Showing papers by "Brown University published in 2001"

Osteoporosis prevention, diagnosis, and therapy

Abstract: OBJECTIVES To clarify the factors associated with prevention, diagnosis, and treatment of osteoporosis, and to present the most recent information available in these areas. PARTICIPANTS From March 27-29, 2000, a nonfederal, nonadvocate, 13-member panel was convened, representing the fields of internal medicine, family and community medicine, endocrinology, epidemiology, orthopedic surgery, gerontology, rheumatology, obstetrics and gynecology, preventive medicine, and cell biology. Thirty-two experts from these fields presented data to the panel and an audience of 699. Primary sponsors were the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institutes of Health Office of Medical Applications of Research. EVIDENCE MEDLINE was searched for January 1995 through December 1999, and a bibliography of 2449 references provided to the panel. Experts prepared abstracts for presentations with relevant literature citations. Scientific evidence was given precedence over anecdotal experience. CONSENSUS PROCESS The panel, answering predefined questions, developed conclusions based on evidence presented in open forum and the literature. The panel composed a draft statement, which was read and circulated to the experts and the audience for public discussion. The panel resolved conflicts and released a revised statement at the end of the conference. The draft statement was posted on the Web on March 30, 2000, and updated with the panel's final revisions within a few weeks. CONCLUSIONS Though prevalent in white postmenopausal women, osteoporosis occurs in all populations and at all ages and has significant physical, psychosocial, and financial consequences. Risks for osteoporosis (reflected by low bone mineral density [BMD]) and for fracture overlap but are not identical. More attention should be paid to skeletal health in persons with conditions associated with secondary osteoporosis. Clinical risk factors have an important but poorly validated role in determining who should have BMD measurement, in assessing fracture risk, and in determining who should be treated. Adequate calcium and vitamin D intake is crucial to develop optimal peak bone mass and to preserve bone mass throughout life. Supplementation with these 2 nutrients may be necessary in persons not achieving recommended dietary intake. Gonadal steroids are important determinants of peak and lifetime bone mass in men, women, and children. Regular exercise, especially resistance and high-impact activities, contributes to development of high peak bone mass and may reduce risk of falls in older persons. Assessment of bone mass, identification of fracture risk, and determination of who should be treated are the optimal goals when evaluating patients for osteoporosis. Fracture prevention is the primary treatment goal for patients with osteoporosis. Several treatments have been shown to reduce the risk of osteoporotic fractures, including those that enhance bone mass and reduce the risk or consequences of falls. Adults with vertebral, rib, hip, or distal forearm fractures should be evaluated for osteoporosis and given appropriate therapy.

Unsupervised Learning by Probabilistic Latent Semantic Analysis

Abstract: This paper presents a novel statistical method for factor analysis of binary and count data which is closely related to a technique known as Latent Semantic Analysis. In contrast to the latter method which stems from linear algebra and performs a Singular Value Decomposition of co-occurrence tables, the proposed technique uses a generative latent class model to perform a probabilistic mixture decomposition. This results in a more principled approach with a solid foundation in statistical inference. More precisely, we propose to make use of a temperature controlled version of the Expectation Maximization algorithm for model fitting, which has shown excellent performance in practice. Probabilistic Latent Semantic Analysis has many applications, most prominently in information retrieval, natural language processing, machine learning from text, and in related areas. The paper presents perplexity results for different types of text and linguistic data collections and discusses an application in automated document indexing. The experiments indicate substantial and consistent improvements of the probabilistic method over standard Latent Semantic Analysis.

Evolution of Asian monsoons and phased uplift of the Himalaya–Tibetan plateau since Late Miocene times

Abstract: The climates of Asia are affected significantly by the extent and height of the Himalayan mountains and the Tibetan plateau1,2,3,4 Uplift of this region began about 50 Myr ago, and further significant increases in altitude of the Tibetan plateau are thought to have occurred about 10–8 Myr ago4,5, or more recently However, the climatic consequences of this uplift remain unclear Here we use records of aeolian sediments from China6,7 and marine sediments from the Indian8,9,10 and North Pacific oceans11 to identify three stages of evolution of Asian climates: first, enhanced aridity in the Asian interior and onset of the Indian and east Asian monsoons, about 9–8 Myr ago; next, continued intensification of the east Asian summer and winter monsoons, together with increased dust transport to the North Pacific Ocean11, about 36–26 Myr ago; and last, increased variability and possible weakening of the Indian and east Asian summer monsoons and continued strengthening of the east Asian winter monsoon since about 26 Myr ago The results of a numerical climate-model experiment, using idealized stepwise increases of mountain–plateau elevation, support the argument that the stages in evolution of Asian monsoons are linked to phases of Himalaya–Tibetan plateau uplift and to Northern Hemisphere glaciation

A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function.

