Evaluation of two interaction techniques for visualization of dynamic graphs

Several techniques for visualization of dynamic graphs are based on different spatial arrangements of a temporal sequence of node-link diagrams. Many studies in the literature have investigated the importance of maintaining the user's mental map across this temporal sequence, but usually each layout is considered as a static graph drawing and the effect of user interaction is disregarded. We conducted a task-based controlled experiment to assess the effectiveness of two basic interaction techniques: the adjustment of the layout stability and the highlighting of adjacent nodes and edges. We found that generally both interaction techniques increase accuracy, sometimes at the cost of longer completion times, and that the highlighting outclasses the stability adjustment for many tasks except the most complex ones.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016

Lentiviral Engineered Fibroblasts Expressing Codon Optimized COL7A1 Restore Anchoring Fibrils in RDEB

Cells therapies, engineered to secrete replacement proteins, are being developed to ameliorate otherwise debilitating diseases. Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects of type VII collagen (C7), a protein essential for anchoring fibril formation at the dermal-epidermal junction (DEJ). Whilst allogeneic fibroblasts injected directly into the dermis can mediate transient disease modulation, autologous gene-modified fibroblasts should evade immunological rejection and support sustained delivery of C7 at the DEJ. We demonstrate the feasibility of such an approach using a therapeutic grade, self-inactivating-lentiviral vector, encoding codon optimized COL7A1, to transduce RDEB fibroblasts under conditions suitable for clinical application. Expression and secretion of C7 was confirmed, with transduced cells exhibiting supra-normal levels of protein expression and ex vivo migration of fibroblasts was restored in functional assays. Gene modified RDEB fibroblasts also deposited C7 at the DEJ of human RDEB skin xenografts placed on NOD-scid IL2Rgamma(null) recipients, with reconstruction of human epidermal structure and regeneration of anchoring fibrils at the DEJ. Fibroblast mediated restoration of protein and structural defects in this RDEB model strongly supports proposed therapeutic applications in man

Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techniques

We evaluated the ability of simple and complex surrogate-indices to identify individuals from an overweight/obese cohort with hepatic insulin-resistance (HEP-IR). Five indices, one previously defined and four newly generated through step-wise linear regression, were created against a single-cohort sample of 77 extensively characterised participants with the metabolic syndrome (age 55.6±1.0 years, BMI 31.5±0.4 kg/m2; 30 males). HEP-IR was defined by measuring endogenous-glucose-production (EGP) with [6–62H2] glucose during fasting and euglycemic-hyperinsulinemic clamps and expressed as EGP*fasting plasma insulin. Complex measures were incorporated into the model, including various non-standard biomarkers and the measurement of body-fat distribution and liver-fat, to further improve the predictive capability of the index. Validation was performed against a data set of the same subjects after an isoenergetic dietary intervention (4 arms, diets varying in protein and fiber content versus control). All five indices produced comparable prediction of HEP-IR, explaining 39–56% of the variance, depending on regression variable combination. The validation of the regression equations showed little variation between the different proposed indices (r2 = 27–32%) on a matched dataset. New complex indices encompassing advanced measurement techniques offered an improved correlation (r = 0.75, P<0.001). However, when validated against the alternative dataset all indices performed comparably with the standard homeostasis model assessment for insulin resistance (HOMA-IR) (r = 0.54, P<0.001). Thus, simple estimates of HEP-IR performed comparable to more complex indices and could be an efficient and cost effective approach in large epidemiological investigations

Factors affecting commencement and cessation of smoking behaviour in Malaysian adults

<p>Abstract</p> <p>Background</p> <p>Tobacco consumption peak in developed countries has passed, however, it is on the increase in many developing countries. Apart from cigarettes, consumption of local hand-rolled cigarettes such as <it>bidi </it>and <it>rokok daun </it>are prevalent in specific communities. Although factors associated with smoking initiation and cessation has been investigated elsewhere, the only available data for Malaysia is on prevalence. This study aims to investigate factors associated with smoking initiation and cessation which is imperative in designing intervention programs.</p> <p>Methods</p> <p>Data were collected from 11,697 adults by trained recording clerks on sociodemographic characteristics, practice of other risk habit and details of smoking such as type, duration and frequency. Smoking commencement and cessation were analyzed using the Kaplan-Meier estimates and log-rank tests. Univariate and multivariate Cox proportional hazard regression models were used to calculate the hazard rate ratios.</p> <p>Results</p> <p>Males had a much higher prevalence of the habit (61.7%) as compared to females (5.8%). Cessation was found to be most common among the Chinese and those regularly consuming alcoholic beverages. Kaplan-Meier plot shows that although males are more likely to start smoking, females are found to be less likely to stop. History of betel quid chewing and alcohol consumption significantly increase the likelihood of commencement (p < 0.0001), while cessation was least likely among Indians, current quid chewers and kretek users (p < 0.01).</p> <p>Conclusions</p> <p>Gender, ethnicity, history of quid chewing and alcohol consumption have been found to be important factors in smoking commencement; while ethnicity, betel quid chewing and type of tobacco smoked influences cessation.</p

