CHARACTERIZING, ASSESSING AND IMPROVING HEALTHCARE REFERRAL COMMUNICATION

Similar to other health care processes, referrals are susceptible to breakdowns. These breakdowns in the referral process can lead to poor continuity of care, slow diagnostic processes, delays and repetition of tests, patient and provider dissatisfaction, and can lead to a loss of confidence in providers. These facts and the necessity for a deeper understanding of referrals in healthcare served as the motivation to conduct a comprehensive study of referrals. The research began with the real problem and need to understand referral communication as a mean to improve patient care. Despite previous efforts to explain referrals and the dynamics and interrelations of the variables that influence referrals there is not a common, contemporary, and accepted definition of what a referral is in the health care context. The research agenda was guided by the need to explore referrals as an abstract concept by: 1) developing a conceptual definition of referrals, and 2) developing a model of referrals, to finally propose a 3) comprehensive research framework. This dissertation has resulted in a standard conceptual definition of referrals and a model of referrals. In addition a mixed-method framework to evaluate referrals was proposed, and finally a data driven model was developed to predict whether a referral would be approved or denied by a specialty service. The three manuscripts included in this dissertation present the basis for studying and assessing referrals using a common framework that should allow an easier comparative research agenda to improve referrals taking into account the context where referrals occur.

Three decades of global methane sources and sinks

Methane is an important greenhouse gas, responsible for about 20 of the warming induced by long-lived greenhouse gases since pre-industrial times. By reacting with hydroxyl radicals, methane reduces the oxidizing capacity of the atmosphere and generates ozone in the troposphere. Although most sources and sinks of methane have been identified, their relative contributions to atmospheric methane levels are highly uncertain. As such, the factors responsible for the observed stabilization of atmospheric methane levels in the early 2000s, and the renewed rise after 2006, remain unclear. Here, we construct decadal budgets for methane sources and sinks between 1980 and 2010, using a combination of atmospheric measurements and results from chemical transport models, ecosystem models, climate chemistry models and inventories of anthropogenic emissions. The resultant budgets suggest that data-driven approaches and ecosystem models overestimate total natural emissions. We build three contrasting emission scenarios � which differ in fossil fuel and microbial emissions � to explain the decadal variability in atmospheric methane levels detected, here and in previous studies, since 1985. Although uncertainties in emission trends do not allow definitive conclusions to be drawn, we show that the observed stabilization of methane levels between 1999 and 2006 can potentially be explained by decreasing-to-stable fossil fuel emissions, combined with stable-to-increasing microbial emissions. We show that a rise in natural wetland emissions and fossil fuel emissions probably accounts for the renewed increase in global methane levels after 2006, although the relative contribution of these two sources remains uncertain.

An Early-Warning System for Hypo-/Hyperglycemic Events Based on Fusion of Adaptive Prediction Models

Introduction: Early warning of future hypoglycemic and hyperglycemic events can improve the safety of type 1 diabetes mellitus (T1DM) patients. The aim of this study is to design and evaluate a hypoglycemia / hyperglycemia early warning system (EWS) for T1DM patients under sensor-augmented pump (SAP) therapy. Methods: The EWS is based on the combination of data-driven online adaptive prediction models and a warning algorithm. Three modeling approaches have been investigated: (i) autoregressive (ARX) models, (ii) auto-regressive with an output correction module (cARX) models, and (iii) recurrent neural network (RNN) models. The warning algorithm performs postprocessing of the models′ outputs and issues alerts if upcoming hypoglycemic/hyperglycemic events are detected. Fusion of the cARX and RNN models, due to their complementary prediction performances, resulted in the hybrid autoregressive with an output correction module/recurrent neural network (cARN)-based EWS. Results: The EWS was evaluated on 23 T1DM patients under SAP therapy. The ARX-based system achieved hypoglycemic (hyperglycemic) event prediction with median values of accuracy of 100.0% (100.0%), detection time of 10.0 (8.0) min, and daily false alarms of 0.7 (0.5). The respective values for the cARX-based system were 100.0% (100.0%), 17.5 (14.8) min, and 1.5 (1.3) and, for the RNN-based system, were 100.0% (92.0%), 8.4 (7.0) min, and 0.1 (0.2). The hybrid cARN-based EWS presented outperforming results with 100.0% (100.0%) prediction accuracy, detection 16.7 (14.7) min in advance, and 0.8 (0.8) daily false alarms. Conclusion: Combined use of cARX and RNN models for the development of an EWS outperformed the single use of each model, achieving accurate and prompt event prediction with few false alarms, thus providing increased safety and comfort.

