Showing papers by "Boston University published in 2004"

What Is a Case Study and What Is It Good for

Abstract: This paper aims to clarify the meaning, and explain the utility, of the case study method, a method often practiced but little understood. A “case study,” I argue, is best defined as an intensive study of a single unit with an aim to generalize across a larger set of units. Case studies rely on the same sort of covariational evidence utilized in non-case study research. Thus, the case study method is correctly understood as a particular way of defining cases, not a way of analyzing cases or a way of modeling causal relations. I show that this understanding of the subject illuminates some of the persistent ambiguities of case study work, ambiguities that are, to some extent, intrinsic to the enterprise. The travails of the case study within the discipline of political science are also rooted in an insufficient appreciation of the methodological tradeoffs that this method calls forth. This paper presents the familiar contrast between case study and non-case study work as a series of characteristic strengths and weaknesses—affinities—rather than as antagonistic approaches to the empirical world. In the end, the perceived hostility between case study and non-case study research is largely unjustified and, perhaps, deserves to be regarded as a misconception. Indeed, the strongest conclusion to arise from this methodological examination concerns the complementarity of single-unit and cross-unit research designs.

Transferring, Translating, and Transforming: An Integrative Framework for Managing Knowledge Across Boundaries

Abstract: The paper examines managing knowledge across boundaries in settings where innovation is desired. Innovation is a useful context because it allows us to explore the negative consequences of the path-dependent nature of knowledge. A framework is developed that describes three progressively complex boundaries--syntactic, semantic, and pragmatic--and three progressively complex processes--transfer, translation, and transformation. The framework is used to specify the practical and political mismatches that occur when innovation is desired and how this relates to the common knowledge that actors use to share and assess each other's domain-specific knowledge. The development and use of a collaborative engineering tool in the early stages of a vehicle's development is presented to illustrate the conceptual and prescriptive value of the framework. The implication of this framework on key topics in the organization theory and strategy literatures is then discussed.

The ENCODE (ENCyclopedia of DNA elements) Project

Abstract: The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (∼1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.

Abstract: Background— Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. Methods and Results— We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. Conclusions— Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.

Fuzzy extractors: How to generate strong keys from biometrics and other noisy data

Abstract: We provide formal definitions and efficient secure techniques for turning biometric information into keys usable for any cryptographic application, and reliably and securely authenticating biometric data.

Pulmonary arterial hypertension.

Abstract: Pulmonary arterial hypertension is a disease of the small pulmonary arteries characterized by vascular narrowing and increased pulmonary vascular resistance, which eventually leads to right ventricular failure. Vasoconstriction, vascular proliferation, remodeling of the pulmonary vessels, and thrombosis are all contributing factors to the increased vascular resistance seen in this disease. Pulmonary arterial hypertension develops as a sporadic disease (idiopathic), as an inherited disorder (familial), or in association with certain conditions (collagen vascular diseases, portal hypertension, human immunodeficiency virus infection, congenital systemic-to-pulmonary shunts, ingestion of drugs or dietary products, or persistent fetal circulation). The pathogenesis of pulmonary arterial hypertension is a complicated, multifactorial process. It seems doubtful that any one factor alone is sufficient to activate the necessary pathways leading to the development of this disease. Rather, clinically apparent pulmonary arterial hypertension most likely develops after a second insult occurs in an individual who is already susceptible owing to genetic factors, environmental exposures, or acquired disorders. Currently, there is no cure for pulmonary arterial hypertension but several novel therapeutic options are now available that can improve symptoms and increase survival.

SEP: A Stable Election Protocol for clustered heterogeneous wireless sensor networks

Abstract: We study the impact of heterogeneity of nodes, in terms of their energy, in wireless sensor networks that are hierarchically clustered. In these networks some of the nodes become cluster heads, aggregate the data of their cluster members and transmit it to the sink. We assume that a percentage of the population of sensor nodes is equipped with additional energy resources—this is a source of heterogeneity which may result from the initial setting or as the operation of the network evolves. We also assume that the sensors are randomly (uniformly) distributed and are not mobile, the coordinates of the sink and the dimensions of the sensor field are known. We show that the behavior of such sensor networks becomes very unstable once the first node dies, especially in the presence of node heterogeneity. Classical clustering protocols assume that all the nodes are equipped with the same amount of energy and as a result, they can not take full advantage of the presence of node heterogeneity. We propose SEP, a heterogeneous-aware protocol to prolong the time interval before the death of the first node (we refer to as stability period), which is crucial for many applications where the feedback from the sensor network must be reliable. SEP is based on weighted election probabilities of each node to become cluster head according to the remaining energy in each node. We show by simulation that SEP always prolongs the stability period compared to (and that the average throughput is greater than) the one obtained using current clustering protocols. We conclude by studying the sensitivity of our SEP protocol to heterogeneity parameters capturing energy imbalance in the network. We found that SEP yields longer stability region for higher values of extra energy brought by more powerful nodes.

Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and Death

Abstract: Background The natriuretic peptides are counterregulatory hormones involved in volume homeostasis and cardiovascular remodeling The prognostic significance of plasma natriuretic peptide levels in apparently asymptomatic persons has not been established Methods We prospectively studied 3346 persons without heart failure Using proportional-hazards regression, we examined the relations of plasma B-type natriuretic peptide and N-terminal pro–atrial natriuretic peptide to the risk of death from any cause, a first major cardiovascular event, heart failure, atrial fibrillation, stroke or transient ischemic attack, and coronary heart disease Results During a mean follow-up of 52 years, 119 participants died and 79 had a first cardiovascular event After adjustment for cardiovascular risk factors, each increment of 1 SD in log B-type natriuretic peptide levels was associated with a 27 percent increase in the risk of death (P=0009), a 28 percent increase in the risk of a first cardiovascular event (P=003), a

Overall C as a measure of discrimination in survival analysis: model specific population value and confidence interval estimation

Abstract: The assessment of the discrimination ability of a survival analysis model is a problem of considerable theoretical interest and important practical applications. This issue is, however, more complex than evaluating the performance of a linear or logistic regression. Several different measures have been proposed in the biostatistical literature. In this paper we investigate the properties of the overall C index introduced by Harrell as a natural extension of the ROC curve area to survival analysis. We develop the overall C index as a parameter describing the performance of a given model applied to the population under consideration and discuss the statistic used as its sample estimate. We discover a relationship between the overall C and the modified Kendall's tau and construct a confidence interval for our measure based on the asymptotic normality of its estimate. Then we investigate via simulations the length and coverage probability of this interval. Finally, we present a real life example evaluating the performance of a Framingham Heart Study model.

Presentation of multivariate data for clinical use: The Framingham Study risk score functions.

Abstract: The Framingham Heart Study has been a leader in the development and dissemination of multivariable statistical models to estimate the risk of coronary heart disease. These models quantify the impact of measurable and modifiable risk factors on the development of coronary heart disease and can be used to generate estimates of risk of coronary heart disease over a predetermined period, for example the next 10 years. We developed a system, which we call a points system, for making these complex statistical models useful to practitioners. The system is easy to use, it does not require a calculator or computer and it simplifies the estimation of risk based on complex statistical models. This system represents an effort to make available a tool for clinicians to aid in their decision-making process regarding treatment and to assist them in motivating patients toward healthy behaviours. The system is also readily available to patients who can easily estimate their own coronary heart disease risk and monitor this risk over time.

Progressive Nitrogen Limitation of Ecosystem Responses to Rising Atmospheric Carbon Dioxide

Abstract: A highly controversial issue in global biogeochemistry is the regulation of terrestrial carbon (C) sequestration by soil nitrogen (N) availability. This controversy translates into great uncertainty in predicting future global terrestrial C sequestration. We propose a new framework that centers on the concept of progressive N limitation (PNL) for studying the interactions between C and N in terrestrial ecosystems. In PNL, available soil N becomes increasingly limiting as C and N are sequestered in long-lived plant biomass and soil organic matter. Our analysis focuses on the role of PNL in regulating ecosystem responses to rising atmospheric carbon dioxide concentration, but the concept applies to any perturbation that initially causes C and N to accumulate in organic forms. This article examines conditions under which PNL may or may not constrain net primary production and C sequestration in terrestrial ecosystems. While the PNL-centered framework has the potential to explain diverse experimental...

Diagnosing network-wide traffic anomalies

Abstract: Anomalies are unusual and significant changes in a network's traffic levels, which can often span multiple links. Diagnosing anomalies is critical for both network operators and end users. It is a difficult problem because one must extract and interpret anomalous patterns from large amounts of high-dimensional, noisy data.In this paper we propose a general method to diagnose anomalies. This method is based on a separation of the high-dimensional space occupied by a set of network traffic measurements into disjoint subspaces corresponding to normal and anomalous network conditions. We show that this separation can be performed effectively by Principal Component Analysis.Using only simple traffic measurements from links, we study volume anomalies and show that the method can: (1) accurately detect when a volume anomaly is occurring; (2) correctly identify the underlying origin-destination (OD) flow which is the source of the anomaly; and (3) accurately estimate the amount of traffic involved in the anomalous OD flow.We evaluate the method's ability to diagnose (i.e., detect, identify, and quantify) both existing and synthetically injected volume anomalies in real traffic from two backbone networks. Our method consistently diagnoses the largest volume anomalies, and does so with a very low false alarm rate.

