Showing papers by "Tufts University published in 2005"

Practice Guidelines for the Diagnosis and Management of Skin and Soft-Tissue Infections

Abstract: EXECUTIVE SUMMARYSoft-tissue infections are common, generally of mild tomodest severity, and are easily treated with a variety ofagents. An etiologic diagnosis of simple cellulitis is fre-quently difficult and generally unnecessary for patientswith mild signs and symptoms of illness. Clinical as-sessment of the severity of infection is crucial, and sev-eral classification schemes and algorithms have beenproposed to guide the clinician [1]. However, mostclinical assessments have been developed from eitherretrospective studies or from an author’s own “clinicalexperience,” illustrating the need for prospectivestudieswith defined measurements of severity coupled to man-agement issues and outcomes.Until then, it is the recommendation of this com-mittee that patients with soft-tissue infection accom-panied by signs and symptoms of systemic toxicity (e.g.,fever or hypothermia, tachycardia [heart rate,

Estimates of optimal vitamin D status

Abstract: Vitamin D has captured attention as an important determinant of bone health, but there is no common definition of optimal vitamin D status. Herein, we address the question: What is the optimal circulating level of 25-hydroxyvitamin D [25(OH)D] for the skeleton? The opinions of the authors on the minimum level of serum 25(OH)D that is optimal for fracture prevention varied between 50 and 80 nmol/l. However, for five of the six authors, the minimum desirable 25(OH)D concentration clusters between 70 and 80 nmol/l. The authors recognize that the average older man and woman will need intakes of at least 20 to 25 mcg (800 to 1,000 IU) per day of vitamin D3 to reach a serum 25(OH)D level of 75 nmol/l. Based on the available evidence, we believe that if older men and women maintain serum levels of 25(OH)D that are higher than the consensus median threshold of 75 nmol/l, they will be at lower risk of fracture.

Cystatin C and the risk of death and cardiovascular events among elderly persons.

Abstract: Background Cystatin C is a serum measure of renal function that appears to be independent of age, sex, and lean muscle mass. We compared creatinine and cystatin C levels as predictors of mortality from cardiovascular causes and from all causes in the Cardiovascular Health Study, a cohort study of elderly persons living in the community. Methods Creatinine and cystatin C were measured in serum samples collected from 4637 participants at the study visit in 1992 or 1993; follow-up continued until June 30, 2001. For each measure, the study population was divided into quintiles, with the fifth quintile subdivided into thirds (designated 5a, 5b, and 5c). Results Higher cystatin C levels were directly associated, in a dose–response manner, with a higher risk of death from all causes. As compared with the first quintile, the hazard ratios (and 95 percent confidence intervals) for death were as follows: second quintile, 1.08 (0.86 to 1.35); third quintile, 1.23 (1.00 to 1.53); fourth quintile, 1.34 (1.09 to 1.66);...

Positive Youth Development, Participation in Community Youth Development Programs, and Community Contributions of Fifth-Grade Adolescents: Findings From the First Wave Of the 4-H Study of Positive Youth Development

Abstract: The 4-H Study of Positive Youth Development (PYD), a longitudinal investigation of a diverse sample of 1,700 fifth graders and 1,117 of their parents, tests developmental contextual ideas linking PYD, youth contributions, and participation in community youth development (YD) programs, representing a key ecological asset. Using data from Wave 1 of the study, structural equation modeling procedures provided evidence for five firstorder latent factors representing the “Five Cs” of PYD (competence, confidence, connection, character, and caring) and for their convergence on a second-order PYD latent construct. A theoretical construct, youth contribution, was also created and examined. Both PYD and YD program participation independently related to contribution. The importance of longitudinal analyses for extending the present results is discussed.

Molecular and cellular basis of cardiovascular gender differences

Abstract: Cardiovascular diseases (CVDs), the major cause of morbidity and mortality for both men and women, occur uncommonly in premenopausal women, but their incidence rises sharply after the menopausal transition. Cardiovascular gender differences are apparent long before CVDs appear in men and women, and improved understanding of the biology underlying these differences has the potential to advance the diagnosis and treatment of CVDs in both sexes. This review considers gender differences in the molecular and cellular physiology of the heart and blood vessels in health and disease, highlighting understudied areas that can help resolve the current controversy regarding hormone replacement therapy and improve cardiovascular health in women.

