Performance of commercial enzyme-linked immunosorbent assays (ELISA) for diagnosis of HSV-1 and HSV-2 infection in a clinical setting

Thesis (Master's)--University of Washington, 2016-06

Measurement of free drug and clinical end-point by high-performance liquid chromatography-mass spectrometry: Applications and implications for pharmacokinetic and pharmacodynamic studies

Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)-mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published methods for the determination of free drug concentrations by HPLC-MS. The development of atmospheric pressure ionisation sources, together with on-line microdialysis or on-line equilibrium dialysis and column switching techniques have reduced sample run times and increased assay efficiency. The availability of such methods will aid in drug development and the clinical use of certain drugs, including anti-convulsants, anti-arrhythmics, immunosuppressants, local anaesthetics, anti-fungals and protease inhibitors. The history of free drug measurement and an overview of the current HPLC-MS applications for these drugs are discussed. Immunosuppressant drugs are used as an example for the application of HPLC-MS in the measurement of drug pharmacodynamics. Potential biomarkers of immunosuppression that could be measured by HPLC-MS include purine nucleoside/nucleotides, drug-protein complexes and phosphorylated peptides. At the proteomic level, two-dimensional gel electrophoresis combined with matrix-assisted laser desorption/ionisation time-of-flight (TOF) MS is a powerful tool for identifying proteins involved in the response to inflammatory mediators. (C) 2003 Elsevier Science B.V. All rights reserved.

Comparative academic performance of medical students in rural and urban clinical settings

OBJECTIVE To determine whether the academic performance of medical students learning in rural settings differs from those learning in urban settings. DESIGN Comparison of results of assessment for 2 full cohorts and 1 part cohort of medical students learning in rural and urban settings in 2002 (209 students), 2003 (226 students) and 2004 (220 students), including results for each specialist rotation in the 3rd year and end-of-year examinations in the 2nd and 4th years. SETTING University of Queensland School of Medicine, Brisbane. Students spent the whole 3rd year (of a 4-year graduate entry programme) conducting 5 specialist 8-week rotations in either the rural clinical division (rural students) or in Brisbane (urban students), all following the same curriculum and taking the same examinations. RESULTS For the 2002 cohort there were no statistically significant differences in academic performance between rural and urban students. For the 2003 cohort the only significant difference was a higher score for rural students in the end of the 4th-year clinical skills examination (65.7 versus 62.3%, P = 0.025). For the 2004 cohort, rural students scored higher in the 3rd-year mental health rotation (79.3 versus 76.2%, P = 0.038) and lower in the medicine rotation (65.5 versus 68.6%, P = 0.037). CONCLUSION Academic performance among students studying in rural and urban settings is comparable.

Clinical techniques to assess the visual and optical performance of intraocular lenses:a review

A number of clinical techniques are available to assess the visual and optical performance of the eye. This report aims to review the advantages and limitations of techniques used in previous studies of patients implanted with intraocular lenses (IOLs), whose designs are ever increasing in optical complexity. Although useful, in-vitro measurements of IOL optical quality cannot account for the wide range of biological variation in ocular anatomy and corneal optics, which will impact on the visual outcome achieved. This further highlights the need for a standardised series of visual performance tests that can be applied to a wide range of IOL designs. The conclusions of this report intend to assistresearchers in developing a comprehensive series of investigations to evaluate IOL performance. Repeatable and reproducible in-vivo assessments of visual and optical performance are desirable to further develop IOL concepts and designs, in the hope of improving current postoperative visual satisfaction. © 2013 Nova Science Publishers, Inc.

To what extent does the Health Professions Admission Test-Ireland predict performance in early undergraduate tests of communication and clinical skills? – An observational cohort study

