Showing papers by "Boston University published in 2003"

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.

Computation and analysis of multiple structural change models

Abstract: In a recent paper, Bai and Perron (1998) considered theoretical issues related to the limiting distribution of estimators and test statistics in the linear model with multiple structural changes. In this companion paper, we consider practical issues for the empirical applications of the procedures. We first address the problem of estimation of the break dates and present an efficient algorithm to obtain global minimizers of the sum of squared residuals. This algorithm is based on the principle of dynamic programming and requires at most least-squares operations of order O(T2) for any number of breaks. Our method can be applied to both pure and partial structural change models. Second, we consider the problem of forming confidence intervals for the break dates under various hypotheses about the structure of the data and the errors across segments. Third, we address the issue of testing for structural changes under very general conditions on the data and the errors. Fourth, we address the issue of estimating the number of breaks. Finally, a few empirical applications are presented to illustrate the usefulness of the procedures. All methods discussed are implemented in a GAUSS program. Copyright © 2002 John Wiley & Sons, Ltd.

Climate-Driven Increases in Global Terrestrial Net Primary Production from 1982 to 1999

Abstract: Recent climatic changes have enhanced plant growth in northern mid-latitudes and high latitudes. However, a comprehensive analysis of the impact of global climatic changes on vegetation productivity has not before been expressed in the context of variable limiting factors to plant growth. We present a global investigation of vegetation responses to climatic changes by analyzing 18 years (1982 to 1999) of both climatic data and satellite observations of vegetation activity. Our results indicate that global changes in climate have eased several critical climatic constraints to plant growth, such that net primary production increased 6% (3.4 petagrams of carbon over 18 years) globally. The largest increase was in tropical ecosystems. Amazon rain forests accounted for 42% of the global increase in net primary production, owing mainly to decreased cloud cover and the resulting increase in solar radiation.

Consumer-Company Identification: A Framework for Understanding Consumers¿ Relationships with Companies

Abstract: In this article, the authors try to determine why and under what conditions consumers enter into strong, committed, and meaningful relationships with certain companies, becoming champions of these companies and their products. Drawing on theories of social identity and organizational identification, the authors propose that strong consumer-company relationships often result from consumers’ identification with those companies, which helps them satisfy one or more important self-definitional needs. The authors elaborate on the nature of consumer-company identification, including the company identity, and articulate a consumer-level conceptual framework that offers propositions regarding the key determinants and consequences of such identification in the marketplace.

Temporal relations of atrial fibrillation and congestive heart failure and their joint influence on mortality: the Framingham Heart Study.

Abstract: Background— Atrial fibrillation (AF) and congestive heart failure (CHF) frequently occur together, but there is limited information regarding their temporal relations and the combined influence of these conditions on mortality. Methods and Results— We studied participants in the Framingham Study with new-onset AF or CHF. Multivariable Cox proportional hazards models with time-dependent variables were used to evaluate whether mortality after AF or CHF was affected by the occurrence and timing of the other condition. Hazard ratios (HRs) were adjusted for time period and cardiovascular risk factors. During the study period, 1470 participants developed AF, CHF, or both. Among 382 individuals with both conditions, 38% had AF first, 41% had CHF first, and 21% had both diagnosed on the same day. The incidence of CHF among AF subjects was 33 per 1000 person-years, and the incidence of AF among CHF subjects was 54 per 1000 person-years. In AF subjects, the subsequent development of CHF was associated with increase...

Noise in eukaryotic gene expression

Abstract: Transcription in eukaryotic cells has been described as quantal, with pulses of messenger RNA produced in a probabilistic manner. This description reflects the inherently stochastic nature of gene expression, known to be a major factor in the heterogeneous response of individual cells within a clonal population to an inducing stimulus. Here we show in Saccharomyces cerevisiae that stochasticity (noise) arising from transcription contributes significantly to the level of heterogeneity within a eukaryotic clonal population, in contrast to observations in prokaryotes, and that such noise can be modulated at the translational level. We use a stochastic model of transcription initiation specific to eukaryotes to show that pulsatile mRNA production, through reinitiation, is crucial for the dependence of noise on transcriptional efficiency, highlighting a key difference between eukaryotic and prokaryotic sources of noise. Furthermore, we explore the propagation of noise in a gene cascade network and demonstrate experimentally that increased noise in the transcription of a regulatory protein leads to increased cell-cell variability in the target gene output, resulting in prolonged bistable expression states. This result has implications for the role of noise in phenotypic variation and cellular differentiation.

