Maternal consumption of fish during the gestational period exposes the fetus to both nutrients, especially the long-chain polyunsaturated fatty acids (LCPUFAs), believed to be beneficial for fetal ...brain development, as well as to the neurotoxicant methylmercury (MeHg). We recently reported that nutrients present in fish may modify MeHg neurotoxicity. Understanding the apparent interaction of MeHg exposure and nutrients present in fish is complicated by the limitations of modeling methods. In this study we fit varying coefficient function models to data from the Seychelles Child Development Nutrition Study (SCDNS) cohort to assess the association of dietary nutrients and children’s development. This cohort of mother–child pairs in the Republic of Seychelles had fish consumption averaging 9 meals per week. Maternal nutritional status was assessed for five different nutritional components known to be present in fish (n-3 LCPUFA, n-6 LCPUFA, iron status, iodine status, and choline) and associated with children’s neurological development. We also included prenatal MeHg exposure (measured in maternal hair). We examined two child neurodevelopmental outcomes (Bayley Scales Infant Development-II (BSID-II) Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI)), each administered at 9 and at 30 months. The varying coefficient models allow the possible interactions between each nutritional component and MeHg to be modeled as a smoothly varying function of MeHg as an effect modifier. Iron, iodine, choline, and n-6 LCPUFA had little or no observable modulation at different MeHg exposures. In contrast the n-3 LCPUFA docosahexaenoic acid (DHA) had beneficial effects on the BSID-II PDI that were reduced or absent at higher MeHg exposures. This study presents a useful modeling method that can be brought to bear on questions involving interactions between covariates, and illustrates the continuing importance of viewing fish consumption during pregnancy as a case of multiple exposures to nutrients and to MeHg. The results encourage more emphasis on a holistic view of the risks and benefits of fish consumption as it relates to infant development.
►Varying coefficient models are tools for examining interactions in exposure settings Associations between MeHg and fish nutrients and developmental outcomes were examined. ► Interactions between MeHg exposure and fish-derived nutrients were modeled using VC. ► Models show beneficial association of DHA with outcomes were reduced as MeHg increases. ► VC models show other measured nutrients unmodulated by increasing MeHg exposure.
CD163, a monocyte and macrophage‐specific surface glycoprotein, which is increased by interleukin‐10 and glucocorticoids, is a scavenger receptor for hemoglobin/haptoglobin complexes. We report a ...rapid and highly reproducible rise in soluble CD163 in the plasma of human volunteers given intravenous lipopolysaccharide (LPS). We also show that LPS induces shedding of CD163 from the surface of isolated monocytes, identifying shedding from monocytes and macrophages as a likely mechanism for the endotoxemia‐associated rise in plasma CD163 in vivo. Studies using the inhibitor TAPI‐0 indicate that a metalloproteinase is responsible for LPS‐mediated shedding of CD163. Finally, we demonstrate a marked increase in surface CD163 expression on circulating monocytes 24 h following experimental endotoxemia. These findings show that CD163 is rapidly mobilized in response to bacterial endotoxin. As hemoglobin can bind LPS and enhance its toxicity, it will be important to determine how cell surface and soluble CD163 influence inflammatory processes during sepsis.
Abstract
Objective. To identify patient-reported outcome (PRO) instruments that assess chronic low back pain (cLBP) symptoms (specifically pain qualities) and/or impacts for potential use in cLBP ...clinical trials to demonstrate treatment benefit and support labeling claims.
Design. Literature review of existing PRO measures.
Methods. Publications detailing existing PRO measures for cLBP were identified, reviewed, and summarized. As recommended by the US Food & Drug Administration (FDA) PRO development guidance, standard measurement characteristics were reviewed, including development history, psychometric properties (validity and reliability), ability to detect change, and interpretation of observed changes.
Results. Thirteen instruments were selected and reviewed: Low Back Pain Bothersomeness Scale, Neuropathic Pain Symptom Inventory, PainDETECT, Pain Quality Assessment Scale Revised, Revised Short Form McGill Pain Questionnaire, Low Back Pain Impact Questionnaire, Oswestry Disability Index, Pain Disability Index, Roland-Morris Disability Questionnaire, Brief Pain Inventory and Brief Pain Inventory Short Form, Musculoskeletal Outcomes Data Evaluation and Management System Spine Module, Orebro Musculoskeletal Pain Questionnaire, and the West Haven-Yale Multidimensional Pain Inventory Interference Scale. The instruments varied in the aspects of pain and/or impacts that they assessed, and none of the instruments fulfilled all criteria for use in clinical trials to support labeling claims based on recommendations outlined in the FDA PRO guidance.
