Color matches in diseased eyes with good acuity: detection of deficits in cone optical density and in chromatic discrimination

Reduced foveal cone optical density in diseased eyes with normal acuity can affect color matches. Using field diameters of 1 ± , 2 ± , 4 ± , and 8 ± , we measured mean color-match midpoints and match widths in patients who had good acuity and who exhibited three categories of eye disease: hereditary macular degeneration (n 12), retinitis pigmentosa (n 19), and glaucoma (n 18). Results were compared with those for normal observers of comparable ages. Mean color-match midpoints were abnormal only for the population with hereditary macular degeneration, indicating a reduction in cone optical density in the central 4 ± . Mean color-match widths were enlarged for both hereditary macular degeneration and retinitis pigmentosa, a result consistent with a reduction in the number of foveal cones

Safety Assessment of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa: The 4-Year DHAX Trial

Citation: Hughbanks-Wheaton DK, Birch DG, Fish GE, et al. Safety assessment of docosahexaenoic acid in X-linked retinitis pigmentosa: the 4-year DHAX trial. Invest Ophthalmol Vis Sci. 2014;55:4958-4966. DOI: 10.1167/iovs.14-14437 PURPOSE. Docosahexaenoic acid (DHA) continues to be evaluated and recommended as treatment and prophylaxis for various diseases. We recently assessed efficacy of high-dose DHA supplementation to slow vision loss in patients with X-linked retinitis pigmentosa (XLRP) in a randomized clinical trial. Because DHA is a highly unsaturated fatty acid, it could serve as a target for free-radical induced oxidation, resulting in increased oxidative stress. Biosafety was monitored during the 4-year trial to determine whether DHA supplementation was associated with identifiable risks. METHODS. Males (n ¼ 78; 7-31 years) meeting entry criteria were enrolled. The modified intent-to-treat cohort (DHA ¼ 33; placebo ¼ 27) adhered to the protocol ‡ 1 year. Participants were randomized to an oral dose of 30 mg/kg/d DHA or placebo plus a daily multivitamin. Comprehensive metabolic analyses were assessed for group differences. Treatment-emergent adverse events including blood chemistry metabolites were recorded. RESULTS. By year 4, supplementation elevated plasma and red blood cell-DHA 4.4-and 3.6-fold, respectively, compared with the placebo group (P < 0.00001). Over the trial duration, no significant differences between DHA and placebo groups were found for vitamin A, vitamin E, platelet aggregation, antioxidant activity, lipoprotein cholesterol, or oxidized LDL levels (all P > 0.14). Adverse events were transient and not considered severe (e.g., gastrointestinal [GI] irritability, blood chemistry alterations). One participant was unable to tolerate persistent GI discomfort. CONCLUSIONS. Long-term, high-dose DHA supplementation to patients with XLRP was associated with limited safety risks in this 4-year trial. Nevertheless, GI symptoms should be monitored in all patients taking high dose DHA especially those with personal or family history of GI disturbances. (ClinicalTrials.gov number, NCT00100230.) Keywords: biosafety, fatty acids, adverse events R etinitis pigmentosa (RP) is a retinal degenerative disease characterized by night blindness and visual field constriction 1 with four underlying inheritance patterns. The X-linked form of RP (XLRP) is among the most severe with night blindness often detectable by age 5 years 2-4 and legal blindness by the second or third decade. Gene defects are known to cause retinal degeneration, yet factors such as environment, diet, stress, and/or metabolism may modify disease severity. Many patients with RP have lower plasma and red blood cell (RBC) levels of the n3 polyunsaturated fatty acid docosahexaenoic acid (DHA; 22:6n3) than normally-sighted controls. 5 Blood DHA was significantly correlated with age-adjusted ERG responses in XLRP such that patients with lower RBC-DHA tended to have lower ERG amplitudes. 6 These findings were similarly documented in approximately 70% of female XLRP carriers (Hoffman DR, et al. IOVS 1998;39:ARVO Abstract 725). A reduction in DHA biosynthesis was demonstrated in XLRP using stable isotopes to assess in vivo metabolism 7 suggesting that downregulation of hepatic D 5 desaturase may contribute to subnormal blood DHA levels. Thus, daily supplementation with DHA may bypass any decrease in DHA biosynthesis. Docosahexaenoic acid comprises 1% to 5% of membrane fatty acids in most human tissues; however, it is the most abundant fatty acid in the retina. 8 This n3 fatty acid can increase membrane fluidity and modify the mobility of vital proteins and activities of retinal enzymes, 9,10 promote photoreceptor differentiation, 11 and antiapoptotic activity. 12 The highly unsaturated nature of DHA makes it a potential target for free radical oxidative damage. Increased polyunsaturated fatty acid (PUFA) intake, particularly long-chain PUFAs (LCPUFAs; >18 carbons), may lead to elevated oxidative stress and subsequent membrane damage. 15 Numerous n3-supplementation studies report elevations in low-and highdensity lipoprotein (LDL and HDL)-cholesterol