Cytokinesis failure generating tetraploids promotes tumorigenesis in p53 -null cells

Abstract: A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies. Here we test this idea by transiently blocking cytokinesis in p53-null (p53-/-) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8-30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models. Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53-/- MMECs.

The Death Toll from Natural Disasters: The Role of Income, Geography, and Institutions

Abstract: Using a new data set on annual deaths from disasters in 73 nations from 1980 to 2002, this paper tests several hypotheses concerning natural-disaster mitigation. Though richer nations do not experience fewer natural disasters than poorer nations, richer nations do suffer less death from disaster. Economic development provides implicit insurance against nature's shocks. Democracies and nations with higher-quality institutions suffer less death from natural disaster. Because climate change is expected to increase the frequency of natural disasters such as floods, these results have implications for the incidence of global warming.

Collecting baseline corticosterone samples in the field: is under 3 min good enough?

Abstract: Evaluating corticosterone (CORT) responses to stress in free-living vertebrates requires knowing the unstressed titers prior to capture. Based upon laboratory data, the assumption has been that samples collected in less than 3 min of capture will reflect these unstressed concentrations. This assumption was tested for six species using samples collected from 945 individuals at 0-6 min after capture. Samples were from five avian species trapped at multiple times of year and one reptilian species, comprising a total of 14 different data sets for comparisons. For seven of 14 data sets, including five species, there was no significant increase in corticosterone titers within 3 min of capture. In six of the 14 data sets, corticosterone titers increased significantly after 2 min, and in one data set, the increase started at 1.5 min. In all seven of the cases showing an increase before 3 min, however, corticosterone titers from the time of increase to 3 min were significantly lower than titers after 30 min of restraint stress. These results indicate a high degree of confidence for these species that samples collected in less than 2 min reflect unstressed (baseline) concentrations, and that samples collected from 2-3 min also will likely reflect baseline concentrations but at worst are near baseline.

A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder.

Abstract: Background: Previous functional neuroimaging studies have demonstrated exaggerated amygdala responses and diminished medial prefrontal cortex responses during the symptomatic state in posttraumatic stress disorder (PTSD). Objectives: To determine whether these abnormalities also occur in response to overtly presented affective stimuli unrelated to trauma; to examine the functional relationship between the amygdala and medial prefrontal cortex and their relationship to PTSD symptom severity in response to these stimuli; and to determine whether responsivity of these regions habituates normally across repeated stimulus presentations in PTSD.

First-trimester or second-trimester screening, or both, for down's syndrome

Abstract: background It is uncertain how best to screen pregnant women for the presence of fetal Down’s syndrome: to perform first-trimester screening, to perform second-trimester screening, or to use strategies incorporating measurements in both trimesters. methods Women with singleton pregnancies underwent first-trimester combined screening (measurement of nuchal translucency, pregnancy-associated plasma protein A [PAPP-A], and the free beta subunit of human chorionic gonadotropin at 10 weeks 3 days through 13 weeks 6 days of gestation) and second-trimester quadruple screening (measurement of alpha-fetoprotein, total human chorionic gonadotropin, unconjugated estriol, and inhibin A at 15 through 18 weeks of gestation). We compared the results of stepwise sequential screening (risk results provided after each test), fully integrated screening (single risk result provided), and serum integrated screening (identical to fully integrated screening, but without nuchal translucency). results First-trimester screening was performed in 38,167 patients; 117 had a fetus with Down’s syndrome. At a 5 percent false positive rate, the rates of detection of Down’s syndrome were as follows: with first-trimester combined screening, 87 percent, 85 percent, and 82 percent for measurements performed at 11, 12, and 13 weeks, respectively; with second-trimester quadruple screening, 81 percent; with stepwise sequential screening, 95 percent; with serum integrated screening, 88 percent; and with fully integrated screening with first-trimester measurements performed at 11 weeks, 96 percent. Paired comparisons found significant differences between the tests, except for the comparison between serum integrated screening and combined screening. conclusions First-trimester combined screening at 11 weeks of gestation is better than secondtrimester quadruple screening but at 13 weeks has results similar to second-trimester quadruple screening. Both stepwise sequential screening and fully integrated screening have high rates of detection of Down’s syndrome, with low false positive rates.

