Consensus on Outcome Measures for Glaucoma Effectiveness Trials: Results From a Delphi and Nominal Group Technique Approaches

PURPOSE: Comparing the relative effectiveness of interventions across glaucoma trials can be problematic due to differences in definitions of outcomes. We sought to identify a key set of clinical outcomes and reach consensus on how best to measure them from the perspective of glaucoma experts.

METHODS: A 2-round electronic Delphi survey was conducted. Round 1 involved 25 items identified from a systematic review. Round 2 was developed based on information gathered in round 1. A 10-point Likert scale was used to quantify importance and consensus of outcomes (7 outcomes) and ways of measuring them (44 measures). Experts were identified through 2 glaucoma societies membership-the UK and Eire Glaucoma Society and the European Glaucoma Society. A Nominal Group Technique (NGT) followed the Delphi process. Results were analyzed using descriptive statistics.

RESULTS: A total of 65 participants completed round 1 out of 320; of whom 56 completed round 2 (86%). Agreement on the importance of outcomes was reached on 48/51 items (94%). Intraocular pressure (IOP), visual field (VF), safety, and anatomic outcomes were classified as highly important. Regarding methods of measurement of IOP, "mean follow-up IOP" using Goldmann applanation tonometry achieved the highest importance, whereas for evaluating VFs "global index mean deviation/defect (MD)" and "rate of VF progression" were the most important. Retinal nerve fiber layer (RNFL) thickness measured by optical coherence tomography (OCT) was identified as highly important. The NGT results reached consensus on "change of IOP (mean of 3 consecutive measurements taken at fixed time of day) from baseline," change of VF-MD values (3 reliable VFs at baseline and follow-up visit) from baseline, and change of RNFL thickness (2 good quality OCT images) from baseline.

CONCLUSIONS: Consensus was reached among glaucoma experts on how best to measure IOP, VF, and anatomic outcomes in glaucoma randomized controlled trials.

Intelligent DMU creation: Nominal CAD model preparation for automated tolerance allocation

This paper examines the integration of a tolerance design process within the Computer-Aided Design (CAD) environment having identified the potential to create an intelligent Digital Mock-Up [1]. The tolerancing process is complex in nature and as such reliance on Computer-Aided Tolerancing (CAT) software and domain experts can create a disconnect between the design and manufacturing disciplines It is necessary to implement the tolerance design procedure at the earliest opportunity to integrate both disciplines and to reduce workload in tolerance analysis and allocation at critical stages in product development when production is imminent.
The work seeks to develop a methodology that will allow for a preliminary tolerance allocation procedure within CAD. An approach to tolerance allocation based on sensitivity analysis is implemented on a simple assembly to review its contribution to an intelligent DMU. The procedure is developed using Python scripting for CATIA V5, with analysis results aligning with those in literature. A review of its implementation and requirements is presented.

Performance projections and design optimization of planar double gate SOI MOSFETs for logic technology applications

In this paper, by investigating the influence of source/drain extension region engineering (also known as gate-source/drain underlap) in nanoscale planar double gate (DG) SOI MOSFETs, we offer new insights into the design of future nanoscale gate-underlap DG devices to achieve ITRS projections for high performance (HP), low standby power (LSTP) and low operating power (LOP) logic technologies. The impact of high-kappa gate dielectric, silicon film thickness, together with parameters associated with the lateral source/drain doping profile, is investigated in detail. The results show that spacer width along with lateral straggle can not only effectively control short-channel effects, thus presenting low off-current in a gate underlap device, but can also be optimized to achieve lower intrinsic delay and higher on-off current ratio (I-on/I-off). Based on the investigation of on-current (I-on), off-current (I-off), I-on/I-off, intrinsic delay (tau), energy delay product and static power dissipation, we present design guidelines to select key device parameters to achieve ITRS projections. Using nominal gate lengths for different technologies, as recommended from ITRS specification, optimally designed gate-underlap DG MOSFETs with a spacer-to-straggle (s/sigma) ratio of 2.3 for HP/LOP and 3.2 for LSTP logic technologies will meet ITRS projection. However, a relatively narrow range of lateral straggle lying between 7 to 8 nm is recommended. A sensitivity analysis of intrinsic delay, on-current and off-current to important parameters allows a comparative analysis of the various design options and shows that gate workfunction appears to be the most crucial parameter in the design of DG devices for all three technologies. The impact of back gate misalignment on I-on, I-off and tau is also investigated for optimized underlap devices.

