Showing papers by "Boston University published in 1993"

Strategic alignment: leveraging information technology for transforming organizations

Abstract: It is cleaaar that eventhough information technology (I/T) has evolved form its traditional orientation of administrative support toward a more strategic role within an organization, there is still a glaring lack of fundamental frameworks within which to understand the potential of I/T for tomorrow's organizations. In this paper, we develop a model for conceptualizing and directing the emerging area of strategic management of information technology. This model, termed the Strategic Allgnment Model, is defined in terms of four fundamental domains of strategic choice: business strategy, information technology strategy, organlzational infrastructure and processes, and information technology Infrastuvture and processes--each with its own underlying dimenslons. We illustrate the power of this model in terms of two fundamental characteristics fo strategic management: strategic fit (the interrelationships between external and internal components) and functional Integration (integration between business and functional domains). More specifically, we derive foru perspectives for gulding management practice in this Important area.

Recovery from mental illness: The guiding vision of the mental health service system in the 1990s.

Abstract: he implementation of deinstitutionalization in the 1960s and 1970s, and the increasing ascendance of the community support system concept and the practice of psychiatric rehabilitation in the 1980s, have laid the foundation for a new 1990s vision of service delivery for people who have mental illness. Recovery from mental illness is the vision that will guide the mental health system in this decade. This article outlines the fundamental services and assumptions of a recovery-oriented mental health system. As the recovery concept becomes better understood, it could have major implications for how future mental health systems are designed. The seeds of the recovery vision were sown in the aftermath of the era of deinstitutionalization. The failures in the implementation of the policy of deinstitutionalization confronted us with the fact that a person with severe mental illness wants and needs more than just symptom relief. People with severe T CHANGING TOWARD THE FUTURE

The American College of Rheumatology preliminary core set of disease activity measures for rheumatoid arthritis clinical trials. The Committee on Outcome Measures in Rheumatoid Arthritis Clinical Trials.

Abstract: Objective. To develop a set of disease activity measures for use in rheumatoid arthritis (RA) clinical trials, as well as to recommend specific methods for assessing each outcome measure. This is not intended to be a restrictive list, but rather, a core set of measures that should be included in all trials. Methods. We evaluated disease activity measures commonly used in RA trials, to determine which measures best met each of 5 types of validity: construct, face, content, criterion, and discriminant. The evaluation consisted of an initial structured review of the literature on the validity of measures, with an analysis of data obtained from clinical trials to fill in gaps in this literature. A committee of experts in clinical trials, health services research, and biostatistics reviewed the validity data. A nominal group process method was used to reach consensus on a core set of disease activity measures. This set was then reviewed and finalized at an international conference on outcome measures for RA clinical trials. The committee also selected specific ways to assess each outcome. Results. The core set of disease activity measures consists of a tender joint count, swollen joint count, patient's assessment of pain, patient's and physician's global assessments of disease activity, patient's assessment of physical function, and laboratory evaluation of 1 acute-phase reactant. Together, these measures sample the broad range of improvement in RA (have content validity), and all are at least moderately sensitive to change (have discriminant validity). Many of them predict other important long-term outcomes in RA, including physical disability, radiographic damage, and death. Other disease activity measures frequently used in clinical trials were not chosen for any one of several reasons, including insensitivity to change or duplication of information provided by one of the core measures (e.g., tender joint score and tender joint count) The committee also proposes specific ways of measuring each outcome. Conclusion. We propose a core set of outcome measures for RA clinical trials. We hope this will decrease the number of outcomes assessed and standardize outcomes assessments. Further, we hope that these measures will be found useful in long-term studies.

Open-loop and closed-loop control of posture: A random-walk analysis of center-of-pressure trajectories

