In statistical learning, high covariate dimensionality poses challenges for robust prediction and... more In statistical learning, high covariate dimensionality poses challenges for robust prediction and inference. To address this challenge, supervised dimension reduction is often performed, where dependence on the outcome is maximized for a selected covariate subspace with smaller dimensionality. Prevalent dimension reduction techniques assume data are i.i.d., which is not appropriate for longitudinal data comprising multiple subjects with repeated measurements over time. In this paper, we derive a decomposition of the Hilbert-Schmidt Independence Criterion as a supervised loss function for longitudinal data, enabling dimension reduction between and within clusters separately, and propose a dimensionality-reduction technique, sklPCA, that performs this decomposed dimension reduction. We also show that this technique yields superior model accuracy compared to the model it extends.
Molecular Psychology: Brain, Behavior, and Society
Studies that apply digital phenotyping and mobile sensing strategies have increased in recent yea... more Studies that apply digital phenotyping and mobile sensing strategies have increased in recent years enabling a better understanding of psychiatric and psychological conditions, as well as neurodegenerative disorders. Although in this context the study of so-called “digital biomarkers” is proliferating, few studies have actually linked digital footprints to biological variables (and when done, the primary focus lay on brain imaging data). It is well established that many psychological phenotypes such as personality, but also psychiatric and neurodegenerative disorders, have a genetic basis – to a different heritability extent. Therefore, in the present opinion article we argue that it is of tremendous importance to also link the field of neurogenetics to the study of digital footprints, as the latter gives myriad insights into human life and in an objective way. The large field of behavioral genetics including the discipline of molecular psychology could profit greatly from focusing ...
Digital data are abundantly available for researchers in the age of the Internet of Things. In th... more Digital data are abundantly available for researchers in the age of the Internet of Things. In the psychological and psychiatric sciences such data can be used in myriad ways to obtain insights into mental states and traits. Most importantly, such data allow researchers to record and analyze behavior in a real-world context, a scientific approach which was expensive and difficult to conduct until only recently. Much research in recent years linked digital footprints to self-report questionnaire data, likely to demonstrate proof of concept(s)—for instance linking socializing on the smartphone to self-reported extraversion (a personality trait linked to socializing)—in the sciences investigating the human mind. The present perspective piece reflects on this approach by revisiting recent work which has been carried out mining smartphone log and social media data and questions if and when self-report data will still be of relevance in psychological/psychiatric research in the near future.
Background Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR).... more Background Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR. Methods Radiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8±1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates. Results The average degree of mitral regurgitation increased from 0.0±0.0 to 2.1±0.7 ( P =0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group...
Background Three-dimensional dynamics of the 3 individual scallops within the posterior mitral le... more Background Three-dimensional dynamics of the 3 individual scallops within the posterior mitral leaflet during acute ischemic mitral regurgitations have not been previously measured. Methods Radiopaque markers were sutured to the mitral annulus, papillary muscle tips, and leaflet edges in 13 sheep. Immediately postoperatively, under open-chest conditions, 3-D marker coordinates were obtained using high-speed biplane videofluoroscopy before and during echocardiographically verified acute ischemic mitral regurgitation produced by occlusion of the left circumflex coronary artery. Results During acute ischemic mitral regurgitation, at end systole, the anterolateral edge of the central scallop was displaced 0.8±0.9 mm laterally and 0.9±0.6 mm apically away from the anterolateral scallop; such displacement correlated with lateral displacement of the lateral annulus (R 2 =0.7, SEE=0.7 mm, P <0.001) and movement of the right lateral annulus away from the nonischemic anterior papillary tip...
Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors... more Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a stateof-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.
Digital phenotyping uses smartphone and wearable signals to measure cognition, mood, and behavior... more Digital phenotyping uses smartphone and wearable signals to measure cognition, mood, and behavior. This promising new approach has been developed as an objective, passive assessment tool for the diagnosis and treatment of mental illness. Digital phenotyping is currently used with informed consent in research studies but is expected to expand to broader uses in healthcare and direct-to-consumer applications. Digital phenotyping could involve the collection of massive amounts of individual data and potential creation of new categories of health and risk assessment data. Because existing ethical and regulatory frameworks for the provision of mental healthcare do not clearly apply to digital phenotyping, it is critical to consider its possible ethical, legal, and social implications. This paper addresses four major areas where guidelines and best practices will be helpful: transparency, informed consent, privacy, and accountability. It will be important to consider these issues early in...