Volatile and persistent real exchange rates with or without sticky prices

The flexible-price two-country monetary model is extended to include a consumption externality with habit persistence. Two methodologies are employed to explore this model's ability to generate volatile and persistent exchange rates. In the first, actual data is used for the exogenous driving processes. In the second, the model is simulated using estimated forcing processes. The theory, in both cases, is capable of explaining the high volatility and persistence of real and nominal exchange rates as well as the high correlation between real and nominal rates. © 2007 Elsevier B.V. All rights reserved.

Solving exchange rate puzzles with neither sticky prices nor trade costs

We present a simple framework in which both the exchange rate disconnect and forward bias puzzles are simultaneously resolved. The flexible-price two-country monetary model is extended to include a consumption externality with habit persistence. Habitpersistence is modeled using Campbell Cochrane preferences with ‘deep’ habits along the lines of the work of Ravn, Schmitt-Grohe and Uribe. By deep habits, we mean habits defined over goods rather than countries. The model is simulated using the artificial economy methodology. It offers a neo-classical explanation of the Meese–Rogoff puzzle and mimics the failure of fundamentals to explain nominal exchange rates in a linear setting. Finally, the model naturally generates the negative slope in the standard forward market regression.

Robust Dynamic Pricing Over Infinite Horizon in The Presence of Model Uncertainty( 2* Journal)

This paper studies a problem of dynamic pricing faced by a retailer with limited inventory, uncertain about the demand rate model, aiming to maximize expected discounted revenue over an infinite time horizon. The retailer doubts his demand model which is generated by historical data and views it as an approximation. Uncertainty in the demand rate model is represented by a notion of generalized relative entropy process, and the robust pricing problem is formulated as a two-player zero-sum stochastic differential game. The pricing policy is obtained through the Hamilton-Jacobi-Isaacs (HJI) equation. The existence and uniqueness of the solution of the HJI equation is shown and a verification theorem is proved to show that the solution of the HJI equation is indeed the value function of the pricing problem. The results are illustrated by an example with exponential nominal demand rate.

The effect of temperature and strain rate on the deformation behaviour, structure development and properties of biaxially stretched PET-clay nanocomposites.

The inclusion of a synthetic fluoromica clay in PET affects its processability via biaxial stretching and stretching temperature (95 °C and 102 °C) and strain rate (1 s-1 and 2 s-1) influence the structuring and properties of the stretched material. The inclusion of clay has little effect on the temperature operating window for the PET–clay but it has a major effect on deformation behaviour which will necessitate the use of much higher forming forces during processing. The strain hardening behaviour of both the filled and unfilled materials is well correlated with tensile strength and tensile modulus. Increasing the stretching temperature to reduce stretching forces has a detrimental effect on clay exfoliation, mechanical and O2 barrier properties. Increasing strain rate has a lesser effect on the strain hardening behaviour of the PET–clay compared with the pure PET and this is attributed to possible adiabatic heating in the PET–clay sample at the higher strain rate. The Halpin–Tsai model is shown to accurately predict the modulus enhancement of the PET–clay materials when a modified particle modulus rather than nominal clay modulus is used.

