Residual Weighted Learning for Estimating Individualized Treatment Rules

Personalized medicine has received increasing attention among statisticians, computer scientists, and clinical practitioners. A major component of personalized medicine is the estimation of individualized treatment rules (ITRs). Recently, Zhao et al. (2012) proposed outcome weighted learning (OWL) to construct ITRs that directly optimize the clinical outcome. Although OWL opens the door to introducing machine learning techniques to optimal treatment regimes, it still has some problems in performance. In this article, we propose a general framework, called Residual Weighted Learning (RWL), to improve finite sample performance. Unlike OWL which weights misclassification errors by clinical outcomes, RWL weights these errors by residuals of the outcome from a regression fit on clinical covariates excluding treatment assignment. We utilize the smoothed ramp loss function in RWL, and provide a difference of convex (d.c.) algorithm to solve the corresponding non-convex optimization problem. By estimating residuals with linear models or generalized linear models, RWL can effectively deal with different types of outcomes, such as continuous, binary and count outcomes. We also propose variable selection methods for linear and nonlinear rules, respectively, to further improve the performance. We show that the resulting estimator of the treatment rule is consistent. We further obtain a rate of convergence for the difference between the expected outcome using the estimated ITR and that of the optimal treatment rule. The performance of the proposed RWL methods is illustrated in simulation studies and in an analysis of cystic fibrosis clinical trial data.Comment: 48 pages, 3 figure

Asymptotics for Marginal Generalized Linear Models With Sparse Correlations

Marginal generalized linear models can be used for clustered and longitudinal data by fitting a model as if the data were independent and using an empirical estimator of parameter standard errors. We extend this approach to data where the number of observations correlated with a given one grows with sample size and show that parameter estimates are consistent and asymptotically Normal with a slower convergence rate than for independent data, and that an information sandwich variance estimator is consistent. We present two problems that motivated this work, the modelling of patterns of HIV genetic variation and the behavior of clustered data estimators when clusters are large

What to Do about Municipal Pensions?

Even before the precipitous market decline of late 2008, pension obligations were threatening the long-term fiscal stability of many municipalities. Urban centers with declining populations and unfavorable retiree-to-employee ratios— such as Pittsburgh, where pension fund liabilities represent a big chunk of the city’s financial woes—have the most serious problems, but underfunded pension plans can be found in dozens of Pennsylvania municipalities of all sizes. In response to the growing awareness of municipal pension problems in Pennsylvania, the Fiscal Policy and Governance Committee of the University of Pittsburgh Institute of Politics formed the Pensions Subcommittee to gather information and consider policy options

Using bacterial biomarkers to identify early indicators of cystic fibrosis pulmonary exacerbation onset

Acute periods of pulmonary exacerbation are the single most important cause of morbidity in cystic fibrosis patients, and may be associated with a loss of lung function. Intervening prior to the onset of a substantially increased inflammatory response may limit the associated damage to the airways. While a number of biomarker assays based on inflammatory markers have been developed, providing useful and important measures of disease during these periods, such factors are typically only elevated once the process of exacerbation has been initiated. Identifying biomarkers that can predict the onset of pulmonary exacerbation at an early stage would provide an opportunity to intervene before the establishment of a substantial immune response, with major implications for the advancement of cystic fibrosis care. The precise triggers of pulmonary exacerbation remain to be determined; however, the majority of models relate to the activity of microbes present in the patient's lower airways of cystic fibrosis. Advances in diagnostic microbiology now allow for the examination of these complex systems at a level likely to identify factors on which biomarker assays can be based. In this article, we discuss key considerations in the design and testing of assays that could predict pulmonary exacerbations

Organisational climate : perspectives on a problematic concept

It is generally accepted that organisations have their own tone or atmosphere whose subtle qualities may be intuitively recognised or felt. In an organisational model the technical term, organisational climate, defines these qualities more precisely so their effects upon organisational participants can be investigated. In school organisations, "school climate", "ethos" and "culture" have been used as synonyms to identify differences assumed to be important for teachers, pupils and parents.\ud Unfortunately, conceptual ambiguity has pervaded climate research for positivist operational definitions appear to have taken precedence over considerations of construct validity. Organisations have been assumed to have one climate which is differentially perceived, and perceptual measurement techniques have been used to identify underlying dimensions. Within this framework, competing assumptions of different researchers have obscured agreement about the nature of climate variables. There has been scant concern for the construct's factorial stability. Conflicting findings which have been difficult to generalise or relate to school effects, have resulted in conceptual confusion. The possibility that organisations may possess multiple climates has hardly been considered. Nor have studies investigated climate as a symbolic construct related to meanings and feelings held by individuals.\ud The present study argues traditional assumptions are too global for the construct to be useful as a focus of research. A qualitative analysis is applied to investigate the extent to which climate as an individual, personal construct can be translated into a global construct of shared meanings at organisational level.\ud Semi-structured interviews are conducted with the head teachers and teachers from two secondary schools. Meanings and feelings about organisational interaction are categorised into hierarchical networks representing emergent organisational-level characteristics. Data interpretation is further supported by quantified data of card-sort and questionnaires from 18 INSET teachers and 37 headteachers in different secondary schools.\ud Results suggest teachers but not head teachers, distinguish between meanings of "organisational climate", "ethos" and "school climate". Their different viewpoints have implications for school management practices. \u

