Adaptive designs in the time to event setting: The potential for benefit and risk

Thesis (Ph.D.)--University of Washington, 2016-06

The comprehensive osteoarthritis test: a simple index for measurement of treatment effects in clinical trials

Objective. To assess the measurement properties of a simple index of symptom severity in osteoarthritis (OA) of the hips and knees. Methods. Both the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the proposed new Comprehensive Osteoarthritis Test (COAT) instrument were completed weekly by 125 subjects in the context of a randomized, 12-week, 3 parallel-arm clinical trial. The reliabilities of the various scales were assessed on a weekly basis by use of Cronbach's alpha coefficients. The validity of the COAT total scale was assessed by correlation with the WOMAC total scale on a weekly basis with correlation coefficients, and in terms of the correlations between subject-level intercepts and slopes over time. The relative responsiveness of the WOMAC and COAT total scales was assessed using a multilevel (longitudinal) multivariate (WOMAC, COAT) linear model. Results. The WOMAC and COAT total scales were highly reliable (mean over weeks: WOMAC alpha = 0.98; COAT alpha = 0.97). The correlations between the WOMAC and COAT scales were very high (mean over weeks = 0.92; subject-level intercepts = 0.91, slopes = 0.88). The COAT total scale was significantly more responsive than the WOMAC total scale in the active treatment (34.8% improvement vs 26.8%; p = 0.002). Conclusion. The COAT total scale is simple to administer, reliable, valid, and responsive to treatment effects.

Characteristics and benefits of professional work - Assessment of their importance over a 30-year career

The Professions in Australia Study is the first longitudinal investigation of the professions in Australia; it spans 33 years. Self-administered questionnaires were distributed on at least eight occasions between 1965 and 1998 to cohorts of students and later practitioners from the professions of engineering, law and medicine. The longitudinal design of this study has allowed for an investigation of individual change over time of three archetypal characteristics of the professions, service, knowledge and autonomy and two of the benefits of professional work, financial rewards and prestige. A cumulative logit random effects model was used to statistically assess changes in the ordinal response scores for measuring importance of the characteristics and benefits through stages of the career path. Individuals were also classified by average trends in response scores over time and hence professions are described through their members' tendency to follow a particular path in attitudes either of change or constancy, in relation to the importance of the five elements (characteristics and benefits). Comparisons in trends are also made between the three professions.

Topographic, haemodynamic and psychophysical investigation of glaucomatous optic neuropathy

Loss of optic nerve head (ONH) axons in primary open angle glaucoma (POAG) has been attributed to both mechanical and vascular factors. Confocal scanning laser ophthalmoscopy (cSLO) provides a promising tool for the topographic follow-up of the ONH in glaucoma, while scanning laser Doppler flowmetry (SLDF) facilitates the rapid non-invasive assessment of retinal capillary blood flow. The purposes of these investigations were to optimise the techniques and explore their potential to classify and monitor disease. Preliminary investigations explored the reproducibility and validity of cSLO and SLDF and showed that: For cSLO: In a model eye, measurements are accurate over a range of axial lengths. For best reproducibility, seven images per visit are required, with a contour line located on Elschnig's scleral ring and transferred automatically between images. For SLDF: Three perfusion images are required for optimum reproducibility. Physiological changes induced by gas perturbation can be measured. Cross-sectional comparison of groups of normal subjects and early POAG patients showed that: cSLO parameters differentiate the early POAG group. Blood volume measured by SLDF showed group differences in superior nasal retina only. Longitudinal investigation of ONH topography, haemodynamic and visual field indices in normal subjects and POAG patients showed that: cSLO detects topographical change over time more frequently in the POAG group. Important parameters include: C:D area ratio, cup and rim area, mean depth in contour, volumes above and below reference and surface. Factor analysis identified "cup" and "rim" factors that can be used to detect change over time in individual patients. Blood flow changes were most apparent in the inferior nasal peripapillary retina of the POAG group. Perimetry is of clinical value for the identification of glaucoma but is less sensitive than cSLO for monitoring glaucomatous change.

