Refracting The Diseased Eye

Refractive error refers to ocular refractive status where images of objects of regard do not fall on the retina in a relaxed eye - the ametropic eye. Thus, objects are perceived as blur. Refractive error is an aberration in an otherwise normal physiological phenomenon and not a disease. Uncorrected refractive errors are the second most causes of blindness after cataract and the cause of almost half of visual impairment. Clinical refraction is a careful scientific procedure employed to correct refractive error. Given that refractive error is the most common reason patients present to the eye care practitioner, a lot of attention must be given to refraction. When an irreversible eye disease co-exist with refractive error, then correction of refractive error under this circumstance; refracting the diseased eye (RDE) become very challenging and painstaking. There will be likelihood of irregularities in the transparent refractive surfaces of the eye due to disease or surgery which make refraction difficult both for the patient and the examiner. Personal clinical experience of the author who is a low vision consultant and review of related literature from textbooks and journals are brought to bear in this article. This paper is a review of the RDE algorithm with delineation of these steps to enable an effective refractive endpoint for the eye with disease. The paper will enable young Optometrists to deal with refractive error masquerading irreversible eye disease. It is also an essential reading for the low vision Optometrist in mastering the art and science of low vision refraction.&nbsp

Plasma inflammatory cytokines and survival of pancreatic cancer patients.

OBJECTIVES: Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome. METHODS: We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for death were estimated using multivariate Cox proportional hazards models. RESULTS: Overall mortality was significantly increased in patients in the top quartile of CRP (HR = 2.52, 95% CI: 1.82-3.49), IL-6 (HR = 2.78, 95% CI: 2.03-3.81), sTNF-RII (HR = 2.00, 95% CI: 1.46-2.72), and MIC-1 (HR = 2.53, 95% CI: 1.83-3.50), compared to those in the bottom quartile (P-trend CONCLUSION: Individual elevated plasma inflammatory cytokines are associated with significant and dramatic reductions in pancreatic cancer patient survival. Furthermore, we observed an independent combined effect of those cytokines on patient survival, suggesting that multiple inflammatory pathways are likely involved in PDAC progression. Future research efforts to target the inflammatory state using combination strategies in pancreatic cancer patients are warranted

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies

A Scalable Automated Diagnostic Feature Extraction System for EEGs

Researchers using Electroencephalograms (“EEGs”) to diagnose clinical outcomes often run into computational complexity problems. In particular, extracting complex, sometimes nonlinear, features from a large number of time-series often require large amounts of processing time. In this paper we describe a distributed system that leverages modern cloud-based technologies and tools and demonstrate that it can effectively, and efficiently, undertake clinical research. Specifically we compare three types of clusters, showing their relative costs (in both time and money) to develop a distributed machine learning pipeline for predicting gestation time based on features extracted from these EEGs

Persistent contaminants and herpesvirus OtHV1 are positively associated with cancer in wild California Sea Lions (Zalophus californianus)

This work was funded by the Geoffrey Hughes Fellowship, the National Institutes of Health (Fogarty International Center) and National Science Foundation joint program for the Ecology of Infectious Disease, the National Marine Fisheries Service Marine Mammal Heath and Stranding Program, and the Natural Environment Research Council grant number NE/R015007/.The prevalence of cancer in wild California sea lions (Zalophus californianus) is one of the highest amongst mammals, with 18–23% of adult animals examined post-mortem over the past 40 years having urogenital carcinoma. To date, organochlorines, genotype and infection with Otarine herpesvirus-1 (OtHV-1) have been identified in separate studies using distinct animals as associated with this carcinoma. Multi-year studies using large sample sizes to investigate the relative importance of multiple factors on marine mammal health are rare due to logistical and ethical challenges. The objective of this study was to use a case control approach with samples from 394 animals collected over 20 years in a multifactorial analysis to explore the relative importance of distinct factors identified to date as associated with sea lion cancer in the likelihood of sea lion carcinoma. Stepwise regression indicated that the best model to explain carcinoma occurrence included herpesvirus status, contaminant exposure, and blubber depth, but not genotype at a single microsatellite locus, PV11. The odds of carcinoma was 43.57 times higher in sea lions infected with OtHV-1 (95% CI 14.61, 129.96, p <0.001), and 1.48 times higher for every unit increase in the loge[contaminant concentrations], ng g–1 (an approximate tripling of concentration), in their blubber (95% CI 1.11, 1.97, p <0.007), after controlling for the effect of blubber depth. These findings demonstrate the importance of contaminant exposure combined with OtHV1 infection, in the potential for cancer occurrence in wild sea lions.Publisher PDFPeer reviewe

Characterizing genomic alterations in cancer by complementary functional associations.

Systematic efforts to sequence the cancer genome have identified large numbers of mutations and copy number alterations in human cancers. However, elucidating the functional consequences of these variants, and their interactions to drive or maintain oncogenic states, remains a challenge in cancer research. We developed REVEALER, a computational method that identifies combinations of mutually exclusive genomic alterations correlated with functional phenotypes, such as the activation or gene dependency of oncogenic pathways or sensitivity to a drug treatment. We used REVEALER to uncover complementary genomic alterations associated with the transcriptional activation of β-catenin and NRF2, MEK-inhibitor sensitivity, and KRAS dependency. REVEALER successfully identified both known and new associations, demonstrating the power of combining functional profiles with extensive characterization of genomic alterations in cancer genomes

Interaction of the Retinoblastoma Protein with Orc1 and Its Recruitment to Human Origins of DNA Replication

Background: The retinoblastoma protein (Rb) is a crucial regulator of cell cycle progression by binding with E2F transcription factor and repressing the expression of a variety of genes required for the G1-S phase transition. Methodology/Principal Findings: Here we show that Rb and E2F1 directly participate in the control of initiation of DNA replication in human HeLa, U2OS and T98G cells by specifically binding to origins of DNA replication in a cell cycle regulated manner. We show that, both in vitro and inside the cells, the largest subunit of the origin recognition complex (Orc1) specifically binds hypo-phosphorylated Rb and that this interaction is competitive with the binding of Rb to E2F1. The displacement of Rb-bound Orc1 by E2F1 at origins of DNA replication marks the progression of the G1 phase of the cell cycle toward the G1-S border. Conclusions/Significance: The participation of Rb and E2F1 in the formation of the multiprotein complex that binds origins of DNA replication in mammalian cells appears to represent an effective mechanism to couple the expression of gene

Coarse-grained simulation reveals key features of HIV-1 capsid self-assembly

The maturation of HIV-1 viral particles is essential for viral infectivity. During maturation, many copies of the capsid protein (CA) self-assemble into a capsid shell to enclose the viral RNA. The mechanistic details of the initiation and early stages of capsid assembly remain to be delineated. We present coarse-grained simulations of capsid assembly under various conditions, considering not only capsid lattice self-assembly but also the potential disassembly of capsid upon delivery to the cytoplasm of a target cell. The effects of CA concentration, molecular crowding, and the conformational variability of CA are described, with results indicating that capsid nucleation and growth is a multi-stage process requiring well-defined metastable intermediates. Generation of the mature capsid lattice is sensitive to local conditions, with relatively subtle changes in CA concentration and molecular crowding influencing self-assembly and the ensemble of structural morphologies