The quality of reporting of diagnostic accuracy studies in glaucoma using the Heidelberg retina tomograph

PURPOSE. Scanning laser tomography with the Heidelberg retina tomograph (HRT; Heidelberg Engineering, Heidelberg, Germany) has been proposed as a useful diagnostic test for glaucoma. This study was conducted to evaluate the quality of reporting of published studies using the HRT for diagnosing glaucoma. METHODS. A validated Medline and hand search of English-language articles reporting on measures of diagnostic accuracy of the HRT for glaucoma was performed. Two reviewers selected and appraised the papers independently. The Standards for Reporting of Diagnostic Accuracy (STARD) checklist was used to evaluate the quality of each publication. RESULTS. A total of 29 articles were included. Interobserver rating agreement was observed in 83% of items (? = 0.76). The number of STARD items properly reported ranged from 5 to 18. Less than a third of studies (7/29) explicitly reported more than half of the STARD items. Descriptions of key aspects of the methodology were frequently missing. For example, the design of the study (prospective or retrospective) was reported in 6 of 29 studies, and details of participant sampling (e.g., consecutive or random selection) were described in 5 of 29 publications. The commonest description of diagnostic accuracy was sensitivity and specificity (25/29) followed by area under the ROC curve (13/29), with 9 of 29 publications reporting both. CONCLUSIONS. The quality of reporting of diagnostic accuracy tests for glaucoma with HRT is suboptimal. The STARD initiative may be a useful tool for appraising the strengths and weaknesses of diagnostic accuracy studies. Copyright © Association for Research in Vision and Ophthalmology.

The Quality of Reporting of Diagnostic Accuracy Studies of Optical Coherence Tomography in Glaucoma

Objective: To evaluate the quality of reporting of diagnostic accuracy studies using optical coherence tomography (OCT) in glaucoma. Design: Descriptive series of published studies. Participants: Published studies reporting a measure of the diagnostic accuracy of OCT for glaucoma. Methods: Review of English language papers reporting measures of diagnostic accuracy of OCT for glaucoma. Papers were identified from a Medline literature search performed in June 2006. Articles were appraised using the 25 items provided by the Standards for Reporting of Diagnostic Accuracy (STARD) initiative. Each item was recorded as full, partially, or not reported. Main Outcome Measures: Degree of compliance with the STARD guidelines. Results: Thirty papers were appraised. Eight papers (26.7%) fully reported more than half of the STARD items. The lowest number of fully reported items in a study was 5 and the highest was 17. Descriptions of key aspects of methodology frequently were missing. For example, details of participant sampling (e.g., consecutive or random selection) were described in only 8 (26.7%) of 30 publications. Measures of statistical uncertainty were reported in 18 (60%) of 30 publications. No single STARD item was fully reported by all the papers. Conclusions: The standard of reporting of diagnostic accuracy studies in glaucoma using OCT was suboptimal. It is hoped that adoption of the STARD guidelines will lead to an improvement in reporting of diagnostic accuracy studies, enabling clearer evidence to be produced for the usefulness of OCT for the diagnosis of glaucoma. © 2007 American Academy of Ophthalmology.

Relative role of deterministic and stochastic determinants of soil animal community: a spatially explicit analysis of oribatid mites

1. Ecologists are debating the relative role of deterministic and stochastic determinants of community structure. Although the high diversity and strong spatial structure of soil animal assemblages could provide ecologists with an ideal ecological scenario, surprisingly little information is available on these assemblages.
2. We studied species-rich soil oribatid mite assemblages from a Mediterranean beech forest and a grassland. We applied multivariate regression approaches and analysed spatial autocorrelation at multiple spatial scales using Moran's eigenvectors. Results were used to partition community variance in terms of the amount of variation uniquely accounted for by environmental correlates (e.g. organic matter) and geographical position. Estimated neutral diversity and immigration parameters were also applied to a soil animal group for the first time to simulate patterns of community dissimilarity expected under neutrality, thereby testing neutral predictions.
3. After accounting for spatial autocorrelation, the correlation between community structure and key environmental parameters disappeared: about 40% of community variation consisted of spatial patterns independent of measured environmental variables such as organic matter. Environmentally independent spatial patterns encompassed the entire range of scales accounted for by the sampling design (from tens of cm to 100 m). This spatial variation could be due to either unmeasured but spatially structured variables or stochastic drift mediated by dispersal. Observed levels of community dissimilarity were significantly different from those predicted by neutral models.
4. Oribatid mite assemblages are dominated by processes involving both deterministic and stochastic components and operating at multiple scales. Spatial patterns independent of the measured environmental variables are a prominent feature of the targeted assemblages, but patterns of community dissimilarity do not match neutral predictions. This suggests that either niche-mediated competition or environmental filtering or both are contributing to the core structure of the community. This study indicates new lines of investigation for understanding the mechanisms that determine the signature of the deterministic component of animal community assembly.