Acute Effects and Recovery Time Following Concussion in Collegiate Football Players: The NCAA Concussion Study

Abstract: ContextLack of empirical data on recovery time following sport-related concussion hampers clinical decision making about return to play after injury.ObjectiveTo prospectively measure immediate effects and natural recovery course relating to symptoms, cognitive functioning, and postural stability following sport-related concussion.Design, Setting, and ParticipantsProspective cohort study of 1631 football players from 15 US colleges. All players underwent preseason baseline testing on concussion assessment measures in 1999, 2000, and 2001. Ninety-four players with concussion (based on American Academy of Neurology criteria) and 56 noninjured controls underwent assessment of symptoms, cognitive functioning, and postural stability immediately, 3 hours, and 1, 2, 3, 5, 7, and 90 days after injury.Main Outcome MeasuresScores on the Graded Symptom Checklist (GSC), Standardized Assessment of Concussion (SAC), Balance Error Scoring System (BESS), and a neuropsychological test battery.ResultsNo player with concussion was excluded from participation; 79 players with concussion (84%) completed the protocol through day 90. Players with concussion exhibited more severe symptoms (mean GSC score 20.93 [95% confidence interval {CI}, 15.65-26.21] points higher than that of controls), cognitive impairment (mean SAC score 2.94 [95% CI, 1.50-4.38] points lower than that of controls), and balance problems (mean BESS score 5.81 [95% CI, –0.67 to 12.30] points higher than that of controls) immediately after concussion. On average, symptoms gradually resolved by day 7 (GSC mean difference, 0.33; 95% CI, −1.41 to 2.06), cognitive functioning improved to baseline levels within 5 to 7 days (day 7 SAC mean difference, −0.03; 95% CI, −1.33 to 1.26), and balance deficits dissipated within 3 to 5 days after injury (day 5 BESS mean difference, −0.31; 95% CI, −3.02 to 2.40). Mild impairments in cognitive processing and verbal memory evident on neuropsychological testing 2 days after concussion resolved by day 7. There were no significant differences in symptoms or functional impairments in the concussion and control groups 90 days after concussion.ConclusionsCollegiate football players may require several days for recovery of symptoms, cognitive dysfunction, and postural instability after concussion. Further research is required to determine factors that predict variability in recovery time after concussion. Standardized measurement of postconcussive symptoms, cognitive functioning, and postural stability may enhance clinical management of athletes recovering from concussion.

Cumulative Effects Associated With Recurrent Concussion in Collegiate Football Players: The NCAA Concussion Study

Abstract: ContextApproximately 300 000 sport-related concussions occur annually in the United States, and the likelihood of serious sequelae may increase with repeated head injury.ObjectiveTo estimate the incidence of concussion and time to recovery after concussion in collegiate football players.Design, Setting, and ParticipantsProspective cohort study of 2905 football players from 25 US colleges were tested at preseason baseline in 1999, 2000, and 2001 on a variety of measures and followed up prospectively to ascertain concussion occurrence. Players injured with a concussion were monitored until their concussion symptoms resolved and were followed up for repeat concussions until completion of their collegiate football career or until the end of the 2001 football season.Main Outcome MeasuresIncidence of concussion and repeat concusion; type and duration of symptoms and course of recovery among players who were injured with a concussion during the seasons.ResultsDuring follow-up of 4251 player-seasons, 184 players (6.3%) had a concussion, and 12 (6.5%) of these players had a repeat concussion within the same season. There was an association between reported number of previous concussions and likelihood of incident concussion. Players reporting a history of 3 or more previous concussions were 3.0 (95% confidence interval, 1.6-5.6) times more likely to have an incident concussion than players with no concussion history. Headache was the most commonly reported symptom at the time of injury (85.2%), and mean overall symptom duration was 82 hours. Slowed recovery was associated with a history of multiple previous concussions (30.0% of those with ≥3 previous concussions had symptoms lasting >1 week compared with 14.6% of those with 1 previous concussion). Of the 12 incident within-season repeat concussions, 11 (91.7%) occurred within 10 days of the first injury, and 9 (75.0%) occurred within 7 days of the first injury.ConclusionsOur study suggests that players with a history of previous concussions are more likely to have future concussive injuries than those with no history; 1 in 15 players with a concussion may have additional concussions in the same playing season; and previous concussions may be associated with slower recovery of neurological function.

