Epidemiology of Eales Disease in the Central Western India

Objective: To investigate the clinical features and propose a new staging system based on the clinicopathological correlation and formulate new guidelines for management of Eales’ disease in healthy young males. Design: Prospective cohort study. Setting: Vitreo Retinal Department of a tertiary eye care center in Western Central India. Participants: Seventy-four eyes diagnosed with Eales’ disease. Materials and methods: From 2004 to 2010, patients clinically diagnosed with Eales’ disease were enrolled in this study using specific inclusion and exclusion criteria. We examined the patients’ anterior and posterior segments thoroughly. We performed the necessary ocular and systemic investigations. We divided the investigations into three stages: inflammatory, ischemic and complications and the patients were treated accordingly. We treated the patients using medical management, photocoagulation or pars plana vitrectomy. The patients were monitored according to standard schedules and formats. All information was documented using a pre-tested online format and statistical analyses were performed using SPSS ver. 17. A p-value < 0.05 was considered to indicate significance. Outcome measures: Visual acuity. Results: The cohort comprised 74 cases with a mean age of 30 ± 8.73 years. The visual acuity of the presenting cohort was < 3/60 in 64.9% of eyes. The final visual outcome was > 6/12 in 40 eyes (54.1%), 6/60 to 6/18 in 14 eyes (18.9%) and < 1/60 in the remaining 9 eyes at a mean follow-up of 592 days. The visual parameters differed significantly pre-and post-treatment. We evaluated the visual outcome following surgical management. Conclusion: We studied epidemiological facts about anterior and posterior segment findings

Clinical characterisation of cardiac involvement in Anderson-Fabry Disease

Background: Anderson – Fabry Disease (AFD) is an X-linked lysosomal storage disorder that results in a deficiency in lysosomal α-galactosidase A. This leads to an accumulation of glycosphingolipids in multiple cell types resulting in the characteristic angiokeratomata, acroparesthesiae, hypohidrosis, and corneal opacities of classical AFD. Although patients with AFD have a reduced life span, the pathogenesis and impact of cardiac involvement on prognosis remain unclear. The aim of this thesis was to clinically characterise cardiac involvement in AFD using a systematic cardiac assessment of a consecutive cohort of patients with AFD. / Methods: A cardiac assessment protocol including history and examination, 12 lead ECG, 24 hour ambulatory ECG monitoring, echocardiography and cardiopulmonary exercise testing were performed in a cohort of 122 consecutive patients. Subgroups had coronary flow reserve and evaluation of serum levels of MMP-9, TIMP-1 and TIMP-2 to assess coronary microvascular function and extracellular matrix (ECM) turnover, respectively. / Results: The main results of the thesis are as follows: (1) Tachy and brady arrhythmias are common and may contribute to premature death; (2) Left ventricular systolic impairment is common and decline in systolic function may represent a measure of disease severity; (3) objective evidence for exercise limitation is common and is related to overall disease severity as assessed with a validated disease severity score; (4) patients with AFD have markedly abnormal coronary microvascular function which does not improve with ERT; (5) patients with AFD have abnormal ECM turnover associated with overall disease severity. / Conclusion: Patients with AFD related cardiomyopathy have progressive disease characterised by heart failure and arrhythmia. It is likely that myocardial ischaemia and abnormal interstitial turnover are related in the pathogenesis of cardiac disease and complications. Patients with AFD need regular and continued cardiac follow up for early identification and treatment of cardiac complications

Cache-oblivious index for approximate string matching

This paper revisits the problem of indexing a text for approximate string matching. Specifically, given a text T of length n and a positive integer k, we want to construct an index of T such that for any input pattern P, we can find all its k-error matches in T efficiently. This problem is well-studied in the internal-memory setting. Here, we extend some of these recent results to external-memory solutions, which are also cache-oblivious. Our first index occupies O((nlog kn)B) disk pages and finds all k-error matches with O((|P|+occ)B+log knloglog Bn) I/Os, where B denotes the number of words in a disk page. To the best of our knowledge, this index is the first external-memory data structure that does not require Ω (|P|+occ+poly(logn)) I/Os. The second index reduces the space to O((nlogn)B) disk pages, and the I/O complexity is O((|P|+occ)B+log k(k+1)nloglogn) . © 2011 Elsevier B.V. All rights reserved.postprin