Monoclonal antibody successes in the clinic

Abstract: Most monoclonal antibodies in clinical trials are owned by small biotech companies. But with blockbuster-sized revenues and approval rates higher than those for small-molecule drugs, that all may be set to change.

Update on the Paris classification of superficial neoplastic lesions in the digestive tract

Abstract: Background and Study Aims: Neoplastic lesions in the digestive-tract mucosa are termed superficial when the depth of invasion is limited to the mucosa and submucosa. The endoscopic appearance has a predictive value for invasion into the submucosa, which is critical for the risk of nodal metastases. Materials and Methods: The endoscopic morphology of superficial lesions can be assessed with a standard video endoscope after spraying of a dye - an iodine-potassium iodide solution for the stratified squamous epithelium, or an indigo carmine solution for the columnar epithelium. In 2002, a workshop was held in Paris to explore the relevance of the Japanese classification. The conclusions were revised in 2003 in Osaka in relation to the definition of the subtypes used in endoscopy and the evaluation of the depth of invasion into the submucosa. In Japan, the description of advanced cancer in the digestive-tract mucosa using types 1 -4 is supplemented by a type 0 when the endoscopic appearance is that of a superficial lesion. Type 0 is divided into three categories: protruding (0-1), nonprotruding and nonexcavated (0-11), and excavated (0-III). Type 0-II lesions are then subdivided into slightly elevated (IIa), flat (IIb), or depressed (IIc). Nonprotruding depressed lesions are associated with a higher risk of submucosal invasion. After endoscopic resection, invasion into the submucosa is an important criterion for the necessity of additional surgical resection. Micrometer analysis of the depth of invasion in the specimen is more precise, and distinct cut-off limits have been established in the esophagus, stomach, and large bowel. Conclusions: The morphology of superficial and nonprotruding neoplastic lesions is relevant to the prognosis. Following endoscopic detection, the lesions are analyzed using chromoendoscopy and assigned a subtype of the type 0 classification. The choice between endoscopicorsurgical treatment is based on this description.

Acute heart failure syndromes: current state and framework for future research.

Abstract: Acute heart failure syndromes (AHFS) poses unique diagnostic and management challenges. This syndrome has recently received attention from researchers, clinicians, regulatory agencies, and the pharmaceutical industry. However, there is no consensus on its definition, epidemiology, pathophysiology, appropriate therapeutic options, and directions for future research. This document is the result of the First and Second International Workshop on Acute Heart Failure Syndrome that took place in May 2004 and April 2005. At these workshops, a selected group of physician scientists, epidemiologists, clinicians, regulatory and governmental funding agencies, and industry representatives from North and South America and Europe convened to develop a platform for future investigative approaches and management of AHFS. Subsequently, emergency physicians, who play a pivotal role in the early management of AHFS, contributed to this document. AHFS is defined as gradual or rapid change in heart failure (HF) signs and symptoms resulting in a need for urgent therapy. These symptoms are primarily the result of severe pulmonary congestion due to elevated left ventricular (LV) filling pressures (with or without low cardiac output). AHFS can occur in patients with preserved or reduced ejection fraction (EF). Concurrent cardiovascular conditions such as coronary heart disease (CHD), hypertension, valvular heart disease, atrial arrhythmias, and/or noncardiac conditions (including renal dysfunction, diabetes, anemia) are often present and may precipitate or contribute to the pathophysiology of this syndrome.1–3 HF hospitalizations have risen steadily, with >1 million in 2004 in the United States4; a similar number has been reported in Europe. In the United States, it is estimated that these hospitalizations account for >75% of the 46 billion dollars spent each year on the care of HF patients.4 Although much has been accomplished in the management of chronic HF, the absence of evidence-based clinical practice guidelines for AHFS is striking in comparison to …

Positive Youth Development A View of the Issues

Abstract: The positive youth development (PYD) perspective is a strength-based conception of adolescence. Derived from developmental systems theory, the perspective stressed that PYD emerges when the potential plasticity of human development is aligned with developmental assets. The research reported in this special issue, which is derived from collaborations among multiple university and community-based laboratories, reflects and extends past theory and research by documenting empirically (a) the usefulness of applying this strength-based view of adolescent development within diverse youth and communities; (b) the adequacy of conceptualizing PYD through Five Cs (competence, confidence, connection, character, and caring); (c) the individual and ecological developmental assets associated with PYD; and (d) implications for community programs and social policies pertinent to youth.

