Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance:a preliminary study

To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). Sixty age- and gender- matched White-European adults (30 IGT and 30 normal glucose tolerance -NGT) were recruited for the study. Fasting plasma glucose, lipids and 24-hour blood pressure (BP) was measured in all subjects. Systemic vascular and endothelial function was assessed using carotid-artery intimal media thickness (cIMT) and flow mediated dilation (FMD). Retinal vascular reactivity was assessed by the Dynamic Retinal Vessel Analyser (DVA). Additionally, blood glutathione (GSH, GSSG and tGSH) and plasma von-Willebrand (vWF) factor levels were also measured. Individuals with IGT demonstrated higher BP values (p<0.001), fasting TG and TG:HDL ratios (p<0.001) than NGT subjects. Furthermore, Total:HDL-C ratios and Framingham scores were raised (p=0.010 and p<0.001 respectively). Blood glutathione levels (GSH, GSSG and tGSH) were lower (p<0.001, p=0.039 and p<0.001 respectively) while plasma vWF was increased (p=0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (p=0.017 and p=0.005, respectively) alongside larger brachial artery diameter (p=0.015), lower FMD% (p=0.026) and GTN induced dilation (GID) (p=0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline fluctuations (BDF) (p=0.026), longer reaction time (RT) (p=0.032) and reduced baseline-corrected flicker response (bFR) (p=0.045). In IGT subjects retinal BDF correlated with and Total:HDL (p= 0.003) and HDL-C (p= 0.004). Arterial RT also correlated with FMD (p=0.017) in IGT but not NGT subjects. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for CVD. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered.

Abnormal visual habituation in pediatric photosensitive epilepsy

Objective - To investigate visual habituation – a measure of visual cortical excitability – in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children. Methods - We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75–P100 and P100–N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75–P100 and P100–N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75–P100 and P100–N145 latencies was also analyzed. Results - Statistical analysis revealed significant differences between the three groups in the slope index of N75–P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks. Conclusions - Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies. Significance This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age.

Pattern integration in the normal and abnormal human visual system

The processing conducted by the visual system requires the combination of signals that are detected at different locations in the visual field. The processes by which these signals are combined are explored here using psychophysical experiments and computer modelling. Most of the work presented in this thesis is concerned with the summation of contrast over space at detection threshold. Previous investigations of this sort have been confounded by the inhomogeneity in contrast sensitivity across the visual field. Experiments performed in this thesis find that the decline in log contrast sensitivity with eccentricity is bilinear, with an initial steep fall-off followed by a shallower decline. This decline is scale-invariant for spatial frequencies of 0.7 to 4 c/deg. A detailed map of the inhomogeneity is developed, and applied to area summation experiments both by incorporating it into models of the visual system and by using it to compensate stimuli in order to factor out the effects of the inhomogeneity. The results of these area summation experiments show that the summation of contrast over area is spatially extensive (occurring over 33 stimulus carrier cycles), and that summation behaviour is the same in the fovea, parafovea, and periphery. Summation occurs according to a fourth-root summation rule, consistent with a “noisy energy” model. This work is extended to investigate the visual deficit in amblyopia, finding that area summation is normal in amblyopic observers. Finally, the methods used to study the summation of threshold contrast over area are adapted to investigate the integration of coherent orientation signals in a texture. The results of this study are described by a two-stage model, with a mandatory local combination stage followed by flexible global pooling of these local outputs. In each study, the results suggest a more extensive combination of signals in vision than has been previously understood.

Patients with early age-related macular degeneration exhibit signs of macro- and micro-vascular disease and abnormal blood glutathione levels

