Showing papers by "Boston University published in 2008"

General Cardiovascular Risk Profile for Use in Primary Care The Framingham Heart Study

Abstract: Background—Separate multivariable risk algorithms are commonly used to assess risk of specific atherosclerotic cardiovascular disease (CVD) events, ie, coronary heart disease, cerebrovascular disease, peripheral vascular disease, and heart failure. The present report presents a single multivariable risk function that predicts risk of developing all CVD and of its constituents. Methods and Results—We used Cox proportional-hazards regression to evaluate the risk of developing a first CVD event in 8491 Framingham study participants (mean age, 49 years; 4522 women) who attended a routine examination between 30 and 74 years of age and were free of CVD. Sex-specific multivariable risk functions (“general CVD” algorithms) were derived that incorporated age, total and high-density lipoprotein cholesterol, systolic blood pressure, treatment for hypertension, smoking, and diabetes status. We assessed the performance of the general CVD algorithms for predicting individual CVD events (coronary heart disease, stroke, peripheral artery disease, or heart failure). Over 12 years of follow-up, 1174 participants (456 women) developed a first CVD event. All traditional risk factors evaluated predicted CVD risk (multivariable-adjusted P0.0001). The general CVD algorithm demonstrated good discrimination (C statistic, 0.763 [men] and 0.793 [women]) and calibration. Simple adjustments to the general CVD risk algorithms allowed estimation of the risks of each CVD component. Two simple risk scores are presented, 1 based on all traditional risk factors and the other based on non–laboratory-based predictors. Conclusions—A sex-specific multivariable risk factor algorithm can be conveniently used to assess general CVD risk and risk of individual CVD events (coronary, cerebrovascular, and peripheral arterial disease and heart failure). The estimated absolute CVD event rates can be used to quantify risk and to guide preventive care. (Circulation. 2008;117: 743-753.)

Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond

Abstract: Identification of key factors associated with the risk of developing cardiovascular disease and quantification of this risk using multivariable prediction algorithms are among the major advances made in preventive cardiology and cardiovascular epidemiology in the 20th century. The ongoing discovery of new risk markers by scientists presents opportunities and challenges for statisticians and clinicians to evaluate these biomarkers and to develop new risk formulations that incorporate them. One of the key questions is how best to assess and quantify the improvement in risk prediction offered by these new models. Demonstration of a statistically significant association of a new biomarker with cardiovascular risk is not enough. Some researchers have advanced that the improvement in the area under the receiver-operating-characteristic curve (AUC) should be the main criterion, whereas others argue that better measures of performance of prediction models are needed. In this paper, we address this question by introducing two new measures, one based on integrated sensitivity and specificity and the other on reclassification tables. These new measures offer incremental information over the AUC. We discuss the properties of these new measures and contrast them with the AUC. We also develop simple asymptotic tests of significance. We illustrate the use of these measures with an example from the Framingham Heart Study. We propose that scientists consider these types of measures in addition to the AUC when assessing the performance of newer biomarkers.

The CMS experiment at the CERN LHC

Abstract: The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1) (10(27)cm(-2)s(-1)). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4 pi solid angle. Forward sampling calorimeters extend the pseudo-rapidity coverage to high values (vertical bar eta vertical bar <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.

Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II.

Abstract: Objective To provide a single source for the best available estimates of the US prevalence of and number of individuals affected by osteoarthritis, polymyalgia rheumatica and giant cell arteritis, gout, fibromyalgia, and carpal tunnel syndrome, as well as the symptoms of neck and back pain. A companion article (part I) addresses additional conditions.

The Alzheimer's Disease Neuroimaging Initiative (ADNI): MRI methods.