To identify digital biomarkers associated with cognitive function, we analyzed human–computer int... more To identify digital biomarkers associated with cognitive function, we analyzed human–computer interaction from 7 days of smartphone use in 27 subjects (ages 18–34) who received a gold standard neuropsychological assessment. For several neuropsychological constructs (working memory, memory, executive function, language, and intelligence), we found a family of digital biomarkers that predicted test scores with high correlations (p < 10−4). These preliminary results suggest that passive measures from smartphone use could be a continuous ecological surrogate for laboratory-based neuropsychological assessment.
Precision medicine models for personalizing achieving sustained behavior change are largely outsi... more Precision medicine models for personalizing achieving sustained behavior change are largely outside of current clinical practice. Yet, changing self-regulatory behaviors is fundamental to the self-management of complex lifestyle-related chronic conditions such as depression and obesity - two top contributors to the global burden of disease and disability. To optimize treatments and address these burdens, behavior change and self-regulation must be better understood in relation to their neurobiological underpinnings. Here, we present the conceptual framework and protocol for a novel study, "Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes (ENGAGE)". The ENGAGE study integrates neuroscience with behavioral science to better understand the self-regulation related mechanisms of behavior change for improving mood and weight outcomes among adults with comorbid depression and obesity. We collect assays of three ...
Annual search marketing spending in the U.S. grew 28% to US$7.9B in 2006, outpaced traditional ma... more Annual search marketing spending in the U.S. grew 28% to US$7.9B in 2006, outpaced traditional marketing and is expected to double by 2010. The large return on investment has led to an increase in demand for search terms while posing new challenges in running a profitable campaign. Campaigns must systematically and repeatedly analyze large amounts of click data, adjust bid inferences across thousands of search terms, maximize conversion statistics and best monetize addollar spend. At Business.com we have developed an econometric model for search marketing. We model demand elasticity using generalized linear and mixed models with random cluster effects across groups of correlated search terms and repeated measures across search engine partners. Bid positions are adjusted daily using either a profit optimization or a portfolio revenue optimization across more than 100,000 search terms. We discuss these techniques, information challenges in the production platform and our results in managing a successful search marketing campaign.
We explore the use of the delay-coordinate- embedding technique to automatically con- struct and ... more We explore the use of the delay-coordinate- embedding technique to automatically con- struct and use probability forecast mod- els. The technique offers distinct advan- tages, including coherent handling of noise and continuous data, over previously ex- plored (1) probability forecast methods em- ploying Bayesian belief networks. We dis- cuss the relationship between the dynamical systems and the probabilistic reasoning ap- proaches to probability forecasting. Finally, we apply the dynamical systems method to a multivariate time series of physiologic mea- surements of an infant with adult respiratory distress syndrome (ARDS).
American journal of physiology. Heart and circulatory physiology, 2002
In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the ... more In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the left atrium (LA), and the central edge of both mitral leaflets to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation (MR). Animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during balloon occlusion of the left anterior descending (LAD), distal circumflex (dLCX), and proximal circumflex (pLCX) coronary arteries. MAA and LA area were calculated from the corresponding markers. LAD occlusion did not alter LA area reduction or presystolic MAA reduction, whereas dLCX occlusion resulted in a mild decrease in the former with no change in the latter. Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area and presystolic MAA reduction and resulted in increased end-diastolic MAA, delayed valve closure from end diastole, and MR. Decreased atrial co...
American journal of physiology. Heart and circulatory physiology, 2003
Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferent... more Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferential phenol ablation of the MA and anterior mitral leaflet (AML) muscle. Radiopaque markers were sutured to the left ventricle, MA, and both mitral leaflets in 18 sheep. In 10 sheep, phenol was applied circumferentially to the atrial surface of the mitral annulus and the hinge region of the AML, whereas 8 sheep served as controls. Animals were studied with biplane video fluoroscopy for computation of 3-D mitral annular area (MAA) and leaflet shape. MAA contraction (MAACont) was determined from maximum to minimum value. Presystolic MAA (PS-MAACont) reduction was calculated as the percentage of total reduction occurring before end diastole. Phenol ablation decreased PS-MAACont (72 +/- 6 vs. 47 +/- 31%, P = 0.04) and delayed valve closure (31 +/- 11 vs. 57 +/- 25 ms, P = 0.017). In control, the AML had a compound sigmoid shape; after phenol, this shape was entirely concave to the atrium duri...