Adaptive Algorithms for Personalized Diabetes Treatment

Dynamic systems, especially in real-life applications, are often determined by inter-/intra-variability, uncertainties and time-varying components. Physiological systems are probably the most representative example in which population variability, vital signal measurement noise and uncertain dynamics render their explicit representation and optimization a rather difficult task. Systems characterized by such challenges often require the use of adaptive algorithmic solutions able to perform an iterative structural and/or parametrical update process towards optimized behavior. Adaptive optimization presents the advantages of (i) individualization through learning of basic system characteristics, (ii) ability to follow time-varying dynamics and (iii) low computational cost. In this chapter, the use of online adaptive algorithms is investigated in two basic research areas related to diabetes management: (i) real-time glucose regulation and (ii) real-time prediction of hypo-/hyperglycemia. The applicability of these methods is illustrated through the design and development of an adaptive glucose control algorithm based on reinforcement learning and optimal control and an adaptive, personalized early-warning system for the recognition and alarm generation against hypo- and hyperglycemic events.

Sensory and conceptual representations in memory: Motor images which cannot be imaged

The paper argues for a distinction between sensory-and conceptual-information storage in the human information-processing system. Conceptual information is characterized as meaningful and symbolic, while sensory information may exist in modality-bound form. Furthermore, it is assumed that sensory information does not contribute to conscious remembering and can be used only in data-driven process reptitions, which can be accompanied by a kind of vague or intuitive feeling. Accordingly, pure top-down and willingly controlled processing, such as free recall, should not have any access to sensory data. Empirical results from different research areas and from two experiments conducted by the authors are presented in this article to support these theoretical distinctions. The experiments were designed to separate a sensory-motor and a conceptual component in memory for two-digit numbers and two-letter items, when parts of the numbers or items were imaged or drawn on a tablet. The results of free recall and recognition are discussed in a theoretical framework which distinguishes sensory and conceptual information in memory.

Measurement of isolated-photon pair production in pp collisions at sqrts=7 TeV with the ATLAS detector

The ATLAS experiment at the LHC has measured the production cross section of events with two isolated photons in the final state, in proton-proton collisions at root s = 7 TeV. The full data set collected in 2011, corresponding to an integrated luminosity of 4.9 fb(-1), is used. The amount of background, from hadronic jets and isolated electrons, is estimated with data-driven techniques and subtracted. The total cross section, for two isolated photons with transverse energies above 25 GeV and 22 GeV respectively, in the acceptance of the electromagnetic calorimeter (vertical bar eta vertical bar < 1.37 and 1.52 < vertical bar eta vertical bar 2.37) and with an angular separation Delta R > 0.4, is 44.0(-4.2)(+3.2) pb. The differential cross sections as a function of the di-photon invariant mass, transverse momentum, azimuthal separation, and cosine of the polar angle of the largest transverse energy photon in the Collins-Soper di-photon rest frame are also measured. The results are compared to the prediction of leading-order parton-shower and next-to-leading-order and next-to-next-to-leading-order parton-level generators.