Obesity and Systemic Oxidative Stress. Clinical Correlates of Oxidative Stress in The Framingham Study

Abstract: Objective— To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population. Methods and Results— We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine–indexed levels of 8-epi-PGF2α as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex-adjusted models, increased urinary creatinine–indexed 8-epi-PGF2α levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine–indexed 8-epi-PGF2α levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF2α levels. Conclusions— Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF2α levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease.

ZDOCK: An initial-stage protein-docking algorithm

Abstract: The development of scoring functions is of great importance to protein docking. Here we present a new scoring function for the initial stage of unbound docking. It combines our recently developed pairwise shape complementarity with desolvation and electrostatics. We compare this scoring function with three other functions on a large benchmark of 49 nonredundant test cases and show its superior performance, especially for the antibody-antigen category of test cases. For 44 test cases (90% of the benchmark), we can retain at least one near-native structure within the top 2000 predictions at the 6 degrees rotational sampling density, with an average of 52 near-native structures per test case. The remaining five difficult test cases can be explained by a combination of poor binding affinity, large backbone conformational changes, and our algorithm's strong tendency for identifying large concave binding pockets. All four scoring functions have been integrated into our Fast Fourier Transform based docking algorithm ZDOCK, which is freely available to academic users at http://zlab.bu.edu/~ rong/dock.

A theory of power-law distributions in financial market fluctuations

Abstract: Insights into the dynamics of a complex system are often gained by focusing on large fluctuations. For the financial system, huge databases now exist that facilitate the analysis of large fluctuations and the characterization of their statistical behaviour. Power laws appear to describe histograms of relevant financial fluctuations, such as fluctuations in stock price, trading volume and the number of trades. Surprisingly, the exponents that characterize these power laws are similar for different types and sizes of markets, for different market trends and even for different countries--suggesting that a generic theoretical basis may underlie these phenomena. Here we propose a model, based on a plausible set of assumptions, which provides an explanation for these empirical power laws. Our model is based on the hypothesis that large movements in stock market activity arise from the trades of large participants. Starting from an empirical characterization of the size distribution of those large market participants (mutual funds), we show that the power laws observed in financial data arise when the trading behaviour is performed in an optimal way. Our model additionally explains certain striking empirical regularities that describe the relationship between large fluctuations in prices, trading volume and the number of trades.

Differential Equations, Dynamical Systems, and an Introduction to Chaos

Abstract: Hirsch, Devaney, and Smale's classic "Differential Equations, Dynamical Systems, and an Introduction to Chaos" has been used by professors as the primary text for undergraduate and graduate level courses covering differential equations. It provides a theoretical approach to dynamical systems and chaos written for a diverse student population among the fields of mathematics, science, and engineering. Prominent experts provide everything students need to know about dynamical systems as students seek to develop sufficient mathematical skills to analyze the types of differential equations that arise in their area of study. The authors provide rigorous exercises and examples clearly and easily by slowly introducing linear systems of differential equations. Calculus is required as specialized advanced topics not usually found in elementary differential equations courses are included, such as exploring the world of discrete dynamical systems and describing chaotic systems. This is a classic text by three of the world's most prominent mathematicians. It continues the tradition of expository excellence. It contains updated material and expanded applications for use in applied studies.

Wound bed preparation: a systematic approach to wound management.

Abstract: The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or “stuck” at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management. This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues; • the current status of wound bed preparation; • an analysis of the acute and chronic wound environments; • how wound healing can take place in these environments; • the role of wound bed preparation in the clinic; • the clinical and cellular components of the wound bed preparation concept; • a detailed analysis of the components of wound bed preparation. (WOUND REP REG 2003;11:1–28)

Inferring genetic networks and identifying compound mode of action via expression profiling

Abstract: The complexity of cellular gene, protein, and metabolite networks can hinder attempts to elucidate their structure and function. To address this problem, we used systematic transcriptional perturbations to construct a first-order model of regulatory interactions in a nine-gene subnetwork of the SOS pathway in Escherichia coli. The model correctly identified the major regulatory genes and the transcriptional targets of mitomycin C activity in the subnetwork. This approach, which is experimentally and computationally scalable, provides a framework for elucidating the functional properties of genetic networks and identifying molecular targets of pharmacological compounds.