Abstract: A new conceptual and theoretical framework for studying the human postural control system is introduced. Mathematical techniques from statistical mechanics are developed and applied to the analysis and interpretation of stabilograms. This work was based on the assumption that the act of maintaining an erect posture could be viewed, in part, as a stochastic process. Twenty-five healthy young subjects were studied under quite-standing conditions. Center-of-pressure (COP) trajectories were analyzed as one-dimensional and two-dimensional random walks. This novel approach led to the extraction of repeatable, physiologically meaningful parameters from stabilograms. It is shown that although individual stabilograms for a single subject were highly variable and random in appearance, a consistent, subject-specific pattern emerged with the generation of averaged stabilogram-diffusion plots (mean square COP displacement vs time interval). In addition, significant inter-subject differences were found in the calculated results. This suggests that the steady-state behavior of the control mechanisms involved in maintaining erect posture can be quite variable even amongst a population of age-matched, anthropometrically similar, healthy individuals. These posturographic analyses also demonstrated that COP trajectories could be modelled as fractional Brownian motion and that at least two control systems-a short-term mechanism and a long-term mechanism-were operating during quit standing. More specifically, the present results suggest that over short-term intervals open-loop control schemes are utilized by the postural control system, whereas over long-term intervals closed-loop control mechanisms are called into play. This work strongly supports the position that much can be learned about the functional organization of the postural control system by studying the steady-state behavior of the human body during periods of undisturbed stance.

On the self-similar nature of Ethernet traffic

Abstract: We demonstrate that Ethernet local area network (LAN) traffic is statistically self-similar, that none of the commonly used traffic models is able to capture this fractal behavior, and that such behavior has serious implications for the design, control, and analysis of high-speed, cell-based networks. Intuitively, the critical characteristic of this self-similar traffic is that there is no natural length of a "burst": at every time scale ranging from a few milliseconds to minutes and hours, similar-looking traffic bursts are evident; we find that aggregating streams of such traffic typically intensifies the self-similarity ("burstiness") instead of smoothing it.Our conclusions are supported by a rigorous statistical analysis of hundreds of millions of high quality Ethernet traffic measurements collected between 1989 and 1992, coupled with a discussion of the underlying mathematical and statistical properties of self-similarity and their relationship with actual network behavior. We also consider some implications for congestion control in high-bandwidth networks and present traffic models based on self-similar stochastic processes that are simple, accurate, and realistic for aggregate traffic.

Trinucleotide repeat length instability and age of onset in Huntington's disease

Abstract: The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

Long-range anticorrelations and non-Gaussian behavior of the heartbeat

Abstract: We find that the successive increments in the cardiac beat-to-beat intervals of healthy subjects display scale-invariant, long-range anticorrelations (up to 10 exp 4 heart beats). Furthermore, we find that the histogram for the heartbeat intervals increments is well described by a Levy (1991) stable distribution. For a group of subjects with severe heart disease, we find that the distribution is unchanged, but the long-range correlations vanish. Therefore, the different scaling behavior in health and disease must relate to the underlying dynamics of the heartbeat.

Computational neuroscience

Abstract: From the Publisher: The thirty original contributions in this book provide a working definition of "computational neuroscience" as the area in which problems lie simultaneously within computer science and neuroscience. They review this emerging field in historical and philosophical overviews and in stimulating summaries of recent results. Leading researchers address the structure of the brain and the computational problems associated with describing an understanding this structure a the synaptic, neural, map, and system levels. Eric L. Schwartz is Professor of Cognitive and Neural Systems at Boston University.

Untreated Blood Pressure Level Is Inversely Related to Cognitive Functioning: The Framingham Study

Abstract: It was hypothesized that blood pressure would be inversely related to cognitive functioning, if unconfounded with antihypertensive medication and measured over many occasions prior to neuropsychological testing. For stroke-free Framingham Study participants aged 55-88 years (n = 1,702), blood pressure levels were averaged over five biennial examinations (1956-1964) when few hypertensives were being treated, and examined in relation to neuropsychological tests administered between 1976 and 1978. With age, education, occupation, cigarette smoking, alcohol consumption, and gender controlled, blood pressure levels and chronicity of hypertension were inversely related to the composite score and measures of attention and memory. This was true for the full sample, for a subsample untreated during blood pressure measurement (n = 1,485), and for a subsample untreated throughout the entire study period (n = 1,038). For example, decline per 10 mmHg increment in blood pressure ranged from -0.04 to -0.07 standard score units (z) for the composite score. A negative finding previously was most likely due to blood pressure measurement concurrently with neuropsychological testing, or too few measurements. Hypertension-associated pathogenic processes may cause mild cognitive impairment, but other mechanisms need to be considered.