Abstract: The Drosophila melanogaster gene insulin-like receptor (InR) is homologous to mammalian insulin receptors as well as to Caenorhabditis elegans daf-2, a signal transducer regulating worm dauer formation and adult longevity. We describe a heteroallelic, hypomorphic genotype of mutant InR, which yields dwarf females with up to an 85% extension of adult longevity and dwarf males with reduced late age-specific mortality. Treatment of the long-lived InR dwarfs with a juvenile hormone analog restores life expectancy toward that of wild-type controls. We conclude that juvenile hormone deficiency, which results from InR signal pathway mutation, is sufficient to extend life-span, and that in flies, insulin-like ligands nonautonomously mediate aging through retardation of growth or activation of specific endocrine tissue.

A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations

Abstract: An important quality of meta-analytic models for research synthesis is their ability to account for both within- and between-study variability. Currently available meta-analytic approaches for studies of diagnostic test accuracy work primarily within a fixed-effects framework. In this paper we describe a hierarchical regression model for meta-analysis of studies reporting estimates of test sensitivity and specificity. The model allows more between- and within-study variability than fixed-effect approaches, by allowing both test stringency and test accuracy to vary across studies. It is also possible to examine the effects of study specific covariates. Estimates are computed using Markov Chain Monte Carlo simulation with publicly available software (BUGS). This estimation method allows flexibility in the choice of summary statistics. We demonstrate the advantages of this modelling approach using a recently published meta-analysis comparing three tests used to detect nodal metastasis of cervical cancer.

The home environments of children in the United States part I: variations by age, ethnicity, and poverty status.

Abstract: Although measures of the home environment have gained wide acceptance in the child development literature, what constitutes the “average” or “typical” home environment in the United States, and how this differs across ethnic groups and poverty status is not known. Item-level data from the National Longitudinal Survey of Youth on four age-related versions of the Home Observation for Measurement of the Environment–Short Form (HOME-SF) from five biennial assessments (1986–1994) were analyzed for the total sample and for four major ethnic groups: European Americans, Asian Americans, African Americans, and Hispanic Americans. The percentages of homes receiving credit on each item of all four versions of the HOME-SF are described. For the majority of items at all four age levels differences between poor and nonpoor families were noted. Differences were also obtained among African American, European American, and Hispanic American families, but the magnitude of the effect for poverty status was greater than for ethnicity, and usually absorbed most of the ethnic group effects on HOME-SF items. For every item at every age, the effects of poverty were proportional across European American, African American, and Hispanic American groups.

Marshall's Scale Economies

Abstract: In this paper, using panel data, I estimate plant level production functions that include variables that allow for two types of scale externalities which plants experie nce in their local industrial environments. First are externalities from other plants in the same industry locally, usually called localization economies or, in a dynamic context, Marshall, Arrow, Romer [MAR] economies. Second are externalities from the scale or diversity of local economic activity outside the own industry involving some type of cross- fertilization, usually called urbanization economies or, in a dynamic context, Jacobs economies. Estimating production functions for plants in high tech industries and in capital goods, or machinery industries, I find that local own industry scale externalities, as measured specifically by the count of other own industry plants locally, have strong productivity effects in high tech but not machinery industries. I find evidence that single plant firms both benefit more from and generate greater external benefits than corporate plants. On timing, I find evidence that high tech single plant firms benefit from the scale of past own industry activity, as well as current activity. I find no evidence of urbanization economies from the diversity of local economic activity outside the own industry and limited evidence of urbanization economies from the overall scale of local economic activity.