The inherent intractability of probabilistic in ference has hindered the application of be lief n... more The inherent intractability of probabilistic in ference has hindered the application of be lief networks to large domains. Noisy OR gates [30] and probabilistic similarity net works [18, 17) escape the complexity of infer ence by restricting model expressiveness. Re cent work in the application of belief-network models to time-series analysis and forecasting [9, 10) has given rise to the additive belief network model (ABNM). We (1) discuss the nature and implications of the approxima tions made by an additive decomposition of a belief network, (2) show greater efficiency in the induction of additive models when avail able data are scarce, (3) generalize proba bilistic inference algorithms to exploit the ad ditive decomposition of ABNMs, (4) show greater efficiency of inference, and (5) com pare results on inference with a simple addi tive belief network.
We have developed a probabilistic forecasting methodology through a synthesis of belief network m... more We have developed a probabilistic forecasting methodology through a synthesis of belief network models and classical time-series analysis. We present the dynamic network model (DNM) and describe methods for con structing, refining, and performing inference with this representation of temporal proba bilistic knowledge. The DNM representation extends static belief-network models to more general dynamic forecasting models by inte grating and iteratively refining contempora neous and time-lagged dependencies. We dis cuss key concepts in terms of a model for fore casting U.S. car sales in Japan.
We describe how we selectively reformulate portions of a belief network that pose difficul ties f... more We describe how we selectively reformulate portions of a belief network that pose difficul ties for solution with a stochastic-simulation algorithm. With employ the selective con• ditioning approach to target specific nodes in a belief network for decomposition, based on the contribution the nodes make to the tractability of stochastic simulation. We re view previous work on BNRAS algorithms randomized approximation algorithms for probabilistic inference. We show how selec tive conditioning can be employed to refor mulate a single BNRAS problem into multiple tractable BNRAS simulation problems. We discuss how we can use another simulation algorithm-logic sampling-to solve a com ponent of the inference problem that provides a means for knitting the solutions of individ ual subproblems into a final result. Finally, we analyze tradeoffs among the computa tional subtasks associated with the selective conditioning approach to reformulation.
The factor size of G, A is the maximum number of edge disjoint perfect matchings in G. We charact... more The factor size of G, A is the maximum number of edge disjoint perfect matchings in G. We characterize the complexity of counting the number of perfect matchings in classes of graphs parameterized by factor size. We describe the simple algorithm, which is an approximation algorithm for the permanent that is a natural simplification of the algorithm suggested by Broder (1986) and analyzed by Jerrum and Sinclair (1988a, b). Compared to the algorithm by Jerrum and Sinclair (1988a, b), the simple algorithm achieves a polynomial speed up in the running time to compute tie permanent. A combinatorial lemma is used to prove that the simple algorithm runs in time n '("if) Thus: (1) for all constants tl> 0, the simple algorithm runs in polynomial time for graphs with factor size at least an; (2) for some constant c, the simple algorithm is the fastest known approximation for graphs with factor size at least clogn. (Compare with the approximation algorithms described in Karmarkar et al. (1988).) We prove the following complementary hardness results. For functions f such that 3 <f(n)< n-3, the exact counting problem for f(n)-regular bipartite graphs is #P-complete. For any a>O, for any function f such that 3<f(n)<n'-", approximate counting for f(n)-regular bipartite graphs is as hard as approximate counting for all bipartite graphs. An announcement of these results appears in Dagum et al. (1988).
Philosophical Transactions of the Royal Society B: Biological Sciences, 2007
Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure... more Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure and functional dynamics of the aortic root throughout the cardiac cycle continues to elude investigators. The last five decades of experimental work have contributed substantially to our current understanding of aortic root dynamics. In this article, we review and summarize the relevant structural analyses, using radiopaque markers and sonomicrometric crystals, concerning aortic root three-dimensional deformations and describe aortic root dynamics in detail throughout the cardiac cycle. We then compare data between different studies and discuss the mechanisms responsible for the modes of aortic root deformation, including the haemodynamics, anatomical and temporal determinants of those deformations. These modes of aortic root deformation are closely coupled to maximize ejection, optimize transvalvular ejection haemodynamics and—perhaps most importantly—reduce stress on the aortic valve ...
