enabled on the one scanner model at our institution equipped with this software. The average decrease in lens dose with OB-TCM ranged from 13.5 to 26.0%. Using the size-specific method to derive the CTDIvol-to-lens dose conversion factor from the effective head diameter for protocols with OB-TCM, the majority of the fitted lens dose values fell within 15-18% of the measured values from the phantom study.

Third, the effect of gantry angulation on lens dose was investigated by measuring the lens dose with TLDs placed within the six anthropomorphic phantoms. The 2-dimensional spatial distribution of dose within the areas of the phantoms containing the orbit was measured with radiochromic film. A method was derived to determine the CTDIvol-to-lens dose conversion factor based upon distance from the primary beam scan range to the lens. The average dose to the lens region decreased substantially for almost all the phantoms (ranging from 67 to 92%) when the orbit was exposed to scattered radiation compared to the primary beam. The effectiveness of this method to reduce lens dose is highly dependent upon the shape and size of the head, which influences whether or not the angled scan range coverage can include the entire brain volume and still avoid the orbit.

The clinical component of this dissertation involved performing retrospective patient studies in the pediatric and adult populations, and reconstructing the lens doses from head CT examinations with the methods derived in the physics component. The cumulative lens doses in the patients selected for the retrospective study ranged from 40 to 1020 mGy in the pediatric group, and 53 to 2900 mGy in the adult group.

This dissertation represents a comprehensive approach to lens of the eye dosimetry in CT imaging of the head. The collected data and derived formulas can be used in future studies on radiation-induced cataracts from repeated CT imaging of the head. Additionally, it can be used in the areas of personalized patient dose management, and protocol optimization and clinician training.

Differential contributions of the mIPS and PMd in the movement planning of reaches investigated through HD-tDCS

To reach for a target, we must formulate a movement plan - a difference vector of the target position with respect to the starting hand position. While it is known that the medial part of the intraparietal sulcus (mIPS) and the dorsal premotor (PMd) activity reflects aspects of a kinematic plan for a reaching movement, it is unclear whether or how the two regions may differ. We investigated the functional roles of the mIPS and PMd in the planning of reaching movements using high definition transcranial direct current stimulation (HD-tDCS) and examined changes in horizontal endpoint error when participants were subjected to anodal and cathodal stimulation. The left mIPS and PMd were functionally localized with fMRI in each participant using an interleaved center-out pointing and saccade task and mapped onto the scalp using Brainsight. We adopted a randomized, single-blind design and applied anodal and cathodal stimulation (2mA for 20 min; 3cm radius 4x1 electrode placement) during 4 separate visits scheduled at least a week apart. Each participant performed 250 baseline, stimulation, and post-stimulation memory-guided reaches starting from one of two initial hand positions (IHPs) to one of 4 briefly flashed targets (20 cm distant, 5 cm apart horizontally) while fixating on a straight-ahead cross located at the target line. Separate 2-way repeated measures ANOVAs of horizontal endpoint error difference after cathodal tDCS at each stimulation site revealed a significant IHP by target position interaction effect at the left mIPS, and significant IHP and target main effects at the left PMd. Behaviorally, these effects corresponded to IHP-dependent contractions after cathodal mIPS tDCS and IHP-independent contractions after cathodal PMd tDCS. These results suggest that the movement vector is not yet formed at the input level of mIPS, but is encoded at the input of PMd. These results also indicate that tDCS is a viable, useful method in investigating movement planning properties through temporary perturbations of the system.

Market reforms and privatisation in the English National Health Service

The article examines developments in the marketisation and privatisation of the English National Health Service, primarily since 1997. It explores the use of competition and contracting out in ancillary services and the levering into public services of private finance for capital developments through the Private Finance Initiative. A substantial part of the article examines the repeated restructuring of the health service as a market in clinical services, initially as an internal market but subsequently as a market increasing opened up to private sector involvement. Some of the implications of market processes for NHS staff and for increased privatisation are discussed. The article examines one episode of popular resistance to these developments, namely the movement of opposition to the 2011 health and social care legislative proposals. The article concludes with a discussion of the implications of these system reforms for the founding principles of the NHS and the sustainability of the service.