Assessing abundance and diversity patterns of soil microarthropod assemblages in northern Victoria Land (Antarctica)

This study aimed to: (1) assess differences between two quantitative sampling methods of soil microarthropods (visual census vs. stone washing) in ice-free areas located along a latitudinal gradient (from 72 degrees 37'S to 74 degrees 42'S) in northern Victoria Land (Antarctica); (2) furnish preliminary results on the abundance and diversity of mites and springtails in the studied areas. Visual census yielded reliable density estimates for adult collembolans and larger prostigmatic mites but did not detect small species. The study updates the distribution of several mites, including the southernmost record of an Oribatida species at global scale. Species composition was correlated with latitude but the uneven abundance distribution and local high beta-diversity probably reflect habitat fragmentation and population isolation. Under this circumstance nested sampling design should be usefully employed. Priorities and suitable methods for studying terrestrial microarthropod communities in continental Antarctica are discussed.

Feleucin-BO1: A Novel Antimicrobial Non-Apeptide Amide from the Skin Secretion of the Toad, Bombina orientalis, and Design of a Potent Broad-Spectrum Synthetic Analogue, Feleucin-K3

Feleucins-BV1 and -BV2 are recently-described prototypes of a novel antimicrobial nonapeptide (AMP) family identified in the skin secretion of the bombinid toad, Bombina variegata. They are encoded on different precursors that also encode a novel bombinin. Here we describe the identification of feleucin-BO1 (FLGLLGSLLamide) which is co-encoded with a different novel bombinin, named feleucin precursor-associated bombinin (FPA-bombinin-BO), from the skin secretion of Bombina orientalis. Synthetic feleucin-BO1 displayed activity against a reference Gram-positive bacterium. Staphylococcus aureus (MIC 34 μM) but was inactive (> 250 μM) against the Gram-negative bacterium, Escherichia coli, and the yeast, Candida albicans. This pattern of activity was similar to that of the prototypes. Design and synthesis of a cationicity-enhanced analogue, feleucin-K3 (F-K3), in which the amino acid residues at positions 3 (G), 6 (G) and 7 (S) of feleucin-BO1 were substituted with Lys (K) residues, resulted in a peptide with significantly-enhanced potency and spectrum of activity. The MICs of F-K3 against the reference microorganisms were 7 μM (S. aureus), 14 μM (E. coli) and 7 μM (C. albicans). These data indicate that the skin secretions of amphibians can continue to provide novel peptide templates for the rational design of analogues with possible therapeutic utility.

Impact of composite ply continuity constraints on aerospace stiffened panel design

Considering the development of aerospace composite components, designing for reduced manufacturing layup cost and structural complexity is increasingly important. While the advantage of composite materials is the ability to tailor designs to various structural loads for minimum mass, the challenge is obtaining a design that is manufacturable and minimizes local ply incompatibility. The focus of the presented research is understanding how the relationships between mass, manufacturability and design complexity, under realistic loads and design requirements, can be affected by enforcing ply continuity in the design process. Presented are a series of sizing case studies on an upper wing cover, designed using conventional analyses and the tabular laminate design process. Introducing skin ply continuity constraints can generate skin designs with minimal ply discontinuities, fewer ply drops and larger ply areas than designs not constrained for continuity. However, the reduced design freedom associated with the addition of these constraints results in a weight penalty over the total wing cover. Perhaps more interestingly, when considering manual hand layup the reduced design complexity is not translated into a reduced recurring manufacturing cost. In contrast, heavier wing cover designs appear to take more time to layup regardless of the laminate design complexity. © 2012 AIAA.

Investigation of Limit Cycle Oscillations Using Aeroelastic-Harmonic Balance Method

This work investigates limit cycle oscillations in the transonic regime. A novel approach to predict Limit Cycle Oscillations using high fidelity analysis is exploited to accelerate calculations. The method used is an Aeroeasltic Harmonic Balance approach, which has been proven to be efficient and able to predict periodic phenomena. The behaviour of limit cycle oscillations is analysed using uncertainty quantification tools based on polynomial chaos expansions. To improve the efficiency of the sampling process for the polynomial-chaos expansions an adaptive sampling procedure is used. These methods are exercised using two problems: a pitch/plunge aerofoil and a delta-wing. Results indicate that Mach n. variability is determinant to the amplitude of the LCO for the 2D test case, whereas for the wing case analysed here, variability in the Mach n. has an almost negligible influence in amplitude variation and the LCO frequency variability has an almost linear relation with Mach number. Further test cases are required to understand the generality of these results.