Background: This pilot study aimed to investigate systemic and retinal vascular function and their relationship to circulatory markers of cardiovascular risk in early age-related macular degeneration (AMD) patients without any already diagnosed systemic vascular pathologies. Methods: Fourteen patients diagnosed with early AMD and 14 age- and gender-matched healthy controls underwent blood pressure, carotid intima-media thickness (C-IMT) and peripheral arterial stiffness measurements. Retinal vascular reactivity was assessed by means of dynamic retinal vessel analysis (DVA) using a modified protocol. Blood analyses were conducted for glutathione levels and plasma levels of total cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). Results: The AMD patients showed significantly greater C-IMT (p = 0.029) and augmentation index (AIx) (p = 0.042) than the age-matched controls. In addition, they demonstrated a shallower retinal arterial dilation slope (Slope AD) (p = 0.005) and a longer retinal venous reaction time (RT) to flickering light (p = 0.026). Blood analyses also revealed that AMD patients exhibited higher oxidized glutathione (GSSG) (p = 0.024), lower redox index (p = 0.043) and higher LDL-C (p = 0.033) levels than the controls. Venous RT parameter correlated positively with blood GSSG levels (r = 0.58, p = 0.038) in AMD subjects, but not in the controls (p > 0.05). Conclusions: Patients diagnosed with early AMD exhibit signs of systemic and retinal vascular alterations that correlated with known risk markers for future cardiovascular morbidity. © 2013 Springer-Verlag Berlin Heidelberg.

Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction

OBJECTIVE: To investigate laboratory evidence of abnormal angiogenesis, hemorheologic factors, endothelial damage/dysfunction, and age-related macular degeneration (ARMD). DESIGN: Comparative cross-sectional study. PARTICIPANTS: We studied 78 subjects (26 men and 52 women; mean age 74 years; standard deviation [SD] 9.0) with ARMD attending a specialist referral clinic. Subjects were compared with 25 healthy controls (mean age, 71 years; SD, 11). INTERVENTION AND OUTCOME MEASURES: Levels of vascular endothelial growth factor (VEGF, an index of angiogenesis), hemorheologic factors (plasma viscosity, hematocrit, white cell count, hemoglobin, platelets), fibrinogen (an index of rheology and hemostasis), and von Willebrand factor (a marker of endothelial dysfunction) were measured. RESULTS: Median plasma VEGF (225 vs. 195 pg/ml, P = 0.019) and mean von Willebrand factor (124 vs. 99 IU/dl, P = 0.0004) were greater in ARMD subjects than the controls. Mean plasma fibrinogen and plasma viscosity levels were also higher in the subjects (both P < 0.0001). There were no significant differences in other indices between cases and controls. When "dry" (drusen, atrophy, n = 28) and "exudative" (n = 50) ARMD subjects were compared, there was no significant differences in VEGF, fibrinogen, viscosity, or von Willebrand factor levels. There were no significant correlations between the measured parameters. Stepwise multiple regression analysis did not demonstrate any significant clinical predictors (age, gender, smoking, body mass index, history of vascular disease, or hypertension) for plasma VEGF or fibrinogen levels, although smoking status was a predictor of plasma von Willebrand factor levels (P < 0.05). CONCLUSIONS: This study suggests an association between markers of angiogenesis (VEGF), hemorheologic factors, hemostasis, endothelial dysfunction, and ARMD. The interaction between abnormal angiogenesis and the components of Virchow's triad for thrombogenesis may in part contribute to the pathogenesis of ARMD.

Abnormal photosensitivity effects and the formation of type IA FBGs

We report the abnormal photosensitivity effects leading to the formation of Type IA FBGs. We show the rate at which these gratings form is related to the intensity of the UV inscription laser. We report the first measurement of the reflection along the gratings’ length.

Abnormal spectral evolution of fiber Bragg gratings in hydrogenated fibers

The properties of fiber Bragg gratings in hydrogenated fibers under conditions of ultraviolet overexposure were investigated. Abnormal spectral evolution of the regenerated grating following erasure of the initial type I grating was observed in the hydrogenated fibers. The regenerated grating also exhibited less temperature sensitivity and an 18 nm shift in the Bragg wavelength.

Abnormal systemic and ocular vascular response to temperature provocation in primary open-angle glaucoma patients:a case for autonomic failure?