RETINAL ANGIOMATOUS PROLIFERATION: A Quantitative Analysis of the Fundoscopic Features of the Fellow Eye

PURPOSE: To quantitatively analyze and compare the fundoscopic features between fellow eyes of retinal angiomatous proliferation and typical exudative age-related macular degeneration and to identify possible predictors of neovascularization. METHODS: Retrospective case-control study. Seventy-nine fellow eyes of unilateral retinal angiomatous proliferation (n = 40) and typical exudative age-related macular degeneration (n = 39) were included. Fundoscopic features of the fellow eyes were assessed using digital color fundus photographs taken at the time of diagnosis of neovascularization in the first affected eye. Grading was performed by two independent graders using RetmarkerAMD, a computer-assisted grading software based on the International Classification and Grading System for age-related macular degeneration. RESULTS: Baseline total number and area (square micrometers) of drusen in the central 1,000, 3,000, and 6,000 μm were considerably inferior in the fellow eyes of retinal angiomatous proliferation, with statistically significant differences (P < 0.05) observed in virtually every location (1,000, 3,000, and 6,000 μm). A soft drusen (≥125 μm) area >510,196 μm2 in the central 6,000 μm was associated with an increased risk of neovascularization (hazard ratio, 4.35; 95% confidence interval [1.56-12.15]; P = 0.005). CONCLUSION: Baseline fundoscopic features of the fellow eye differ significantly between retinal angiomatous proliferation and typical exudative age-related macular degeneration. A large area (>510,196 μm2) of soft drusen in the central 6,000 μm confers a significantly higher risk of neovascularization and should be considered as a phenotypic risk factor.

RETINAL ANGIOMATOUS PROLIFERATION: A Quantitative Analysis of the Fundoscopic Features of the Fellow Eye

PURPOSE: To quantitatively analyze and compare the fundoscopic features between fellow eyes of retinal angiomatous proliferation and typical exudative age-related macular degeneration and to identify possible predictors of neovascularization. METHODS: Retrospective case-control study. Seventy-nine fellow eyes of unilateral retinal angiomatous proliferation (n = 40) and typical exudative age-related macular degeneration (n = 39) were included. Fundoscopic features of the fellow eyes were assessed using digital color fundus photographs taken at the time of diagnosis of neovascularization in the first affected eye. Grading was performed by two independent graders using RetmarkerAMD, a computer-assisted grading software based on the International Classification and Grading System for age-related macular degeneration. RESULTS: Baseline total number and area (square micrometers) of drusen in the central 1,000, 3,000, and 6,000 μm were considerably inferior in the fellow eyes of retinal angiomatous proliferation, with statistically significant differences (P < 0.05) observed in virtually every location (1,000, 3,000, and 6,000 μm). A soft drusen (≥125 μm) area >510,196 μm2 in the central 6,000 μm was associated with an increased risk of neovascularization (hazard ratio, 4.35; 95% confidence interval [1.56-12.15]; P = 0.005). CONCLUSION: Baseline fundoscopic features of the fellow eye differ significantly between retinal angiomatous proliferation and typical exudative age-related macular degeneration. A large area (>510,196 μm2) of soft drusen in the central 6,000 μm confers a significantly higher risk of neovascularization and should be considered as a phenotypic risk factor.

The role of dinucleoside polyphosphates on the ocular surface and other eye structures

Dinucleoside polyphosphates comprises a group of dinucleotides formed by two nucleosides linked by a variable number of phosphates, abbreviated NpnN (where n represents the number of phosphates). These compounds are naturally occurring substances present in tears, aqueous humour and in the retina. As the consequence of their presence, these dinucleotides contribute to many ocular physiological processes. On the ocular surface, dinucleoside polyphosphates can stimulate tear secretion, mucin release from goblet cells and they help epithelial wound healing by accelerating cell migration rate. These dinucleotides can also stimulate the presence of proteins known to protect the ocular surface against microorganisms, such as lysozyme and lactoferrin. One of the latest discoveries is the ability of some dinucleotides to facilitate the paracellular way on the cornea, therefore allowing the delivery of compounds, such as antiglaucomatous ones, more easily within the eye. The compound Ap4A has been described being abnormally elevated in patient's tears suffering of dry eye, Sjogren syndrome, congenital aniridia, or after refractive surgery, suggesting this molecule as biomarker for dry eye condition. At the intraocular level, some diadenosine polyphosphates are abnormally elevated in glaucoma patients, and this can be related to the stimulation of a P2Y2 receptor that increases the chloride efflux and water movement in the ciliary epithelium. In the retina, the dinucleotide dCp4U, has been proven to be useful to help in the recovery of retinal detachments. Altogether, dinucleoside polyphosphates are a group of compounds which present relevant physiological actions but which also can perform promising therapeutic benefits.