Abstract: Dementia, one of the most feared associates of increasing longevity, represents a pressing public health problem and major research priority. Alzheimer's disease (AD) is the most common form of dementia, affecting many millions around the world. There is currently no cure for AD, but large numbers of novel compounds are currently under development that have the potential to modify the course of the disease and slow its progression. There is a pressing need for imaging biomarkers to improve understanding of the disease and to assess the efficacy of these proposed treatments. Structural magnetic resonance imaging (MRI) has already been shown to be sensitive to presymptomatic disease (1-10) and has the potential to provide such a biomarker. For use in large-scale multicenter studies, however, standardized methods that produce stable results across scanners and over time are needed. The Alzheimer's Disease Neuroimaging Initiative (ADNI) study is a longitudinal multisite observational study of elderly individuals with normal cognition, mild cognitive impairment (MCI), or AD (11,12). It is jointly funded by the National Institutes of Health (NIH) and industry via the Foundation for the NIH. The study will assess how well information (alone or in combination) obtained from MRI, (18F)-fludeoyglucose positron emission tomography (FDG PET), urine, serum, and cerebrospinal fluid (CSF) biomarkers, as well as clinical and neuropsychometric assessments, can measure disease progression in the three groups of elderly subjects mentioned above. At the 55 participating sites in North America, imaging, clinical, and biologic samples will be collected at multiple time points in 200 elderly cognitively normal, 400 MCI, and 200 AD subjects. All subjects will be scanned with 1.5 T MRI at each time point, and half of these will also be scanned with FDG PET. Subjects not assigned to the PET arm of the study will be eligible for 3 T MRI scanning. The goal is to acquire both 1.5 T and 3 T MRI studies at multiple time points in 25% of the subjects who do not undergo PET scanning [R2C1]. CSF collection at both baseline and 12 months is targeted for 50% of the subjects. Sampling varies by clinical group. Healthy elderly controls will be sampled at 0, 6, 12, 24, and 36 months. Subjects with MCI will be sampled at 0, 6, 12, 18, 24, and 36 months. AD subjects will be sampled at 0, 6, 12, and 24 months. Major goals of the ADNI study are: to link all of these data at each time point and make this repository available to the general scientific community; to develop technical standards for imaging in longitudinal studies; to determine the optimum methods for acquiring and analyzing images; to validate imaging and biomarker data by correlating these with concurrent psychometric and clinical assessments; and to improve methods for clinical trials in MCI and AD. The ADNI study overall is divided into cores, with each core managing ADNI-related activities within its sphere of expertise: clinical, informatics, biostatistics, biomarkers, and imaging. The purpose of this report is to describe the MRI methods and decision-making process underlying the selection of the MRI protocol employed in the ADNI study.

Fission and selective fusion govern mitochondrial segregation and elimination by autophagy

Abstract: Accumulation of depolarized mitochondria within β-cells has been associated with oxidative damage and development of diabetes. To determine the source and fate of depolarized mitochondria, individual mitochondria were photolabeled and tracked through fusion and fission. Mitochondria were found to go through frequent cycles of fusion and fission in a ‘kiss and run' pattern. Fission events often generated uneven daughter units: one daughter exhibited increased membrane potential (Δψm) and a high probability of subsequent fusion, while the other had decreased membrane potential and a reduced probability for a fusion event. Together, this pattern generated a subpopulation of non-fusing mitochondria that were found to have reduced Δψm and decreased levels of the fusion protein OPA1. Inhibition of the fission machinery through DRP1K38A or FIS1 RNAi decreased mitochondrial autophagy and resulted in the accumulation of oxidized mitochondrial proteins, reduced respiration and impaired insulin secretion. Pulse chase and arrest of autophagy at the pre-proteolysis stage reveal that before autophagy mitochondria lose Δψm and OPA1, and that overexpression of OPA1 decreases mitochondrial autophagy. Together, these findings suggest that fission followed by selective fusion segregates dysfunctional mitochondria and permits their removal by autophagy.

Resolving inflammation : dual anti-inflammatory and pro-resolution lipid mediators

Abstract: Active resolution of acute inflammation is a previously unrecognized interface between innate and adaptive immunity. Once thought to be a passive process, the resolution of inflammation is now shown to involve active biochemical programmes that enable inflamed tissues to return to homeostasis. This Review presents new cellular and molecular mechanisms for the resolution of inflammation, revealing key roles for eicosanoids, such as lipoxins, and recently discovered families of endogenous chemical mediators, termed resolvins and protectins. These mediators have anti-inflammatory and pro-resolution properties, thereby protecting organs from collateral damage, stimulating the clearance of inflammatory debris and promoting mucosal antimicrobial defence.

Case Selection Techniques in Case Study Research A Menu of Qualitative and Quantitative Options

Abstract: How can scholars select cases from a large universe for in-depth case study analysis? Random sampling is not typically a viable approach when the total number of cases to be selected is small. Hence attention to purposive modes of sampling is needed. Yet, while the existing qualitative literature on case selection offers a wide range of suggestions for case selection, most techniques discussed require in-depth familiarity of each case. Seven case selection procedures are considered, each of which facilitates a different strategy for within-case analysis. The case selection procedures considered focus on typical, diverse, extreme, deviant, influential, most similar, and most different cases. For each case selection procedure, quantitative approaches are discussed that meet the goals of the approach, while still requiring information that can reasonably be gathered for a large number of cases.