Evaluating the use of testate amoebae for palaeohydrological reconstruction in permafrost peatlands

The melting of high-latitude permafrost peatlands is a major concern due to a potential positive feedback on global climate change. We examine the ecology of testate amoebae in permafrost peatlands, based on sites in Sweden (~ 200 km north of the Arctic Circle). Multivariate statistical analysis confirms that water-table depth and moisture content are the dominant controls on the distribution of testate amoebae, corroborating the results from studies in mid-latitude peatlands. We present a new testate amoeba-based water table transfer function and thoroughly test it for the effects of spatial autocorrelation, clustered sampling design and uneven sampling gradients. We find that the transfer function has good predictive power; the best-performing model is based on tolerance-downweighted weighted averaging with inverse deshrinking (performance statistics with leave-one-out cross validation: R2 = 0.87, RMSEP = 5.25 cm). The new transfer function was applied to a short core from Stordalen mire, and reveals a major shift in peatland ecohydrology coincident with the onset of the Little Ice Age (c. AD 1400). We also applied the model to an independent contemporary dataset from Stordalen and find that it outperforms predictions based on other published transfer functions. The new transfer function will enable palaeohydrological reconstruction from permafrost peatlands in Northern Europe, thereby permitting greatly improved understanding of the long-term ecohydrological dynamics of these important carbon stores as well as their responses to recent climate change.

The Application of Semiconductor Photocatalysis for the Removal of Cyanotoxins from Water and Design Concepts for Solar Photocatalytic Reactors for Large Scale Water Treatment

There has been a significant increase in the occurrence of cyanobacterial blooms in freshwaters over the past few decades due to escalating nutrient levels. These cyanobacteria release a range of toxins, for example microcystins which are chemically very stable. Many cyanotoxins are consequently very difficult to remove from water using existing treatment technologies. Semiconductor photocatalysis, however, has proven to be a very effective process for the removal of these compounds from water. In this chapter we consider the application of this highly versatile and exciting technology for the decomposition of cyanotoxins. Furthermore design concepts for solar photocatalytic reactors that could be utilized for the removal of these toxins are also considered

Transcending Boundaries of Creativity: Active learning in the Design Studio

This essay investigates the changing dynamics of interaction and paradigm of communication in the design studio. It analyses the process of practical implementation of interactive tools in architectural education which placed the
diversity of students’ cultural experiences, contextual awareness and individual interests as crucial resource for design innovation and inquiry. Building on Brian Lawson’s thesis on creativity in design thinking, this research project undertook
comprehensive investigation of students’ satisfaction of their roles in the studio and the room for liberal thought they are given to elaborate on genuine approach to architectural matters. The cyclical development of interactive learning strategy is explored through two different settings: first, it analyses architectural students’ position as passive/active in the studio, considering their relationships with tutors’ ideals; second, it reports on empirical strategy of students-led workshops at British schools of architecture, during which students have taken the lead of their creative design agenda. The practical implementation of interactive learning tools proved influential in helping students to personalize their design direction and to build a sense of confidence and independence.

Design and Analysis of Inexact Floating-Point Adders

Power has become a key constraint in nanoscale inte-grated circuit design due to the increasing demands for mobile computing and higher integration density. As an emerging compu-tational paradigm, an inexact circuit offers a promising approach to significantly reduce both dynamic and static power dissipation for error-tolerant applications. In this paper, an inexact floating-point adder is proposed by approximately designing an exponent sub-tractor and mantissa adder. Related operations such as normaliza-tion and rounding are also dealt with in terms of inexact computing. An upper bound error analysis for the average case is presented to guide the inexact design; it shows that the inexact floating-point adder design is dependent on the application data range. High dynamic range images are then processed using the proposed inexact floating-point adders to show the validity of the inexact design; comparison results show that the proposed inexact floating-point adders can improve the power consumption and power-delay product by 29.98% and 39.60%, respectively.

Comparison of granulometric methods and sampling strategies used in marine habitat classification and Ecological Status assessment

Sediment particle size analysis (PSA) is routinely used to support benthic macrofaunal community distribution data in habitat mapping and Ecological Status (ES) assessment. No optimal PSA Method to explain variability in multivariate macrofaunal distribution has been identified nor have the effects of changing sampling strategy been examined. Here, we use benthic macrofaunal and PSA grabs from two embayments in the south of Ireland. Four frequently used PSA Methods and two common sampling strategies are applied. A combination of laser particle sizing and wet/dry sieving without peroxide pre-treatment to remove organics was identified as the optimal Method for explaining macrofaunal distributions. ES classifications and EUNIS sediment classification were robust to changes in PSA Method. Fauna and PSA samples returned from the same grab sample significantly decreased macrofaunal variance explained by PSA and caused ES to be classified as lower. Employing the optimal PSA Method and sampling strategy will improve benthic monitoring. © 2012 Elsevier Ltd.

