Objective probability and quantum fuzziness

This paper offers a critique of the Bayesian interpretation of quantum mechanics with particular focus on a paper by Caves, Fuchs, and Schack containing a critique of the "objective preparations view" or OPV. It also aims to carry the discussion beyond the hardened positions of Bayesians and proponents of the OPV. Several claims made by Caves et al. are rebutted, including the claim that different pure states may legitimately be assigned to the same system at the same time, and the claim that the quantum nature of a preparation device cannot legitimately be ignored. Both Bayesians and proponents of the OPV regard the time dependence of a quantum state as the continuous dependence on time of an evolving state of some kind. This leads to a false dilemma: quantum states are either objective states of nature or subjective states of belief. In reality they are neither. The present paper views the aforesaid dependence as a dependence on the time of the measurement to whose possible outcomes the quantum state serves to assign probabilities. This makes it possible to recognize the full implications of the only testable feature of the theory, viz., the probabilities it assigns to measurement outcomes...Comment: 21 pages, no graphics, inspired by "Subjective probability and quantum certainty" (quant-ph/0608190 v2

Age-related macular degeneration: a disease of systemic or local complement dysregulation?

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in developed countries. The role of complement in the development of AMD is now well-established. While some studies show evidence of complement dysregulation within the eye, others have demonstrated elevated systemic complement activation in association with AMD. It is unclear which one is the primary driver of disease. This has important implications for designing novel complement-based AMD therapies. We present a summary of the current literature and suggest that intraocular rather than systemic modulation of complement may prove more effective

Chlamydia infection status, genotype, and age-related macular degeneration

PURPOSE: To evaluate whether Chlamydia (C.) infections are associated with age-related macular degeneration (AMD) and to assess if this association is influenced by the complement factor H (CFH) Y402H or the high temperature requirement A serine peptidase 1 (HTRA1) rs11200638 risk genotypes.METHODS: One hundred ninety-nine AMD patients with early and late forms of the disease and 100 unaffected controls, at least 50 years old were included in the study. Patients in the AMD and control groups were selected based on known CFH Y402H variant genotype status (one third homozygous CC, one third heterozygous CT, and one third wild-type TT). Plasma from all patients and controls was tested for C. pneumoniae, C. trachomatis, and C. psittaci IgG seropositivity using a micro-immunofluorescent assay to establish previous infection status. Assays were conducted blind to risk genotypes and the results analyzed using univariate and multivariate (logistic regression) analysis.RESULTS:IgG seropositivity to C. pneumoniae was most prevalent (69.2%, n=207), followed by C. trachomatis (7.4%, n=22) and C. psittaci (3.3%, n=10). No association was found between each of the three Chlamydia species IgG seropositivity and AMD status or severity (early/late). There was also no significant association between Chlamydia species IgG seropositivity and AMD status or severity, in patients carrying at least one CFH Y402H risk allele (C) or HTRA1 rs11200638 risk allele (A), with univariate or logistic regression analysis. CONCLUSIONS:Chlamydia infection status does not appear to be associated with AMD status or severity. The presence of CFH Y402H and HTRA1 rs11200638 risk genotypes does not alter this negative association

Correction. Central macular choriocapillaris impairment as a manifestation of microvascular disease in eyes with subretinal drusenoid deposits

No abstract availabl

Serum vascular endothelial growth factor levels in the IVAN trial; relationships with drug, dosing and systemic serious adverse events:Serum VEGF associations with drug, dosing and systemic SAEs