Conclusions. There is an unmet need for a validated PRO instrument to evaluate cLBP-related symptoms and impacts for use in clinical trials.
To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking.
Double-blind, double-dummy, randomized, 3-arm trial with a nicotine patch (21 mg), ...nicotine gum (2 and 4 mg), or a placebo patch and gum; all participants received cognitive-behavioral group therapy.
Inner-city, outpatient clinic on the East Coast. Subjects. Thirteen- to 17-year-old adolescents who smoked > or =10 cigarettes per day (CPD), scored > or =5 on the Fagerstrom Test of Nicotine Dependence, and were motivated to quit smoking. Intervention. Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy, with a follow-up visit at 6 months (3 months after the end of treatment).
Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide (CO) levels of < or =6 ppm, in intent-to-treat analyses, and smoking reduction (CPD and thiocyanate concentrations) among trial completers.
A total of 120 participants were randomized (72% white, 70% female; age: 15.2 +/- 1.33 years; smoking: 18.8 +/- 8.56 CPD; Fagerstrom Test of Nicotine Dependence score: 7.04 +/- 1.29) from 1999 to 2003. Participants started smoking at 11.2 +/- 1.98 years of age and had been smoking daily for 2.66 +/- 1.56 years; 75% had at least 1 current psychiatric diagnosis. Mean compliance across groups was higher for the patch (mean: 78.4-82.8%) than for the gum (mean: 38.5-50.7%). Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all randomized participants showed CO-confirmed prolonged abstinence rates of 18% for the active-patch group, 6.5% for the active-gum group, and 2.5% for the placebo group; the difference between the active-patch and placebo arms was statistically significant. There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes. Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group. Mean smoking rates, but not CO or thiocyanate concentrations, decreased significantly in all 3 arms but not as a function of treatment group.
Nicotine patch therapy combined with cognitive-behavioral intervention was effective, compared with placebo, for treatment of tobacco dependence among adolescent smokers. Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking. Additional study of nicotine gum, with enhanced instructional support, is needed to assess its efficacy among adolescent smokers.
We describe the mixed-methods (qualitative and quantitative) development and preliminary validation of the Patient Assessment for Low Back Pain-Symptoms (PAL-S), a patient-reported outcome measure ...for use in chronic low back pain (cLBP) clinical trials. Qualitative methods (concept elicitation and cognitive interviews) were used to identify and refine symptom concepts and quantitative methods (classical test theory and Rasch measurement theory) were used to evaluate item- and scale-level performance of the measure using an iterative approach. Patients with cLBP participated in concept elicitation interviews (N = 43), cognitive interviews (N = 38), and interview-based assessment of paper-to-electronic mode equivalence (N = 8). A web-based sample of patients with self-reported cLBP participated in quantitative studies to evaluate preliminary (N = 598) and revised (n = 401) drafts and a physician-diagnosed cohort of patients with cLBP (N = 45) participated in preliminary validation of the measure. The PAL-S contained 14 items describing symptoms (overall pain, sharp, prickling, sensitive, tender, radiating, shocking, shooting, burning, squeezing, muscle spasms, throbbing, aching, and stiffness). Item-level performance, scale structure, and scoring seemed to be appropriate. One-week test-retest reproducibility was acceptable (intraclass correlation coefficient 0.81 95% confidence interval, 0.61-0.91). Convergent validity was demonstrated with total score and MOS-36 Bodily Pain (Pearson correlation -0.79), Neuropathic Pain Symptom Inventory (0.73), Roland-Morris Disability Questionnaire (0.67), and MOS-36 Physical Functioning (-0.65). Individual item scores and total score discriminated between numeric rating scale tertile groups and painDETECT categories. Respondent interpretation of paper and electronic administration modes was equivalent. The PAL-S has demonstrated content validity and is potentially useful to assess treatment benefit in cLBP clinical trials.
SN 2002cx: The Most Peculiar Known Type Ia Supernova Li, Weidong; Filippenko, Alexei V.; Chornock, Ryan ...
