Optimal power budget in quasi-linear dispersion-managed fiber links

We develop a theory of an optimal distribution of the gain of in-line amplifiers in dispersion-managed transmission systems. As an example of the application of the general method we propose a design of the line with periodically imbalanced in-line amplification.

A new algorithm for the relationship between vision and ametropia

Refraction simulators used for undergraduate training at Aston University did not realistically reflect variations in the relationship between vision and ametropia. This was because they used an algorithm, taken from the research literature, that strictly only applied to myopes or older hyperopes and did not factor in age and pupil diameter. The aim of this study was to generate new algorithms that overcame these limitations. Clinical data were collected from the healthy right eyes of 873 white subjects aged between 20 and 70 years. Vision and refractive error were recorded along with age and pupil diameter. Re-examination of 34 subjects enabled the calculation of coefficients of repeatability. The study population was slightly biased towards females and included many contact lens wearers. Sex and contact lens wear were, therefore, recorded in order to determine whether these might influence the findings. In addition, iris colour and cylinder axis orientation were recorded as these might also be influential. A novel Blur Sensitivity Ratio (BSR) was derived by dividing vision (expressed as minimum angle of resolution) by refractive error (expressed as a scalar vector, U). Alteration of the scalar vector, to account for additional vision reduction due to oblique cylinder axes, was not found to be useful. Decision tree analysis showed that sex, contact lens wear, iris colour and cylinder axis orientation did not influence the BSR. The following algorithms arose from two stepwise multiple linear regressions: BSR (myopes) = 1.13 + (0.24 x pupil diameter) + (0.14 x U) BSR (hyperopes) = (0.11 x pupil diameter) + (0.03 x age) - 0.22 These algorithms together accounted for 84% of the observed variance. They showed that pupil diameter influenced vision in both forms of ametropia. They also showed the age-related decline in the ability to accommodate in order to overcome reduced vision in hyperopia.

Interest groups in multiple streams:specifying their involvement in the framework

Although interests inhabit a central place in the multiple streams framework (MSF), interest groups have played only a minor role in theoretical and empirical studies until now. In Kingdon’s original conception, organized interests are a key variable in the politics stream. Revisiting Kingdon’s concept with a particular focus on interest groups and their activities—in different streams and at various levels—in the policy process, we take this argument further. In particular, we argue that specifying groups’ roles in other streams adds value to the explanatory power of the framework. To do this, we look at how interest groups affect problems, policies, and politics. The influence of interest groups within the streams is explained by linking the MSF with literature on interest intermediation. We show that depending on the number of conditions and their activity level, interest groups can be involved in all three streams. We illustrate this in case studies reviewing labor market policies in Germany and chemicals regulation at the European level.

Evaluation of hemifield sector analysis protocol in multifocal visual evoked potential objective perimetry for the diagnosis and early detection of glaucomatous field defects

CONCLUSIONS: The new HSA protocol used in the mfVEP testing can be applied to detect glaucomatous visual field defects in both glaucoma and glaucoma suspect patients. Using this protocol can provide information about focal visual field differences across the horizontal midline, which can be utilized to differentiate between glaucoma and normal subjects. Sensitivity and specificity of the mfVEP test showed very promising results and correlated with other anatomical changes in glaucoma field loss. PURPOSE: Multifocal visual evoked potential (mfVEP) is a newly introduced method used for objective visual field assessment. Several analysis protocols have been tested to identify early visual field losses in glaucoma patients using the mfVEP technique, some were successful in detection of field defects, which were comparable to the standard automated perimetry (SAP) visual field assessment, and others were not very informative and needed more adjustment and research work. In this study we implemented a novel analysis approach and evaluated its validity and whether it could be used effectively for early detection of visual field defects in glaucoma. METHODS: Three groups were tested in this study; normal controls (38 eyes), glaucoma patients (36 eyes) and glaucoma suspect patients (38 eyes). All subjects had a two standard Humphrey field analyzer (HFA) test 24-2 and a single mfVEP test undertaken in one session. Analysis of the mfVEP results was done using the new analysis protocol; the hemifield sector analysis (HSA) protocol. Analysis of the HFA was done using the standard grading system. RESULTS: Analysis of mfVEP results showed that there was a statistically significant difference between the three groups in the mean signal to noise ratio (ANOVA test, p < 0.001 with a 95% confidence interval). The difference between superior and inferior hemispheres in all subjects were statistically significant in the glaucoma patient group in all 11 sectors (t-test, p < 0.001), partially significant in 5 / 11 (t-test, p < 0.01), and no statistical difference in most sectors of the normal group (1 / 11 sectors was significant, t-test, p < 0.9). Sensitivity and specificity of the HSA protocol in detecting glaucoma was 97% and 86%, respectively, and for glaucoma suspect patients the values were 89% and 79%, respectively.

