The relationship between CFH and ARMS2 genotypes and neuroretinal function in persons without age-related macular degeneration

Purpose: To determine whether neuroretinal function differs in healthy persons with and without common risk gene variants for age- related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare those findings in persons with manifest early AMD. Methods and Participants: Neuroretinal function was assessed with the multifocal electroretinogram (mfERG) (VERIS, Redwood City, CA,) in 32 participants (22 healthy persons with no clinical signs of AMD and 10 early AMD patients). The 22 healthy participants with no AMD were risk genotypes for either the CFH (rs380390) and/or ARMS2 (rs10490920). We used a slow flash mfERG paradigm (3 inserted frames) and a 103 hexagon stimulus array. Recordings were made with DTL electrodes; fixation and eye movements were monitored online. Trough N1 to peak P1 (N1P1) response densities and P1-implicit times (IT) were analysed in 5 concentric rings. Results: N1P1 response densities (mean ± SD) for concentric rings 1-3 were on average significantly higher in at-risk genotypes (ring 1: 17.97 nV/deg2 ± 1.9, ring 2: 11.7 nV/deg2 ±1.3, ring 3: 8.7 nV/deg2 ± 0.7) compared to those without risk (ring 1: 13.7 nV/deg2 ± 1.9, ring 2: 9.2 nV/deg2 ±0.8, ring 3: 7.3 nV/deg2 ± 1.1) and compared to persons with early AMD (ring 1: 15.3 nV/deg2 ± 4.8, ring 2: 9.1 nV/deg2 ±2.3, ring 3 nV/deg2: 7.3± 1.3) (p<0.5). The group implicit times, P1-ITs for ring 1 were on average delayed in the early AMD patients (36.4 ms ± 1.0) compared to healthy participants with (35.1 ms ± 1.1) or without risk genotypes (34.8 ms ±1.3), although these differences were not significant. Conclusion: Neuroretinal function in persons with normal fundi can be differentiated into subgroups based on their genetics. Increased neuroretinal activity in persons who carry AMD risk genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Assessment of neuroretinal function in healthy persons genetically susceptible to AMD may be a useful early biomarker before there is clinical manifestation of AMD.

Temporal summation of intrinsically photosensitive retinal ganglion cell (ipRGC) contributions to the human pupil.

Purpose: IpRGCs mediate non-image forming functions including photoentrainment and the pupil light reflex (PLR). Temporal summation increases visual sensitivity and decreases temporal resolution for image forming vision, but the summation properties of nonimage forming vision are unknown. We investigated the temporal summation of inner (ipRGC) and outer (rod/cone) retinal inputs to the PLR. Method: The consensual PLR of the left eye was measured in six participants with normal vision using a Maxwellian view infrared pupillometer. Temporal summation was investigated using a double-pulse protocol (100 ms stimulus pairs; 0–1024 ms inter-stimulus interval, ISI) presented to the dilated fellow right eye (Tropicamide 1%). Stimulus lights (blue λmax = 460 nm; red λmax = 638 nm) biased activity to inneror outer retinal inputs to non-image forming vision. Temporal summation was measured suprathreshold (15.2 log photons.cm−2.s−1 at the cornea) and subthreshold (11.4 log photons.cm−2.s−1 at the cornea). Results: RM-ANOVAs showed the suprathreshold and subthreshold 6 second post illumination pupil response (PIPR: expressed as percentage baseline diameter) did not significantly vary for red or blue stimuli (p > .05). The PIPR for a subthreshold red 16 ms double-pulse control condition did not significantly differ with ISI (p > .05). The maximum constriction amplitude for red and blue 100 ms double- pulse stimuli did not significantly vary with ISI (p > .05). Conclusion: The non-significant changes in suprathreshold PIPR and subthreshold maximum pupil constriction indicate that inner retinal ipRGC inputs and outer retinal photoreceptor inputs to the PLR do not show temporal summation. The results suggest a fundamental difference between the temporal summation characteristics of image forming and non-image forming vision.