Prediction error and accuracy of intraocular lens power calculation in pediatric patient comparing SRK II and Pediatric IOL Calculator

<p>Abstract</p> <p>Background</p> <p>Despite growing number of intraocular lens power calculation formulas, there is no evidence that these formulas have good predictive accuracy in pediatric, whose eyes are still undergoing rapid growth and refractive changes. This study is intended to compare the prediction error and the accuracy of predictability of intraocular lens power calculation in pediatric patients at 3 month post cataract surgery with primary implantation of an intraocular lens using SRK II versus Pediatric IOL Calculator for pediatric intraocular lens calculation. Pediatric IOL Calculator is a modification of SRK II using Holladay algorithm. This program attempts to predict the refraction of a pseudophakic child as he grows, using a Holladay algorithm model. This model is based on refraction measurements of pediatric aphakic eyes. Pediatric IOL Calculator uses computer software for intraocular lens calculation.</p> <p>Methods</p> <p>This comparative study consists of 31 eyes (24 patients) that successfully underwent cataract surgery and intraocular lens implantations. All patients were 12 years old and below (range: 4 months to 12 years old). Patients were randomized into 2 groups; SRK II group and Pediatric IOL Calculator group using envelope technique sampling procedure. Intraocular lens power calculations were made using either SRK II or Pediatric IOL Calculator for pediatric intraocular lens calculation based on the printed technique selected for every patient. Thirteen patients were assigned for SRK II group and another 11 patients for Pediatric IOL Calculator group. For SRK II group, the predicted postoperative refraction is based on the patient's axial length and is aimed for emmetropic at the time of surgery. However for Pediatric IOL Calculator group, the predicted postoperative refraction is aimed for emmetropic spherical equivalent at age 2 years old. The postoperative refractive outcome was taken as the spherical equivalent of the refraction at 3 month postoperative follow-up. The data were analysed to compare the mean prediction error and the accuracy of predictability of intraocular lens power calculation between SRK II and Pediatric IOL Calculator.</p> <p>Results</p> <p>There were 16 eyes in SRK II group and 15 eyes in Pediatric IOL Calculator group. The mean prediction error in the SRK II group was 1.03 D (SD, 0.69 D) while in Pediatric IOL Calculator group was 1.14 D (SD, 1.19 D). The SRK II group showed lower prediction error of 0.11 D compared to Pediatric IOL Calculator group, but this was not statistically significant (p = 0.74). There were 3 eyes (18.75%) in SRK II group achieved acccurate predictability where the refraction postoperatively was within ± 0.5 D from predicted refraction compared to 7 eyes (46.67%) in the Pediatric IOL Calculator group. However the difference of the accuracy of predictability of postoperative refraction between the two formulas was also not statistically significant (p = 0.097).</p> <p>Conclusions</p> <p>The prediction error and the accuracy of predictability of postoperative refraction in pediatric cataract surgery are comparable between SRK II and Pediatric IOL Calculator. The existence of the Pediatric IOL Calculator provides an alternative to the ophthalmologist for intraocular lens calculation in pediatric patients. Relatively small sample size and unequal distribution of patients especially the younger children (less than 3 years) with a short time follow-up (3 months), considering spherical equivalent only.</p

Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report

BACKGROUND: Despite improvements in the safety and efficacy of endovascular procedures, considerable morbidity may still be attributed to vasospasm. Vasospasm has proven amenable to pharmacological intervention such as nitrates, intravenous calcium channel blockers (CCBs), and intra-arterial papaverine, particularly in small vessels. However, few studies have focused on medium to large vessel spasm. Here we report the use of an intra-arterial CCB, verapamil, to treat flow-limiting mechanically-induced spasm of the common carotid artery (CCA) in a primate. We believe this to be the first such report of its kind. CASE PRESENTATION: As part of a study assessing the placement feasibility and safety of a catheter capable of delivering intra-arterial cerebroprotective therapy, a female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of acute spasm. The protocol dictated that the catheter remain in the CCA for 12 hours. Upon completion of the protocol, arteriography revealed a marked decrease in CCA size (mean cross-sectional area reduction = 31.6 ± 1.9%) localized along the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and arteriography was performed 10 minutes later. Image analysis at 6 points along the CCA revealed a 21.0 ± 1.7% mean increase in vessel diameter along the length of the catheter corresponding to a 46.7 ± 4.0% mean increase in cross-sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg during the procedure. CONCLUSIONS: Intraluminal CCBs like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm in medium to large-sized vessels such as the CCA

Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009

Insulin resistance is a hallmark of type 2 diabetes mellitus and is associated with a metabolic and cardiovascular cluster of disorders (dyslipidaemia, hypertension, obesity [especially visceral], glucose intolerance, endothelial dysfunction), each of which is an independent risk factor for cardiovascular disease (CVD). Multiple prospective studies have documented an association between insulin resistance and accelerated CVD in patients with type 2 diabetes, as well as in non-diabetic individuals. The molecular causes of insulin resistance, i.e. impaired insulin signalling through the phosphoinositol-3 kinase pathway with intact signalling through the mitogen-activated protein kinase pathway, are responsible for the impairment in insulin-stimulated glucose metabolism and contribute to the accelerated rate of CVD in type 2 diabetes patients. The current epidemic of diabetes is being driven by the obesity epidemic, which represents a state of tissue fat overload. Accumulation of toxic lipid metabolites (fatty acyl CoA, diacylglycerol, ceramide) in muscle, liver, adipocytes, beta cells and arterial tissues contributes to insulin resistance, beta cell dysfunction and accelerated atherosclerosis, respectively, in type 2 diabetes. Treatment with thiazolidinediones mobilises fat out of tissues, leading to enhanced insulin sensitivity, improved beta cell function and decreased atherogenesis. Insulin resistance and lipotoxicity represent the missing links (beyond the classical cardiovascular risk factors) that help explain the accelerated rate of CVD in type 2 diabetic patients

Actos Now for the prevention of diabetes (ACT NOW) study

Abstract Background Impaired glucose tolerance (IGT) is a prediabetic state. If IGT can be prevented from progressing to overt diabetes, hyperglycemia-related complications can be avoided. The purpose of the present study was to examine whether pioglitazone (ACTOS®) can prevent progression of IGT to type 2 diabetes mellitus (T2DM) in a prospective randomized, double blind, placebo controlled trial. Methods/Design 602 IGT subjects were identified with OGTT (2-hour plasma glucose = 140–199 mg/dl). In addition, IGT subjects were required to have FPG = 95–125 mg/dl and at least one other high risk characteristic. Prior to randomization all subjects had measurement of ankle-arm blood pressure, systolic/diastolic blood pressure, HbA1C, lipid profile and a subset had frequently sampled intravenous glucose tolerance test (FSIVGTT), DEXA, and ultrasound determination of carotid intima-media thickness (IMT). Following this, subjects were randomized to receive pioglitazone (45 mg/day) or placebo, and returned every 2–3 months for FPG determination and annually for OGTT. Repeat carotid IMT measurement was performed at 18 months and study end. Recruitment took place over 24 months, and subjects were followed for an additional 24 months. At study end (48 months) or at time of diagnosis of diabetes the OGTT, FSIVGTT, DEXA, carotid IMT, and all other measurements were repeated. Primary endpoint is conversion of IGT to T2DM based upon FPG ≥ 126 or 2-hour PG ≥ 200 mg/dl. Secondary endpoints include whether pioglitazone can: (i) improve glycemic control (ii) enhance insulin sensitivity, (iii) augment beta cell function, (iv) improve risk factors for cardiovascular disease, (v) cause regression/slow progression of carotid IMT, (vi) revert newly diagnosed diabetes to normal glucose tolerance. Conclusion ACT NOW is designed to determine if pioglitazone can prevent/delay progression to diabetes in high risk IGT subjects, and to define the mechanisms (improved insulin sensitivity and/or enhanced beta cell function) via which pioglitazone exerts its beneficial effect on glucose metabolism to prevent/delay onset of T2DM. Trial Registration clinical trials.gov identifier: NCT0022096