The Potential and Challenges of Nanopore Sequencing

Abstract: A nanopore-based device provides single-molecule detection and analytical capabilities that are achieved by electrophoretically driving molecules in solution through a nano-scale pore. The nanopore provides a highly confined space within which single nucleic acid polymers can be analyzed at high throughput by one of a variety of means, and the perfect processivity that can be enforced in a narrow pore ensures that the native order of the nucleobases in a polynucleotide is reflected in the sequence of signals that is detected. Kilobase length polymers (single-stranded genomic DNA or RNA) or small molecules (e.g., nucleosides) can be identified and characterized without amplification or labeling, a unique analytical capability that makes inexpensive, rapid DNA sequencing a possibility. Further research and development to overcome current challenges to nanopore identification of each successive nucleotide in a DNA strand offers the prospect of 'third generation' instruments that will sequence a diploid mammalian genome for ∼$1,000 in ∼24 h.

Discursive Institutionalism: The Explanatory Power of Ideas and Discourse

Abstract: The newest “new institutionalism,” discursive institutionalism, lends insight into the role of ideas and discourse in politics while providing a more dynamic approach to institutional change than the older three new institutionalisms. Ideas are the substantive content of discourse. They exist at three levels—policies, programs, and philosophies—and can be categorized into two types, cognitive and normative. Discourse is the interactive process of conveying ideas. It comes in two forms: the coordinative discourse among policy actors and the communicative discourse between political actors and the public. These forms differ in two formal institutional contexts; simple polities have a stronger communicative discourse and compound polities a stronger coordinative discourse. The institutions of discursive institutionalism, moreover, are not external-rule-following structures but rather are simultaneously structures and constructs internal to agents whose “background ideational abilities” within a given “meanin...

The Dishonesty of Honest People: A Theory of Self-Concept Maintenance

Abstract: Dishonesty plays a large role in the economy. Causes for (dis)honest behavior seem to be based partially on external rewards, and partially on internal rewards. Here, we investigate how such external and internal rewards work in concert to produce (dis)honesty. We propose and test a theory of self-concept maintenance that allows people to engage to some level in dishonest behavior, thereby benefiting from external benefits of dishonesty, while maintaining their positive view about themselves in terms of being honest individuals. The results show that (1) given the opportunity to engage in beneficial dishonesty, people will engage in such behaviors; (2) the amount of dishonesty is largely insensitive to either the expected external benefits or the costs associated with the deceptive acts; (3) people know about their actions but do not update their self-concepts; (4) causing people to become more aware of their internal standards for honesty decreases their tendency for deception; and (5) increasing the "degrees of freedom" that people have to interpret their actions increases their tendency for deception. We suggest that dishonesty governed by self-concept maintenance is likely to be prevalent in the economy, and understanding it has important implications for designing effective methods to curb dishonesty.Former working paper titles:“(Dis)Honesty: A Combination of Internal and External Rewards” and "Almost Honest: Internal and External Motives for Honesty")

The Immunological Genome Project: networks of gene expression in immune cells

Abstract: nology is an ideal field for the application of systems approaches, with its detailed descriptions of cell types (over 200 immune cell types are defined in the scope of the Immunological Genome Project (ImmGen)), wealth of reagents and easy access to cells. Thanks to the broad and robust approaches allowed by gene-expression microarrays and related techniques, the transcriptome is probably the only ‘-ome’ that can be reliably tackled in its entirety. Generating a complete perspective of gene expression in the immune system

Cognitive-behavioral therapy for adult anxiety disorders: a meta-analysis of randomized placebo-controlled trials

Abstract: Objective Cognitive-behavioral therapy (CBT) is frequently used for various adult anxiety disorders, but there has been no systematic review of randomized placebo-controlled trials. The present study meta-analytically reviewed the efficacy of CBT versus placebo for adult anxiety disorders.