Perils of managing the service profit chain:the role of time lags and feedback loops

The tendency of managers to focus on short-term results rather than on sustained company success is of particular importance to retail marketing managers, because marketing activities involve expenditures which may only pay off in the longer term. To address the issue of myopic management, our study shows how the complexity of the service profit chain (SPC) can cause managers to make suboptimal decisions. Hence, our paper departs from past research by recognizing that understanding the temporal interplay between operational investments, employee satisfaction, customer satisfaction, and operating profit is essential to achieving sustained success. In particular, we intend to improve understanding of the functioning of the SPC with respect to time lags and feedback loops. Results of our large-scale longitudinal study set in a multi-outlet retail chain reveal time-lag effects between operational investments and employee satisfaction, as well as between customer satisfaction and performance. These findings, along with evidence of a negative interaction effect of employee satisfaction on the relationship between current performance and future investments, show the substantial risk of mismanaging the SPC. We identify specific situations in which the dynamic approach leads to superior marketing investment decisions, when compared to the conventional static view of the SCP. These insights provide valuable managerial guidance for effectively managing the SPC over time. © 2012 New York University.

Early marketing matters:a time-varying parameter approach to persistence modeling

Are persistent marketing effects most likely to appear right after the introduction of a product? The authors give an affirmative answer to this question by developing a model that explicitly reports how persistent and transient marketing effects evolve over time. The proposed model provides managers with a valuable tool to evaluate their allocation of marketing expenditures over time. An application of the model to many pharmaceutical products, estimated through (exact initial) Kalman filtering, indicates that both persistent and transient effects occur predominantly immediately after a brand's introduction. Subsequently, the size of the effects declines. The authors theoretically and empirically compare their methodology with methodology based on unit root testing and demonstrate that the need for unit root tests creates difficulties in applying conventional persistence modeling. The authors recommend that marketing models should either accommodate persistent effects that change over time or be applied to mature brands or limited time windows only.

The topics they are a-changing - characterising topics with time-stamped semantic graphs

DBpedia has become one of the major sources of structured knowledge extracted from Wikipedia. Such structures gradually re-shape the representation of Topics as new events relevant to such topics emerge. Such changes make evident the continuous evolution of topic representations and introduce new challenges to supervised topic classification tasks, since labelled data can rapidly become outdated. Here we analyse topic changes in DBpedia and propose the use of semantic features as a more stable representation of a topic. Our experiments show promising results in understanding how the relevance of features to a topic changes over time.

On the k-anonymization of time-varying and multi-layer social graphs

The popularity of online social media platforms provides an unprecedented opportunity to study real-world complex networks of interactions. However, releasing this data to researchers and the public comes at the cost of potentially exposing private and sensitive user information. It has been shown that a naive anonymization of a network by removing the identity of the nodes is not sufficient to preserve users’ privacy. In order to deal with malicious attacks, k -anonymity solutions have been proposed to partially obfuscate topological information that can be used to infer nodes’ identity. In this paper, we study the problem of ensuring k anonymity in time-varying graphs, i.e., graphs with a structure that changes over time, and multi-layer graphs, i.e., graphs with multiple types of links. More specifically, we examine the case in which the attacker has access to the degree of the nodes. The goal is to generate a new graph where, given the degree of a node in each (temporal) layer of the graph, such a node remains indistinguishable from other k-1 nodes in the graph. In order to achieve this, we find the optimal partitioning of the graph nodes such that the cost of anonymizing the degree information within each group is minimum. We show that this reduces to a special case of a Generalized Assignment Problem, and we propose a simple yet effective algorithm to solve it. Finally, we introduce an iterated linear programming approach to enforce the realizability of the anonymized degree sequences. The efficacy of the method is assessed through an extensive set of experiments on synthetic and real-world graphs.

Global variations and time trends in the prevalence of childhood myopia, a systematic review and quantitative meta-analysis:implications for aetiology and early prevention

The aim of this review was to quantify the global variation in childhood myopia prevalence over time taking account of demographic and study design factors. A systematic review identified population-based surveys with estimates of childhood myopia prevalence published by February 2015. Multilevel binomial logistic regression of log odds of myopia was used to examine the association with age, gender, urban versus rural setting and survey year, among populations of different ethnic origins, adjusting for study design factors. 143 published articles (42 countries, 374 349 subjects aged 1- 18 years, 74 847 myopia cases) were included. Increase in myopia prevalence with age varied by ethnicity. East Asians showed the highest prevalence, reaching 69% (95% credible intervals (CrI) 61% to 77%) at 15 years of age (86% among Singaporean-Chinese). Blacks in Africa had the lowest prevalence; 5.5% at 15 years (95% CrI 3% to 9%). Time trends in myopia prevalence over the last decade were small in whites, increased by 23% in East Asians, with a weaker increase among South Asians. Children from urban environments have 2.6 times the odds of myopia compared with those from rural environments. In whites and East Asians sex differences emerge at about 9 years of age; by late adolescence girls are twice as likely as boys to be myopic. Marked ethnic differences in age-specific prevalence of myopia exist. Rapid increases in myopia prevalence over time, particularly in East Asians, combined with a universally higher risk of myopia in urban settings, suggest that environmental factors play an important role in myopia development, which may offer scope for prevention.