Background: Internationally, tests of general mental ability are used in the selection of medical students. Examples include the Medical College Admission Test, Undergraduate Medicine and Health Sciences Admission Test and the UK Clinical Aptitude Test. The most widely used measure of their efficacy is predictive validity.A new tool, the Health Professions Admission Test- Ireland (HPAT-Ireland), was introduced in 2009. Traditionally, selection to Irish undergraduate medical schools relied on academic achievement. Since 2009, Irish and EU applicants are selected on a combination of their secondary school academic record (measured predominately by the Leaving Certificate Examination) and HPAT-Ireland score. This is the first study to report on the predictive validity of the HPAT-Ireland for early undergraduate assessments of communication and clinical skills. Method. Students enrolled at two Irish medical schools in 2009 were followed up for two years. Data collected were gender, HPAT-Ireland total and subsection scores; Leaving Certificate Examination plus HPAT-Ireland combined score, Year 1 Objective Structured Clinical Examination (OSCE) scores (Total score, communication and clinical subtest scores), Year 1 Multiple Choice Questions and Year 2 OSCE and subset scores. We report descriptive statistics, Pearson correlation coefficients and Multiple linear regression models. Results: Data were available for 312 students. In Year 1 none of the selection criteria were significantly related to student OSCE performance. The Leaving Certificate Examination and Leaving Certificate plus HPAT-Ireland combined scores correlated with MCQ marks.In Year 2 a series of significant correlations emerged between the HPAT-Ireland and subsections thereof with OSCE Communication Z-scores; OSCE Clinical Z-scores; and Total OSCE Z-scores. However on multiple regression only the relationship between Total OSCE Score and the Total HPAT-Ireland score remained significant; albeit the predictive power was modest. Conclusion: We found that none of our selection criteria strongly predict clinical and communication skills. The HPAT- Ireland appears to measures ability in domains different to those assessed by the Leaving Certificate Examination. While some significant associations did emerge in Year 2 between HPAT Ireland and total OSCE scores further evaluation is required to establish if this pattern continues during the senior years of the medical course.

Long term performance evaluation of small-diameter vascular grafts based on polyvinyl alcohol hydrogel and dextran and MSCs-based therapies using the ovine pre-clinical animal model.

The functional and structural performance of a 5 cm synthetic small diameter vascular graft (SDVG) produced by the copolymerization of polyvinyl alcohol hydrogel with low molecular weight dextran (PVA/Dx graft) associated to mesenchymal stem cells (MSCs)-based therapies and anticoagulant treatment with heparin, clopidogrel and warfarin was tested using the ovine model during the healing period of 24 weeks. The results were compared to the ones obtained with standard expanded polyetetrafluoroethylene grafts (ePTFE graft). Blood flow, vessel and graft diameter measurements, graft appearance and patency rate (PR), thrombus, stenosis and collateral vessel formation were evaluated by B-mode ultrasound, audio and color flow Doppler. Graft and regenerated vessels morphologic evaluation was performed by scanning electronic microscopy (SEM), histopathological and immunohistochemical analysis. All PVA/Dx grafts could maintain a similar or higher PR and systolic / diastolic laminar blood flow velocities were similar to ePTFE grafts. CD14 (macrophages) and α-actin (smooth muscle) staining presented similar results in PVA/Dx/MSCs and ePTFE graft groups. Fibrosis layer was lower and endothelial cells were only detected at graft-artery transitions where it was added the MSCs. In conclusion, PVA/Dx graft can be an excellent scaffold candidate for vascular reconstruction, including clinic mechanically challenging applications, such as SDVGs, especially when associated to MSCs-based therapies to promote higher endothelialization and lower fibrosis of the vascular prosthesis, but also higher PR values.

A grounded theory study of nursing students’ experiences in the off-campus clinical setting

Poor workplace relations are an issue of concern in many workplaces and this phenomenon is not restricted to the nursing profession. The issue of workplace violence in nursing is well documented and there are an increasing number of studies which have investigated the notion of horizontal violence amongst graduate nurses. The impact that poor workplace relations has on the development of a professional identity by nursing students in the off-campus clinical setting is significant in light of the current global shortage of nurses. There is a dearth of knowledge in understanding how Australian undergraduate nursing students experience the off-campus clinical setting and subsequently develop a professional identity as a nurse. Therefore the aim of this study was to discover and describe the phenomena in order to develop a substantive theory that explains the experiences of the undergraduate nursing students in a regional setting. Constructivist grounded theory methods were utilised in the conduct of the study. A sample of 29 participants was recruited permitting the formulation of a substantive theory regarding the development of a professional identity in nursing students. This substantive theory contributes knowledge relevant to the undergraduate nursing students, nurse educators, nursing workforce planners, and the tertiary educational institutions offering nursing. This is achieved through discovering, describing and explaining the phenomenon of ‘anxiety’ which the nursing students experience as a result of the interrelationship and interactions of tradition bearing, staff and student performance. These interactions intersect to form expectations of where the student fits within the hierarchy of the facility and the nursing profession in general. An understanding of the issues associated with tradition bearing, staff performance, and student performance and the impact that the interaction of these conditions has upon the student’s developing professional identity as a nurse is necessary to allow for the implementation of corrective strategies.