The Journal of Thoracic and Cardiovascular Surgery, 2002
Objective: Stentless mitral xenografts offer potential clinical benefits because they mimic the n... more Objective: Stentless mitral xenografts offer potential clinical benefits because they mimic the normal bileaflet mitral valve. How best to implant them and their hemodynamic performance and durability, however, remain unknown. Methods: A stentless porcine mitral xenograft valve (Medtronic physiologic mitral valve) was implanted in 7 sheep with papillary muscle sewing tubes attached with transmural left ventricular sutures. Radiopaque markers were inserted on the leaflets, annular cuff, papillary tips, and left ventricle. After 10 Ϯ 5 days, the animals were studied with biplane videofluoroscopy to determine 3-dimensional marker coordinates at baseline and during dobutamine infusion. Transesophageal echocardiography assessed mitral regurgitation and valvular gradients. Mitral annular area was calculated from the annular markers. Physiologic mitral valve leaflet and annular dynamics were compared with 8 native sheep valves. Results: Average mitral regurgitation grade at baseline was 1.2 Ϯ 1.0 (range, 0-4), and the mean transvalvular pressure gradients were 3.6 Ϯ 1.3 and 6.2 Ϯ 2.2 mm Hg during baseline and dobutamine infusion, respectively. Xenograft mitral annular area contraction throughout the cardiac cycle was reduced (6% Ϯ 6% vs 13% Ϯ 4% for physiologic mitral valve and control valve, respectively; P ϭ .03). Physiologic mitral valve leaflet geometry during closure differed from the native valve, with the anterior leaflet being convex to the atrium and with little motion of the posterior leaflet. Three animals survived more than 3 months; good healing of the annular cuff and papillary muscle tubes was demonstrated. Conclusion: This stentless xenograft mitral valve substitute had low gradients at baseline and during stress conditions early postoperatively, with mild mitral regurgitation. Preliminary analysis of healing characteristics appeared favorable at 3 months. Additional studies are needed to determine long-term xenograft mitral valve performance and resistance to calcification. S tentless mitral xenografts might offer potential clinical benefits because the durability of all currently available porcine semilunar bioprostheses in the high-stress mitral position is suboptimal compared with that in the aortic position. A xenograft mitral bioprosthesis is naturally bileaflet, which would better mimic nature's design for the atrioventricular position; theoretically, this should translate into enhanced clinical durability (freedom from structural valve dysfunction). The hemodynamic performance, durability, and technical feasibility of implanting unstented mitral xenografts, however, still need to be determined. Limited clinical experience
In statistical learning, high covariate dimensionality poses challenges for robust prediction and... more In statistical learning, high covariate dimensionality poses challenges for robust prediction and inference. To address this challenge, supervised dimension reduction is often performed, where dependence on the outcome is maximized for a selected covariate subspace with smaller dimensionality. Prevalent dimension reduction techniques assume data are i.i.d., which is not appropriate for longitudinal data comprising multiple subjects with repeated measurements over time. In this paper, we derive a decomposition of the Hilbert-Schmidt Independence Criterion as a supervised loss function for longitudinal data, enabling dimension reduction between and within clusters separately, and propose a dimensionality-reduction technique, sklPCA, that performs this decomposed dimension reduction. We also show that this technique yields superior model accuracy compared to the model it extends.
Molecular Psychology: Brain, Behavior, and Society
Studies that apply digital phenotyping and mobile sensing strategies have increased in recent yea... more Studies that apply digital phenotyping and mobile sensing strategies have increased in recent years enabling a better understanding of psychiatric and psychological conditions, as well as neurodegenerative disorders. Although in this context the study of so-called “digital biomarkers” is proliferating, few studies have actually linked digital footprints to biological variables (and when done, the primary focus lay on brain imaging data). It is well established that many psychological phenotypes such as personality, but also psychiatric and neurodegenerative disorders, have a genetic basis – to a different heritability extent. Therefore, in the present opinion article we argue that it is of tremendous importance to also link the field of neurogenetics to the study of digital footprints, as the latter gives myriad insights into human life and in an objective way. The large field of behavioral genetics including the discipline of molecular psychology could profit greatly from focusing ...