Augmenting the 6-3-5 method with design information

This paper describes a comparative study between the 6-3-5 Method and the ICR Grid. The ICR Grid is an evolved variant of 6-3-5 intended to better integrate information into the concept generation process. Unlike a conventional 6-3-5 process where participants continually sketch concepts, using the ICR Grid (the name derived from its Inform, Create, Reflect activities and structured, grid-like output) participants are additionally required to undertake information search tasks, use specific information items for concept development, and reflect on the merit of concepts as the session progresses. The results indicate that although the quantity of concepts was lower, the use of information had a positive effect in a number of areas, principally the quality and variety of output. Although grounded in the area of product development, this research is applicable to any organisation undertaking idea generation and problem solving. As well as providing insights on the transference of information to concepts, it holds additional interest for studies on the composition and use of digital libraries

Stability and sensitivity of water T2 obtained with IDEAL-CPMG in healthy and fat-infiltrated skeletal muscle

Quantifying muscle water T2 (T2 -water) independently of intramuscular fat content is essential in establishing T2 -water as an outcome measure for imminent new therapy trials in neuromuscular diseases. IDEAL-CPMG combines chemical shift fat-water separation with T2 relaxometry to obtain such a measure. Here we evaluate the reproducibility and B1 sensitivity of IDEAL-CPMG T2 -water and fat fraction (f.f.) values in healthy subjects, and demonstrate the potential of the method to quantify T2 -water variation in diseased muscle displaying varying degrees of fatty infiltration. The calf muscles of 11 healthy individuals (40.5 ± 10.2 years) were scanned twice at 3 T with an inter-scan interval of 4 weeks using IDEAL-CPMG, and 12 patients with hypokalemic periodic paralysis (HypoPP) (42.3 ± 11.5 years) were also imaged. An exponential was fitted to the signal decay of the separated water and fat components to determine T2 -water and the fat signal amplitude muscle regions manually segmented. Overall mean calf-level muscle T2 -water in healthy subjects was 31.2 ± 2.0 ms, without significant inter-muscle differences (p = 0.37). Inter-subject and inter-scan coefficients of variation were 5.7% and 3.2% respectively for T2 -water and 41.1% and 15.4% for f.f. Bland-Altman mean bias and ±95% coefficients of repeatability were for T2 -water (0.15, -2.65, 2.95) ms and f.f. (-0.02, -1.99, 2.03)%. There was no relationship between T2 -water (ρ = 0.16, p = 0.07) or f.f. (ρ = 0.03, p = 0.7761) and B1 error or any correlation between T2 -water and f.f. in the healthy subjects (ρ = 0.07, p = 0.40). In HypoPP there was a measurable relationship between T2 -water and f.f. (ρ = 0.59, p < 0.001). IDEAL-CPMG provides a feasible way to quantify T2 -water in muscle that is reproducible and sensitive to meaningful physiological changes without post hoc modeling of the fat contribution. In patients, IDEAL-CPMG measured elevations in T2 -water and f.f. while showing a weak relationship between these parameters, thus showing promise as a practical means of quantifying muscle water in patient populations

Can quantitative analysis of multi-parametric MRI independently predict failure of focal salvage HIFU therapy in men with radio-recurrent prostate cancer?