Design, synthesis and validation of an inhibitor of CGRP degradation

Introduction: In addition to their afferent role in detection and signalling noxious stimuli, neuropeptide-containing sensory nerves may initiate and maintain chronic inflammation in diseases such as periodontitis by an efferent process known as neurogenic inflammation. Neuropeptides are susceptible to cleavage by peptidases, and therefore, the exact location and level of expression of peptidases are major determinants of neuropeptide action. Previous studies in our laboratory showed that enzyme components of gingival crevicular fluid (GCF) from periodontitis sites selectively inactivated the neuropeptide calcitonin gene-related peptide (CGRP), known to have a role in inhibiting osteoclastic bone resorption. Objectives: The aim of this study was to design and synthesise a specific inhibitor to prevent the degradation of CGRP by components of GCF. Methods: A hydroxamate-based inhibitor with a biotinylated tag was designed to ensure selectivity for CGRP and ease of use for future purification strategies. The biotinylated peptide hydroxamate contained the P1-P4 amino acid sequence of the potential CGRP cleavage site and was synthesised by solid-phase methods using standard Fmoc chemistry. Inhibition of CGRP metabolism by GCF was determined by MALDI-mass spectrometry (MALDI-MS) using pooled GCF samples from periodontitis patients as a crude source of the CGRP-degrading enzyme. Results: MALDI-MS analysis of CGRP degradation showed almost complete inhibition in the presence of the biotinylated inhibitor. Our results showed that the rate-limiting step in the cleavage of CGRP is endopeptidase cleavage, followed by carboxypeptidase attack. Conclusion: This study demonstrates that the enzyme component of GCF responsible for the degradation of CGRP can be inhibited by a biotinylated hydroxamate modelled on a potential endopeptidase cleavage site. The biotin tag on the inhibitor will facilitate our future purification of the CGRP-cleavage enzyme using a streptavidin-agarose column.

Association Between Results of a Gene Expression Signature Assay and Recurrence-Free Interval in Patients With Stage II Colon Cancer in Cancer and Leukemia Group B 9581 (Alliance)

PURPOSE: Conventional staging methods are inadequate to identify patients with stage II colon cancer (CC) who are at high risk of recurrence after surgery with curative intent. ColDx is a gene expression, microarray-based assay shown to be independently prognostic for recurrence-free interval (RFI) and overall survival in CC. The objective of this study was to further validate ColDx using formalin-fixed, paraffin-embedded specimens collected as part of the Alliance phase III trial, C9581.

PATIENTS AND METHODS: C9581 evaluated edrecolomab versus observation in patients with stage II CC and reported no survival benefit. Under an initial case-cohort sampling design, a randomly selected subcohort (RS) comprised 514 patients from 901 eligible patients with available tissue. Forty-nine additional patients with recurrence events were included in the analysis. Final analysis comprised 393 patients: 360 RS (58 events) and 33 non-RS events. Risk status was determined for each patient by ColDx. The Self-Prentice method was used to test the association between the resulting ColDx risk score and RFI adjusting for standard prognostic variables.

RESULTS: Fifty-five percent of patients (216 of 393) were classified as high risk. After adjustment for prognostic variables that included mismatch repair (MMR) deficiency, ColDx high-risk patients exhibited significantly worse RFI (multivariable hazard ratio, 2.13; 95% CI, 1.3 to 3.5; P < .01). Age and MMR status were marginally significant. RFI at 5 years for patients classified as high risk was 82% (95% CI, 79% to 85%), compared with 91% (95% CI, 89% to 93%) for patients classified as low risk.

CONCLUSION: ColDx is associated with RFI in the C9581 subsample in the presence of other prognostic factors, including MMR deficiency. ColDx could be incorporated with the traditional clinical markers of risk to refine patient prognosis.

Design and Implementation of a Low Cost Virtual Rugby Decision Making Interactive

The paper describes the design and implementation of a novel low cost virtual rugby decision making interactive for use in a visitor centre. Original laboratory-based experimental work in decision making in rugby, using a virtual reality headset [1] is adapted for use in a public visitor centre, with consideration given to usability, costs, practicality and health and safety. Movement of professional rugby players was captured and animated within a virtually recreated stadium. Users then interact with these virtual representations via use of a lowcost sensor (Microsoft Kinect) to attempt to block them. Retaining the principles of perception and action, egocentric viewpoint, immersion, sense of presence, representative design and game design the system delivers an engaging and effective interactive to illustrate the underlying scientific principles of deceptive movement. User testing highlighted the need for usability, system robustness, fair and accurate scoring, appropriate level of difficulty and enjoyment.