Competition, Imitation and Growth with Step-by-Step Innovation

Abstract: Is more intense product market competition and imitation good or bad for growth? This question is addressed in the context of an endogenous growth model with "step-by-step" innovations, in which technological laggards must first catch up with the leading-edge technology before battling for technological leadership in the future. In contrast to earlier Schumpeterian models in which innovations are always made by outsider firms who earn no rents if they fail to innovate and become monopolies if they do innovate, here we find: first, that the usual Schumpeterian effect of more intense product market competition (PMC) is almost always outweighed by the increased incentive for firms to innovate in order to escape competition, so that PMC has a positive effect on growth; second, that a little imitation is almost always growth-enhancing, as it promotes more frequent neck-and-neck competition, but too much imitation is unambiguously growth-reducing. The model thus points to complementary roles for competition (anti-trust) policy and patent policy.

Mouse type I IFN-producing cells are immature APCs with plasmacytoid morphology.

Abstract: We show here that mouse interferon-alpha (IFN-alpha)-producing cells (mIPCs) are a unique subset of immature antigen-presenting cells (APCs) that secrete IFN-alpha upon stimulation with viruses. mIPCs have a plasmacytoid morphology, can be stained with an antibody to Ly6G and Ly6C (anti-Ly6G/C) and are Ly6C+B220+CD11cloCD4+; unlike other dendritic cell subsets, however, they do not express CD8alpha or CD11b. Although mIPCs undergo apoptosis in vitro, stimulation with viruses, IFN-alpha or CpG oligonucleotides enhanced their survival and T cell stimulatory activity. In vivo, mIPCs were the main producers of IFN-alpha in cytomegalovirus-infected mice, as depletion of Ly6G+/C+ cells abrogated IFN-alpha production. mIPCs produced interleukin 12 (IL-12) in response to viruses and CpG oligodeoxynucleotides, but not bacterial products. Although different pathogens can selectively engage various APC subsets for IL-12 production, IFN-alpha production is restricted to mIPCs' response to viral infection.

Using Internet Technology to Deliver a Behavioral Weight Loss Program

Abstract: ContextRapid increases in access to the Internet have made it a viable mode for public health intervention. No controlled studies have evaluated this resource for weight loss.ObjectiveTo determine whether a structured Internet behavioral weight loss program produces greater initial weight loss and changes in waist circumference than a weight loss education Web site.DesignRandomized, controlled trial conducted from April to December 1999.Setting and ParticipantsNinety-one healthy, overweight adult hospital employees aged 18 to 60 years with a body mass index of 25 to 36 kg/m2. Analyses were performed for the 65 who had complete follow-up data.InterventionsParticipants were randomly assigned to a 6-month weight loss program of either Internet education (education; n = 32 with complete data) or Internet behavior therapy (behavior therapy; n = 33 with complete data). All participants were given 1 face-to-face group weight loss session and access to a Web site with organized links to Internet weight loss resources. Participants in the behavior therapy group received additional behavioral procedures, including a sequence of 24 weekly behavioral lessons via e-mail, weekly online submission of self-monitoring diaries with individualized therapist feedback via e-mail, and an online bulletin board.Main Outcome MeasuresBody weight and waist circumference, measured at 0, 3, and 6 months, compared the 2 intervention groups.ResultsRepeated-measures analyses showed that the behavior therapy group lost more weight than the education group (P = .005). The behavior therapy group lost a mean (SD) of 4.0 (2.8) kg by 3 months and 4.1 (4.5) kg by 6 months. Weight loss in the education group was 1.7 (2.7) kg at 3 months and 1.6 (3.3) kg by 6 months. More participants in the behavior therapy than education group achieved the 5% weight loss goal (45% vs 22%; P = .05) by 6 months. Changes in waist circumference were also greater in the behavior therapy group than in the education group at both 3 months (P = .001) and 6 months (P = .005).ConclusionsParticipants who were given a structured behavioral treatment program with weekly contact and individualized feedback had better weight loss compared with those given links to educational Web sites. Thus, the Internet and e-mail appear to be viable methods for delivery of structured behavioral weight loss programs.

Black holes at the Large Hadron Collider.