The trace amine associated receptor (TAAR6) gene is not associated with schizophrenia in the Irish Case-Control Study of Schizophrenia (ICCSS) sample

To replicate previous association between TAAR6 and schizophrenia, including our own finding in the Irish Study of High Density Schizophrenia Families (ISHDSF) sample, we genotyped 12 single nucleotide polymorphisms (SNPs) in the Irish Case-Control Study of Schizophrenia (ICCSS) sample. Only rs9389020 provided nominal evidence for association (p

The birth place of the type Ic supernova 2007gr

We report our attempts to locate the progenitor of the peculiar Type Ic SN 2007gr in Hubble Space Telescope (HST) preexplosion images of the host galaxy, NGC 1058. Aligning adaptive optics Altair/NIRI imaging of SN 2007gr from the Gemini ( North) Telescope with the preexplosion HST WFPC2 images, we identify the supernova (SN) position on the HST frames with an accuracy of 20 mas. Although nothing is detected at the SN position, we show that it lies on the edge of a bright source 134 +/- 23 mas (6.9 pc) from its nominal center. On the basis of its luminosity, we suggest that this object is possibly an unresolved, compact, and coeval cluster and that the SN progenitor was a cluster member, although we note that model profile fitting favors a single bright star. We find two solutions for the age of this assumed cluster: 7 -/+ 0.5 Myr and 20 - 30 Myr, with turnoff masses of 28 +/- M-circle dot and 12 - 9 M-circle dot, respectively. Preexplosion ground-based K- band images marginally favor the younger cluster 4 age/higher turnoff mass. Assuming the SN progenitor was a cluster member, the turnoff mass provides the best estimate for its initial mass. More detailed observations, after the SN has faded, should determine whether the progenitor was indeed part of a cluster and, if so, allow an age estimate to within similar to 2 Myr, thereby favoring either a high-mass single star or lower-mass interacting binary progenitor.

A virtual inspection framework for precision manufacturing of aerofoil components

The finite element method plays an extremely important role in forging process design as it provides a valid means to quantify forging errors and thereby govern die shape modification to improve the dimensional accuracy of the component. However, this dependency on process simulation could raise significant problems and present a major drawback if the finite element simulation results were inaccurate. This paper presents a novel approach to assess the dimensional accuracy and shape quality of aeroengine blades formed from finite element hot-forging simulation. The proposed virtual inspection system uses conventional algorithms adopted by modern coordinate measurement processes as well as the latest free-form surface evaluation techniques to provide a robust framework for virtual forging error assessment. Established techniques for the physical registration of real components have been adapted to localise virtual models in relation to a nominal Design Coordinate System. Blades are then automatically analysed using a series of intelligent routines to generate measurement data and compute dimensional errors. The results of a comparison study indicate that the virtual inspection results and actual coordinate measurement data are highly comparable, validating the approach as an effective and accurate means to quantify forging error in a virtual environment. Consequently, this provides adequate justification for the implementation of the virtual inspection system in the virtual process design, modelling and validation of forged aeroengine blades in industry.

TRANSITION TO FILAMENTARY REGIME IN LASER-PLASMA INTERACTION EVIDENCED BY 2-OMEGA-EMISSION

The level of second-harmonic light emitted from a laser-exploded foil plasma at nominal irradiance up to 3.10(13) W/cm2 was found to be extremely sensitive to both target position and irradiance on target. Either a small target displacement or a small increase in irradiance resulted in a jump of the 2omega level of more than three orders of magnitude. Correspondingly, a transition was observed from a 2omega source pattern clearly signed by the original laser spot pattern to unstable patterns of filaments whose size is consistent with the maximum growth of the instability.