Informational Influence in Organizations: An Integrated Approach to Knowledge Adoption

Abstract: This research investigates how knowledge workers are influenced to adopt the advice that they receive in mediated contexts. The research integrates the Technology Acceptance Model (Davis 1989) with dual-process models of informational influence (e.g., Petty and Cacioppo 1986, Chaiken and Eagly 1976) to build a theoretical model of information adoption. This model highlights the assessment of information usefulness as a mediator of the information adoption process. Importantly, the model draws on the dual-process models to make predictions about the antecedents of informational usefulness under different processing conditions.The model is investigated qualitatively first, using interviews of a sample of 40 consultants, and then quantitatively on another sample of 63 consultants from the same international consulting organization. Data reflect participants' perceptions of actual e-mails they received from colleagues consisting of advice or recommendations. Results support the model, suggesting that the process models used to understand information adoption can be generalized to the field of knowledge management, and thatusefulness serves a mediating role between influence processes and information adoption. Organizational knowledge work is becoming increasingly global. This research offers a model for understanding knowledge transfer using computer-mediated communication.

Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice.

Abstract: The most common inherited [correct] form of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease affecting adult motor neurons, is caused by dominant mutations in the ubiquitously expressed Cu-Zn superoxide dismutase (SOD1) In chimeric mice that are mixtures of normal and SOD1 mutant-expressing cells, toxicity to motor neurons is shown to require damage from mutant SOD1 acting within nonneuronal cells Normal motor neurons in SOD1 mutant chimeras develop aspects of ALS pathology Most important, nonneuronal cells that do not express mutant SOD1 delay degeneration and significantly extend survival of mutant-expressing motor neurons

Major Risk Factors as Antecedents of Fatal and Nonfatal Coronary Heart Disease Events

Abstract: ContextA frequently cited concept is that individual major risk factors for coronary heart disease (CHD) are absent in many patients (perhaps >50%) with CHD. However, prior studies have not systematically evaluated the extent to which CHD patients have previous exposure to at least 1 risk factor, including diabetes, cigarette smoking, or clinically elevated levels of cholesterol or blood pressure.ObjectiveTo determine the frequency of exposure to major CHD risk factors.Design, Setting, and ParticipantsThree prospective cohort studies were included: the Chicago Heart Association Detection Project in Industry, with a population sample of 35 642 employed men and women aged 18 to 59 years; screenees for the Multiple Risk Factor Intervention Trial, including 347 978 men aged 35 to 57 years; and a population-based sample of 3295 men and women aged 34 to 59 years from the Framingham Heart Study (FHS). Follow-up lasted 21 to 30 years across the studies.Main Outcome MeasuresFatal CHD in all cohorts and nonfatal myocardial infarction (MI) in the FHS, compared by exposure to major CHD risk factors, defined as total cholesterol of at least 240 mg/dL (≥6.22 mmol/L), systolic blood pressure of at least 140 mm Hg, diastolic blood pressure of at least 90 mm Hg, cigarette smoking, and diabetes. Participants were stratified by sex and age (18-39 vs 40-59 years).ResultsFor fatal CHD (n = 20 995), exposure to at least 1 clinically elevated major risk factor ranged from 87% to 100%. Among those aged 40 to 59 years at baseline with fatal CHD (n = 19 263), exposure to at least 1 major risk factor ranged from 87% to 94%. For nonfatal MI, prior exposure was documented in 92% (95% CI, 87%-96%) (n = 167) of men aged 40 to 59 years at baseline and in 87% (95% CI, 80%-94%) (n = 94) of women in this age group.ConclusionsAntecedent major CHD risk factor exposures were very common among those who developed CHD, emphasizing the importance of considering all major risk factors in determining CHD risk estimation and in attempting to prevent clinical CHD. These results challenge claims that CHD events commonly occur in persons without exposure to at least 1 major CHD risk factor.