PURPOSE. To assess systemic and ocular vascular reactivity in response to warm and cold provocation in untreated patients with primary open-angle glaucoma and normal control subjects. METHODS. Twenty-four patients with primary open-angle glaucoma and 22 normal control subjects were subjected to a modified cold pressor test involving immersion of the right hand in 40°C warm water followed by 4°C cold water exposure, and finger and ocular blood flow were assessed by means of peripheral laser Doppler flowmetry and retinal flowmetry, respectively. Finger and body temperature as well as intraocular pressure, systemic blood pressure, systemic pulse pressure, heart rate, and ocular perfusion pressure were also monitored. RESULTS. The patients with glaucoma demonstrated an increase in diastolic blood pressure (P = 0.023), heart rate (P = 0.010), and mean ocular perfusion pressure (P = 0.039) during immersion of the tested hand in 40°C water. During cold provocation, the patients demonstrated a significant decrease in finger (P = 0.0003) and ocular blood flow (the parameter velocity measured at the temporal neuroretinal rim area; P = 0.021). Normal subjects did not demonstrate any blood flow or finger temperature changes during immersion of the tested hand in 40°C water (P > 0.05); however, they exhibited increases in systolic blood pressure (P = 0.034) and pulse pressure (P = 0.0009) and a decrease in finger blood flow (P = 0.0001) during cold provocation. In normal subjects, the ocular blood flow was unchanged during high- and low-temperature challenge. CONCLUSIONS. Cold provocation elicits a different blood pressure, and ocular blood flow response in patients with primary open-angle glaucoma compared with control subjects. These findings suggest a systemic autonomic failure and ocular vascular dysregulation in POAG patients.

Dynamic modeling and analysis of single-stage boost inverters under normal and abnormal conditions

Inverters play key roles in connecting sustainable energy (SE) sources to the local loads and the ac grid. Although there has been a rapid expansion in the use of renewable sources in recent years, fundamental research, on the design of inverters that are specialized for use in these systems, is still needed. Recent advances in power electronics have led to proposing new topologies and switching patterns for single-stage power conversion, which are appropriate for SE sources and energy storage devices. The current source inverter (CSI) topology, along with a newly proposed switching pattern, is capable of converting the low dc voltage to the line ac in only one stage. Simple implementation and high reliability, together with the potential advantages of higher efficiency and lower cost, turns the so-called, single-stage boost inverter (SSBI), into a viable competitor to the existing SE-based power conversion technologies.^ The dynamic model is one of the most essential requirements for performance analysis and control design of any engineering system. Thus, in order to have satisfactory operation, it is necessary to derive a dynamic model for the SSBI system. However, because of the switching behavior and nonlinear elements involved, analysis of the SSBI is a complicated task.^ This research applies the state-space averaging technique to the SSBI to develop the state-space-averaged model of the SSBI under stand-alone and grid-connected modes of operation. Then, a small-signal model is derived by means of the perturbation and linearization method. An experimental hardware set-up, including a laboratory-scaled prototype SSBI, is built and the validity of the obtained models is verified through simulation and experiments. Finally, an eigenvalue sensitivity analysis is performed to investigate the stability and dynamic behavior of the SSBI system over a typical range of operation. ^

Use of Hemoglobin A1C to Detect Haitian-Americans with Undiagnosed Type 2 Diabetes

OBJECTIVE: To evaluate the validity of hemoglobin A1C (A1C) as a diagnostic tool for type 2 diabetes and to determine the most appropriate A1C cutoff point for diagnosis in a sample of Haitian-Americans. SUBJECTS AND METHODS: Subjects (n = 128) were recruited from Miami-Dade and Broward counties, FL. Receiver operating characteristics (ROC) analysis was run in order to measure sensitivity and specificity of A1C for detecting diabetes at different cutoff points. RESULTS: The area under the ROC curve was 0.86 using fasting plasma glucose ≥ 7.0 mmol/L as the gold standard. An A1C cutoff point of 6.26% had sensitivity of 80% and specificity of 74%, whereas an A1C cutoff point of 6.50% (recommended by the American Diabetes Association – ADA) had sensitivity of 73% and specificity of 89%. CONCLUSIONS: A1C is a reliable alternative to fasting plasma glucose in detecting diabetes in this sample of Haitian-Americans. A cutoff point of 6.26% was the optimum value to detect type 2 diabetes.

Factors affecting BMI and hemoglobin levels of mothers and infants in Kuwait

If you are the rightful copyright holder of this dissertation or thesis and wish to have it removed from the Open Access Collection, please submit a request to dcc@fiu.edu and include clear identification of the work, preferably with URL.