The cultivation of human retinal pigment epithelial cells on Bombyx mori silk fibroin

We have presently evaluated membranes prepared from Bombyx mori silk fibroin (BMSF), for their potential use as a prosthetic Bruch’s membrane and carrier substrate for human retinal pigment epithelial (RPE) cell transplantation. Porous BMSF membranes measuring 3 μm in thickness were prepared from aqueous solutions (3% w/v) containing poly(ethylene oxide) (0.09%). The permeability coefficient for membranes was between 3 and 9 × 10-5 cm/s by using Allura red or 70 kDa FITC-dextran respectively. Average pore size (± sd) was 4.9 ± 2.3 µm and 2.9 ± 1.5 µm for upper and lower membrane surfaces respectively. Optimal attachment of ARPE-19 cells to BMSF membrane was achieved by pre-coating with vitronectin (1 µg/mL). ARPE-19 cultures maintained in low serum on BMSF membranes for approximately 8 weeks, developed a cobble-stoned morphology accompanied by a cortical distribution of F-actin and ZO-1. Similar results were obtained using primary cultures of human RPE cells, but cultures took noticeably longer to establish on BMSF compared with tissue culture plastic. These findings encourage further studies of BMSF as a substrate for RPE cell transplantation.

In situ SANS study of the surface and pore filling adsorption of subcritical and supercritical CO2 in porous silica as a function of pore size

We applied small-angle neutron scattering (SANS) and ultra small-angle neutron scattering (USANS) to monitor evolution of the CO2 adsorption in porous silica as a function of CO2 pressure and temperature in pores of different sizes. The range of pressures (0 < P < 345 bar) and temperatures (T=18 OC, 35 OC and 60 OC) corresponded to subcritical, near critical and supercritical conditions of bulk fluid. We observed that the adsorption behavior of CO2 is fundamentally different in large and small pores with the sizes D > 100 Å and D < 30 Å, respectively. Scattering data from large pores indicate formation of a dense adsorbed film of CO2 on pore walls with the liquid-like density (ρCO2)ads≈0.8 g/cm3. The adsorbed film coexists with unadsorbed fluid in the inner pore volume. The density of unadsorbed fluid in large pores is temperature and pressure dependent: it is initially lower than (ρCO2)ads and gradually approaches it with pressure. In small pores compressed CO2 gas completely fills the pore volume. At the lowest pressures of the order of 10 bar and T=18 OC, the fluid density in smallest pores available in the matrix with D ~ 10 Å exceeds bulk fluid density by a factor of ~ 8. As pressure increases, progressively larger pores become filled with the condensed CO2. Fluid densification is only observed in pores with sizes less than ~ 25 – 30 Å. As the density of the invading fluid reaches (ρCO2)bulk~ 0.8 g/cm3, pores of all sizes become uniformly filled with CO2 and the confinement effects disappear. At higher densities the fluid in small pores appears to follow the equation of state of bulk CO2 although there is an indication that the fluid density in the inner volume of large pores may exceed the density of the adsorbed layer. The equivalent internal pressure (Pint) in the smallest pores exceeds the external pressure (Pext) by a factor of ~ 5 for both sub- and supercritical CO2. Pint gradually approaches Pext as D → 25 – 30 Å and is independent of temperature in the studied range of 18 OC ≤ T ≤ 60 OC. The obtained results demonstrate certain similarity as well as differences between adsorption of subcritical and supercritical CO2 in disordered porous silica. High pressure small angle scattering experiments open new opportunities for in situ studies of the fluid adsorption in porous media of interest to CO2 sequestration, energy storage, and heterogeneous catalysis.

Retinal and choroidal thickness in myopic anisometropia

Purpose: To compare the retinal thickness (RT) and choroidal thickness (ChT) between the fellow eyes of non-amblyopic myopic anisometropes. Methods: The eyes of 22 non-amblyopic myopic anisometropes (1 D spherical equivalent refraction [SER] anisometropia) were examined using spectral domain optical coherence tomography (SD-OCT). Customised software was used to register, align and average multiple foveal OCT B-Scan images from each subject in order to enhance image quality. Two independent masked observers manually determined the RT and ChT from each SD-OCT image up to 2.5 mm nasal and temporal to the fovea. Axial length (AXL) was measured using optical low coherence biometry during relaxed accommodation. Results: The mean SER anisometropia was 1.74 ± 0.95 D and the mean interocular AXL difference was 0.58 ± 0.41 mm. There was no significant difference in foveal RT between the fellow eyes (P > 0.05). Mean subfoveal ChT was significantly thinner in the more myopic eye (252 ± 46 μm compared to the fellow, less myopic eye (286 ± 58 μm) (P < 0.001). There was a moderate correlation between the interocular difference in subfoveal ChT and the interocular difference in AXL (r = -0.50, P < 0.01). Asian anisometropes displayed more regionally symmetrical (nasal-temporal)interocular differences in ChT profile compared to Caucasians. Conclusions: RT was similar between the fellow eyes of myopic anisometropes; however, the subfoveal choroid was significantly thinner in the more myopic (longer) eye of this anisometropic cohort. The interocular asymmetry in ChT correlated with the interocular difference in AXL.