Wireless Infrared Communications

Abstract: Wireless infrared communications can be used to establish short range high-data-rate wireless links. The primary commercial applications are short-term cable-less connectivity for information exchange and wireless local area networking. In the article, the major optical design issues and communication design issues are discussed. An overview of current systems and standards is provided, along with a comparison of infrared systems to radio systems. Keywords: wireless infrared communications; channel modeling; digital modulation; IRDA

A multiple Lyapunov function approach to stabilization of fuzzy control systems

Abstract: This paper addresses stability analysis and stabilization for Takagi-Sugeno fuzzy systems via a so-called fuzzy Lyapunov function which is a multiple Lyapunov function. The fuzzy Lyapunov function is defined by fuzzily blending quadratic Lyapunov functions. Based on the fuzzy Lyapunov function approach, we give stability conditions for open-loop fuzzy systems and stabilization conditions for closed-loop fuzzy systems. To take full advantage of a fuzzy Lyapunov function, we propose a new parallel distributed compensation (PDC) scheme that feedbacks the time derivatives of premise membership functions. The new PDC contains the ordinary PDC as a special case. A design example illustrates the utility of the fuzzy Lyapunov function approach and the new PDC stabilization method.

Lysyl oxidase: Properties, specificity, and biological roles inside and outside of the cell

Abstract: Lysyl oxidase (LO) plays a critical role in the formation and repair of the extracellular matrix (ECM) by oxidizing lysine residues in elastin and collagen, thereby initiating the formation of covalent crosslinkages which stabilize these fibrous proteins. Its catalytic activity depends upon both its copper cofactor and a unique carbonyl cofactor and has been shown to extend to a variety of basic globular proteins, including histone H1. Although the three-dimensional structure of LO has yet to be determined, the present treatise offers hypotheses based upon its primary sequence, which may underlie the prominent electrostatic component of its unusual substrate specificity as well as the catalysis-suppressing function of the propeptide domain of prolysyl oxidase. Recent studies have demonstrated that LO appears to function within the cell in a manner, which strongly modifies cellular activity. Newly discovered LO-like proteins also likely play unique roles in biology. © 2002 Wiley-Liss, Inc.

The Contribution of Interleukin-1 and Tumor Necrosis Factor to Periodontal Tissue Destruction

Abstract: Interleukin (IL)-1 and tumor necrosis factor (TNF) represent proinflammatory cytokines that stimulate a number of events which occur during periodontal disease. These include the induction of adhesion molecules and other mediators that facilitate and amplify the inflammatory response, the stimulation of matrix metalloproteinase, and bone resorption. The activity of these cytokines coincides with the critical events that occur during periodontal disease, namely, loss of attachment and bone resorption. The use of antagonists to IL-1 and TNF in experimental periodontitis have demonstrated a cause-and-effect relationship between the activity of these cytokines and the spread of an inflammatory front to deeper areas in the connective tissue, loss of connective tissue attachment, osteoclast formation, and loss of alveolar bone. In addition, the loss of fibroblasts that occurs during infection with periodontal pathogens is, in part, mediated by TNF. Thus, much of the damage that occurs during periodontal tissue ...

Effect of Hydroxyurea on Mortality and Morbidity in Adult Sickle Cell Anemia: Risks and Benefits Up to 9 Years of Treatment

Abstract: ContextHydroxyurea increases levels of fetal hemoglobin (HbF) and decreases morbidity from vaso-occlusive complications in patients with sickle cell anemia (SCA). High HbF levels reduce morbidity and mortality.ObjectiveTo determine whether hydroxyurea attenuates mortality in patients with SCA.DesignLong-term observational follow-up study of mortality in patients with SCA who originally participated in the randomized, double-blind, placebo-controlled Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), conducted in 1992-1995, to determine if hydroxyurea reduces vaso-occlusive events. In the MSH Patients' Follow-up, conducted in 1996-2001, patients could continue, stop, or start hydroxyurea. Data were collected during the trial and in the follow-up period.SettingInpatients and outpatients in 21 sickle cell referral centers in the United States and Canada.PatientsTwo-hundred ninety-nine adult patients with frequent painful episodes enrolled in the follow-up. Follow-up data through May 2001 were complete for 233 patients.InterventionIn the MSH, patients were randomly assigned to receive hydroxyurea (n = 152) or placebo (n = 147).Main Outcome MeasureMortality, HbF levels, painful episodes, acute chest syndrome, and blood cell counts. The randomized trial was not designed to detect specified differences in mortality.ResultsSeventy-five of the original 299 patients died, 28% from pulmonary disease. Patients with reticulocyte counts less than 250 000/mm3 and hemoglobin levels lower than 9 g/dL had increased mortality (P = .002). Cumulative mortality at 9 years was 28% when HbF levels were lower than 0.5 g/dL after the trial was completed compared with 15% when HbF levels were 0.5 g/dL or higher (P = .03 ). Individuals who had acute chest syndrome during the trial had 32% mortality compared with 18% of individuals without acute chest syndrome (P = .02). Patients with 3 or more painful episodes per year during the trial had 27% mortality compared with 17% of patients with less frequent episodes (P = .06). Taking hydroxyurea was associated with a 40% reduction in mortality (P = .04) in this observational follow-up with self-selected treatment. There were 3 cases of cancer, 1 fatal.ConclusionsAdult patients taking hydroxyurea for frequent painful sickle cell episodes appear to have reduced mortality after 9 of years follow-up. Survival was related to HbF levels and frequency of vaso-occlusive events. Whether indications for hydroxyurea treatment should be expanded is unknown.