Driving performance in persons with hemianopia and quadrantanopia assessed under in-traffic conditions

Purpose: To evaluate the on-road driving performance of persons with homonymous hemianopia or quadrantanopia in comparison to age-matched controls with normal visual fields. Methods: Participants were 22 hemianopes and eight quadrantanopes (mean age 53 years) and 30 persons with normal visual fields (mean age 52 years) and were either current drivers or aiming to resume driving. All participants completed a battery of tests of vision (ETDRS visual acuity, Pelli-Robson letter contrast sensitivity, Humphrey visual fields), cognitive tests (trials A and B, Mini Mental State Examination, Digit Symbol Substitution) and an on-road driving assessment. Driving performance was assessed in a dual-brake vehicle with safety monitored by a certified driving rehabilitation specialist. Backseat evaluators masked to the clinical characteristics of participants independently rated driving performance along a 22.7 kilometre route involving urban and interstate driving. Results: Seventy-three per cent of the hemianopes, 88 per cent of quadrantanopes and all of the drivers with normal fields received safe driving ratings. Those hemianopic and quadrantanopic drivers rated as unsafe tended to have problems with maintaining appropriate lane position, steering steadiness and gap judgment compared to controls. Unsafe driving was associated with slower visual processing speed and impairments in contrast sensitivity, visual field sensitivity and executive function. Conclusions: Our findings suggest that some drivers with hemianopia or quadrantanopia are capable of safe driving performance, when compared to those of the same age with normal visual fields. This finding has important implications for the assessment of fitness to drive in this population.

The effect of prolonged reading on visual functions and reading performance in students with low vision

This study is the first to investigate the effect of prolonged reading on reading performance and visual functions in students with low vision. The study focuses on one of the most common modes of achieving adequate magnification for reading by students with low vision, their close reading distance (proximal or relative distance magnification). Close reading distances impose high demands on near visual functions, such as accommodation and convergence. Previous research on accommodation in children with low vision shows that their accommodative responses are reduced compared to normal vision. In addition, there is an increased lag of accommodation for higher stimulus levels as may occur at close reading distance. Reduced accommodative responses in low vision and higher lag of accommodation at close reading distances together could impact on reading performance of students with low vision especially during prolonged reading tasks. The presence of convergence anomalies could further affect reading performance. Therefore, the aims of the present study were 1) To investigate the effect of prolonged reading on reading performance in students with low vision 2) To investigate the effect of prolonged reading on visual functions in students with low vision. This study was conducted as cross-sectional research on 42 students with low vision and a comparison group of 20 students with normal vision, aged 7 to 20 years. The students with low vision had vision impairments arising from a range of causes and represented a typical group of students with low vision, with no significant developmental delays, attending school in Brisbane, Australia. All participants underwent a battery of clinical tests before and after a prolonged reading task. An initial reading-specific history and pre-task measurements that included Bailey-Lovie distance and near visual acuities, Pelli-Robson contrast sensitivity, ocular deviations, sensory fusion, ocular motility, near point of accommodation (pull-away method), accuracy of accommodation (Monocular Estimation Method (MEM)) retinoscopy and Near Point of Convergence (NPC) (push-up method) were recorded for all participants. Reading performance measures were Maximum Oral Reading Rates (MORR), Near Text Visual Acuity (NTVA) and acuity reserves using Bailey-Lovie text charts. Symptoms of visual fatigue were assessed using the Convergence Insufficiency Symptom Survey (CISS) for all participants. Pre-task measurements of reading performance and accuracy of accommodation and NPC were compared with post-task measurements, to test for any effects of prolonged reading. The prolonged reading task involved reading a storybook silently for at least 30 minutes. The task was controlled for print size, contrast, difficulty level and content of the reading material. Silent Reading Rate (SRR) was recorded every 2 minutes during prolonged reading. Symptom scores and visual fatigue scores were also obtained for all participants. A visual fatigue analogue scale (VAS) was used to assess visual fatigue during the task, once at the beginning, once at the middle and once at the end of the task. In addition to the subjective assessments of visual fatigue, tonic accommodation was monitored using a photorefractor (PlusoptiX CR03™) every 6 minutes during the task, as an objective assessment of visual fatigue. Reading measures were done at the habitual reading distance of students with low vision and at 25 cms for students with normal vision. The initial history showed that the students with low vision read for significantly shorter periods at home compared to the students with normal vision. The working distances of participants with low vision ranged from 3-25 cms and half of them were not using any optical devices for magnification. Nearly half of the participants with low vision were able to resolve 8-point print (1M) at 25 cms. Half of the participants in the low vision group had ocular deviations and suppression at near. Reading rates were significantly reduced in students with low vision compared to those of students with normal vision. In addition, there were a significantly larger number of participants in the low vision group who could not sustain the 30-minute task compared to the normal vision group. However, there were no significant changes in reading rates during or following prolonged reading in either the low vision or normal vision groups. Individual changes in reading rates were independent of their baseline reading rates, indicating that the changes in reading rates during prolonged reading cannot be predicted from a typical clinical assessment of reading using brief reading tasks. Contrary to previous reports the silent reading rates of the students with low vision were significantly lower than their oral reading rates, although oral and silent reading was assessed using different methods. Although the visual acuity, contrast sensitivity, near point of convergence and accuracy of accommodation were significantly poorer for the low vision group compared to those of the normal vision group, there were no significant changes in any of these visual functions following prolonged reading in either group. Interestingly, a few students with low vision (n =10) were found to be reading at a distance closer than their near point of accommodation. This suggests a decreased sensitivity to blur. Further evaluation revealed that the equivalent intrinsic refractive errors (an estimate of the spherical dioptirc defocus which would be expected to yield a patient’s visual acuity in normal subjects) were significantly larger for the low vision group compared to those of the normal vision group. As expected, accommodative responses were significantly reduced for the low vision group compared to the expected norms, which is consistent with their close reading distances, reduced visual acuity and contrast sensitivity. For those in the low vision group who had an accommodative error exceeding their equivalent intrinsic refractive errors, a significant decrease in MORR was found following prolonged reading. The silent reading rates however were not significantly affected by accommodative errors in the present study. Suppression also had a significant impact on the changes in reading rates during prolonged reading. The participants who did not have suppression at near showed significant decreases in silent reading rates during and following prolonged reading. This impact of binocular vision at near on prolonged reading was possibly due to the high demands on convergence. The significant predictors of MORR in the low vision group were age, NTVA, reading interest and reading comprehension, accounting for 61.7% of the variances in MORR. SRR was not significantly influenced by any factors, except for the duration of the reading task sustained; participants with higher reading rates were able to sustain a longer reading duration. In students with normal vision, age was the only predictor of MORR. Participants with low vision also reported significantly greater visual fatigue compared to the normal vision group. Measures of tonic accommodation however were little influenced by visual fatigue in the present study. Visual fatigue analogue scores were found to be significantly associated with reading rates in students with low vision and normal vision. However, the patterns of association between visual fatigue and reading rates were different for SRR and MORR. The participants with low vision with higher symptom scores had lower SRRs and participants with higher visual fatigue had lower MORRs. As hypothesized, visual functions such as accuracy of accommodation and convergence did have an impact on prolonged reading in students with low vision, for students whose accommodative errors were greater than their equivalent intrinsic refractive errors, and for those who did not suppress one eye. Those students with low vision who have accommodative errors higher than their equivalent intrinsic refractive errors might significantly benefit from reading glasses. Similarly, considering prisms or occlusion for those without suppression might reduce the convergence demands in these students while using their close reading distances. The impact of these prescriptions on reading rates, reading interest and visual fatigue is an area of promising future research. Most importantly, it is evident from the present study that a combination of factors such as accommodative errors, near point of convergence and suppression should be considered when prescribing reading devices for students with low vision. Considering these factors would also assist rehabilitation specialists in identifying those students who are likely to experience difficulty in prolonged reading, which is otherwise not reflected during typical clinical reading assessments.