Publications of the Astronomical Society of the Pacific,
04/2003, Letnik:
115, Številka:
806
Journal Article
Recenzirano
Odprti dostop
We present photometric and spectroscopic observations of supernova (SN) 2002cx, which reveal it to be unique among all observed Type Ia supernovae (SNe Ia). SN 2002cx exhibits an SN 1991T–like ...premaximum spectrum, an SN 1991bg–like luminosity, and expansion velocities roughly half those of normal SNe Ia. Photometrically, SN 2002cx has a broad peak in theRband and a plateau phase in theIband, and slow late‐time decline. TheB−Vcolor evolution is nearly normal, but theV−RandV−Icolors are very red. Early‐time spectra of SN 2002cx evolve very quickly and are dominated by lines from Fe‐group elements; features from intermediate‐mass elements (Ca, S, Si) are weak or absent. Mysterious emission lines are observed around 7000 Å at about 3 weeks after maximum brightness. The nebular spectrum of SN 2002cx is also unique, consisting of narrow iron and cobalt lines. The observations of SN 2002cx are inconsistent with the observed spectral/photometric sequence and provide a major challenge to our understanding of SNe Ia. No existing theoretical model can successfully explain all observed aspects of SN 2002cx.
We describe qualitative and quantitative development and preliminary validation of the Patient Assessment for Low Back Pain-Impacts (PAL-I), a patient-reported outcome measure for use in chronic low ...back pain (cLBP) clinical trials. Concept elicitation and cognitive interviews (qualitative methods) were used to identify and refine symptom concepts. Classical test theory and Rasch measurement theory (quantitative methods) were used to evaluate item-level and scale-level performance of the PAL-I using an iterative approach between qualitative and quantitative methods. Patients with cLBP participated in concept elicitation interviews (N = 43), cognitive interviews (N = 38), and assessment of paper-to-electronic format equivalence (N = 8). A web-based sample of self-reported patients with cLBP participated in quantitative studies to evaluate preliminary (N = 598) and revised (n = 401) drafts and patients with physician-diagnosed cLBP (N = 45) participated in preliminary validation of the PAL-I. The instrument contained 9 items describing cLBP impacts (walking, sitting, standing, lifting, sleep, social activities, travelling, climbing, and body movements). Item-level performance, scale structure, and scoring seemed to be appropriate. One-week test-retest reproducibility was acceptable (intraclass correlation coefficient 0.88 95% confidence interval, 0.78-0.94). Convergent validity was demonstrated with PAL-I total score and Roland-Morris Disability Questionnaire (Pearson correlation 0.82), MOS-36 Physical Functioning (-0.71), and MOS-36 Bodily Pain (-0.71). Individual item scores and total score discriminated between numeric rating scale tertile groups and painDETECT categories. Interpretation of paper and electronic administration modes was equivalent. The PAL-I demonstrated content validity and is potentially useful to assess treatment benefit in clinical trials of cLBP therapies.
Superdirectivity in MIMO systems Morris, M.L.; Jensen, M.A.; Wallace, J.W.
IEEE transactions on antennas and propagation,
09/2005, Letnik:
53, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Multiantenna systems such as devices for multiple-input-multiple-output (MIMO) communication can theoretically use array superdirectivity to optimally exploit the propagation channel. In traditional ...analyses of MIMO systems, such superdirectivity is not observed due to the commonly applied constraint that limits the excitation current magnitudes. However, when an electromagnetically appropriate constraint on the power radiated by the array is applied, the computed capacity can include effects of transmit superdirectivity. A similar result occurs at the receiver for spatially colored noise. This paper formulates the MIMO system capacity under these circumstances and provides a framework for computing this capacity when the level of tolerable superdirectivity (as measured by the superdirectivity Q factor) is constrained. Example computations using the framework illustrate the impact that superdirectivity can have on achievable MIMO system performance.
This study examines the relationship between psychosocial factors, ethnicity, disease activity and quality of life in systemic lupus erythematosus. Methods: One hundred and twenty-five adult ...Caucasian and Hispanic lupus patients were recruited from four Southern California medical centers. Linear regression analysis was performed to assess the correlation of ethnicity, socioeconomic factors (age, income), and disease activity (patient and physician reported), as well as psychological (depression, internality, helplessness) variables with quality of life (QOL) as measured by the Short Form (SF)-36. Hierarchical multiple regression analysis was then used to determine the stepwise contribution of the above determinants on the eight domains of the SF-36 questionnaire. Results: Depression negatively correlated with QOL in both Caucasians (r −0.488 to −0.660) and Hispanics (r −0.456 to −0.723). Patient-reported disease activity was moderately related (r −0.456 to −0.698) to seven of the eight SF-36 domains in Hispanics, and none in Caucasians. Physician-reported disease activity, measured by SLEDAI, did not correlate with QOL among Hispanics or Caucasians. When linear and hierarchical regression was used, depression significantly correlated (p < 0.0001) with the majority of the SF-36 domains, except general health, while age had a significant effect in only one domain of the SF-36, physical functioning (p < 0.0001). Conclusion: Depression, and not disease activity, appears to have a major influence on quality of life in both Hispanic and Caucasian patients in this lupus cohort.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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