Psychosocial morbidity in women with abnormal cervical cytology managed by cytological surveillance or initial colposcopy : longitudinal analysis from the TOMBOLA randomised trial

We are grateful for the co-operation and assistance that we received from NHS staff in the co-ordinating centres and clinical sites. We thank the women who participated in TOMBOLA. The TOMBOLA trial was supported by the Medical Research Council (G9700808) and the NHS in England and Scotland. The TOMBOLA Group comprises the following: Grant-holders: University of Aberdeen and NHS Grampian, Aberdeen, Scotland: Maggie Cruickshank, Graeme Murray, David Parkin, Louise Smart, Eric Walker, Norman Waugh (Principal Investigator 2004–2008) University of Nottingham and Nottingham NHS, Nottingham, England: Mark Avis, Claire Chilvers, Katherine Fielding, Rob Hammond, David Jenkins, Jane Johnson, Keith Neal, Ian Russell, Rashmi Seth, Dave Whynes University of Dundee and NHS Tayside, Dundee, Tayside: Ian Duncan, Alistair Robertson (deceased) University of Ottawa, Ottawa, Canada: Julian Little (Principal Investigator 1999–2004) National Cancer Registry, Cork, Ireland: Linda Sharp Bangor University, Bangor, Wales: Ian Russell University of Hull, Hull, England: Leslie G Walker Staff in clinical sites and co-ordinating centres Grampian Breda Anthony, Sarah Bell, Adrienne Bowie, Katrina Brown (deceased), Joe Brown, Kheng Chew, Claire Cochran, Seonaidh Cotton, Jeannie Dean, Kate Dunn, Jane Edwards, David Evans, Julie Fenty, Al Finlayson, Marie Gallagher, Nicola Gray, Maureen Heddle, Alison Innes, Debbie Jobson, Mandy Keillor, Jayne MacGregor, Sheona Mackenzie, Amanda Mackie, Gladys McPherson, Ike Okorocha, Morag Reilly, Joan Rodgers, Alison Thornton, Rachel Yeats Tayside Lindyanne Alexander, Lindsey Buchanan, Susan Henderson, Tine Iterbeke, Susanneke Lucas, Gillian Manderson, Sheila Nicol, Gael Reid, Carol Robinson, Trish Sandilands Nottingham Marg Adrian, Ahmed Al-Sahab, Elaine Bentley, Hazel Brook, Claire Bushby, Rita Cannon, Brenda Cooper, Ruth Dowell, Mark Dunderdale, Dr Gabrawi, Li Guo, Lisa Heideman, Steve Jones, Salli Lawson, Zoë Philips, Christopher Platt, Shakuntala Prabhakaran, John Rippin, Rose Thompson, Elizabeth Williams, Claire Woolley Statistical analysis Seonaidh Cotton, Kirsten Harrild, John Norrie, Linda Sharp External Trial Steering Committee Nicholas Day (chair, 1999–2004), Theresa Marteau (chair 2004-), Mahesh Parmar, Julietta Patnick and Ciaran Woodman.

Impact of Hemoglobin Levels and Anemia on Mortality in Acute Stroke : Analysis of UK Regional Registry Data, Systematic Review, and Meta‐Analysis

Funding Sources The NNUH Stroke and TIA Register is maintained by the NNUH NHS Foundation Trust Stroke Services and data management for this study is supported by the NNUH Research and Development Department through Research Capability Funds.

Glycated hemoglobin, body weight and blood pressure in type 2 diabetes patients initiating dapagliflozin treatment in primary care:a retrospective study