Reinventing grounded theory: some questions about theory, ground and discovery

Grounded theory’s popularity persists after three decades of broad-ranging critique. In this article three problematic notions are discussed—‘theory,’ ‘ground’ and ‘discovery’—which linger in the continuing use and development of grounded theory procedures. It is argued that far from providing the epistemic security promised by grounded theory, these notions—embodied in continuing reinventions of grounded theory—constrain and distort qualitative inquiry, and that what is contrived is not in fact theory in any meaningful sense, that ‘ground’ is a misnomer when talking about interpretation and that what ultimately materializes following grounded theory procedures is less like discovery and more akin to invention. The procedures admittedly provide signposts for qualitative inquirers, but educational researchers should be wary, for the significance of interpretation, narrative and reflection can be undermined in the procedures of grounded theory

Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

INTRODUCTION: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. METHODS: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. RESULTS: Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. DISCUSSION: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Improving accountability through alignment: the role of academic health science centres and networks in England.

BACKGROUND: As in many countries around the world, there are high expectations on academic health science centres and networks in England to provide high-quality care, innovative research, and world-class education, while also supporting wealth creation and economic growth. Meeting these expectations increasingly depends on partnership working between university medical schools and teaching hospitals, as well as other healthcare providers. However, academic-clinical relationships in England are still characterised by the "unlinked partners" model, whereby universities and their partner teaching hospitals are neither fiscally nor structurally linked, creating bifurcating accountabilities to various government and public agencies. DISCUSSION: This article focuses on accountability relationships in universities and teaching hospitals, as well as other healthcare providers that form core constituent parts of academic health science centres and networks. The authors analyse accountability for the tripartite mission of patient care, research, and education, using a four-fold typology of accountability relationships, which distinguishes between hierarchical (bureaucratic) accountability, legal accountability, professional accountability, and political accountability. Examples from North West London suggest that a number of mechanisms can be used to improve accountability for the tripartite mission through alignment, but that the simple creation of academic health science centres and networks is probably not sufficient. SUMMARY: At the heart of the challenge for academic health science centres and networks is the separation of accountabilities for patient care, research, and education in different government departments. Given that a fundamental top-down system redesign is now extremely unlikely, local academic and clinical leaders face the challenge of aligning their institutions as a matter of priority in order to improve accountability for the tripartite mission from the bottom up. It remains to be seen which alignment mechanisms are most effective, and whether they are strong enough to counter the separation of accountabilities for the tripartite mission at the national level, the on-going structural fragmentation of the health system in England, and the unprecedented financial challenges that it faces. Future research should focus on determining the comparative effectiveness of different alignment mechanisms, developing standardised metrics and key performance indicators, evaluating and assessing academic health science centres and networks, and empirically addressing leadership issues

Diets of the Sympatric Pacific Sheath-Tailed Bat (Emballonura semicaudata rotensis) and Mariana Swiftlet (Aerodramus bartschi) on Aguiguan, Mariana Islands

v. ill. 23 cm.Also available through BioOne: http://www.bioone.org/doi/abs/10.2984/65.3.301QuarterlyThe Pacific sheath-tailed bat (Emballonura semicaudata rotensis) and Mariana swiftlet (Aerodramus bartschi ) are two rare insectivorous taxa restricted to the southern Mariana Islands in western Micronesia. It is believed that populations of both have dwindled because of impacts to their food resources. However, there is little information on the food habits of A. bartschi and none exists for E. s. rotensis. In an effort to better understand the habits of both, we investigated their diets using guano analysis. Guano was collected from two roosts in caves during a 2-week period in June and July at the onset of the rainy season. Important orders of insects consumed (percentage volume) by bats roosting at one cave included hymenopterans (64%), coleopterans (10%), lepidopterans (8%), isopterans (8%), and psocopterans (5%), whereas those at a second cave included lepidopterans (45%), hymenopterans (41%), coleopterans (10%), and isopterans (5%). Swiftlets, which roosted in only one of the caves, fed mostly on hymenopterans (88%) and hemipterans (6%). Significant differences existed between the two taxa in several insect orders eaten, with E. s. rotensis consuming more lepidopterans and coleopterans and A. bartschi taking more hymenopterans and hemipterans. Within Hymenoptera, bats fed more on ichneumoideans, whereas swiftlets ate more formicid alates and chalicidoideans. This new information on the feeding habits of E. s. rotensis and A. bartschi provides insight on the complexity of their diets during June and July, and serves as baseline information for future studies and management of their habitat