Subduction factory 1. Theoretical mineralogy, densities, seismic wave speeds, and H 2 O contents

Abstract: [1] We present a new compilation of physical properties of minerals relevant to subduction zones and new phase diagrams for mid-ocean ridge basalt, lherzolite, depleted lherzolite, harzburgite, and serpentinite. We use these data to calculate H2O content, density and seismic wave speeds of subduction zone rocks. These calculations provide a new basis for evaluating the subduction factory, including (1) the presence of hydrous phases and the distribution of H2O within a subduction zone; (2) the densification of the subducting slab and resultant effects on measured gravity and slab shape; and (3) the variations in seismic wave speeds resulting from thermal and metamorphic processes at depth. In considering specific examples, we find that for ocean basins worldwide the lower oceanic crust is partially hydrated (<1.3 wt % H2O), and the uppermost mantle ranges from unhydrated to � 20% serpentinized (� 2.4 wt % H2O). Anhydrous eclogite cannot be distinguished from harzburgite on the basis of wave speeds, but its � 6% greater density may render it detectable through gravity measurements. Subducted hydrous crust in cold slabs can persist to several gigapascals at seismic velocities that are several percent slower than the surrounding mantle. Seismic velocities and VP/VS ratios indicate that mantle wedges locally reach 60–80% hydration. INDEX TERMS: 3040 Marine Geology and Geophysics: Plate tectonics (8150, 8155, 8157, 8158); 3660 Mineralogy and Petrology: Metamorphic petrology; 3919 Mineral Physics: Equations of state; 5199 Physical Properties of Rocks: General or miscellaneous; 8123 Tectonophysics: Dynamics, seismotectonics; KEYWORDS: subduction, seismic velocities, mineral physics, H2O

Subduction factory 2. Are intermediate-depth earthquakes in subducting slabs linked to metamorphic dehydration reactions?

Abstract: [1] New thermal-petrologic models of subduction zones are used to test the hypothesis that intermediate-depth intraslab earthquakes are linked to metamorphic dehydration reactions in the subducting oceanic crust and mantle. We show that there is a correlation between the patterns of intermediate-depth seismicity and the locations of predicted hydrous minerals: Earthquakes occur in subducting slabs where dehydration is expected, and they are absent from parts of slabs predicted to be anhydrous. We propose that a subductingoceanicplatecanconsistoffourpetrologicallyandseismicallydistinctlayers:(1) hydrated, fine-grained basaltic upper crust dehydrating under equilibrium conditions and producing earthquakes facilitated by dehydration embrittlement; (2) coarse-grained, locally hydrated gabbroic lower crust that produces some earthquakes during dehydration but transformschieflyaseismicallytoeclogiteatdepthsbeyondequilibrium;(3)locallyhydrated uppermost mantle dehydrating under equilibrium conditions and producing earthquakes; and (4) anhydrous mantle lithosphere transforming sluggishly and aseismically to denser minerals. Fluid generated through dehydration reactions can move via at least three distinct flowpaths:percolationthroughlocal,transient,reaction-generatedhigh-permeabilityzones; flow through mode I cracks produced by the local stress state; and postseismic flow through fault zones. INDEX TERMS: 7218 Seismology: Lithosphere and upper mantle; 7230 Seismology: Seismicity and seismotectonics; 8123 Tectonophysics: Dynamics, seismotectonics; 8135 Tectonophysics: Evolution of the Earth: Hydrothermalsystems (8424); 3660 Mineralogyand Petrology: Metamorphicpetrology;