Purpose: To describe serum vascular endothelial growth factor (sVEGF) in patients with neovascular age-related macular degeneration (nAMD) receiving anti-VEGF agents and associations between sVEGF and systemic serious adverse events (SSAEs). Design: Exploratory analyses of a randomized controlled trial that enrolled 610 participants with nAMD and compared 2 anti-VEGF antibodies, ranibizumab and bevacizumab, and 2 treatment regimens, monthly vs. discontinuous, with 2 years’ follow-up. Participants: Adults aged 50+ years with treatment-naïve nAMD and a visual acuity of ≥25 letters (Snellen equivalent 20/320) in the affected eye. Methods: Intravitreal injection of anti-VEGF antibodies. Main Outcome Measures: sVEGF and occurrence of SSAE, with particular interest in arteriothromboembolic events (ATE) and immunologically mediated events (IME). Results: On average, sVEGF (measured at months 0, 1, 11, 12, 23, and 24) decreased from a geometric mean of 168 pg/mL at baseline to 64 pg/mL at month 24. The decrease was greater with bevacizumab than with ranibizumab and was dependent on time since last treatment; at month 24 sVEGF was 11% lower with bevacizumab if treated ≥3 months previously, 51% lower if treated 2 months previously, and 76% lower if treated the previous month, compared with ranibizumab. The hazard of experiencing an ATE increased with age (hazard ratio [HR] = 2.01; 95% confidence interval [CI] = 1.32–3.05; P = 0.001) and higher sVEGF (HR = 1.16; 95% CI = 1.03–1.30, per 100 unit rise in sVEGF; P = 0.013). There was no association between sVEGF and the hazard of an IME (HR = 1.01; 95% CI = 0.76–1.33; P = 0.942); however, the hazard of an IME was significantly increased by treatment with bevacizumab compared with ranibizumab (HR = 3.53; 95% CI = 1.35–9.22; P = 0.010). The hazard of an “other SSAE” (not categorized as ATE or IME) increased with age (HR 1.51, 95% CI 1.14–2.01, P = 0.005) and decreased if an injection had been administered within the previous month (HR = 0.68; 95% CI = 0.45–1.03; P = 0.069). Conclusions: The decrease in sVEGF is greater with bevacizumab than with ranibizumab, but this difference is eliminated when treatment is withheld for 3 months. Higher sVEGF increased the hazard of an ATE and bevacizumab increases the hazard of an IME compared with ranibizumab.</p

Patient acceptability of home monitoring for neovascular age-related macular degeneration reactivation:a qualitative study

Neovascular age-related macular degeneration (nAMD) is a chronic, progressive condition and the commonest cause of visual disability in older adults. This study formed part of a diagnostic test accuracy study to quantify the ability of three index home monitoring (HM) tests (one paper-based and two digital tests) to identify reactivation in nAMD. The aim of this qualitative research was to investigate patients’ or participants’ views about acceptability and explore adherence to weekly HM. Semi-structured interviews were held with 78/297 participants (26%), with close family members (n = 11) and with healthcare professionals involved in training participants in HM procedures (n = 9) (n = 98 in total). A directed thematic analytical approach was applied to the data using a deductive and inductive coding framework informed by theories of technology acceptance. Five themes emerged related to: 1. The role of HM; 2. Suitability of procedures and instruments; 3. Experience of HM; 4. Feasibility of HM in usual practice; and 5. Impediments to patient acceptability of HM. Various factors influenced acceptability including a patient’s understanding about the purpose of monitoring. While initial training and ongoing support were regarded as essential for overcoming unfamiliarity with use of digital technology, patients viewed HM as relatively straightforward and non-burdensome. There is a need for further research about how use of performance feedback, level of support and nature of tailoring might facilitate further the implementation of routinely conducted HM. Home monitoring was acceptable to patients and they recognised its potential to reduce clinic visits during non-active treatment phases. Findings have implications for implementation of digital HM in the care of older people with nAMD and other long-term conditions

The Alzheimer's-related amyloid beta peptide is internalised by R28 neuroretinal cells and disrupts the microtubule associated protein 2 (MAP-2)