The impact of legislation on divorce : a hazard function approach

The paper examines the impact of the introduction of no-fault divorce legislation in Australia. The approach used is rather novel, a hazard model of the divorce rate is estimated with the role of legislation captured via a time-varying covariate. The paper concludes that contrary to US empirical evidence, no-fault divorce legislation appears to have had a positive impact upon the divorce rate in Australia.

Towards a Dynamic IS Function

With the growing importance of IS for organizations and the continuous stream of new IT developments, the IS function in organizations becomes more critical but is also more challenged. For example, how should the IS function deal with the consumerization of IT or what is the added value of the IS function when it comes to SaaS and the Cloud? In this paper we argue that IS research is in need of a dynamic perspective on the IS function. The IS function has to become more focused on building and adapting IS capabilities in a changing environment. We discuss that there has been an overreliance on the Resource Based View so far for understanding the IS function and capabilities and introduce Dynamic Capabilities Theory as an additional theoretical perspective, which has only been limitedly addressed in IS literature yet. We present a first conceptualization of the dynamic IS function and discuss IS capabilities frameworks and individual IS capabilities from a dynamic perspective. These initial insights demonstrate the contribution of a dynamic perspective on the IS function itself.

Binocular rivalry and visuospatial ability in individuals with schizophrenia

Visual abnormalities, both at the sensory input and the higher interpretive levels, have been associated with many of the symptoms of schizophrenia. Individuals with schizophrenia typically experience distortions of sensory perception, resulting in perceptual hallucinations and delusions that are related to the observed visual deficits. Disorganised speech, thinking and behaviour are commonly experienced by sufferers of the disorder, and have also been attributed to perceptual disturbances associated with anomalies in visual processing. Compounding these issues are marked deficits in cognitive functioning that are observed in approximately 80% of those with schizophrenia. Cognitive impairments associated with schizophrenia include: difficulty with concentration and memory (i.e. working, visual and verbal), an impaired ability to process complex information, response inhibition and deficits in speed of processing, visual and verbal learning. Deficits in sustained attention or vigilance, poor executive functioning such as poor reasoning, problem solving, and social cognition, are all influenced by impaired visual processing. These symptoms impact on the internal perceptual world of those with schizophrenia, and hamper their ability to navigate their external environment. Visual processing abnormalities in schizophrenia are likely to worsen personal, social and occupational functioning. Binocular rivalry provides a unique opportunity to investigate the processes involved in visual awareness and visual perception. Binocular rivalry is the alternation of perceptual images that occurs when conflicting visual stimuli are presented to each eye in the same retinal location. The observer perceives the opposing images in an alternating fashion, despite the sensory input to each eye remaining constant. Binocular rivalry tasks have been developed to investigate specific parts of the visual system. The research presented in this Thesis provides an explorative investigation into binocular rivalry in schizophrenia, using the method of Pettigrew and Miller (1998) and comparing individuals with schizophrenia to healthy controls. This method allows manipulations to the spatial and temporal frequency, luminance contrast and chromaticity of the visual stimuli. Manipulations to the rival stimuli affect the rate of binocular rivalry alternations and the time spent perceiving each image (dominance duration). Binocular rivalry rate and dominance durations provide useful measures to investigate aspects of visual neural processing that lead to the perceptual disturbances and cognitive dysfunction attributed to schizophrenia. However, despite this promise the binocular rivalry phenomenon has not been extensively explored in schizophrenia to date. Following a review of the literature, the research in this Thesis examined individual variation in binocular rivalry. The initial study (Chapter 2) explored