Relative influence of gaze and static arm position in the Superior Parietal Lobule of the macaque monkey during reaching

The superior parietal lobule (SPL) of macaques is classically described as an associative cortex implicated in visuospatial perception, planning and control of reaching and grasping movements (De Vitis et al., 2019; Galletti et al., 2003, 2018, 2022; Fattori et al., 2017; Hadjidimitrakis et al., 2015). These processes are the result of the integration of signals related to different sensory modalities. During a goal-directed action, eye and limb information are combined to ensure that the hand is transported at the gazed target location and the arm is maintained steady in the final position. The SPL areas V6A, PEc and PE contain cells sensitive to the direction of gaze and limb position but less is known about the degree of independent encoding of these signals. In this thesis, we evaluated the influence of eye and arm position information upon single neuron activity of areas V6A, PEc and PE during the holding period after the execution of arm reaching movement, when the gaze and hand are both still at the reach target. Two male macaques (Macaca fascicularis) performed a reaching task while single unit activity was recorded from areas V6A, PEc and PE. We found that neurons in all these areas were modulated by eye and static arm positions with a joint encoding of gaze and somatosensory signals in V6A and PEc and a mostly separate processing of the two signals in PE. The elaboration of this information reflects the functional gradient found in the SPL with the caudal sector characterized by visuo-somatic properties in comparison to the rostral sector dominated by somatosensory signals. This evidence well agree also with the recent reallocation of areas V6A and PEc in Brodmann’s area 7 depending on their similar structural and functional features with respect to PE belonging to Brodmann’s area 5 (Gamberini et al., 2020).

Toll-like Receptor 4 Activation Promotes Cardiac Arrhythmias By Decreasing The Transient Outward Potassium Current (ito) Through An Irf3-dependent And Myd88-independent Pathway.

Cardiac arrhythmias are one of the main causes of death worldwide. Several studies have shown that inflammation plays a key role in different cardiac diseases and Toll-like receptors (TLRs) seem to be involved in cardiac complications. In the present study, we investigated whether the activation of TLR4 induces cardiac electrical remodeling and arrhythmias, and the signaling pathway involved in these effects. Membrane potential was recorded in Wistar rat ventricle. Ca(2+) transients, as well as the L-type Ca(2+) current (ICaL) and the transient outward K(+) current (Ito), were recorded in isolated myocytes after 24 h exposure to the TLR4 agonist, lipopolysaccharide (LPS, 1 μg/ml). TLR4 stimulation in vitro promoted a cardiac electrical remodeling that leads to action potential prolongation associated with arrhythmic events, such as delayed afterdepolarization and triggered activity. After 24 h LPS incubation, Ito amplitude, as well as Kv4.3 and KChIP2 mRNA levels were reduced. The Ito decrease by LPS was prevented by inhibition of interferon regulatory factor 3 (IRF3), but not by inhibition of interleukin-1 receptor-associated kinase 4 (IRAK4) or nuclear factor kappa B (NF-κB). Extrasystolic activity was present in 25% of the cells, but apart from that, Ca(2+) transients and ICaL were not affected by LPS; however, Na(+)/Ca(2+) exchanger (NCX) activity was apparently increased. We conclude that TLR4 activation decreased Ito, which increased AP duration via a MyD88-independent, IRF3-dependent pathway. The longer action potential, associated with enhanced Ca(2+) efflux via NCX, could explain the presence of arrhythmias in the LPS group.

An Eye On Sickle Cell Retinopathy.

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Comparative Metagenomic Analysis Of Coral Microbial Communities Using A Reference-independent Approach.

By comparing the SEED and Pfam functional profiles of metagenomes of two Brazilian coral species with 29 datasets that are publicly available, we were able to identify some functions, such as protein secretion systems, that are overrepresented in the metagenomes of corals and may play a role in the establishment and maintenance of bacteria-coral associations. However, only a small percentage of the reads of these metagenomes could be annotated by these reference databases, which may lead to a strong bias in the comparative studies. For this reason, we have searched for identical sequences (99% of nucleotide identity) among these metagenomes in order to perform a reference-independent comparative analysis, and we were able to identify groups of microbial communities that may be under similar selective pressures. The identification of sequences shared among the metagenomes was found to be even better for the identification of groups of communities with similar niche requirements than the traditional analysis of functional profiles. This approach is not only helpful for the investigation of similarities between microbial communities with high proportion of unknown reads, but also enables an indirect overview of gene exchange between communities.

Detection Of Explosives On The Surface Of Banknotes By Raman Hyperspectral Imaging And Independent Component Analysis.

The aim of this study was to develop a methodology using Raman hyperspectral imaging and chemometric methods for identification of pre- and post-blast explosive residues on banknote surfaces. The explosives studied were of military, commercial and propellant uses. After the acquisition of the hyperspectral imaging, independent component analysis (ICA) was applied to extract the pure spectra and the distribution of the corresponding image constituents. The performance of the methodology was evaluated by the explained variance and the lack of fit of the models, by comparing the ICA recovered spectra with the reference spectra using correlation coefficients and by the presence of rotational ambiguity in the ICA solutions. The methodology was applied to forensic samples to solve an automated teller machine explosion case. Independent component analysis proved to be a suitable method of resolving curves, achieving equivalent performance with the multivariate curve resolution with alternating least squares (MCR-ALS) method. At low concentrations, MCR-ALS presents some limitations, as it did not provide the correct solution. The detection limit of the methodology presented in this study was 50μgcm(-2).