Event-relating to potential dementia. Semantic processing in the course of healthy and pathological aging

While most healthy elderly are able to manage their everyday activities, studies showed that there are both stable and declining abilities during healthy aging. For example, there is evidence that semantic memory processes which involve controlled retrieval mechanism decrease, whereas the automatic functioning of the semantic network remains intact. In contrast, patients with Alzheimer’s disease (AD) suffer from episodic and semantic memory impairments aggravating their daily functioning. In AD, severe episodic as well as semantic memory deficits are observable. While the hallmark symptom of episodic memory decline in AD is well investigated, the underlying mechanisms of semantic memory deterioration remain unclear. By disentangling the semantic memory impairments in AD, the present thesis aimed to improve early diagnosis and to find a biomarker for dementia. To this end, a study on healthy aging and a study with dementia patients were conducted investigating automatic and controlled semantic word retrieval. Besides the inclusion of AD patients, a group of participants diagnosed with semantic dementia (SD) – showing isolated semantic memory loss – was assessed. Automatic and controlled semantic word retrieval was measured with standard neuropsychological tests and by means of event-related potentials (ERP) recorded during the performance of a semantic priming (SP) paradigm. Special focus was directed to the N400 or N400-LPC (late positive component) complex, an ERP that is sensitive to the semantic word retrieval. In both studies, data driven topographical analyses were applied. Furthermore, in the patient study, the combination of the individual baseline cerebral blood flow (CBF) with the N400 topography of each participant was employed in order to relate altered functional electrophysiology to the pathophysiology of dementia. Results of the aging study revealed that the automatic semantic word retrieval remains stable during healthy aging, the N400-LPC complex showed a comparable topography in contrast to the young participants. Both patient groups showed automatic SP to some extent, but strikingly the ERP topographies were altered compared to healthy controls. Most importantly, the N400 was identified as a putative marker for dementia. In particular, the degree of the topographical N400 similarity was demonstrated to separate healthy elderly from demented patients. Furthermore, the marker was significantly related to baseline CBF reduction in brain areas relevant for semantic word retrieval. Summing up, the first major finding of the present thesis was that all groups showed semantic priming, but that the N400 topography differed significantly between healthy and demented elderly. The second major contribution was the identification of the N400 similarity as a putative marker for dementia. To conclude, the present thesis added evidence of preserved automatic processing during healthy aging. Moreover, a possible marker which might contribute to an improved diagnosis and lead consequently to a more effective treatment of dementia was presented and has to be further developed.

Dispersive approach to hadronic light-by-light scattering and the muon ɡ − 2

The largest uncertainties in the Standard Model calculation of the anomalous magnetic moment of the muon (ɡ − 2)μ come from hadronic contributions. In particular, it can be expected that in a few years the subleading hadronic light-by-light (HLbL) contribution will dominate the theory uncertainty. We present a dispersive description of the HLbL tensor. This new, model-independent approach opens up an avenue towards a data-driven determination of the HLbL contribution to the (ɡ − 2)μ.

Dispersion relation for hadronic light-by-light scattering: theoretical foundations

In this paper we make a further step towards a dispersive description of the hadronic light-by-light (HLbL) tensor, which should ultimately lead to a data-driven evaluation of its contribution to (g − 2) μ . We first provide a Lorentz decomposition of the HLbL tensor performed according to the general recipe by Bardeen, Tung, and Tarrach, generalizing and extending our previous approach, which was constructed in terms of a basis of helicity amplitudes. Such a tensor decomposition has several advantages: the role of gauge invariance and crossing symmetry becomes fully transparent; the scalar coefficient functions are free of kinematic singularities and zeros, and thus fulfill a Mandelstam double-dispersive representation; and the explicit relation for the HLbL contribution to (g − 2) μ in terms of the coefficient functions simplifies substantially. We demonstrate explicitly that the dispersive approach defines both the pion-pole and the pion-loop contribution unambiguously and in a model-independent way. The pion loop, dispersively defined as pion-box topology, is proven to coincide exactly with the one-loop scalar QED amplitude, multiplied by the appropriate pion vector form factors.

Hadronic light-by-light scattering and the muon g−2

The largest uncertainties in the Standard Model calculation of the anomalous magnetic moment of the muon (g − 2)μ come from hadronic contributions. In particular, it can be expected that in a few years the subleading hadronic light-by-light (HLbL) contribution will dominate the theory uncertainty. We present a dispersive description of the HLbL tensor, which is based on unitarity, analyticity, crossing symmetry, and gauge invariance. Such a model-independent Approach opens up an avenue towards a data-driven determination of the HLbL contribution to the (g − 2)μ.