A Twin Study of Genetic and Environmental Contributions to Liability for Posttraumatic Stress Symptoms

Abstract: • We studied 4042 Vietnam era veteran monozygotic and dizygotic male twin pairs to determine the effects of heredity, shared environment, and unique environment on the liability for 15 self-reported posttraumatic stress disorder symptoms included in the symptom categories of reexperiencing the trauma, avoidance of stimuli related to the trauma, and increased arousal. Quantitative genetic analysis reveals that inheritance has a substantial influence on liability for all symptoms. Symptoms in the reexperiencing cluster and one symptom in the avoidance and numbing cluster are strongly associated with combat exposure, and monozygotic pairs are more highly concordant for combat exposure than dizygotic pairs. By fitting a bivariate genetic model, we show that there are significant genetic influences on symptom liability, even after adjusting for differences in combat exposure; genetic factors account for 13% to 30% of the variance in liability for symptoms in the reexperiencing cluster, 30% to 34% for symptoms in the avoidance cluster, and 28% to 32% for symptoms in the arousal cluster. There is no evidence that shared environment contributes to the development of posttraumatic stress disorder symptoms.

The effect of postmenopausal estrogen therapy on bone density in elderly women.

Abstract: Background Estrogen therapy prevents bone loss in postmenopausal women who take it early in the postmenopausal period. The risk of fracture is highest much later in life, however. We studied whether bone mass in elderly women was affected by earlier estrogen use and how long women needed to take estrogen for it to have a beneficial effect on bone density later in life. Methods In 1988 and 1989, we measured bone mineral density at the femur, spine, shaft of the radius, and ultradistal radius in 670 white women in the Framingham Study cohort (mean age, 76 years; range, 68 to 96). These women had been followed prospectively through menopause and had been asked repeatedly about estrogen therapy. After excluding women who began taking estrogen after a fracture, we investigated whether postmenopausal estrogen therapy affected bone density; in these analyses we adjusted for age, weight, height, cigarette smoking, physical activity, and age at menopause. Results A total of 212 women (31.6 percent) had received es...

Periconceptional folic acid exposure and risk of occurrent neural tube defects.

Abstract: Objectives. —A recent controlled trial has established that use of a 4-mg folic acid supplement before and during early pregnancy reduces the risk of recurrent neural tube defects (NTDs) by 72%. The present study was designed to determine whether folic acid also reduces the risk of first (occurrent) NTDs. Design. —Case-control study. Setting. —Tertiary and birth hospitals in metropolitan areas of Boston, Mass, Philadelphia, Pa, and Toronto, Ontario. Participants. —Mothers of 436 occurrent cases with NTDs and mothers of 2615 controls with other major malformations. Main Outcome Measures. —The prevalence of use of multivitamins containing folic acid was compared between mothers of cases and controls. Results. —The mothers of 17% of cases and 3% of controls reported knowledge of the folic acid—NTD hypothesis and were excluded from further analysis. For daily use of multivitamins containing folic acid in the periconceptional period (28 days before through 28 days after the last menstrual period), the relative risk (RR) (and 95% confidence interval) was 0.4 (0.2 to 0.6). The most commonly used dose of folic acid was 0.4 mg, and the RR estimate was 0.3 (95% confidence interval, 0.1 to 0.6). For dietary folate, there was a dose-related decline in risk according to the quintile of intake ( P for trend=.02). Conclusion. —These findings suggest that daily periconceptional intake of 0.4 mg of folic acid (the dose most commonly contained in over-the-counter multivitamin preparations) reduces the risk of occurrent NTDs by approximately 60%. A relatively high dietary intake of folate may also reduce the risk. ( JAMA . 1993;269:1257-1261)

Coupled Nonlinear Oscillators and the Symmetries of Animal Gaits

Abstract: Animal locomotion typically employs several distinct periodic patterns of leg movements, known as gaits. It has long been observed that most gaits possess a degree of symmetry. Our aim is to draw attention to some remarkable parallels between the generalities of coupled nonlinear oscillators and the observed symmetries of gaits, and to describe how this observation might impose constraints on the general structure of the neural circuits, i.e. central pattern generators, that control locomotion. We compare the symmetries of gaits with the symmetry-breaking oscillation patterns that should be expected in various networks of symmetrically coupled nonlinear oscillators. We discuss the possibility that transitions between gaits may be modeled as symmetry-breaking bifurcations of such oscillator networks. The emphasis is on general model-independent features of such networks, rather than on specific models. Each type of network generates a characteristic set of gait symmetries, so our results may be interpreted as an analysis of the general structure required of a central pattern generator in order to produce the types of gait observed in the natural world. The approach leads to natural hierarchies of gaits, ordered by symmetry, and to natural sequences of gait bifurcations. We briefly discuss how the ideas could be extended to hexapodal gaits.