Digital data are abundantly available for researchers in the age of the Internet of Things. In th... more Digital data are abundantly available for researchers in the age of the Internet of Things. In the psychological and psychiatric sciences such data can be used in myriad ways to obtain insights into mental states and traits. Most importantly, such data allow researchers to record and analyze behavior in a real-world context, a scientific approach which was expensive and difficult to conduct until only recently. Much research in recent years linked digital footprints to self-report questionnaire data, likely to demonstrate proof of concept(s)—for instance linking socializing on the smartphone to self-reported extraversion (a personality trait linked to socializing)—in the sciences investigating the human mind. The present perspective piece reflects on this approach by revisiting recent work which has been carried out mining smartphone log and social media data and questions if and when self-report data will still be of relevance in psychological/psychiatric research in the near future.
Background Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR).... more Background Acute posterolateral ischemia in sheep results in ischemic mitral regurgitation (IMR). While complete ring annuloplasty prevents acute IMR, partial annuloplasty rings may offer a more physiologic repair, but are untested in animal models of IMR. Methods Radiopaque markers were placed on the LV, mitral annulus (MA), and leaflets in 13 sheep. Seven sheep served as controls, and 6 had a St. Jude Tailor partial flexible ring implanted (29 mm in 5, 31 mm in 1). After 8±1 day, the animals were studied with biplane videofluoroscopy and echocardiography before and during acute posterolateral LV ischemia (balloon occlusion of circumflex artery). Mitral annular area (MAA), septal-lateral annular diameter (SL), annular perimeters, and leaflet edge separation were calculated from 3-D marker coordinates. Results The average degree of mitral regurgitation increased from 0.0±0.0 to 2.1±0.7 ( P =0.0006) in the control group during acute ischemia but remained unchanged in the Tailor group...
Background Three-dimensional dynamics of the 3 individual scallops within the posterior mitral le... more Background Three-dimensional dynamics of the 3 individual scallops within the posterior mitral leaflet during acute ischemic mitral regurgitations have not been previously measured. Methods Radiopaque markers were sutured to the mitral annulus, papillary muscle tips, and leaflet edges in 13 sheep. Immediately postoperatively, under open-chest conditions, 3-D marker coordinates were obtained using high-speed biplane videofluoroscopy before and during echocardiographically verified acute ischemic mitral regurgitation produced by occlusion of the left circumflex coronary artery. Results During acute ischemic mitral regurgitation, at end systole, the anterolateral edge of the central scallop was displaced 0.8±0.9 mm laterally and 0.9±0.6 mm apically away from the anterolateral scallop; such displacement correlated with lateral displacement of the lateral annulus (R 2 =0.7, SEE=0.7 mm, P <0.001) and movement of the right lateral annulus away from the nonischemic anterior papillary tip...
Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors... more Adverse posttraumatic neuropsychiatric sequelae (APNS) are common among civilian trauma survivors and military veterans. These APNS, as traditionally classified, include posttraumatic stress, postconcussion syndrome, depression, and regional or widespread pain. Traditional classifications have come to hamper scientific progress because they artificially fragment APNS into siloed, syndromic diagnoses unmoored to discrete components of brain functioning and studied in isolation. These limitations in classification and ontology slow the discovery of pathophysiologic mechanisms, biobehavioral markers, risk prediction tools, and preventive/treatment interventions. Progress in overcoming these limitations has been challenging because such progress would require studies that both evaluate a broad spectrum of posttraumatic sequelae (to overcome fragmentation) and also perform in-depth biobehavioral evaluation (to index sequelae to domains of brain function). This article summarizes the methods of the Advancing Understanding of RecOvery afteR traumA (AURORA) Study. AURORA conducts a large-scale (n = 5000 target sample) in-depth assessment of APNS development using a stateof-the-art battery of self-report, neurocognitive, physiologic, digital phenotyping, psychophysical, neuroimaging, and genomic assessments, beginning in the early aftermath of trauma and continuing for 1 year. The goals of AURORA are to achieve improved phenotypes, prediction tools, and understanding of molecular mechanisms to inform the future development and testing of preventive and treatment interventions.