the effect of systematically altering the properties of the stimuli (i.e. spatial and temporal frequency, luminance contrast and chromaticity) on binocular rivalry rate and dominance durations in healthy individuals (n=20). The findings showed that altering the stimuli with respect to temporal frequency and luminance contrast significantly affected rate. This is significant as processing of temporal frequency and luminance contrast have consistently been demonstrated to be abnormal in schizophrenia. The current research then explored binocular rivalry in schizophrenia. The primary research question was, "Are binocular rivalry rates and dominance durations recorded in participants with schizophrenia different to those of the controls?" In this second study binocular rivalry data that were collected using low- and highstrength binocular rivalry were compared to alternations recorded during a monocular rivalry task, the Necker Cube task to replicate and advance the work of Miller et al., (2003). Participants with schizophrenia (n=20) recorded fewer alternations (i.e. slower alternation rates) than control participants (n=20) on both binocular rivalry tasks, however no difference was observed between the groups on the Necker cube task. Magnocellular and parvocellular visual pathways, thought to be abnormal in schizophrenia, were also investigated in binocular rivalry. The binocular rivalry stimuli used in this third study (Chapter 4) were altered to bias the task for one of these two pathways. Participants with schizophrenia recorded slower binocular rivalry rates than controls in both binocular rivalry tasks. Using a ‘within subject design’, binocular rivalry data were compared to data collected from a backwardmasking task widely accepted to bias both these pathways. Based on these data, a model of binocular rivalry, based on the magnocellular and parvocellular pathways that contribute to the dorsal and ventral visual streams, was developed. Binocular rivalry rates were compared with performance on the Benton’s Judgment of Line Orientation task, in individuals with schizophrenia compared to healthy controls (Chapter 5). The Benton’s Judgment of Line Orientation task is widely accepted to be processed within the right cerebral hemisphere, making it an appropriate task to investigate the role of the cerebral hemispheres in binocular rivalry, and to investigate the inter-hemispheric switching hypothesis of binocular rivalry proposed by Pettigrew and Miller (1998, 2003). The data were suggestive of intra-hemispheric rather than an inter-hemispheric visual processing in binocular rivalry. Neurotransmitter involvement in binocular rivalry, backward masking and Judgment of Line Orientation in schizophrenia were investigated using a genetic indicator of dopamine receptor distribution and functioning; the presence of the Taq1 allele of the dopamine D2 receptor (DRD2) receptor gene. This final study (Chapter 6) explored whether the presence of the Taq1 allele of the DRD2 receptor gene, and thus, by inference the distribution of dopamine receptors and dopamine function, accounted for the large individual variation in binocular rivalry. The presence of the Taq1 allele was associated with slower binocular rivalry rates or poorer performance in the backward masking and Judgment of Line Orientation tasks seen in the group with schizophrenia. This Thesis has contributed to what is known about binocular rivalry in schizophrenia. Consistently slower binocular rivalry rates were observed in participants with schizophrenia, indicating abnormally-slow visual processing in this group. These data support previous studies reporting visual processing abnormalities in schizophrenia and suggest that a slow binocular rivalry rate is not a feature specific to bipolar disorder, but may be a feature of disorders with psychotic features generally. The contributions of the magnocellular or dorsal pathways and parvocellular or ventral pathways to binocular rivalry, and therefore to perceptual awareness, were investigated. The data presented supported the view that the magnocellular system initiates perceptual awareness of an image and the parvocellular system maintains the perception of the image, making it available to higher level processing occurring within the cortical hemispheres. Abnormal magnocellular and parvocellular processing may both contribute to perceptual disturbances that ultimately contribute to the cognitive dysfunction associated with schizophrenia. An alternative model of binocular rivalry based on these observations was proposed.