American Pain Society recommendations for improving the quality of acute and cancer pain management: American Pain Society quality of care task force

Abstract: Background The American Pain Society (APS) set out to revise and expand its 1995 Quality Improvement Guidelines for the Treatment of Acute Pain and Cancer Pain and to facilitate improvements in the quality of pain management in all care settings. Methods Eleven multidisciplinary members of the APS with expertise in quality improvement or measurement participated in the update. Five experts from organizations that focus on health care quality reviewed the final recommendations. MEDLINE and Cumulative Index to Nursing and Allied Health Literature databases were searched (1994-2004) to identify articles on pain quality measurement and quality improvement published after the development of the 1995 guidelines. The APS task force revised and expanded recommendations on the basis of the systematic review of published studies. The more than 3000 members of the APS were invited to provide input, and the 5 experts provided additional comments. The task force synthesized reviewers’ comments into the final set of recommendations. Results The recommendations specify that all care settings formulate structured, multilevel systems approaches (sensitive to the type of pain, population served, and setting of care) that ensure prompt recognition and treatment of pain, involvement of patients and families in the pain management plan, improved treatment patterns, regular reassessment and adjustment of the pain management plan as needed, and measurement of processes and outcomes of pain management. Conclusion Efforts to improve the quality of pain management must move beyond assessment and communication of pain to implementation and evaluation of improvements in pain treatment that are timely, safe, evidence based, and multimodal.

Heterogeneity testing in meta-analysis of genome searches.

Abstract: Genome searches for identifying susceptibility loci for the same complex disease often give inconclusive or inconsistent results. Genome Search Meta-analysis (GSMA) is an established non-parametric method to identify genetic regions that rank high on average in terms of linkage statistics (e.g., lod scores) across studies. Meta-analysis typically aims not only to obtain average estimates, but also to quantify heterogeneity. However, heterogeneity testing between studies included in GSMA has not been developed yet. Heterogeneity may be produced by differences in study designs, study populations, and chance, and the extent of heterogeneity might influence the conclusions of a meta-analysis. Here, we propose and explore metrics that indicate the extent of heterogeneity for specific loci in GSMA based on Monte Carlo permutation tests. We have also developed software that performs both the GSMA and the heterogeneity testing. To illustrate the concept, the proposed methodology was applied to published data from meta-analyses of rheumatoid arthritis (4 scans) and schizophrenia (20 scans). In the first meta-analysis, we identified 11 bins with statistically low heterogeneity and 8 with statistically high heterogeneity. The respective numbers were 9 and 6 for the schizophrenia meta-analysis. For rheumatoid arthritis, bins 6.2 (the HLA region that is a well-documented susceptibility locus for the disease) and 16.3 (16q12.2-q23.1) had both high average ranks and low between-study heterogeneity. For schizophrenia, this was seen for bin 3.2 (3p25.3-p22.1) and heterogeneity was still significantly low after adjusting for its high average rank. Concordance was high between the proposed metrics and between weighted and unweighted analyses. Data from genome searches should be synthesized and interpreted considering both average ranks and heterogeneity between studies.

Inflammation-induced lymphangiogenesis in the cornea arises from CD11b-positive macrophages

Abstract: In the inflamed cornea, there is a parallel outgrowth of blood and lymphatic vessels into the normally avascular cornea. We tested whether adaptive and/or innate immune cells were actively involved in the genesis of new lymphatic vessels. Our results indicate that innate immune cells (CD11b+ macrophages, but not CD11c+ dendritic cells) physically contributed to lymphangiogenesis under pathological conditions and that bone marrow–derived CD11b+ macrophages expressed lymphatic endothelial markers such as LYVE-1 and Prox-1 under inflamed conditions in the corneal stromata of mice. Furthermore, blood vascular endothelial cells that expressed the Tie2 promoter did not contribute to newly formed lymphatic vessels under inflamed conditions. Our in vitro experiments demonstrated that CD11b+ macrophages alone were capable of forming tube-like structures that expressed markers of lymphatic endothelium such as LYVE-1 and podoplanin. The novel finding that CD11b+ macrophages are critical for the development of inflammation-dependent lymphangiogenesis in the eye suggests a new mechanism of lymphangiogenesis.

Physical activity and sedentary behavior: a review of longitudinal studies of weight and adiposity in youth.