Abstract: If the scale of quantum gravity is near TeV, the CERN Large Hadron Collider will be producing one black hole (BH) about every second. The decays of the BHs into the final states with prompt, hard photons, electrons, or muons provide a clean signature with low background. The correlation between the BH mass and its temperature, deduced from the energy spectrum of the decay products, can test Hawking's evaporation law and determine the number of large new dimensions and the scale of quantum gravity.

Blood Transfusion in Elderly Patients with Acute Myocardial Infarction

Abstract: Background Anemia may have adverse effects in patients with coronary artery disease. However, the benefit of blood transfusion in elderly patients with acute myocardial infarction and various degrees of anemia is uncertain. Methods We conducted a retrospective study of data on 78,974 Medicare beneficiaries 65 years old or older who were hospitalized with acute myocardial infarction. Patients were categorized according to the hematocrit on admission (5.0 to 24.0 percent, 24.1 to 27.0 percent, 27.1 to 30.0 percent, 30.1 to 33.0 percent, 33.1 to 36.0 percent, 36.1 to 39.0 percent, or 39.1 to 48.0 percent), and data were evaluated to determine whether there was an association between the use of transfusion and 30-day mortality. Results Patients with lower hematocrit values on admission had higher 30-day mortality rates. Blood transfusion was associated with a reduction in 30-day mortality among patients whose hematocrit on admission fell into the categories ranging from 5.0 to 24.0 percent (adjusted odds rati...

Mortality, CD4 Cell Count Decline, and Depressive Symptoms Among HIV-Seropositive Women: Longitudinal Analysis From the HIV Epidemiology Research Study

Abstract: ContextThe impact of depression on morbidity and mortality among women with human immunodeficiency virus (HIV) has not been examined despite the fact that women with HIV have substantially higher rates of depression than their male counterparts.ObjectiveTo determine the association of depressive symptoms with HIV-related mortality and decline in CD4 lymphocyte counts among women with HIV.DesignThe HIV Epidemiologic Research Study, a prospective, longitudinal cohort study conducted from April 1993 through January 1995, with follow-up through March 2000.SettingFour academic medical centers in Baltimore, Md; Bronx, NY; Providence, RI; and Detroit, Mich.ParticipantsA total of 765 HIV-seropositive women aged 16 to 55 years.Main Outcome MeasuresHIV-related mortality and CD4 cell count slope decline over a maximum of 7 years, compared among women with limited or no depressive symptoms, intermittent depressive symptoms, or chronic depressive symptoms, as measured using the self-report Center for Epidemiologic Studies Depression Scale.ResultsIn multivariate analyses controlling for clinical, treatment, and other factors, women with chronic depressive symptoms were 2 times more likely to die than women with limited or no depressive symptoms (relative risk [RR], 2.0; 95% confidence interval [CI], 1.0-3.8). Among women with CD4 cell counts of less than 200 × 106/L, HIV-related mortality rates were 54% for those with chronic depressive symptoms (RR, 4.3; 95% CI, 1.6-11.6) and 48% for those with intermittent depressive symptoms (RR, 3.5; 95% CI, 1.1-10.5) compared with 21% for those with limited or no depressive symptoms. Chronic depressive symptoms were also associated with significantly greater decline in CD4 cell counts after controlling for other variables in the model, especially among women with baseline CD4 cell counts of less than 500 × 106/L and baseline viral load greater than 10 000 copies/µL.ConclusionsOur results indicate that depressive symptoms among women with HIV are associated with HIV disease progression, controlling for clinical, substance use, and sociodemographic characteristics. These results highlight the importance of adequate diagnosis and treatment of depression among women with HIV. Further research is needed to determine if treatment of depression can not only enhance the mental health of women with HIV but also impede disease progression and mortality.