The influence on unaided vision of age, pupil diameter and spherocylindrical refractive error

Background - The aim was to derive equations for the relationship between unaided vision and age, pupil diameter, iris colour and sphero-cylindrical refractive error. Methods - Data were collected from 663 healthy right eyes of white subjects aged 20 to 70 years. Subjective sphero-cylindrical refractive errors ranged from -6.8 to +9.4 D (mean spherical equivalent), -1.5 to +1.9 D (orthogonal component, J0) and -0.8 to 1.0 D (oblique component, J45). Cylinder axis orientation was orthogonal in 46 per cent of the eyes and oblique in 18 per cent. Unaided vision (-0.3 to +1.3 logMAR), pupil diameter (2.3 to 7.5 mm) and iris colour (67 per cent light/blue irides) was recorded. The sample included mostly females (60 per cent) and many contact lens wearers (42 per cent) and so the influences of these parameters were also investigated. Results - Decision tree analysis showed that sex, iris colour, contact lens wear and cylinder axis orientation did not influence the relationship between unaided vision and refractive error. New equations for the dependence of the minimum angle of resolution on age and pupil diameter arose from step backwards multiple linear regressions carried out separately on the myopes (2.91.scalar vector +0.51.pupil diameter -3.14 ) and hyperopes (1.55.scalar vector + 0.06.age – 3.45 ). Conclusion - The new equations may be useful in simulators designed for teaching purposes as they accounted for 81 per cent (for myopes) and 53 per cent (for hyperopes) of the variance in measured data. In comparison, previously published equations accounted for not more than 76 per cent (for myopes) and 24 per cent (for hyperopes) of the variance depending on whether they included pupil size. The new equations are, as far as is known to the authors, the first to include age. The age-related decline in accommodation is reflected in the equation for hyperopes.

Parameterized Link Functions in Generalized Linear Random Effect Models: a Case Study on Breast Cancer Treatment

In non-linear random effects some attention has been very recently devoted to the analysis ofsuitable transformation of the response variables separately (Taylor 1996) or not (Oberg and Davidian 2000) from the transformations of the covariates and, as far as we know, no investigation has been carried out on the choice of link function in such models. In our study we consider the use of a random effect model when a parameterized family of links (Aranda-Ordaz 1981, Prentice 1996, Pregibon 1980, Stukel 1988 and Czado 1997) is introduced. We point out the advantages and the drawbacks associated with the choice of this data-driven kind of modeling. Difficulties in the interpretation of regression parameters, and therefore in understanding the influence of covariates, as well as problems related to loss of efficiency of estimates and overfitting, are discussed. A case study on radiotherapy usage in breast cancer treatment is discussed.

Estimation of global systematic risk for securities listed in multiple markets

The market model is the most frequently estimated model in financial economics and has proven extremely useful in the estimation of systematic risk. In this era of rapid globalization of financial markets there has been a substantial increase in cross listings of stocks in foreign and regional capital markets. As many as a third to a half of the stocks in some major exchanges are foreign listed. The multiple listings of stocks has major implications for the estimation of systematic risk. The traditiona1 method of estimating the market model by using data from only one market will lead to misleading estimates of beta. This study demonstrates that the estimator for systematic risk and the methodology itself changes when stocks are listed in multiple markets. General expressions are developed to obtain the estimator of global beta under a variety of assumptions about the error terms of the market models for different capital markets. The assumptions pertain both to the volatilities of the abnormal returns in each market, and to the relationship between the markets. ^ Explicit expressions are derived for the estimation of global systematic risk beta when the returns are homoscedastic and also under different heteroscedastic conditions both within and/or between markets. These results for the estimation of global beta are further extended when return generating process follows an autoregressive scheme.^

Alterations in Glutathione Levels and Apoptotic Regulators Are Associated with Acquisition of Arsenic Trioxide Resistance in Multiple Myeloma

Arsenic trioxide (ATO) has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2–3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH) levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH) are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

Reference gene selection and RNA preservation protocol in the cat flea, Ctenocephalides felis, for gene expression studies

This work was supported by a Knowledge Transfer Network BBSRC Industrial Case (#414 BB/L502467/1) studentship in association Zoetis Inc.