A Short-Term Trial of Butyrate to Stimulate Fetal-Globin-Gene Expression in the β-Globin Disorders

Abstract: Background Fetal-globin (γ-globin) chains inhibit the polymerization of hemoglobin S (sickle hemoglobin) and can functionally substitute for the β-globin chains that are defective or absent in patients with the β-thalassemias. Identifying safe mechanisms to stimulate fetal-hemoglobin production is therefore of great interest. Previous studies have shown that administering butyrate selectively stimulates the promoter of the human fetal-globin gene and leads to increases in γ-globin-gene expression in the developing fetus, cultured cells, and animal models. Methods To determine whether butyrate can stimulate fetal-globin production in humans, we treated three patients (3 to 13 years old) with sickle cell anemia and three patients (7 to 27 years old) with β-thalassemia syndromes with a short course of intravenous infusions of arginine butyrate. The drug was infused continuously for either two or three weeks; the initial dose was 500 mg per kilogram of body weight per day. Globin-chain ratios, proportions of ...

Aligning Academic Task and Participation Status through Revoicing: Analysis of a Classroom Discourse Strategy

Abstract: “Revoicing” by teachers in classroom group conversations creates participant frameworks that facilitate students' “alignment” with academic tasks and their socialization to roles and identities in intellectual discourse. Three examples demonstrate the potential of “revoicing” to: (1) position students in differing alignments with propositions and allow them to claim or disclaim ownership of their position; (2) share reformulations in ways that credit students with teachers' warranted inferences; (3) scaffold and recast problem-solution strategies of non-native-language students.

Fear of Falling among the Community-Dwelling Elderly:

Abstract: To assess the incidence of falls and the prevalence, intensity, and covariates of fear of falling among community-dwelling elderly, the authors surveyed a random sample of 196 residents (> or = 58 years of age) of housing developments for the elderly in Brookline and Plymouth, Massachusetts. Forty-three percent reported having fallen in recent years, 28% in the last year. Of those who had fallen within the year prior to the interview, 65% reported injury, 44% sought medical attention, and 15% required hospitalization as a consequence of their fall(s). Fear of falling ranked first when compared to other common fears (i.e., fear of robbery, financial fears). Self-rated health status and experience of previous falls were significantly associated with fear of falling. Further analysis suggests that fear of falling may affect social interaction, independent of risks for falling.

A mutation in CFTR produces different phenotypes depending on chromosomal background

Abstract: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene but the association between mutation (genotype) and disease presentation (phenotype) is not straightforward. We have been investigating whether variants in the CFTR gene that alter splicing efficiency of exon 9 can affect the phenotype produced by a mutation. A missense mutation, R117H, which has been observed in three phenotypes, was found to occur on two chromosome backgrounds with intron 8 variants that have profoundly different effects upon splicing efficiency. A close association is shown between chromosome background of the R117H mutation and phenotype. These findings demonstrate that the genetic context in which a mutation occurs can play a significant role in determining the type of illness produced.

Nutrition and health risks in the elderly: the nutrition screening initiative.

Abstract: OBJECTIVES. The Nutrition Screening Initiative is a national collaborative effort committed to the identification and treatment of nutritional problems in older persons. METHODS. A 14-item checklist of characteristics associated with nutritional status was administered to a random sample of Medicare beneficiaries, aged 70 years and older, in New England. Regression analysis was used to derive item weights that would predict poor nutrient intakes and low perceived health status. Sensitivity and specificity values were reviewed to define low, moderate, and high nutritional risk scores. RESULTS. A revised checklist containing 10 yes/no items was adopted. Scores of 6 or more points defined persons at high nutritional risk. Twenty-four percent of the Medicare population was estimated to be at high nutritional risk according to the checklist. Among those in the high-risk group, 56% perceived their health to be "fair" or "poor" and 38% had dietary intakes below 75% of the recommended dietary allowances for three...

Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy.