Trans-Planckian problem of inflationary cosmology

Abstract: In most current models of inflation based on a weakly self-coupled scalar matter field minimally coupled to gravity, the period of inflation lasts so long that, at the beginning of the inflationary period, the physical wavelengths of comoving scales which correspond to the present large-scale structure of the Universe were smaller than the Planck length. Thus, the usual computations of the spectrum of fluctuations in these models involve extrapolating low-energy physics (both in the matter and gravitational sector) into regions where this physics is not applicable. In this article we study the dependence of the usual predictions of inflation for the spectrum of cosmological fluctuations on the hidden assumptions about super-Planck scale physics. We introduce a class of modified dispersion relations to mimic possible effects of super-Planck scale physics, and find that, given an initial state determined by minimizing the energy density, for dispersions relations introduced by Unruh the spectrum is unchanged, whereas for a class of dispersion relations similar to those used by Corley and Jacobson (which involve a more radical departure from the usual linear relation) important deviations from the usual predictions of inflation can be obtained. Some implications of this result for the unification of fundamental physicsmore » and early Universe cosmology are discussed.« less

Kirsten ras mutations in patients with colorectal cancer: the ‘RASCAL II’ study

Abstract: Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras incolorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, which was reanalysed when information on 4268 patients from 42 centres in 21 countries had been entered. After predetermined exclusion criteria were applied, data on 3439 patients were entered into a multivariate analysis. This found that of the 12 possible mutations on codons 12 and 13 of Kirsten ras, only one mutation on codon 12, glycine to valine, found in 8.6% of all patients, had a statistically significant impact on failure-free survival (P=0.004, HR 1.3) and overall survival (P=0.008, HR 1.29). This mutation appeared to have a greater impact on outcome in Dukes' C cancers (failure-free survival, P=0.008, HR 1.5, overall survival P=0.02, HR 1.45) than in Dukes' B tumours (failure-free survival, P=0.46, HR 1.12, overall survival P=0.36, HR 1.15). Ki-ras mutations may occur early in the development of pre-cancerous adenomas in the colon and rectum. However, this collaborative study suggests that not only is the presence of a codon 12 glycine to valine mutation important for cancer progression but also that it may predispose to more aggressive biological behaviour in patients with advanced colorectal cancer. ⌐ 2001 Cancer Research Campaign.

The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis.

Abstract: Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

Biosynthesis of Complex Polyketides in a Metabolically Engineered Strain of E. coli

Abstract: The macrocyclic core of the antibiotic erythromycin, 6-deoxyerythronolide B (6dEB), is a complex natural product synthesized by the soil bacterium Saccharopolyspora erythraea through the action of a multifunctional polyketide synthase (PKS). The engineering potential of modular PKSs is hampered by the limited capabilities for molecular biological manipulation of organisms (principally actinomycetes) in which complex polyketides have thus far been produced. To address this problem, a derivative of Escherichia coli has been genetically engineered. The resulting cellular catalyst converts exogenous propionate into 6dEB with a specific productivity that compares well with a high-producing mutant of S. erythraea that has been incrementally enhanced over decades for the industrial production of erythromycin.

Optic flow is used to control human walking

Abstract: How is human locomotion visually controlled? Fifty years ago, it was proposed that we steer to a goal using optic flow, the pattern of motion at the eye that specifies the direction of locomotion. However, we might also simply walk in the perceived direction of a goal. These two hypotheses normally predict the same behavior, but we tested them in an immersive virtual environment by displacing the optic flow from the direction of walking, violating the laws of optics. We found that people walked in the visual direction of a lone target, but increasingly relied on optic flow as it was added to the display. The visual control law for steering toward a goal is a linear combination of these two variables weighted by the magnitude of flow, thereby allowing humans to have robust locomotor control under varying environmental conditions.

The home environments of children in the United States part II: relations with behavioral development through age thirteen.

Abstract: This study examined the frequency with which children were exposed to various parental actions, materials, events, and conditions as part of their home environments, and how those exposures related to their well-being. Part 1 focused on variations by age, ethnicity, and poverty status. In Part 2 of the study, relations between major aspects of the home environment (including maternal responsiveness, learning stimulation, and spanking) and developmental outcomes for children from birth through age 13 were investigated. The outcomes examined were early motor and social development, vocabulary development, achievement, and behavior problems. These relations were examined in both poor and nonpoor European American, African American, and Hispanic American families using hierarchical linear modeling. The most consistent relations found were those between learning stimulation and children's developmental status, with relations for parental responsiveness and spanking varying as a function of outcome, age, ethnicity, and poverty status. The evidence indicated slightly stronger relations for younger as compared with older children.