Treefrogs in Forested Swamps at the La Selva Biological Station: Assemblage Variation through Space and Time

Swamp-breeding treefrogs form conspicuous components of many tropical forest sites, yet remain largely understudied. The La Selva Biological Station, a rainforest reserve in Costa Rica, harbors a rich swamp-breeding treefrog fauna that has been studied in only one of the many swamps found at the site. To understand if the species composition of treefrogs at La Selva varies over space or time, frogs were censused in 1982-83, 1994-95, 2005 and 2011 at two ponds located in the reserve. Data on treefrog habitat utilization were also collected. Species composition varied spatially only in 2011. Temporal variation was observed at both ponds for all groups tested. Habitat use varied among species and between swamps. The pattern of variation suggests that temporally dynamic systems such as temporary Neotropical forest swamps will converge and diverge in species composition over time.

A retrospective-longitudinal examination of the relationship between apportionment of seat time in community-college algebra courses and student academic performance

During the past decade, there has been a dramatic increase by postsecondary institutions in providing academic programs and course offerings in a multitude of formats and venues (Biemiller, 2009; Kucsera & Zimmaro, 2010; Lang, 2009; Mangan, 2008). Strategies pertaining to reapportionment of course-delivery seat time have been a major facet of these institutional initiatives; most notably, within many open-door 2-year colleges. Often, these enrollment-management decisions are driven by the desire to increase market-share, optimize the usage of finite facility capacity, and contain costs, especially during these economically turbulent times. So, while enrollments have surged to the point where nearly one in three 18-to-24 year-old U.S. undergraduates are community college students (Pew Research Center, 2009), graduation rates, on average, still remain distressingly low (Complete College America, 2011). Among the learning-theory constructs related to seat-time reapportionment efforts is the cognitive phenomenon commonly referred to as the spacing effect, the degree to which learning is enhanced by a series of shorter, separated sessions as opposed to fewer, more massed episodes. This ex post facto study explored whether seat time in a postsecondary developmental-level algebra course is significantly related to: course success; course-enrollment persistence; and, longitudinally, the time to successfully complete a general-education-level mathematics course. Hierarchical logistic regression and discrete-time survival analysis were used to perform a multi-level, multivariable analysis of a student cohort (N = 3,284) enrolled at a large, multi-campus, urban community college. The subjects were retrospectively tracked over a 2-year longitudinal period. The study found that students in long seat-time classes tended to withdraw earlier and more often than did their peers in short seat-time classes (p < .05). Additionally, a model comprised of nine statistically significant covariates (all with p-values less than .01) was constructed. However, no longitudinal seat-time group differences were detected nor was there sufficient statistical evidence to conclude that seat time was predictive of developmental-level course success. A principal aim of this study was to demonstrate—to educational leaders, researchers, and institutional-research/business-intelligence professionals—the advantages and computational practicability of survival analysis, an underused but more powerful way to investigate changes in students over time.

Trends in blindness due to diabetic retinopathy among adults aged 18-69 years over a decade in Ireland

Aims: To describe trends in the incidence of visual impairment and blindness due to diabetic retinopathy among adults aged 18–69 years in Ireland between 2004 and 2013. Methods: Data on visual impairment due to diabetic retinopathy in adults aged 18–69 years or over who are registered with the National Council for the Blind of Ireland, (2004–2013) were analysed. Annual incidence rates were calculated for the adult population and the population with diagnosed diabetes. Poisson regression was used to test for changes in rates over time. The relative, attributable and population risk of blindness and visual impairment due to diabetic retinopathy were calculated for 2013. Results: Over the decade, the prevalence of diagnosed diabetes increased from 2.1% to 3.6%. Among people with diagnosed diabetes, the incidence of visual impairment due to diabetic retinopathy increased from 6.4 (95% CI 2.4–13.9) per 100,000 in 2004 to 11.7 (95% CI 5.9–21.0) per 100,000 in 2013. The incidence of blindness due to diabetic retinopathy varied from 31.9 per 100,000 (95% CI 21.6–45.7) in 2004 to 14.9 per 100,000 (95% CI 8.2–25.1) in 2013. Conclusions: Our findings indicate the need for increased attention to preventive measures for microvascular complications among adults with diabetes in Ireland. Retinopathy screening has been standardised in Ireland, these findings provide useful baseline statistics to monitor the impact of this population-based screening programme.