Abstract: The nuclear pore complex spans the nuclear envelope and functions as a macromolecular transporter in the ATP-dependent process of nucleocytoplasmic transport. In this report, we present three dimensional (3D) structures for both membrane-associated and detergent-extracted Xenopus NPCs, imaged in frozen buffers by cryo-electron microscopy. A comparison of the differing configurations present in the 3D maps suggests that the spokes may possess an intrinsic conformational flexibility. When combined with recent data from a 3D map of negatively stained NPCs (Hinshaw, J. E., B. O. Carragher, and R. A. Milligan. 1992. Cell. 69:1133-1141), these observations suggest a minimal domain model for the spoke-ring complex which may account for the observed plasticity of this assembly. Moreover, lumenal domains in adjacent spokes are interconnected by radial arm dimers, forming a lumenal ring that may be responsible for anchoring the NPC within the nuclear envelope pore. Importantly, the NPC transporter is visualized as a centrally tapered cylinder that spans the entire width of the NPC, in a direction normal to the nuclear envelope. The central positioning, tripartite structure, and hollow nature of the transporter suggests that it may form a macromolecular transport channel, with a globular gating domain at each end. Finally, the packing of the transporter within the spokes creates a set of eight internal channels that may be responsible, in part, for the diffusion of ions and small molecules across the nuclear envelope.

Rapid synchronization through fast threshold modulation

Abstract: Synchronization properties of locally coupled neural oscillators were investigated analytically and by computer simulation. When coupled in a manner that mimics excitatory chemical synapses, oscillators having more than one time scale (relaxation oscillators) are shown to approach synchrony using mechanisms very different from that of oscillators with a more sinusoidal waveform. The relaxation oscillators make critical use of fast modulations of their thresholds, leading to a rate of synchronization relatively independent of coupling strength within some basin of attraction; this rate is faster for oscillators that have conductance-based features than for neural caricatures such as the FitzHugh-Nagumo equations that lack such features. Computer simulations of one-dimensional arrays show that oscillators in the relaxation regime synchronize much more rapidly than oscillators with the same equations whose parameters have been modulated to yield a more sinusoidal waveform. We present a heuristic explanation of this effect based on properties of the coupling mechanisms that can affect the way the synchronization scales with array length. These results suggest that the emergent synchronization behavior of oscillating neural networks can be dramatically influenced by the intrinsic properties of the network components. Possible implications for perceptual feature binding and attention are discussed.

Temporal Lobe Regions on Magnetic Resonance Imaging Identify Patients With Early Alzheimer's Disease

Abstract: • Objective. —The goal of the study was to examine the volume of selected brain regions in a group of mildly impaired patients with Alzheimer's disease (AD). Five regions were selected for analysis, all of which have been reported to show substantial change in the majority of patients with AD at some time in the course of disease. Design. —Case-control study with the experimenter "blinded." Setting. —Hospital-based magnetic resonance imaging center. Participants. —Fifteen subjects, eight patients with the diagnosis of probable dementia of the Alzheimer type made in concordance with National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria and seven age-matched healthy control subjects. Results. —Three of the volumetric measures were significantly different between patients with AD and controls: the hippocampus, the temporal horn of the lateral ventricles, and the temporal lobe. Two of the measures did not significantly differentiate patients with AD and controls: the amygdala and the basal forebrain. A discriminant function analysis demonstrated that a linear combination of the volumes of the hippocampus and the temporal horn of the lateral ventricles differentiated 100% of the patients and controls from one another. Conclusions. —The results suggest that the hippocampus and the temporal horn of the lateral ventricles may be useful as antemortem markers of AD in mildly impaired patients.

Positional sequencing by hybridization

Abstract: This invention is directed to methods and reagents useful for sequencing nucleic acid targets utilizing sequencing by hybridization technology comprising probes, arrays of probes and methods whereby sequence information is obtained rapidly and efficiently in discrete packages. That information can be used for the detection, identification, purification and complete or partial sequencing of a particular target nucleic acid. When coupled with a ligation step, these methods can be performed under a single set of hybridization conditions. The invention also relates to the replication of probe arrays and methods for making and replicating arrays of probes which are useful for the large scale manufacture of diagnostic aids used to screen biological samples for specific target sequences. Array created using PCR technology may comprise probes with 5'-and/or 3'-overhangs.