Risk factors for cerebral edema in children with diabetic ketoacidosis.

Abstract: Background Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. Methods In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression, we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. Results A comparison of the children i...

Robust Localization in Reverberant Rooms

Abstract: Talker localization with microphone arrays has received significant attention lately as a means for the automated tracking of individuals in an enclosure and as a necessary component of any general purpose speech capture system. Several algorithmic approaches are available for speech source localization with multi-channel data. This chapter summarizes the current field and comments on the general merits and shortcomings of each genre. A new localization method is then presented in detail. By utilizing key features of existing methods, this new algorithm is shown to be significantly more robust to acoustical conditions, particularly reverberation effects, than the traditional localization techniques in use today.

Exact correlators of giant gravitons from dual N=4 SYM theory

Abstract: A class of correlation functions of half-BPS composite operators are computed exactly ( at finite N ) in the zero coupling limit of N = 4 SYM theory. These have a simple dependence on the four-dimensional spacetime coordinates and are related to correlators in a one-dimensional Matrix Model with complex Matrices obtained by dimensional reduction of N = 4 SYM on a three-sphere. A key technical tool is Frobenius-Schur duality between symmetric and Unitary groups and the results are expressed simply in terms of U(N) group integrals or equivalently in terms of Littlewood-Richardson coefficients. These correlation functions are used to understand the existence/properties of giant gravitons and related solutions in the string theory dual on AdS5 × S 5 . Some of their properties hint at integrability in N = 4 SYM.

Distinct mesodermal signals, including BMPs from the septum transversum mesenchyme, are required in combination for hepatogenesis from the endoderm

Abstract: Mesodermal signaling is critical for patterning the embryonic endoderm into different tissue domains. Classical tissue transplant experiments in the chick and recent studies in the mouse indicated that interactions with the cardiogenic mesoderm are necessary and sufficient to induce the liver in the ventral foregut endoderm. Using molecular markers and functional assays, we now show that septum transversum mesenchyme cells, a distinct mesoderm cell type, are closely apposed to the ventral endoderm and contribute to hepatic induction. Specifically, using a mouse Bmp4 null mutation and an inhibitor of BMPs, we find that BMP signaling from the septum transversum mesenchyme is necessary to induce liver genes in the endoderm and to exclude a pancreatic fate. BMPs apparently function, in part, by affecting the levels of the GATA4 transcription factor, and work in parallel to FGF signaling from the cardiac mesoderm. BMP signaling also appears critical for morphogenetic growth of the hepatic endoderm into a liver bud. Thus, the endodermal domain for the liver is specified by simultaneous signaling from distinct mesodermal sources.

Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial.

Abstract: Objective To compare paroxetine with placebo and imipramine with placebo for the treatment of adolescent depression. Method After a 7- to 14-day screening period, 275 adolescents with major depression began 8 weeks of double-blind paroxetine (20–40 mg), imipramine (gradual upward titration to 200–300 mg), or placebo. The two primary outcome measures were endpoint response (Hamilton Rating Scale for Depression [HAM-D] score ≤8 or ≥50% reduction in baseline HAM-D) and change from baseline HAM-D score. Other depression-related variables were (1) HAM-D depressed mood item; (2) depression item of the Schedule for Affective Disorders and Schizophrenia for Adolescents-Lifetime version (K-SADS-L); (3) Clinical Global Impression (CGI) improvement scores of 1 or 2; (4) nine-item depression subscale of K-SADS-L; and (5) mean CGI improvement scores. Results Paroxetine demonstrated significantly greater improvement compared with placebo in HAM-D total score ≤8, HAM-D depressed mood item, K-SADS-L depressed mood item, and CGI score of 1 or 2. The response to imipramine was not significantly different from placebo for any measure. Neither paroxetine nor imipramine differed significantly from placebo on parent-or self-rating measures. Withdrawal rates for adverse effects were 9.7% and 6.9% for paroxetine and placebo, respectively. Of 31.5% of subjects stopping imipramine therapy because of adverse effects, nearly one third did so because of adverse cardiovascular effects. Conclusions Paroxetine is generally well tolerated and effective for major depression in adolescents.

A bipotential precursor population for pancreas and liver within the embryonic endoderm.