A metamaterial absorber for the terahertz regime: Design, fabrication and characterization

Abstract: We present a metamaterial that acts as a strongly resonant absorber at terahertz frequencies. Our design consists of a bilayer unit cell which allows for maximization of the absorption through independent tuning of the electrical permittivity and magnetic permeability. An experimental absorptivity of 70% at 1.3 terahertz is demonstrated. We utilize only a single unit cell in the propagation direction, thus achieving an absorption coefficient α=2000 cm-1. These metamaterials are promising candidates as absorbing elements for thermally based THz imaging, due to their relatively low volume, low density, and narrow band response.

Detrended Cross-Correlation Analysis : A New Method for Analyzing Two Nonstationary Time Series

Abstract: Here we propose a new method, detrended cross-correlation analysis, which is a generalization of detrended fluctuation analysis and is based on detrended covariance. This method is designed to investigate power-law cross correlations between different simultaneously recorded time series in the presence of nonstationarity. We illustrate the method by selected examples from physics, physiology, and finance.

Target atmospheric CO2: Where should humanity aim?

Abstract: Paleoclimate data show that climate sensitivity is ~3 deg-C for doubled CO2, including only fast feedback processes. Equilibrium sensitivity, including slower surface albedo feedbacks, is ~6 deg-C for doubled CO2 for the range of climate states between glacial conditions and ice-free Antarctica. Decreasing CO2 was the main cause of a cooling trend that began 50 million years ago, large scale glaciation occurring when CO2 fell to 450 +/- 100 ppm, a level that will be exceeded within decades, barring prompt policy changes. If humanity wishes to preserve a planet similar to that on which civilization developed and to which life on Earth is adapted, paleoclimate evidence and ongoing climate change suggest that CO2 will need to be reduced from its current 385 ppm to at most 350 ppm. The largest uncertainty in the target arises from possible changes of non-CO2 forcings. An initial 350 ppm CO2 target may be achievable by phasing out coal use except where CO2 is captured and adopting agricultural and forestry practices that sequester carbon. If the present overshoot of this target CO2 is not brief, there is a possibility of seeding irreversible catastrophic effects.

A Meta-Analytic Review of Psychosocial Interventions for Substance Use Disorders

Abstract: Objective: Despite significant advances in psychosocial treatments for substance use disorders, the relative success of these approaches has not been well documented. In this meta-analysis, the authors provide effect sizes for various types of psychosocial treatments, as well as abstinence and treatment-retention rates for cannabis, cocaine, opiate, and polysubstance abuse and dependence treatment trials. Method: With a comprehensive series of literature searches, the authors identified a total of 34 well-controlled treatment conditions—five for cannabis, nine for cocaine, seven for opiate, and 13 for polysubstance users—representing the treatment of 2,340 patients. Psychosocial treatments evaluated included contingency management, relapse prevention, general cognitive behavior therapy, and treatments combining cognitive behavior therapy and contingency management. Results: Overall, controlled trial data suggest that psychosocial treatments provide benefits reflecting a moderate effect size according to C...

Parenting Stress in Mothers and Fathers of Toddlers with Autism Spectrum Disorders: Associations with Child Characteristics

Abstract: Elevated parenting stress is observed among mothers of older children with autism spectrum disorders (ASD), but little is known about parents of young newly-diagnosed children. Associations between child behavior and parenting stress were examined in mothers and fathers of 54 toddlers with ASD (mean age = 26.9 months). Parents reported elevated parenting stress. Deficits/delays in children's social relatedness were associated with overall parenting stress, parent-child relationship problems, and distress for mothers and fathers. Regulatory problems were associated with maternal stress, whereas externalizing behaviors were associated with paternal stress. Cognitive functioning, communication deficits, and atypical behaviors were not uniquely associated with parenting stress. Clinical assessment of parental stress, acknowledging differences in parenting experiences for mothers and fathers of young children with ASD, is needed.

Genomewide analysis of PRC1 and PRC2 occupancy identifies two classes of bivalent domains

Abstract: In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2,000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation, followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes—the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes, and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes in pluripotent cells.

Towards environmental systems biology of Shewanella

Abstract: Bacteria of the genus Shewanella are known for their versatile electron-accepting capacities, which allow them to couple the decomposition of organic matter to the reduction of the various terminal electron acceptors that they encounter in their stratified environments. Owing to their diverse metabolic capabilities, shewanellae are important for carbon cycling and have considerable potential for the remediation of contaminated environments and use in microbial fuel cells. Systems-level analysis of the model species Shewanella oneidensis MR-1 and other members of this genus has provided new insights into the signal-transduction proteins, regulators, and metabolic and respiratory subsystems that govern the remarkable versatility of the shewanellae.