Self-regulated learning and executive function : exploring the relationships in a sample of adolescent males

This study investigated relationships between SRL and EF in a sample of 254 school-aged adolescent males. Two hypotheses were tested: that self-reported measures of SRL and EF are closely related and that as different aspects of EF mature during adolescence, the corresponding components of SRL should also improve, leading to an age-related increase in the correlation between EF and SRL. Two self-report instruments were used: the strategies for self-regulated learning survey (SSRLS) and the behavioural rating instrument of executive function (BRIEF). Strong correlations between the measures of EF and SRL were found, especially in areas associated with metacognitive processes. Correlations between EF and SRL were found, with weaker correlations between behavioural regulation and SRL were found to be weaker for the younger participants in the sample while the relationship between EF and SRL appears to grow stronger during the initial years of high school even though self-reported levels of EF along with motivation for SRL and important components of SRL such as goal setting and planning were found to decrease with age. Decreasing levels of motivation for learning during adolescence are speculated to moderate the deployment of SRL and EF in a school context.

Steps toward the validation of the Trendelenburg Test : the effect of experimentally reduced hip abductor muscle function on frontal plane mechanics

Objective: To investigate the validity of the Trendelenburg test (TT) using an ultrasound-guided nerve block (UNB) of the superior gluteal nerve and determine whether the reduction in hip abductor muscle (HABD) strength would result in the theorized mechanical compensatory strategies measured during the TT. Design: Quasi-experimental. Setting: Hospital. Participants: Convenience sample of 9 healthy men. Only participants with no current or previous injury to the lumbar spine, pelvis, or lower extremities, and no previous surgeries were included. Interventions: Ultrasound-guided nerve block. Main Outcome Measures: Hip abductor muscle strength (percent body weight [%BW]), contralateral pelvic drop (cPD), change in contralateral pelvic drop (Delta cPD), ipsilateral hip adduction, and ipsilateral trunk sway (TRUNK) measured in degrees. Results: The median age and weight of the participants were 31 years (interquartile range [IQR], 22-32 years) and 73 kg (IQR, 67-81 kg), respectively. An average 52% reduction of HABD strength (z = 2.36, P = 0.02) resulted after the UNB. No differences were found in cPD or Delta cPD (z = 0.01, P = 0.99, z = 20.67, P = 0.49, respectively). Individual changes in biomechanics showed no consistency between participants and nonsystematic changes across the group. One participant demonstrated the mechanical compensations described by Trendelenburg. Conclusions: The TT should not be used as a screening measure for HABD strength in populations demonstrating strength greater than 30% BW but should be reserved for use with populations with marked HABD weakness. Clinical Relevance: This study presents data regarding a critical level of HABD strength required to support the pelvis during the TT.

Steps towards the validation of the Trendelenburg test : The effect of experimentally reduced hip abductor muscle function on frontal plane mechanics

Introduction: The Trendelenburg Test (TT) is used to assess the functional strength of the hip abductor muscles (HABD), their ability to control frontal plane motion of the pelvis, and the ability of the lumbopelvic complex to transfer load into single leg stance. Rationale: Although a standard method to perform the test has been described for use within clinical populations, no study has directly investigated Trendelenburg’s hypotheses. Purpose: To investigate the validity of the TT using an ultrasound guided nerve block (UNB) of the superior gluteal nerve and determine whether the reduction in HABD strength would result in the theorized mechanical compensatory strategies measured during the TT. Methods: Quasi-experimental design using a convenience sample of nine healthy males. Only subjects with no current or previous injury to the lumbar spine, pelvis, or lower extremities, and no previous surgeries were included. Force dynamometry was used to evaluation HABD strength (%BW). 2D mechanics were used to evaluate contralateral pelvic drop (cMPD), change in contralateral pelvic drop (∆cMPD), ipsilateral hip adduction (iHADD) and ipsilateral trunk sway (TRUNK) measured in degrees (°). All measures were collected prior to and following a UNB on the superior gluteal nerve performed by an interventional radiologist. Results: Subjects’ age was median 31yrs (IQR:22-32yrs); and weight was median 73kg (IQR:67-81kg). An average 52% reduction of HABD strength (z=2.36,p=0.02) resulted following the UNB. No differences were found in cMPD or ∆cMPD (z=0.01,p= 0.99, z=-0.67,p=0.49). Individual changes in biomechanics show no consistency between subjects and non-systematic changes across the group. One subject demonstrated the mechanical compensations described by Trendelenburg. Discussion: The TT should not be used as screening measure for HABD strength in populations demonstrating strength greater than 30%BW but reserved for use with populations with marked HABD weakness. Importance: This study presents data regarding a critical level of HABD strength required to support the pelvis during the TT.