A coalescent analysis for modeling the mutation process in colorectal cancer

Colorectal cancer is the forth most common diagnosed cancer in the United States. Every year about a hundred forty-seven thousand people will be diagnosed with colorectal cancer and fifty-six thousand people lose their lives due to this disease. Most of the hereditary nonpolyposis colorectal cancer (HNPCC) and 12% of the sporadic colorectal cancer show microsatellite instability. Colorectal cancer is a multistep progressive disease. It starts from a mutation in a normal colorectal cell and grows into a clone of cells that further accumulates mutations and finally develops into a malignant tumor. In terms of molecular evolution, the process of colorectal tumor progression represents the acquisition of sequential mutations. ^ Clinical studies use biomarkers such as microsatellite or single nucleotide polymorphisms (SNPs) to study mutation frequencies in colorectal cancer. Microsatellite data obtained from single genome equivalent PCR or small pool PCR can be used to infer tumor progression. Since tumor progression is similar to population evolution, we used an approach known as coalescent, which is well established in population genetics, to analyze this type of data. Coalescent theory has been known to infer the sample's evolutionary path through the analysis of microsatellite data. ^ The simulation results indicate that the constant population size pattern and the rapid tumor growth pattern have different genetic polymorphic patterns. The simulation results were compared with experimental data collected from HNPCC patients. The preliminary result shows the mutation rate in 6 HNPCC patients range from 0.001 to 0.01. The patients' polymorphic patterns are similar to the constant population size pattern which implies the tumor progression is through multilineage persistence instead of clonal sequential evolution. The results should be further verified using a larger dataset. ^

The Comal County Needs Assessment Youth Survey

A crucial link in preserving and protecting the future of our communities resides in maintaining the health and well being of our youth. While every member of the community owns an opinion regarding where to best utilize monies for prevention and intervention, the data to support such opinion is often scarce. In an effort to generate data-driven indices for community planning and action, the United Way of Comal County, Texas partnered with the University Of Texas - Houston Health Science Center, School Of Public Health to accomplish a county-specific needs assessment. A community-based participatory research emphasis utilizing the Mobilization for Action through Planning and Partnership (MAPP) format developed by the National Association of City and County Health Officials (NACCHO) was implemented to engage community members in identifying and addressing community priorities. The single greatest area of consensus and concern identified by community members was the health and well being of the youth population. Thus, a youth survey, targeting these specific areas of community concern, was designed, coordinated and administered to all 9-11th grade students in the county. 20% of the 3,698 completed surveys (72% response rate) were randomly selected for analysis. These 740 surveys were coded and scanned into an electronic survey database. Statistical analysis provided youth-reported data on the status of the multiple issues affecting the health and well being of the community's youth. These data will be reported back to the community stakeholders, as part of the larger Comal County Needs Assessment, for the purposes of community planning and action. Survey data will provide community planners with an awareness of the high risk behaviors and habit patterns amongst their youth. This knowledge will permit more effective targeting of the means for encouraging healthy behaviors and preventing the spread of disease. Further, the community-oriented, population-based nature of this effort will provide answers to questions raised by the community and will provide an effective launching pad for the development and implementation of targeted, preventive health strategies. ^

The Open Door Mission: Measuring and predicting outcomes of one community-based substance abuse treatment program