Introduction - The present study aimed to describe characteristics of patients with type 2 diabetes (T2D) in UK primary care initiated on dapagliflozin, post-dapagliflozin changes in glycated hemoglobin (HbA1c), body weight and blood pressure, and reasons for adding dapagliflozin to insulin. Methods - Retrospective study of patients with T2D in the Clinical Practice Research Datalink with first prescription for dapagliflozin. Patients were included in the study if they: (1) had a first prescription for dapagliflozin between November 2012 and September 2014; (2) had a Read code for T2D; (3) were registered with a practice for at least 6 months before starting dapagliflozin; and (4) remained registered for at least 3 months after initiation. A questionnaire ascertained reason(s) for adding dapagliflozin to insulin. Results - Dapagliflozin was most often used as triple therapy (27.7%), dual therapy with metformin (25.1%) or added to insulin (19.2%). Median therapy duration was 329 days [95% confidence interval (CI) 302–361]. Poor glycemic control was the reason for dapagliflozin initiation for 93.1% of insulin-treated patients. Avoiding increases in weight/body mass index and insulin resistance were the commonest reasons for selecting dapagliflozin versus intensifying insulin. HbA1c declined by mean of 9.7 mmol/mol (95% CI 8.5–10.9) (0.89%) 14–90 days after starting dapagliflozin, 10.2 mmol/mol (95% CI 8.9–11.5) (0.93%) after 91–180 days and 12.6 mmol/mol (95% CI 11.0–14.3) (1.16%) beyond 180 days. Weight declined by mean of 2.6 kg (95% CI 2.3–2.9) after 14–90 days, 4.3 kg (95% CI 3.8–4.7) after 91–180 days and 4.6 kg (95% CI 4.0–5.2) beyond 180 days. In patients with measurements between 14 and 90 days after starting dapagliflozin, systolic and diastolic blood pressure decreased by means of 4.5 (95% CI −5.8 to −3.2) and 2.0 (95% CI −2.9 to −1.2) mmHg, respectively from baseline. Similar reductions in systolic and diastolic blood pressure were observed after 91–180 days and when follow-up extended beyond 180 days. Results were consistent across subgroups. Conclusion - HbA1c, body weight and blood pressure were reduced after initiation of dapagliflozin in patients with T2D in UK primary care and the changes were consistent with randomized clinical trials.

Assessment of Two Diabetes Point-of-Care Analyzers Measuring Hemoglobin A1c in the Peruvian Amazon

Aims: Measurement of glycated hemoglobin (HbA1c) is an important indicator of glucose control over time. Point-of-care (POC) devices allow for rapid and convenient measurement of HbA1c, greatly facilitating diabetes care. We assessed two POC analyzers in the Peruvian Amazon where laboratory-based HbA1c testing is not available.

Methods: Venous blood samples were collected from 203 individuals from six different Amazonian communities with a wide range of HbA1c, 4.4-9.0% (25-75 mmol/mol). The results of the Afinion AS100 and the DCA Vantage POC analyzers were compared to a central laboratory using the Premier Hb9210 high-performance liquid chromatography (HPLC) method. Imprecision was assessed by performing 14 successive tests of a single blood sample.

Results: The correlation coefficient r for POC and HPLC results was 0.92 for the Afinion and 0.93 for the DCA Vantage. The Afinion generated higher HbA1c results than the HPLC (mean difference = +0.56% [+6 mmol/mol]; p < 0.001), as did the DCA Vantage (mean difference = +0.32% [4 mmol/mol]). The bias observed between POC and HPLC did not vary by HbA1c level for the DCA Vantage (p = 0.190), but it did for the Afinion (p < 0.001). Imprecision results were: CV = 1.75% for the Afinion, CV = 4.01% for the DCA Vantage. Sensitivity was 100% for both devices, specificity was 48.3% for the Afinion and 85.1% for the DCA Vantage, positive predictive value (PPV) was 14.4% for the Afinion and 34.9% for the DCA Vantage, and negative predictive value (NPV) for both devices was 100%. The area under the receiver operating characteristic (ROC) curve was 0.966 for the Afinion and 0.982 for the DCA Vantage. Agreement between HPLC and POC in classifying diabetes and prediabetes status was slight for the Afinion (Kappa = 0.12) and significantly different (McNemar’s statistic = 89; p < 0.001), and moderate for the DCA Vantage (Kappa = 0.45) and significantly different (McNemar’s statistic = 28; p < 0.001).

Conclusions: Despite significant variation of HbA1c results between the Afinion and DCA Vantage analyzers compared to HPLC, we conclude that both analyzers should be considered in health clinics in the Peruvian Amazon for therapeutic adjustments if healthcare workers are aware of the differences relative to testing in a clinical laboratory. However, imprecision and bias were not low enough to recommend either device for screening purposes, and the local prevalence of anemia and malaria may interfere with diagnostic determinations for a substantial portion of the population.