Measuring Scope of Practice Enactment among Primary Care Registered Nurses in Ontario

Background: Primary care is the sector of health care in which patients first establish contact with the health system, are provided person-focused care over time for all new or common needs, and receive coordinated integrated health services provided elsewhere by other members of the health care team. Registered Nurses (RNs) in Canada provide care within this sector in varying roles. The extent to which RNs enact their full scope of practice in primary care settings in Canada is not known. The Actual Scope of Practice questionnaire (ASCOP) is a 26 item Likert scale questionnaire developed by researchers in Canada and validated in the acute care setting to measure the extent to which RNs apply the knowledge, skills and competencies of the professional full scope of practice. Similar to the acute care setting, there is a need to measure scope of practice enactment in the primary care setting. Objectives: The overall aim of this thesis was to measure scope of practice enactment in the primary care setting. Two research objectives were addressed: (1) to revise and adapt the ASCOP questionnaire for use in the primary care setting, and (2) to determine internal consistency, construct validity, and sensitivity of the modified instrument, the ASCOP-PC. Methods: To address the first objective, a narrative literature review and synthesis and an expert panel review was conducted. To address the second objective a cross-sectional survey of 178 RNs working in primary care organizations in Ontario was conducted Results: The ASCOP, with few modifications, addressed key attributes of nursing scope of practice in the primary care setting. The ASCOP-PC yielded acceptable alpha coefficients ranging from 0.66 to 0.91 and explained variances from 44.2 to 62.6. Total mean score of 5.16 suggests that RNs within these models of care almost always engage in activities reflected in the ASCOP-PC. Interpretation: Findings from this study support the use of a the modified ASCOP questionnaire as a reliable and valid measure of scope of practice enactment among primary care nurses in the primary care setting.

The pervasiveness and trajectory of methodological choices: A 20 year review of human resource management research

This paper examines the methodological choices of researchers studying the HR practices–outcome relationship via a content analysis of 281 studies published across the last twenty years. The prevalence and trajectory of change over time are reported for a wide range of methodological choices relevant to internal, external, construct, and statistical conclusion validity. While the results indicate a high incidence of potentially problematic cross-sectional, single informant, and single level designs, they also reveal significant improvements over time across many validity relevant methodological choices. This broad based improvement in the methodological underpinnings of HR research suggests that researchers and practitioners can view the findings reported in the HR literature with increasing confidence. Directions for future research are provided.

Threat Analysis of BlackEnergy Malware for Synchrophasor based Real-time Control and Monitoring in Smart Grid

The BlackEnergy malware targeting critical infrastructures has a long history. It evolved over time from a simple DDoS platform to a quite sophisticated plug-in based malware. The plug-in architecture has a persistent malware core with easily installable attack specific modules for DDoS, spamming, info-stealing, remote access, boot-sector formatting etc. BlackEnergy has been involved in several high profile cyber physical attacks including the recent Ukraine power grid attack in December 2015. This paper investigates the evolution of BlackEnergy and its cyber attack capabilities. It presents a basic cyber attack model used by BlackEnergy for targeting industrial control systems. In particular, the paper analyzes cyber threats of BlackEnergy for synchrophasor based systems which are used for real-time control and monitoring functionalities in smart grid. Several BlackEnergy based attack scenarios have been investigated by exploiting the vulnerabilities in two widely used synchrophasor communication standards: (i) IEEE C37.118 and (ii) IEC 61850-90-5. Specifically, the paper addresses reconnaissance, DDoS, man-in-the-middle and replay/reflection attacks on IEEE C37.118 and IEC 61850-90-5. Further, the paper also investigates protection strategies for detection and prevention of BlackEnergy based cyber physical attacks.