P.I.C.U., H.D.U., A.O.A. What treatment do we provide?: Current descriptions of the function of intensive care for inpatient Psychiatric Health Care.

Purpose – This paper adds to growing research of psychiatric intensive care units (PICU) by recounting descriptions of psychiatric intensive care settings and discusses the perceptions held by nurses of the organisational interfaces, arrangements and provisions of care in these settings. Design/methodology/approach – Data gathered from focus groups held with nurses from two PICUs was used to establish terminology, defining attributes, related concepts, antecedents, values, processes and concepts related to current practices. A literature search was conducted to permit a review of the conceptual arrangements and contemporary understanding of intensive care for people experiencing acute psychiatric illness based on the perspectives held by the nurses from the focus groups. Findings – Dissonance between service needs and the needs and management of individual patients overshadow strategies to implement comprehensive recovery-oriented approaches. Three factors are reported in this paper that influence standards and procedural practice in PICU; organisational structures; physical structures; and subtype nomenclature. Practical implications – Acute inpatient care is an important part of a comprehensive approach to mental health services. Commonly intensive acute care is delivered in specialised wards or units co-located with acute mental health inpatient units mostly known as PICU. Evidence of the most effective treatment and approaches in intensive care settings that support comprehensive recovery for improved outcomes is nascent. Originality/value – Current descriptions from nurses substantiate wide variations in the provisions, design and classifications of psychiatric intensive care. Idiosyncratic and localised conceptions of psychiatric intensive care are not adequately entailing effective treatment and methods in support of recovery principles for improved and comprehensive outcomes. The authors suggest that more concrete descriptions, guidelines, training and policies for provision of intensive psychiatric health care encompassing the perspective of nursing professionals, would reinforce conceptual construction and thus optimum treatments within a comprehensive, recovery-oriented approach to mental health services.

Risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory : a matched case-control study

Background: Side effects of the medications used for procedural sedation and analgesia in the cardiac catheterisation laboratory are known to cause impaired respiratory function. Impaired respiratory function poses considerable risk to patient safety as it can lead to inadequate oxygenation. Having knowledge about the conditions that predict impaired respiratory function prior to the procedure would enable nurses to identify at-risk patients and selectively implement intensive respiratory monitoring. This would reduce the possibility of inadequate oxygenation occurring. Aim: To identify pre-procedure risk factors for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory. Design: Retrospective matched case–control. Methods: 21 cases of impaired respiratory function were identified and matched to 113 controls from a consecutive cohort of patients over 18 years of age. Conditional logistic regression was used to identify risk factors for impaired respiratory function. Results: With each additional indicator of acute illness, case patients were nearly two times more likely than their controls to experience impaired respiratory function (OR 1.78; 95% CI 1.19–2.67; p = 0.005). Indicators of acute illness included emergency admission, being transferred from a critical care unit for the procedure or requiring respiratory or haemodynamic support in the lead up to the procedure. Conclusion: Several factors that predict the likelihood of impaired respiratory function were identified. The results from this study could be used to inform prospective studies investigating the effectiveness of interventions for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterisation laboratory.

Acute illness is a risk factor for impaired respiratory function during nurse-administered procedural sedation and analgesia in the cardiac catheterization laboratory

Impaired respiratory function (IRF) during procedural sedation and analgesia (PSA) poses considerable risk to patient safety as it can lead to inadequate oxygenation and ventilation. Risk factors that can be screened prior to the procedure have not been identified for the cardiac catheterization laboratory (CCL).

A family of Alltop functions that are EA-inequivalent to the cubic function

Sequences with optimal correlation properties are much sought after for applications in communication systems. In 1980, Alltop (\emph{IEEE Trans. Inf. Theory} 26(3):350-354, 1980) described a set of sequences based on a cubic function and showed that these sequences were optimal with respect to the known bounds on auto and crosscorrelation. Subsequently these sequences were used to construct mutually unbiased bases (MUBs), a structure of importance in quantum information theory. The key feature of this cubic function is that its difference function is a planar function. Functions with planar difference functions have been called \emph{Alltop functions}. This paper provides a new family of Alltop functions and establishes the use of Alltop functions for construction of sequence sets and MUBs.