Age-related Macular Degeneration (AMD) is a common, irreversible blinding condition that leads to the loss of central vision. AMD has a complex aetiology with both genetic as well as environmental risks factors, and share many similarities with Alzheimer's disease. Recent findings have contributed significantly to unravelling its genetic architecture that is yet to be matched by molecular insights. Studies are made more challenging by observations that aged and AMD retinas accumulate the highly pathogenic Alzheimer's-related Amyloid beta (A?) group of peptides, for which there appears to be no clear genetic basis. Analyses of human donor and animal eyes have identified retinal A? aggregates in retinal ganglion cells (RGC), the inner nuclear layer, photoreceptors as well as the retinal pigment epithelium. A? is also a major drusen constituent; found correlated with elevated drusen-load and age, with a propensity to aggregate in retinas of advanced AMD. Despite this evidence, how such a potent driver of neurodegeneration might impair the neuroretina remains incompletely understood, and studies into this important aspect of retinopathy remains limited. In order to address this we exploited R28 rat retinal cells which due to its heterogeneous nature, offers diverse neuroretinal cell-types in which to study the molecular pathology of A?. R28 cells are also unaffected by problems associated with the commonly used RGC-5 immortalised cell-line, thus providing a well-established model in which to study dynamic A? effects at single-cell resolution. Our findings show that R28 cells express key neuronal markers calbindin, protein kinase C and the microtubule associated protein-2 (MAP-2) by confocal immunofluorescence which has not been shown before, but also calretinin which has not been reported previously. For the first time, we reveal that retinal neurons rapidly internalised A?1-42, the most cytotoxic and aggregate-prone amongst the A? family. Furthermore, exposure to physiological amounts of A?1-42 for 24 h correlated with impairment to neuronal MAP-2, a cytoskeletal protein which regulates microtubule dynamics in axons and dendrites. Disruption to MAP-2 was transient, and had recovered by 48 h, although internalised A? persisted as discrete puncta for as long as 72 h. To assess whether A? could realistically localise to living retinas to mediate such effects, we subretinally injected nanomolar levels of oligomeric A?1-42 into wildtype mice. Confocal microscopy revealed the presence of focal A? deposits in RGC, the inner nuclear and the outer plexiform layers 8 days later, recapitulating naturally-occurring patterns of A? aggregation in aged retinas. Our novel findings describe how retinal neurons internalise A? to transiently impair MAP-2 in a hitherto unreported manner. MAP-2 dysfunction is reported in AMD retinas, and is thought to be involved in remodelling and plasticity of post-mitotic neurons. Our insights suggest a molecular pathway by which this could occur in the senescent eye leading to complex diseases such as AMD

Cohort profile:rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

Purpose: the retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study.Participants: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs.Findings to date: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes.Future plans: the collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia

Long term follow-up of a family with GUCY2D dominant cone dystrophy

AIM: To describe long term follow-up in a family with GUCY2D dominant cone dystrophy. METHODS: Optical coherence tomography scans and fundus autofluorescence images were obtained. Flash and pattern electroretinograms (ERGs) and occipital pattern reversal visual evoked potentials were recorded. RESULTS: Two members of the same family (father and son) were identified to have the heterozygous R838C mutation in the GUCY2D gene. The father presented at the age of 45 with bilateral bull’s eye maculopathy and temporal disc pallor. Over 13y of serial follow up visits, the bull’s eye maculopathy progressed gradually into macular atrophy. Electrophysiological tests were significantly degraded suggesting poor macular function. Spectral-domain optical coherence tomography (SD-OCT) scans showed progressive loss and disruption of the ellipsoid layer at the foveal level. His son presented at the age of 16 with bilateral granular retinal pigment epithelial changes in both maculae. Electrophysiological testing was initially borderline normal but has gradually deteriorated to show reduced cone ERGs and macula function. SD-OCT demonstrated gradual macular thinning and atrophy bilaterally. Unlike his father, there was no disruption of the ellipsoid layer. CONCLUSION: Both family members exhibited gradual changes in their fundi, electrophysiological testing and multimodal imaging. Changes were milder than those observed in other mutations of the same gene