A new landscape of arts-based buildings and comparative cultural policies on the island of Ireland: the curse of Jocasta's necklace

Much current cultural policy research focuses on activity traditionally viewed as arts practice: visual arts, music, literature and dance. Architecture’s role in the discussion of cultural policy is, however, less certain and thus less frequently interrogated. The study presented here both addresses this dearth of in-depth research while also contributing to the interdisciplinary discussion of cultural policy in wider terms. In seeking to better understand how architectural culture is regulated and administered in a specific case study, it unpacks how the complicated relationships of nominal and explicit policies on both sides of the Irish/Northern Irish border contributed to the significant expansion of arts-based buildings 1995-2008. It contrasts political and cultural motivations behind these projects during a period of significant economic growth, investment and inward immigration. Data has been gathered from both official published policies as well as interviews with elite actors in the decision-making field and architects who produced the buildings of interest in both countries. With the sizeable number of arts-based buildings now completed in both Republic of Ireland and Northern Ireland, one must wonder if this necklace of buildings is, like Jocasta’s, a thing of both beauty and redolent with a potential future curse. It is the goal of this project to contribute to the larger applied and critical discussion of these issues and to engage with future policy design, administration and, certainly, evaluation.

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10-9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated.

A new landscape of arts-based buildings and comparative cultural policies on the island of Ireland: the curse of Jocasta's necklace

Much current cultural policy research focuses on activity traditionally viewed as arts practice: visual arts, music, literature and dance. Architecture’s role in the discussion of cultural policy is, however, less certain and thus less frequently interrogated. The study presented here both addresses this dearth of in-depth research while also contributing to the interdisciplinary discussion of cultural policy in wider terms. In seeking to better understand how architectural culture is regulated and administered in a specific case study, it unpacks how the complicated relationships of nominal and explicit policies on both sides of the Irish/Northern Irish border contributed to the significant expansion of arts-based buildings 1995-2008. It contrasts political and cultural motivations behind these projects during a period of significant economic growth, investment and inward immigration. Data has been gathered from both official published policies as well as interviews with elite actors in the decision-making field and architects who produced the buildings of interest in both countries. With the sizeable number of arts-based buildings now completed in both Republic of Ireland and Northern Ireland, one must wonder if this necklace of buildings is, like Jocasta’s, a thing of both beauty and redolent with a potential future curse. It is the goal of this project to contribute to the larger applied and critical discussion of these issues and to engage with future policy design, administration and, certainly, evaluation.

Environmental indifference? A critique of environmentally deterministic theories of peatland archaeological site construction in Ireland

Climate change, whether gradual or sudden, has frequently been invoked as a causal factor to explain many aspects of cultural change during the prehistoric and early historic periods. Critiquing such theories has often proven difficult, not least because of the imprecise dating of many aspects of the palaeoclimate or archaeological records and the difficulties of merging the two strands of research. Here we consider one example of the archaeological record – peatland site construction in Ireland – which has previously been interpreted in terms of social response to climate change and examine whether close scrutiny of the archaeological and palaeoenvironmental records uphold the climatically deterministic hypotheses. We evaluate evidence for phasing in the temporal distribution of trackways and related sites in Irish peatlands, of which more than 3,500 examples have been recorded, through the examination of ~350 dendrochronological and 14C dates from these structures. The role of climate change in influencing when such sites were constructed is assessed by comparing visually and statistically the frequency of sites over the last 4,500 years with well-dated, multi-proxy climate reconstructions from Irish peatlands. We demonstrate that national patterns of “peatland activity” exist that indicate that the construction of sites in bogs was neither a constant nor random phenomenon. Phases of activity (i.e. periods in which the number of structures increased), as well as the ‘lulls’ that separate them, show no consistent correlation with periods of wetter or drier conditions on the bogs, suggesting that the impetus for the start or cessation of such activity was not climatically-determined. We propose that trigger(s) for peatland site construction in Ireland must instead also be sought within the wider, contemporary social background. Perhaps not surprisingly, a comparison with archaeological and palynological evidence shows that peatland activity tends to occur at times of more expansive settlement and land-use, suggesting that the bogs were used when the landscape was being more widely occupied. Interestingly, the lulls in peatland site construction coincide with transitional points between nominal archaeological phases, typically defined on the basis of their material culture, implying that there may indeed have been a cultural discontinuity at these times. © 2012 Elsevier Ltd. All rights reserved.