Experimental demonstration of frequency-agile terahertz metamaterials

Abstract: Metamaterials exhibit numerous novel effects1,2,3,4,5 and operate over a large portion of the electromagnetic spectrum6,7,8,9,10. Metamaterial devices based on these effects include gradient-index lenses11,12, modulators for terahertz radiation13,14,15 and compact waveguides16. The resonant nature of metamaterials results in frequency dispersion and narrow bandwidth operation where the centre frequency is fixed by the geometry and dimensions of the elements comprising the metamaterial composite. The creation of frequency-agile metamaterials would extend the spectral range over which devices function and, further, enable the manufacture of new devices such as dynamically tunable notch filters. Here, we demonstrate such frequency-agile metamaterials operating in the far-infrared by incorporating semiconductors in critical regions of metallic split-ring resonators. For this first-generation device, external optical control results in tuning of the metamaterial resonance frequency by ∼20%. Our approach is integrable with current semiconductor technologies and can be implemented in other regions of the electromagnetic spectrum. Metamaterials that possess frequency tunability enable new device functions. By external optical control through the incorporation of semiconductors in metallic split-ring resonators, the researchers provide an elegant solution to frequency-agile terahertz metamaterials.

Free access to Landsat imagery.

Abstract: ![Figure][1] Free image. This Landsat 5 image of the southeastern corner of the Black Sea is part of the general U.S. archive that will be accessible for free under the new USGS policy. CREDIT: BOSTON UNIVERSITY CENTER FOR REMOTE SENSING We are entering a new era in the Landsat Program, the oldest and most venerable of our Earth-observing satellite programs. With little fanfare, the U.S. Geological Survey (USGS) has begun providing imagery for free over the Internet. Throughout the history of the Landsat Program, the cost and access to imagery has always limited our ability to study our planet and the way it is changing. Beginning with a pilot program to provide “Web-enabled” access to Landsat 7 images of the United States that were collected between 2003 and this year, the USGS now plans to provide top-quality image products for free upon request for the entire U.S. archive, including over 2 million images back to Landsat 1 (1972) [for details and schedules, see ([1][2])]. The release by NASA and the USGS in January 2008 of a new Landsat Data Distribution Policy ([2][3]) was a key step to this goal. Free imagery will enable reconstruction of the history of Earth's surface back to 1972, chronicling both anthropogenic and natural changes during a time when our population doubled and the impacts of climate change became noticeable. The Landsat Science Team: 1. 1.[↵][4]USGS Technical Announcement ([http://landsat.usgs.gov/images/squares/USGS\_Landsat\_Imagery_Release.pdf][5]). 2. 2.[↵][6]Landsat Missions ([http://ldcm.usgs.gov/pdf/Landsat\_Data\_Policy.pdf][7]). [1]: pending:yes [2]: #ref-1 [3]: #ref-2 [4]: #xref-ref-1-1 "View reference 1. in text" [5]: http://landsat.usgs.gov/images/squares/USGS_Landsat_Imagery_Release.pdf [6]: #xref-ref-2-1 "View reference 2. in text" [7]: http://ldcm.usgs.gov/pdf/Landsat_Data_Policy.pdf

The inner jet of an active galactic nucleus as revealed by a radio-to-γ-ray outburst

Abstract: Blazars are the most extreme active galactic nuclei. They possess oppositely directed plasma jets emanating at near light speeds from accreting supermassive black holes. According to theoretical models, such jets are propelled by magnetic fields twisted by differential rotation of the black hole's accretion disk or inertial-frame-dragging ergosphere1, 2, 3. The flow velocity increases outward along the jet in an acceleration and collimation zone containing a coiled magnetic field4, 5. Detailed observations of outbursts of electromagnetic radiation, for which blazars are famous, can potentially probe the zone. It has hitherto not been possible to either specify the location of the outbursts or verify the general picture of jet formation. Here we report sequences of high-resolution radio images and optical polarization measurements of the blazar BL Lacertae. The data reveal a bright feature in the jet that causes a double flare of radiation from optical frequencies to TeV -ray energies, as well as a delayed outburst at radio wavelengths. We conclude that the event starts in a region with a helical magnetic field that we identify with the acceleration and collimation zone predicted by the theories. The feature brightens again when it crosses a standing shock wave corresponding to the bright 'core' seen on the images.