Digital phenotyping uses smartphone and wearable signals to measure cognition, mood, and behavior... more Digital phenotyping uses smartphone and wearable signals to measure cognition, mood, and behavior. This promising new approach has been developed as an objective, passive assessment tool for the diagnosis and treatment of mental illness. Digital phenotyping is currently used with informed consent in research studies but is expected to expand to broader uses in healthcare and direct-to-consumer applications. Digital phenotyping could involve the collection of massive amounts of individual data and potential creation of new categories of health and risk assessment data. Because existing ethical and regulatory frameworks for the provision of mental healthcare do not clearly apply to digital phenotyping, it is critical to consider its possible ethical, legal, and social implications. This paper addresses four major areas where guidelines and best practices will be helpful: transparency, informed consent, privacy, and accountability. It will be important to consider these issues early in...
To identify digital biomarkers associated with cognitive function, we analyzed human–computer int... more To identify digital biomarkers associated with cognitive function, we analyzed human–computer interaction from 7 days of smartphone use in 27 subjects (ages 18–34) who received a gold standard neuropsychological assessment. For several neuropsychological constructs (working memory, memory, executive function, language, and intelligence), we found a family of digital biomarkers that predicted test scores with high correlations (p < 10−4). These preliminary results suggest that passive measures from smartphone use could be a continuous ecological surrogate for laboratory-based neuropsychological assessment.
Precision medicine models for personalizing achieving sustained behavior change are largely outsi... more Precision medicine models for personalizing achieving sustained behavior change are largely outside of current clinical practice. Yet, changing self-regulatory behaviors is fundamental to the self-management of complex lifestyle-related chronic conditions such as depression and obesity - two top contributors to the global burden of disease and disability. To optimize treatments and address these burdens, behavior change and self-regulation must be better understood in relation to their neurobiological underpinnings. Here, we present the conceptual framework and protocol for a novel study, "Engaging self-regulation targets to understand the mechanisms of behavior change and improve mood and weight outcomes (ENGAGE)". The ENGAGE study integrates neuroscience with behavioral science to better understand the self-regulation related mechanisms of behavior change for improving mood and weight outcomes among adults with comorbid depression and obesity. We collect assays of three ...
Annual search marketing spending in the U.S. grew 28% to US$7.9B in 2006, outpaced traditional ma... more Annual search marketing spending in the U.S. grew 28% to US$7.9B in 2006, outpaced traditional marketing and is expected to double by 2010. The large return on investment has led to an increase in demand for search terms while posing new challenges in running a profitable campaign. Campaigns must systematically and repeatedly analyze large amounts of click data, adjust bid inferences across thousands of search terms, maximize conversion statistics and best monetize addollar spend. At Business.com we have developed an econometric model for search marketing. We model demand elasticity using generalized linear and mixed models with random cluster effects across groups of correlated search terms and repeated measures across search engine partners. Bid positions are adjusted daily using either a profit optimization or a portfolio revenue optimization across more than 100,000 search terms. We discuss these techniques, information challenges in the production platform and our results in managing a successful search marketing campaign.
We explore the use of the delay-coordinate- embedding technique to automatically con- struct and ... more We explore the use of the delay-coordinate- embedding technique to automatically con- struct and use probability forecast mod- els. The technique offers distinct advan- tages, including coherent handling of noise and continuous data, over previously ex- plored (1) probability forecast methods em- ploying Bayesian belief networks. We dis- cuss the relationship between the dynamical systems and the probabilistic reasoning ap- proaches to probability forecasting. Finally, we apply the dynamical systems method to a multivariate time series of physiologic mea- surements of an infant with adult respiratory distress syndrome (ARDS).