Grabbing Your Attention: The Impact of Finding a First Target in Multiple-Target Search

For over 50 years, the Satisfaction of Search effect, and more recently known as the Subsequent Search Miss (SSM) effect, has plagued the field of radiology. Defined as a decrease in additional target accuracy after detecting a prior target in a visual search, SSM errors are known to underlie both real-world search errors (e.g., a radiologist is more likely to miss a tumor if a different tumor was previously detected) and more simplified, lab-based search errors (e.g., an observer is more likely to miss a target ‘T’ if a different target ‘T’ was previously detected). Unfortunately, little was known about this phenomenon’s cognitive underpinnings and SSM errors have proven difficult to eliminate. However, more recently, experimental research has provided evidence for three different theories of SSM errors: the Satisfaction account, the Perceptual Set account, and the Resource Depletion account. A series of studies examined performance in a multiple-target visual search and aimed to provide support for the Resource Depletion account—a first target consumes cognitive resources leaving less available to process additional targets.

To assess a potential mechanism underlying SSM errors, eye movements were recorded in a multiple-target visual search and were used to explore whether a first target may result in an immediate decrease in second-target accuracy, which is known as an attentional blink. To determine whether other known attentional distractions amplified the effects of finding a first target has on second-target detection, distractors within the immediate vicinity of the targets (i.e., clutter) were measured and compared to accuracy for a second target. To better understand which characteristics of attention were impacted by detecting a first target, individual differences within four characteristics of attention were compared to second-target misses in a multiple-target visual search.

The results demonstrated that an attentional blink underlies SSM errors with a decrease in second-target accuracy from 135ms-405ms after detection or re-fixating a first target. The effects of clutter were exacerbated after finding a first target causing a greater decrease in second-target accuracy as clutter increased around a second-target. The attentional characteristics of modulation and vigilance were correlated with second- target misses and suggest that worse attentional modulation and vigilance are predictive of more second-target misses. Taken together, these result are used as the foundation to support a new theory of SSM errors, the Flux Capacitor theory. The Flux Capacitor theory predicts that once a target is found, it is maintained as an attentional template in working memory, which consumes attentional resources that could otherwise be used to detect additional targets. This theory not only proposes why attentional resources are consumed by a first target, but encompasses the research in support of all three SSM theories in an effort to establish a grand, unified theory of SSM errors.

Mixtures of g-priors in Generalized Linear Models

Mixtures of Zellner's g-priors have been studied extensively in linear models and have been shown to have numerous desirable properties for Bayesian variable selection and model averaging. Several extensions of g-priors to Generalized Linear Models (GLMs) have been proposed in the literature; however, the choice of prior distribution of g and resulting properties for inference have received considerably less attention. In this paper, we extend mixtures of g-priors to GLMs by assigning the truncated Compound Confluent Hypergeometric (tCCH) distribution to 1/(1+g) and illustrate how this prior distribution encompasses several special cases of mixtures of g-priors in the literature, such as the Hyper-g, truncated Gamma, Beta-prime, and the Robust prior. Under an integrated Laplace approximation to the likelihood, the posterior distribution of 1/(1+g) is in turn a tCCH distribution, and approximate marginal likelihoods are thus available analytically. We discuss the local geometric properties of the g-prior in GLMs and show that specific choices of the hyper-parameters satisfy the various desiderata for model selection proposed by Bayarri et al, such as asymptotic model selection consistency, information consistency, intrinsic consistency, and measurement invariance. We also illustrate inference using these priors and contrast them to others in the literature via simulation and real examples.

Effects of retirement on cognitive function: A gender and international perspecive

Background: As the global population is ageing, studying cognitive impairments including dementia, one of the leading causes of disability in old age worldwide, is of fundamental importance to public health. As a major transition in older age, a focus on the complex impacts of the duration, timing, and voluntariness of retirement on health is important for policy changes in the future. Longer retirement periods, as well as leaving the workforce early, have been associated with poorer health, including reduced cognitive functioning. These associations are hypothesized to differ based on gender, as well as on pre-retirement educational and occupational experiences, and on post-retirement social factors and health conditions. Methods: A cross-sectional study is conducted to determine the relationship between duration and timing of retirement and cognitive function, using data from the five sites of International Mobility in Aging Study (IMIAS). Cognitive function is assessed using the Leganes Cognitive Test (LCT) scores in 2012. Data are analyzed using multiple linear regressions. Analyses are also done by site/region separately (Canada, Latin America, and Albania). Robustness checks are done with an analysis of cognitive change from 2012 to 2014, the effect of voluntariness of retirement on cognitive function. An instrumental variable (IV) approach is also applied to the cross-sectional and longitudinal analyses as a robustness check to address the potential endogeneity of the retirement variable. Results: Descriptive statistics highlight differences between men and women, as well as between sites. In linear regression analysis, there was no relationship between timing or duration of retirement and cognitive function in 2012, when adjusting for site/region. There was no association between retirement characteristics and cognitive function in site/region/stratified analyses. In IV analysis, longer retirement and on time or late retirement was associated with lower cognitive function among men. In IV analysis, there is no relationship between retirement characteristics and cognitive function among women. Conclusions: While results of the thesis suggest a negative effect of retirement on cognitive function, especially among men, the relationship remains uncertain. A lack of power results in the inability to draw conclusions for site/region-specific analysis and site-adjusted analysis in both linear and IV regressions.