UAS Literary & Arts Journal

Proof copy provided by Tidal Echoes.Featuring the work of students, faculty, and staff of the University of Alaska Southeast and members of the community.A Note from Loren, Sometimes Known as Senior Editor -- A Letter from Josh, Affectionately Known as “Sugah” (say it with a southern accent) -- A Note from Emily Wall -- On the Move -- Dangly Jangly Things -- Taco Surf -- Midwestern Trash -- On the Distaff Side -- Christmas Joy -- The Three Little McCormicks -- Trollin’ Ray’s Brain: An Interview with Ray Troll -- His Long Coat Turning -- First Autumn -- Pinta Cove Birthday Gifts -- September Wings -- When in Rome -- Early Morning Conspiracy Theory -- Flesh Wound -- Two Ravens, Five Ways -- Shades of Brown: The Question -- Hayfield-Clarke Psychiatric Center -- Hardscrabble -- Smoked Meat Sandwiches -- Slime Squishing Through Gold: An Interview with Nora Marks Dauenhauer -- Berries -- Buds -- Grandpa Jakwteen in Eclipse -- Cross Talk -- Voices -- Trouble -- Flying Home -- Snorkeling at Hanauma Bay -- Genocide -- Raven, Saving It for Later -- Mama Abel’s -- Settling In -- Blue -- Dad at 27 -- Dad photographs mother -- Backyard theatre & Oz -- Love-in, Easter Day, 1968 -- Topanga Corral -- Swallowing Senora -- Keeping Time on the Kee Nax Trail -- Ode to Ching -- Beneath the Surface (chapter title) -- A Visit from the Wild -- Teacher’s Pets -- Centennial -- See Spot Rot -- With Salsa -- Moonbaby -- The Fine Art of Raising a Tarpaulin -- Prologue -- Epiphany 2008 -- View of Auke Lake -- Shark Fins -- Translating Pasternak -- Raven Boys -- Institutional Back Door -- Uneasy Disguise -- Christmas Wind -- The Life and Times of the Orlando Bloom Fan Club -- Writer & Artist Biographie

The ABCs and beyond: Developing an operations research agenda on comprehensive behavior change approaches for HIV prevention: Report from a technical meeting

In April 2003, the Horizons Program sponsored a one-day technical meeting to develop and set priorities for an operations research agenda to study effective behavior change strategies for HIV risk reduction, particularly those that focus on the “ABC” behaviors: abstinence or delaying sex, being faithful or partner reduction, and condom use. Representatives from more than 20 organizations and programs involved in prevention research and programming discussed epidemiological, behavioral, psychosocial, and structural factors that may help determine the effectiveness of promoting the ABCs and other prevention programs. During the meeting, specific opportunities for collaborations and areas of particular interest for each group were discussed, with the goal of permitting each organization to focus on its strengths while working together toward similar outcomes. As noted in this report, the Horizons partnership plans to pursue some of the key operations research questions that were identified by the technical experts

Estimating selection pressures on HIV-1 using phylogenetic likelihood models

Human immunodeficiency virus (HIV-1) can rapidly evolve due to selection pressures exerted by HIV-specific immune responses, antiviral agents, and to allow the virus to establish infection in different compartments in the body. Statistical models applied to HIV-1 sequence data can help to elucidate the nature of these selection pressures through comparisons of non-synonymous (or amino acid changing) and synonymous (or amino acid preserving) substitution rates. These models also need to take into account the non-independence of sequences due to their shared evolutionary history. We review how we have developed these methods and have applied them to characterize the evolution of HIV-1 in vivo.To illustrate our methods, we present an analysis of compartment-specific evolution of HIV-1 env in blood and cerebrospinal fluid and of site-to-site variation in the gag gene of subtype C HIV-1