American journal of physiology. Heart and circulatory physiology, 2002
In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the ... more In six sheep, radiopaque markers were placed on the left ventricle (LV), the mitral annulus, the left atrium (LA), and the central edge of both mitral leaflets to investigate the effects of acute LV ischemia on atrial contraction, mitral annular area (MAA), and mitral regurgitation (MR). Animals were studied with biplane videofluoroscopy and transesophageal echocardiography before and during balloon occlusion of the left anterior descending (LAD), distal circumflex (dLCX), and proximal circumflex (pLCX) coronary arteries. MAA and LA area were calculated from the corresponding markers. LAD occlusion did not alter LA area reduction or presystolic MAA reduction, whereas dLCX occlusion resulted in a mild decrease in the former with no change in the latter. Neither occlusion resulted in MR. pLCX occlusion, however, significantly decreased LA area and presystolic MAA reduction and resulted in increased end-diastolic MAA, delayed valve closure from end diastole, and MR. Decreased atrial co...
American journal of physiology. Heart and circulatory physiology, 2003
Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferent... more Mitral annular (MA) and leaflet three-dimensional (3-D) dynamics were examined after circumferential phenol ablation of the MA and anterior mitral leaflet (AML) muscle. Radiopaque markers were sutured to the left ventricle, MA, and both mitral leaflets in 18 sheep. In 10 sheep, phenol was applied circumferentially to the atrial surface of the mitral annulus and the hinge region of the AML, whereas 8 sheep served as controls. Animals were studied with biplane video fluoroscopy for computation of 3-D mitral annular area (MAA) and leaflet shape. MAA contraction (MAACont) was determined from maximum to minimum value. Presystolic MAA (PS-MAACont) reduction was calculated as the percentage of total reduction occurring before end diastole. Phenol ablation decreased PS-MAACont (72 +/- 6 vs. 47 +/- 31%, P = 0.04) and delayed valve closure (31 +/- 11 vs. 57 +/- 25 ms, P = 0.017). In control, the AML had a compound sigmoid shape; after phenol, this shape was entirely concave to the atrium duri...
The inherent intractability of probabilistic in ference has hindered the application of be lief n... more The inherent intractability of probabilistic in ference has hindered the application of be lief networks to large domains. Noisy OR gates [30] and probabilistic similarity net works [18, 17) escape the complexity of infer ence by restricting model expressiveness. Re cent work in the application of belief-network models to time-series analysis and forecasting [9, 10) has given rise to the additive belief network model (ABNM). We (1) discuss the nature and implications of the approxima tions made by an additive decomposition of a belief network, (2) show greater efficiency in the induction of additive models when avail able data are scarce, (3) generalize proba bilistic inference algorithms to exploit the ad ditive decomposition of ABNMs, (4) show greater efficiency of inference, and (5) com pare results on inference with a simple addi tive belief network.
We have developed a probabilistic forecasting methodology through a synthesis of belief network m... more We have developed a probabilistic forecasting methodology through a synthesis of belief network models and classical time-series analysis. We present the dynamic network model (DNM) and describe methods for con structing, refining, and performing inference with this representation of temporal proba bilistic knowledge. The DNM representation extends static belief-network models to more general dynamic forecasting models by inte grating and iteratively refining contempora neous and time-lagged dependencies. We dis cuss key concepts in terms of a model for fore casting U.S. car sales in Japan.
We describe how we selectively reformulate portions of a belief network that pose difficul ties f... more We describe how we selectively reformulate portions of a belief network that pose difficul ties for solution with a stochastic-simulation algorithm. With employ the selective con• ditioning approach to target specific nodes in a belief network for decomposition, based on the contribution the nodes make to the tractability of stochastic simulation. We re view previous work on BNRAS algorithms randomized approximation algorithms for probabilistic inference. We show how selec tive conditioning can be employed to refor mulate a single BNRAS problem into multiple tractable BNRAS simulation problems. We discuss how we can use another simulation algorithm-logic sampling-to solve a com ponent of the inference problem that provides a means for knitting the solutions of individ ual subproblems into a final result. Finally, we analyze tradeoffs among the computa tional subtasks associated with the selective conditioning approach to reformulation.