Characterization of IGH locus breakpoints in multiple myeloma indicates a subset of translocations appear to occur in pregerminal center B cells.

Translocations in myeloma are thought to occur solely in mature B cells in the germinal center through class switch recombination (CSR). We used a targeted captured technique followed by massively parallel sequencing to determine the exact breakpoints in both the immunoglobulin heavy chain (IGH) locus and the partner chromosome in 61 presentation multiple myeloma samples. The majority of samples (62%) have a breakpoint within the switch regions upstream of the IGH constant genes and are generated through CSR in a mature B cell. However, the proportion of CSR translocations is not consistent between cytogenetic subgroups. We find that 100% of t(4;14) are CSR-mediated; however, 21% of t(11;14) and 25% of t(14;20) are generated through DH-JH recombination activation gene-mediated mechanisms, indicating they occur earlier in B-cell development at the pro-B-cell stage in the bone marrow. These 2 groups also generate translocations through receptor revision, as determined by the breakpoints and mutation status of the segments used in 10% and 50% of t(11;14) and t(14;20) samples, respectively. The study indicates that in a significant number of cases the translocation-based etiological events underlying myeloma may arise at the pro-B-cell hematological progenitor cell level, much earlier in B-cell development than was previously thought.

The Clinical Impact and Molecular Biology of del(17p) in Multiple Myeloma Treated with Conventional or Thalidomide-Based Therapy

Hemizygous deletion of 17p (del(17p)) has been identified as a variable associated with poor prognosis in myeloma, although its impact in the context of thalidomide therapy is not well described. The clinical outcome of 85 myeloma patients with del(17p) treated in a clinical trial incorporating both conventional and thalidomide-based induction therapies was examined. The clinical impact of deletion, low expression, and mutation of TP53 was also determined. Patients with del(17p) did not have inferior response rates compared to patients without del(17p), but, despite this, del(17p) was associated with impaired overall survival (OS) (median OS 26.6 vs. 48.5 months, P <0.001). Within the del(17p) group, thalidomide induction therapy was associated with improved response rates compared to conventional therapy, but there was no impact on OS. Thalidomide maintenance was associated with impaired OS, although our analysis suggests that this effect may have been due to confounding variables. A minimally deleted region on 17p13.1 involving 17 genes was identified, of which only TP53 and SAT2 were underexpressed. TP53 was mutated in <1% in patients without del(17p) and in 27% of patients with del(17p). The higher TP53 mutation rate in samples with del(17p) suggests a role for TP53 in these clinical outcomes. In conclusion, del(17p) defined a patient group associated with short survival in myeloma, and although thalidomide induction therapy was associated with improved response rates, it did not impact OS, suggesting that alternative therapeutic strategies are required for this group. (C) 2011 Wiley-Liss, Inc.

Deletions of CDKN2C in Multiple Myeloma: Biological and Clinical Implications

Purpose: Deletions of chromosome 1 have been described in 7% to 40% of cases of myeloma with inconsistent clinical consequences. CDKN2C at 1p32.3 has been identified in myeloma cell lines as the potential target of the deletion. We tested the clinical impact of 1p deletion and used high-resolution techniques to define the role of CDKN2C in primary patient material.Experimental Design: We analyzed 515 cases of monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and newly diagnosed multiple myeloma using fluorescence in situ hybridization (FISH) for deletions of CDKN2C. In 78 myeloma cases, we carried out Affymetrix single nucleotide polymorphism mapping and U133 Plus 2.0 expression arrays. In addition, we did mutation, methylation, and Western blotting analysis.Results: By FISH we identified deletion of 1p32.3 (CDKN2C) in 3 of 66 MGUS (4.5%), 4 of 39 SMM (10.3%), and 55 of 369 multiple myeloma cases (15%). We examined the impact of copy number change at CDKN2C on overall survival (OS), and found that the cases with either hemizygous or homozygous deletion of CDKN2C had a worse OS compared with cases that were intact at this region (22 months versus 38 months; P = 0.003). Using gene mapping we identified three homozygous deletions at 1p32.3, containing CDKN2C, all of which lacked expression of CDKN2C. Cases with homozygous deletions of CDKN2C were the most proliferative myelomas, defined by an expression-based proliferation index, consistent with its biological function as a cyclin-dependent kinase inhibitor.Conclusions: Our results suggest that deletions of CDKN2C are important in the progression and clinical outcome of myeloma.