Abstract: The pancreas emerges independently from dorsal and ventral domains of embryonic gut endoderm. Gene inactivation experiments in mice have identified factors required for dorsal pancreas development, but factors that initiate the ventral pancreas have remained elusive. In this study, we investigated the hypothesis that the emergence of the ventral pancreas is related to the emergence of the liver. We find that the liver and ventral pancreas are specified at the same time and in the same general domain of cells. Using embryo tissue explantation experiments, we find that the default fate of the ventral foregut endoderm is to activate the pancreas gene program. FGF signalling from the cardiac mesoderm diverts this endoderm to express genes for liver instead of those for pancreas. No evidence was found to indicate that the cell type choice for pancreas or liver involves a selection for growth or viability. Cardiac mesoderm or FGF induces the local expression of sonic hedgehog, which in turn is inhibitory to pancreas but not to liver. The bipotential precursor cell population for pancreas and liver in embryonic development and its fate selection by FGF has features that appear to be recapitulated in the adult pancreas and are reflected in the evolution of these organs.

Superplastic deformation of ice: Experimental observations

Abstract: Creep experiments on fine-grained ice reveal the existence of three creep regimes: (1) a dislocation creep regime; (2) a superplastic flow regime in which grain boundary sliding is an important deformation process; and (3) a basal slip creep regime in which the strain rate is limited by basal slip. Dislocation creep in ice is likely climb-limited, is characterized by a stress exponent of 4.0, and is independent of grain size. Superplastic flow is characterized by a stress exponent of 1.8 and depends inversely on grain size to the 1.4 power. Basal slip limited creep is characterized by a stress exponent of 2.4 and is independent of grain size. A fourth creep mechanism, diffusional flow, which usually occurs at very low stresses, is inaccessible at practical laboratory strain rates even for our finest grain sizes of approximately 3 micrometers. A constitutive equation based on these experimental results that includes flow laws for these four creep mechanisms is described. This equation is in excellent agreement with published laboratory creep data for coarse-grained samples at high temperatures. Superplastic flow of ice is the rate-limiting creep mechanism over a wide range of temperatures and grain sizes at stresses less than or equal to 0.1 MPa, conditions which overlap those occurring in glaciers, ice sheets, and icy planetary interiors.

Spirituality and medical practice: using the HOPE questions as a practical tool for spiritual assessment.

Abstract: The relationship between spirituality and medicine has been the focus of considerable interest in recent years. Studies suggest that many patients believe spirituality plays an important role in their lives, that there is a positive correlation between a patient's spirituality or religious commitment and health outcomes, and that patients would like physicians to consider these factors in their medical care. A spiritual assessment as part of a medical encounter is a practical first step in incorporating consideration of a patient's spirituality into medical practice. The HOPE questions provide a formal tool that may be used in this process. The HOPE concepts for discussion are as follows: H--sources of hope, strength, comfort, meaning, peace, love and connection; O--the role of organized religion for the patient; P--personal spirituality and practices; E--effects on medical care and end-of-life decisions.

Guidelines for the management of intravascular catheter-related infections.

Abstract: These guidelines from the Infectious Diseases Society of America (IDSA), the American College of Critical Care Medicine (for the Society of Critical Care Medicine), and the Society for Healthcare Epidemiology of America contain recommendations for the management of adults and children with, and diagnosis of infections related to, peripheral and nontunneled central venous catheters (CVCs), pulmonary artery catheters, tunneled central catheters, and implantable devices. The guidelines, written for clinicians, contain IDSA evidence-based recommendations for assessment of the quality and strength of the data. Recommendations are presented according to the type of catheter, the infecting organism, and the associated complications. Intravascular catheter-related infections are a major cause of morbidity and mortality in the United States. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida albicans most commonly cause catheter-related bloodstream infection. Management of catheter-related infection varies according to the type of catheter involved. After appropriate cultures of blood and catheter samples are done, empirical iv antimicrobial therapy should be initiated on the basis of clinical clues, the severity of the patient's acute illness, underlying disease, and the potential pathogen (s) involved. In most cases of nontunneled CVC-related bacteremia and fungemia, the CVC should be removed.