Obesity and the Risk of New-Onset Atrial Fibrillation

Abstract: ContextObesity is associated with atrial enlargement and ventricular diastolic dysfunction, both known predictors of atrial fibrillation (AF). However, it is unclear whether obesity is a risk factor for AF.ObjectiveTo examine the association between body mass index (BMI) and the risk of developing AF.Design, Setting, and ParticipantsProspective, community-based observational cohort in Framingham, Mass. We studied 5282 participants (mean age, 57 [SD, 13] years; 2898 women [55%]) without baseline AF (electrocardiographic AF or arterial flutter). Body mass index (calculated as weight in kilograms divided by square of height in meters) was evaluated as both a continuous and a categorical variable (normal defined as <25.0; overweight, 25.0 to <30.0; and obese, ≥30.0). In addition to adjusting for clinical confounders by multivariable techniques, we also examined models including echocardiographic left atrial diameter to examine whether the influence of obesity was mediated by changes in left atrial dimensions.Main Outcome MeasureAssociation between BMI or BMI category and risk of developing new-onset AF.ResultsDuring a mean follow-up of 13.7 years, 526 participants (234 women) developed AF. Age-adjusted incidence rates for AF increased across the 3 BMI categories in men (9.7, 10.7, and 14.3 per 1000 person-years) and women (5.1, 8.6, and 9.9 per 1000 person-years). In multivariable models adjusted for cardiovascular risk factors and interim myocardial infarction or heart failure, a 4% increase in AF risk per 1-unit increase in BMI was observed in men (95% confidence interval [CI], 1%-7%; P = .02) and in women (95% CI, 1%-7%; P = .009). Adjusted hazard ratios for AF associated with obesity were 1.52 (95% CI, 1.09-2.13; P = .02) and 1.46 (95% CI, 1.03-2.07; P = .03) for men and women, respectively, compared with individuals with normal BMI. After adjustment for echocardiographic left atrial diameter in addition to clinical risk factors, BMI was no longer associated with AF risk (adjusted hazard ratios per 1-unit increase in BMI, 1.00 [95% CI, 0.97-1.04], P = .84 in men; 0.99 [95% CI, 0.96-1.02], P = .56 in women).ConclusionsObesity is an important, potentially modifiable risk factor for AF. The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population burden of AF.

Ghost condensation and a consistent infrared modification of gravity

Abstract: We propose a theoretically consistent modification of gravity in the infrared, which is compatible with all current experimental observations. This is an analog of the Higgs mechanism in general relativity, and can be thought of as arising from ghost condensation — a background where a scalar field has a constant velocity, = M2. The ghost condensate is a new kind of fluid that can fill the universe, which has the same equation of state, ρ = −p, as a cosmological constant, and can hence drive de Sitter expansion of the universe. However, unlike a cosmological constant, it is a physical fluid with a physical scalar excitation, which can be described by a systematic effective field theory at low energies. The excitation has an unusual low-energy dispersion relation ω2 ~ 4/M2. If coupled to matter directly, it gives rise to small Lorentz-violating effects and a new long-range 1/r2 spin dependent force. In the ghost condensate, the energy that gravitates is not the same as the particle physics energy, leading to the possibility of both sources that can gravitate and anti-gravitate. The newtonian potential is modified with an oscillatory behavior starting at the distance scale MPl/M2 and the time scale MPl2/M3. This theory opens up a number of new avenues for attacking cosmological problems, including inflation, dark matter and dark energy.

Targeted Anticytokine Therapy in Patients with Chronic Heart Failure: Results of the Randomized Etanercept Worldwide Evaluation (RENEWAL)

Abstract: Background— Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure. Methods and Results— Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction ≤0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n=373) or subcutaneous etanercept in doses of 25 mg every week (n=375) or 25 mg twice per week (n=375). In RENAISSANCE, patients received placebo (n=309), etanercept 25 mg twice per week (n=308), or etanercept 25 mg 3 times per week (n=308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE ( P =0.17) or RECOVER ( P =0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk=1.1, 95% CI 0.91 to 1.33, P =0.33). Conclusions— The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.