Abstract: To review the published prospective observational studies of the relationship of physical activity and sedentary behavior with the development of overweight and adiposity, with an emphasis on methodologic issues. Sample size, population studied, length of follow-up, assessment of exposure (physical activity, inactivity, or sedentary behavior), assessment of outcome (relative weight, overweight, % body fatness, adiposity), statistical approach, and main findings were extracted, summarized, and key methodological issues highlighted. In total, 17 studies of physical activity and 15 studies of inactivity/sedentary behavior were identified; as these were not mutually exclusive, 20 unique studies were reviewed. Results were mixed, with most studies showing an inverse association of physical activity with weight or fatness outcomes and/or a direct association of inactivity/sedentary behavior with weight or fatness outcomes. The effects identified were generally of small magnitude. Imprecise measurement of activity exposures likely weakens the observed relationships. Most studies used a pre–post design and had limited duration of follow-up (≤2 y). Studies with longer and more frequent follow-up did not always use the most advantageous statistical approach. On balance, the available evidence from prospective observational studies suggests that increased physical activity and decreased sedentary behavior are protective against relative weight and fatness gains over childhood and adolescence. In addition to improved measurement methods, longer and more frequent follow-up as well as truly longitudinal analysis methods would help establish these important prevention and intervention targets, and identify subgroups or development periods where interventions would likely be effective.

Macular Segmentation with Optical Coherence Tomography

Abstract: Purpose To develop a software algorithm to perform automated segmentation of retinal layer structures on linear macular optical coherence tomography (StratusOCT; Carl Zeiss Meditec, Inc., Dublin, CA) scan images and to test its performance in discriminating normal from glaucomatous eyes in comparison with conventional circumpapillary nerve fiber layer (cpNFL) thickness measurement.

Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction

Abstract: We have identified a subpopulation of stem cells within adult human BM, isolated at the single-cell level, that self-renew without loss of multipotency for more than 140 population doublings and exhibit the capacity for differentiation into cells of all 3 germ layers. Based on surface marker expression, these clonally expanded human BM-derived multipotent stem cells (hBMSCs) do not appear to belong to any previously described BM-derived stem cell population. Intramyocardial transplantation of hBMSCs after myocardial infarction resulted in robust engraftment of transplanted cells, which exhibited colocalization with markers of cardiomyocyte (CMC), EC, and smooth muscle cell (SMC) identity, consistent with differentiation of hBMSCs into multiple lineages in vivo. Furthermore, upregulation of paracrine factors including angiogenic cytokines and antiapoptotic factors, and proliferation of host ECs and CMCs, were observed in the hBMSC-transplanted hearts. Coculture of hBMSCs with CMCs, ECs, or SMCs revealed that phenotypic changes of hBMSCs result from both differentiation and fusion. Collectively, the favorable effect of hBMSC transplantation after myocardial infarction appears to be due to augmentation of proliferation and preservation of host myocardial tissues as well as differentiation of hBMSCs for tissue regeneration and repair. To our knowledge, this is the first demonstration that a specific population of multipotent human BM-derived stem cells can induce both therapeutic neovascularization and endogenous and exogenous cardiomyogenesis.

Water‐Stable Silk Films with Reduced β‐Sheet Content

Abstract: Silk fibers have outstanding mechanical properties. These fibers are insoluble in organic solvents and water, are biocompatible, and exhibit slow biodegradation in vitro and in vivo due to the hydrophobic nature of the protein and the presence of a high content of β-sheet structure. Regenerated silk fibroin can be processed into a variety of materials normally stabilized by the induction of β-sheet formation through the use of solvents or by physical stretching. To extend the biomaterial utility of silk proteins, options to form water-stable silk-based materials with reduced β-sheet formation would be desirable. To address this need for more rapidly degradable silk biomaterials, we report the preparation of water-stable films from regenerated silk fibroin solutions, with reduced β-sheet content. The keys to this process are the preparation of concentrated (8 % by weight) aqueous solutions of fibroin and a subsequent water-based annealing procedure. These new materials degrade more rapidly due to the reduced β-sheet content, as determined in vitro via enzymatic hydrolysis, yet support human adult stem-cell expansion in vitro in a similar or improved fashion to the crystallized proteins in film form. These new silk-based materials extend the range of biomaterial properties that can be generated from this unique family of proteins.