The objectives of this study were to identify and measure the average outcomes of the Open Door Mission's nine-month community-based substance abuse treatment program, identify predictors of successful outcomes, and make recommendations to the Open Door Mission for improving its treatment program.^ The Mission's program is exclusive to adult men who have limited financial resources: most of which were homeless or dependent on parents or other family members for basic living needs. Many, but not all, of these men are either chemically dependent or have a history of substance abuse.^ This study tracked a cohort of the Mission's graduates throughout this one-year study and identified various indicators of success at short-term intervals, which may be predictive of longer-term outcomes. We tracked various levels of 12-step program involvement, as well as other social and spiritual activities, such as church affiliation and recovery support.^ Twenty-four of the 66 subjects, or 36% met the Mission's requirements for success. Specific to this success criteria; Fifty-four, or 82% reported affiliation with a home church; Twenty-six, or 39% reported full-time employment; Sixty-one, or 92% did not report or were not identified as having any post-treatment arrests or incarceration, and; Forty, or 61% reported continuous abstinence from both drugs and alcohol.^ Five research-based hypotheses were developed and tested. The primary analysis tool was the web-based non-parametric dependency modeling tool, B-Course, which revealed some strong associations with certain variables, and helped the researchers generate and test several data-driven hypotheses. Full-time employment is the greatest predictor of abstinence: 95% of those who reported full time employment also reported continuous post-treatment abstinence, while 50% of those working part-time were abstinent and 29% of those with no employment were abstinent. Working with a 12-step sponsor, attending aftercare, and service with others were identified as predictors of abstinence.^ This study demonstrates that associations with abstinence and the ODM success criteria are not simply based on one social or behavioral factor. Rather, these relationships are interdependent, and show that abstinence is achieved and maintained through a combination of several 12-step recovery activities. This study used a simple assessment methodology, which demonstrated strong associations across variables and outcomes, which have practical applicability to the Open Door Mission for improving its treatment program. By leveraging the predictive capability of the various success determination methodologies discussed and developed throughout this study, we can identify accurate outcomes with both validity and reliability. This assessment instrument can also be used as an intervention that, if operationalized to the Mission’s clients during the primary treatment program, may measurably improve the effectiveness and outcomes of the Open Door Mission.^

Bayesian adaptive designs in early phase clinical trials

There are two practical challenges in the phase I clinical trial conduct: lack of transparency to physicians, and the late onset toxicity. In my dissertation, Bayesian approaches are used to address these two problems in clinical trial designs. The proposed simple optimal designs cast the dose finding problem as a decision making process for dose escalation and deescalation. The proposed designs minimize the incorrect decision error rate to find the maximum tolerated dose (MTD). For the late onset toxicity problem, a Bayesian adaptive dose-finding design for drug combination is proposed. The dose-toxicity relationship is modeled using the Finney model. The unobserved delayed toxicity outcomes are treated as missing data and Bayesian data augment is employed to handle the resulting missing data. Extensive simulation studies have been conducted to examine the operating characteristics of the proposed designs and demonstrated the designs' good performances in various practical scenarios.^

Classification of coral reef types in Torres Strait (GIS files in zip-archive 319 kB)

Coral reefs represent major accumulations of calcium carbonate (CaCO3). The particularly labyrinthine network of reefs in Torres Strait, north of the Great Barrier Reef (GBR), has been examined in order to estimate their gross CaCO3 productivity. The approach involved a two-step procedure, first characterising and classifying the morphology of reefs based on a classification scheme widely employed on the GBR and then estimating gross CaCO3 productivity rates across the region using a regional census-based approach. This was undertaken by independently verifying published rates of coral reef community gross production for use in Torres Strait, based on site-specific ecological and morphological data. A total of 606 reef platforms were mapped and classified using classification trees. Despite the complexity of the maze of reefs in Torres Strait, there are broad morphological similarities with reefs in the GBR. The spatial distribution and dimensions of reef types across both regions are underpinned by similar geological processes, sea-level history in the Holocene and exposure to the same wind/wave energetic regime, resulting in comparable geomorphic zonation. However, the presence of strong tidal currents flowing through Torres Strait and the relatively shallow and narrow dimensions of the shelf exert a control on local morphology and spatial distribution of the reef platforms. A total amount of 8.7 million tonnes of CaCO3 per year, at an average rate of 3.7 kg CaCO3 m-2 yr-1 (G), were estimated for the studied area. Extrapolated production rates based on detailed and regional census-based approaches for geomorphic zones across Torres Strait were comparable to those reported elsewhere, particularly values for the GBR based on alkalinity-reduction methods. However, differences in mapping methodologies and the impact of reduced calcification due to global trends in coral reef ecological decline and changing oceanic physical conditions warrant further research. The novel method proposed in this study to characterise the geomorphology of reef types based on classification trees provides an objective and repeatable data-driven approach that combined with regional census-based approaches has the potential to be adapted and transferred to different coral reef regions, depicting a more accurate picture of interactions between reef ecology and geomorphology.