The empirical status of empirically supported psychotherapies: assumptions, findings, and reporting in controlled clinical trials.

Abstract: This article provides a critical review of the assumptions and findings of studies used to establish psychotherapies as empirically supported. The attempt to identify empirically supported therapies (ESTs) imposes particular assumptions on the use of randomized controlled trial (RCT) methodology that appear to be valid for some disorders and treatments (notably exposure-based treatments of specific anxiety symptoms) but substantially violated for others. Meta-analytic studies support a more nuanced view of treatment efficacy than implied by a dichotomous judgment of supported versus unsupported. The authors recommend changes in reporting practices to maximize the clinical utility of RCTs, describe alternative methodologies that may be useful when the assumptions underlying EST methodology are violated, and suggest a shift from validating treatment packages to testing intervention strategies and theories of change that clinicians can integrate into empirically informed therapies.

Sensor networks for emergency response: challenges and opportunities

Abstract: Sensor networks, a new class of devices has the potential to revolutionize the capture, processing, and communication of critical data for use by first responders. CodeBlue integrates sensor nodes and other wireless devices into a disaster response setting and provides facilities for ad hoc network formation, resource naming and discovery, security, and in-network aggregation of sensor-produced data. We designed CodeBlue for rapidly changing, critical care environments. To test it, we developed two wireless vital sign monitors and a PDA-based triage application for first responders. Additionally, we developed MoteTrack, a robust radio frequency (RF)-based localization system, which lets rescuers determine their location within a building and track patients. Although much of our work on CodeBlue is preliminary, our initial experience with medical care sensor networks raised many exciting opportunities and challenges.

Sleep-Disordered Breathing, Glucose Intolerance, and Insulin Resistance The Sleep Heart Health Study

Abstract: Clinic-based studies suggest that sleep-disordered breathing (SDB) is associated with glucose intolerance and insulin resistance. However, in the available studies, researchers have not rigorously controlled for confounding variables to assess the independent relation between SDB and impaired glucose metabolism. The objective of this study was to determine whether SDB was associated with glucose intolerance and insulin resistance among community-dwelling subjects (n=2,656) participating in the Sleep Heart Health Study (1994-1999). SDB was characterized with the respiratory disturbance index and measurements of oxygen saturation during sleep. Fasting and 2-hour glucose levels measured during an oral glucose tolerance test were used to assess glycemic status. Relative to subjects with a respiratory disturbance index of less than 5.0 events/hour (the reference category), subjects with mild SDB (5.0-14.9 events/hour) and moderate to severe SDB (> or =15 events/hour) had adjusted odds ratios of 1.27 (95% confidence interval: 0.98, 1.64) and 1.46 (95% confidence interval: 1.09, 1.97), respectively, for fasting glucose intolerance (p for trend < 0.01). Sleep-related hypoxemia was also associated with glucose intolerance independently of age, gender, body mass index, and waist circumference. The results of this study suggest that SDB is independently associated with glucose intolerance and insulin resistance and may lead to type 2 diabetes mellitus.

Results of a Home-Based Environmental Intervention among Urban Children with Asthma

Abstract: background Children with asthma who live in the inner city are exposed to multiple indoor allergens and environmental tobacco smoke in their homes. Reductions in these triggers of asthma have been difficult to achieve and have seldom been associated with decreased morbidity from asthma. The objective of this study was to determine whether an environmental intervention tailored to each child’s allergic sensitization and environmental risk factors could improve asthma-related outcomes. methods We enrolled 937 children with atopic asthma (age, 5 to 11 years) in seven major U.S. cities in a randomized, controlled trial of an environmental intervention that lasted one year (intervention year) and included education and remediation for exposure to both allergens and environmental tobacco smoke. Home environmental exposures were assessed every six months, and asthma-related complications were assessed every two months during the intervention and for one year after the intervention. results For every 2-week period, the intervention group had fewer days with symptoms than did the control group both during the intervention year (3.39 vs. 4.20 days, P<0.001) and the year afterward (2.62 vs. 3.21 days, P<0.001), as well as greater declines in the levels of allergens at home, such as Dermatophagoides farinae (Der f1) allergen in the bed (P<0.001) and on the bedroom floor (P=0.004), D. pteronyssinus in the bed (P=0.007), and cockroach allergen on the bedroom floor (P<0.001). Reductions in the levels of cockroach allergen and dust-mite allergen (Der f1) on the bedroom floor were significantly correlated with reduced complications of asthma (P<0.001). conclusions Among inner-city children with atopic asthma, an individualized, home-based, comprehensive environmental intervention decreases exposure to indoor allergens, including cockroach and dust-mite allergens, resulting in reduced asthma-associated morbidity.