OBJECTIVES: Focal salvage HIFU is a feasible therapeutic option in some men who have recurrence after primary radiotherapy for prostate cancer. We aimed to determine if multi-parametric quantitative parameters, in addition to clinical factors, might have a role in independently predicting focal salvage HIFU outcomes. METHODS: A retrospective registry analysis included 150 consecutive men who underwent focal salvage HIFU (Sonablate500) (2006-2015); 89 had mpMRI available. Metastatic disease was excluded by nodal assessment on pelvic MRI, a radioisotope bone-scan and/or choline or FDG PET/CT scan. All men had mpMRI and either transperineal template prostate mapping biopsy or targeted and systematic TRUS-biopsy. mpMRI included T2-weighted, diffusion-weighted and dynamic contrast-enhancement. Pre-HIFU quantitative mpMRI data was obtained using Horos DICOM Viewer v3.3.5 for general MRI parameters and IB DCE v2.0 plug-in. Progression-free survival (PFS) was defined by biochemical failure and/or positive localized or distant imaging results and/or positive biopsy and/or systemic therapy and/or metastases/prostate cancer-specific death. Potential predictors of PFS were analyzed by univariable and multivariable Cox-regression. RESULTS: Median age at focal salvage HIFU was 71 years (interquartile range [IQR] 65-74.5) and median PSA pre-focal salvage treatment was 5.8ng/ml (3.8-8). Median follow-up was 35 months (23-47) and median time to failure was 15 months (7.8-24.3). D-Amico low, intermediate and high-risk disease was present in 1% (1/89), 40% (36/89) and 43% (38/89) prior to focal salvage HIFU (16% missing data). 56% (50/89) failed by the composite outcome. A total of 22 factors were evaluated on univariable and 8 factors on multivariable analysis. The following quantitative parameters were included: Ktrans, Kep, Ve, Vp, IS, rTTP and TTP. On univariable analysis, PSA, prostate volume at time of radiotherapy failure and Ve (median) value were predictors for failure. Ve represents extracellular fraction of the whole tissue volume. On multivariable analysis, only Ve (median) value remained as an independent predictor. CONCLUSIONS: One pharmacokinetic quantitative parameter based on DCE sequences seems to independently predict failure following focal salvage HIFU for radio-recurrent prostate cancer. This likely relates to the tumor microenvironment producing heat-sinks which counter the heating effect of HIFU. Further validation in larger datasets and evaluating mechanisms to reduce heat-sinks are required

Lung Clearance Index (LCI) is Stable in Most Primary Ciliary Dyskinesia (PCD) Patients Managed in a Specialist Centre:a Pilot Study

Primary ciliary dyskinesia is a condition in which abnormal cilia structure or function leads to reduced mucociliary clearance and obstructive lung disease. Twenty-nine patients had lung clearance index (LCI) measured in 2009 and we attempted to perform a 5-year follow-up. Only 12 patients could be re-recruited, but in this small group LCI was stable over the 5 years, which confirms previous data showing that spirometry is also stable in these patients over the medium term. The two patients with the highest LCI in 2009 had since died, despite one having relatively preserved spirometry at the time. These data may be used to inform sample size calculations of future studies

Use of an electromagnetic colonoscope to assess maneuvers associated with cecal intubation

<p>Abstract</p> <p>Background</p> <p>Safe and effective colonoscopy is aided by the use of endoscopic techniques and maneuvers (ETM) during the examination including patient repositioning, stiffening of the endoscope and abdominal pressure.</p> <p>Aim</p> <p>To better understand the use and value of ETM during colonoscopy by using a device that allows real-time imaging of the colonoscope insertion shaft.</p> <p>Methods</p> <p>The use of ETM during colonoscopy and their success was recorded. Experienced colonoscopists and endoscopy assistants used a commercially available electromagnetic (EM) transmitter and a special adult variable stiffness instrument with 12 embedded sensors to examine 46 patients. In 5 of these a special EM probe passed through the instrument channel of a standard pediatric variable stiffness colonoscope was used instead of the EM colonoscope.</p> <p>Results</p> <p>Thirty-nine men and 7 women with a mean age of 64 years (range 33–90) were studied. The cecum was intubated in 93.5% (43/46). The mean time to reach the cecum was 10.6 minutes (range 3–25). ETM were used a total of 174 times in 41 of the patients to assist with cecal intubation. When ETM were required to reach the cecum, and the cecum was intubated, an average of 3.82 ETM/patient was used. While ETM were used most often when the tip of the colonoscope was in the left side of the colon (rectum 5.0%, sigmoid colon 20.7%, descending colon 5.0%, and splenic flexure 11.6%), when the instrument was in the transverse colon (14.8%), hepatic flexure (20.7%) and ascending colon (19.8%) the use of ETM was also required. When the colonoscope tip was in the transverse colon, hepatic flexure and ascending colon, ETM success rates were less (61.1%, 52.0%, and 41.7% respectively) compared to the left colon success rates (rectum 83.3%, sigmoid colon 84.0%, descending colon 100%, and splenic flexure 85.7%).</p> <p>Conclusion</p> <p>The EM colonoscope allows imaging of the insertion shaft without fluoroscopy and is a useful device for evaluating the efficacy of ETM. ETM are important tools of the colonoscopist and are used most often in the left colon where they are most effective.</p