Clinical investigation of asmofilcon A silicone hydrogel lenses

Purpose. To investigate the clinical and subjective performance of asmofilcon A, a new third generation silicone hydrogel contact lens during 6-night extended wear (EW) over 6 months. Methods. A prospective, randomized, single-masked study was conducted. Sixty experienced daily wear soft contact lens wearers were randomly assigned to wear either asmofilcon A or senofilcon A contact lenses bilaterally for 6 months on an EW basis. Evaluations were conducted at contact lens delivery and after 1 week, 4 weeks, 3 and 6 months of EW. Results. Fifty subjects (83%) successfully completed the study. Two subjects experienced adverse events; one unilateral red eye with asmofilcon A and one asymptomatic infiltrate with senofilcon A. There were no significant differences in high or low contrast distance visual acuity between asmofilcon A and senofilcon A; however, low contrast distance visual acuity decreased significantly over time with both contact lens types (p < 0.05). The two lens types did not vary significantly with respect to any of the objective and subjective measures assessed (p > 0.05). Superior palpebral conjunctival injection showed a statistically significant increase over time with both lens types (p < 0.05). Both lens types were rated highly with respect to overall comfort, with subjects reporting 14 or 15 h of comfortable lens wearing time per day at each of the study visits (p > 0.05). Overall satisfaction ratings were also very high at all visits, with median scores of 95 (86 to 99) for asmofilcon A and 90 (85 to 96) for senofilcon A at 6 months (p > 0.05). Conclusions. Over 6 months of EW, the asmofilcon A contact lens performed in a similar manner to senofilcon A with respect to visual acuity, ocular health, and contact lens performance measures. Longer-term EW studies are required to investigate the changes over time observed with both lens types.