Stress Granule Assembly Is Mediated by Prion-like Aggregation of TIA-1

Abstract: TIA-1 is an RNA binding protein that promotes the assembly of stress granules (SGs), discrete cytoplasmic inclusions into which stalled translation initiation complexes are dynamically recruited in cells subjected to environmental stress. The RNA recognition motifs of TIA-1 are linked to a glutamine-rich prion-related domain (PRD). Truncation mutants lacking the PRD domain do not induce spontaneous SGs and are not recruited to arsenite-induced SGs, whereas the PRD forms aggregates that are recruited to SGs in low-level-expressing cells but prevent SG assembly in high-level-expressing cells. The PRD of TIA-1 exhibits many characteristics of prions: concentration-dependent aggregation that is inhibited by the molecular chaperone heat shock protein (HSP)70; resistance to protease digestion; sequestration of HSP27, HSP40, and HSP70; and induction of HSP70, a feedback regulator of PRD disaggregation. Substitution of the PRD with the aggregation domain of a yeast prion, SUP35-NM, reconstitutes SG assembly, confirming that a prion domain can mediate the assembly of SGs. Mouse embryomic fibroblasts (MEFs) lacking TIA-1 exhibit impaired ability to form SGs, although they exhibit normal phosphorylation of eukaryotic initiation factor (eIF)2alpha in response to arsenite. Our results reveal that prion-like aggregation of TIA-1 regulates SG formation downstream of eIF2alpha phosphorylation in response to stress.

Impact of Obesity on Plasma Natriuretic Peptide Levels

Abstract: Background— The mechanisms linking obesity to hypertension have not been established, but sodium retention and excessive sympathetic tone are key contributors. The natriuretic peptides are important regulators of sodium homeostasis and neurohormonal activation, raising the possibility that obese individuals have an impaired natriuretic peptide response. Methods and Results— We examined the relations of plasma B-type natriuretic peptide (BNP) and N-terminal proatrial natriuretic peptide (N-ANP) to body mass index in 3389 Framingham Study participants (1803 women) without heart failure. Multivariable regression analyses were performed, adjusting for clinical and echocardiographic covariates. BNP levels below the assay detection limit and N-ANP levels in the lowest sex-specific quartile were categorized as low. Multivariable-adjusted mean plasma BNP levels in lean (<25 kg/m2), overweight (25 to 29.9 kg/m2), and obese (≥30 kg/m2) men were 21.4, 15.5, and 12.7 pg/mL, respectively (trend P <0.0001). Corresponding values in women were 21.1, 16.3, and 13.1 pg/mL (trend P <0.001). A similar pattern was noted for plasma N-ANP. Obese individuals had higher odds of having low plasma BNP (multivariable-adjusted odds ratios: men, 2.51; 95% CI, 1.71 to 3.68; women, 1.84; 95% CI, 1.32 to 2.58) and low plasma N-ANP (odds ratios: men, 4.81; 95% CI, 2.98 to 7.76; women, 2.85; 95% CI, 2.01 to 4.04) compared with lean individuals. Diabetes also was associated with low plasma natriuretic peptide levels, and the negative effects of obesity and diabetes on natriuretic peptide levels were additive. Conclusions— Obese individuals have low circulating natriuretic peptide levels, which may contribute to their susceptibility to hypertension and hypertension-related disorders. Received August 12, 2003; revision received November 11, 2003; accepted November 14, 2003.

The molecular basis of skeletal muscle atrophy.

Abstract: Skeletal muscle atrophy attributable to muscular inactivity has significant adverse functional consequences. While the initiating physiological event leading to atrophy seems to be the loss of musc...

Mothers and Sons: Preference Formation and Female Labor Force Dynamics

Abstract: This paper argues that the growing presence of a new type of man—one brought up in a family in which the mother worked—has been a significant factor in the increase in female labor force participation over time. We present cross-sectional evidence showing that the wives of men whose mothers worked are themselves significantly more likely to work. We use variation in the importance of World War II as a shock to women's labor force participation—as proxied by variation in the male draft rate across U. S. states—to provide evidence in support of the intergenerational consequences of our propagation mechanism.