The factor size of G, A is the maximum number of edge disjoint perfect matchings in G. We charact... more The factor size of G, A is the maximum number of edge disjoint perfect matchings in G. We characterize the complexity of counting the number of perfect matchings in classes of graphs parameterized by factor size. We describe the simple algorithm, which is an approximation algorithm for the permanent that is a natural simplification of the algorithm suggested by Broder (1986) and analyzed by Jerrum and Sinclair (1988a, b). Compared to the algorithm by Jerrum and Sinclair (1988a, b), the simple algorithm achieves a polynomial speed up in the running time to compute tie permanent. A combinatorial lemma is used to prove that the simple algorithm runs in time n '("if) Thus: (1) for all constants tl> 0, the simple algorithm runs in polynomial time for graphs with factor size at least an; (2) for some constant c, the simple algorithm is the fastest known approximation for graphs with factor size at least clogn. (Compare with the approximation algorithms described in Karmarkar et al. (1988).) We prove the following complementary hardness results. For functions f such that 3 <f(n)< n-3, the exact counting problem for f(n)-regular bipartite graphs is #P-complete. For any a>O, for any function f such that 3<f(n)<n'-", approximate counting for f(n)-regular bipartite graphs is as hard as approximate counting for all bipartite graphs. An announcement of these results appears in Dagum et al. (1988).
Philosophical Transactions of the Royal Society B: Biological Sciences, 2007
Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure... more Since the fifteenth century beginning with Leonardo da Vinci's studies, the precise structure and functional dynamics of the aortic root throughout the cardiac cycle continues to elude investigators. The last five decades of experimental work have contributed substantially to our current understanding of aortic root dynamics. In this article, we review and summarize the relevant structural analyses, using radiopaque markers and sonomicrometric crystals, concerning aortic root three-dimensional deformations and describe aortic root dynamics in detail throughout the cardiac cycle. We then compare data between different studies and discuss the mechanisms responsible for the modes of aortic root deformation, including the haemodynamics, anatomical and temporal determinants of those deformations. These modes of aortic root deformation are closely coupled to maximize ejection, optimize transvalvular ejection haemodynamics and—perhaps most importantly—reduce stress on the aortic valve ...
The Journal of Thoracic and Cardiovascular Surgery, 2002
Objective: Stentless mitral xenografts offer potential clinical benefits because they mimic the n... more Objective: Stentless mitral xenografts offer potential clinical benefits because they mimic the normal bileaflet mitral valve. How best to implant them and their hemodynamic performance and durability, however, remain unknown. Methods: A stentless porcine mitral xenograft valve (Medtronic physiologic mitral valve) was implanted in 7 sheep with papillary muscle sewing tubes attached with transmural left ventricular sutures. Radiopaque markers were inserted on the leaflets, annular cuff, papillary tips, and left ventricle. After 10 Ϯ 5 days, the animals were studied with biplane videofluoroscopy to determine 3-dimensional marker coordinates at baseline and during dobutamine infusion. Transesophageal echocardiography assessed mitral regurgitation and valvular gradients. Mitral annular area was calculated from the annular markers. Physiologic mitral valve leaflet and annular dynamics were compared with 8 native sheep valves. Results: Average mitral regurgitation grade at baseline was 1.2 Ϯ 1.0 (range, 0-4), and the mean transvalvular pressure gradients were 3.6 Ϯ 1.3 and 6.2 Ϯ 2.2 mm Hg during baseline and dobutamine infusion, respectively. Xenograft mitral annular area contraction throughout the cardiac cycle was reduced (6% Ϯ 6% vs 13% Ϯ 4% for physiologic mitral valve and control valve, respectively; P ϭ .03). Physiologic mitral valve leaflet geometry during closure differed from the native valve, with the anterior leaflet being convex to the atrium and with little motion of the posterior leaflet. Three animals survived more than 3 months; good healing of the annular cuff and papillary muscle tubes was demonstrated. Conclusion: This stentless xenograft mitral valve substitute had low gradients at baseline and during stress conditions early postoperatively, with mild mitral regurgitation. Preliminary analysis of healing characteristics appeared favorable at 3 months. Additional studies are needed to determine long-term xenograft mitral valve performance and resistance to calcification. S tentless mitral xenografts might offer potential clinical benefits because the durability of all currently available porcine semilunar bioprostheses in the high-stress mitral position is suboptimal compared with that in the aortic position. A xenograft mitral bioprosthesis is naturally bileaflet, which would better mimic nature's design for the atrioventricular position; theoretically, this should translate into enhanced clinical durability (freedom from structural valve dysfunction). The hemodynamic performance, durability, and technical feasibility of implanting unstented mitral xenografts, however, still need to be determined. Limited clinical experience
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Papers by Paul Dagum