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This work systematically investigates the effect of carbon on the phase stability and room- temperature tensile performance of an annealed Fe40.4Ni11.3Mn34.8Al7.5Cr6 (at%) high entropy alloy without (HEA) and with 1.1% carbon (CHEA). Four annealing conditions were investigated: 773 K for 13 d and 42 d, 973 K for 20 d, and 1073 K and 1423 K for 24 h. The resulting microstructures were analyzed using a combination of scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and atom probe tomography (APT). Vickers hardness testing and room- temperature tensile testing were used to determine the mechanical properties of the annealed HEA and the CHEA. APT composition profiles revealed fine Ni,Mn,Al-enriched matrix precipitates in the CHEA annealed at 773 K for 13 d. After ageing at 773 K for 42 d, colonies of (Ni,Fe)2MnAl- enriched Heusler phase lamellae were observed at the grain boundaries (GBs) and in the matrix for the HEA, while GB lamellar colonies of Mn,Cr-enriched M23C6 carbides were observed for the CHEA. Due to the presence of the GB carbides, the resulting room-temperature elongation to fracture for the CHEA annealed at 773 K for 42 d was ~1% compared to ~11% for the HEA given the same anneal. At higher annealing temperatures, the microstructure contains Ni,Al-rich and Mn,Cr,C-rich precipitates that alternate along the GBs and appear to be associated with each other in the matrix. Electron diffraction analysis indicates the aforementioned Ni,Al-precipitates and Mn,Cr-carbides have b.c.c. and f.c.c. crystal structures, respectively. Once again, a low elongation to fracture (2%) was seen for the carbon-containing material compared to its un-doped counterpart (23%) which solely contained Ni,Al-rich b.c.c. precipitates.

Multi-principle component alloys (MPCAs) differ from traditional alloys in that they consist of four or more elements or components each with concentrations of 5–35 at. %. Since the first eutectic multi-principle component alloy (MPCA) was produced in 2008, there has been a growing number of papers on developing eutectic MPCAs as potential structural materials. Eutectic MPCAs can show high ambient temperature yield strengths that increase with decreasing interlamellar spacing, λ, according to either λ−1/2 or λ−1, similar to that observed in pearlitic steels, with a tradeoff between this increased strength and reduced tensile ductility. Ambient temperature tensile ductility has been observed in eutectic MPCAs only when one phase is f.c.c. and when the harder second phase is itself deformable. The yield strength in eutectic MPCAs has been shown to decrease with increasing temperature, and, limited data suggest that, this is related to the softening of the harder phase. Annealing of as-cast eutectic MPCAs, which are not typically at equilibrium, can produce precipitation of fine particles that further increase the strength, and which often reduce the ductility. Both thermo-mechanical processing and nitriding can increase the strengths of eutectic MPCAs by transforming the lamellar eutectic into equi-axed grains and producing fine AlN particles (in aluminum-containing MPCAs), respectively. The properties of eutectic MPCAs can largely be explained by models used for traditional alloys. While a number of different elements have been used to produce eutectic MPCAs, the design of eutectic MPCAs for structural applications should avoid the use of expensive elements like cobalt and niobium, which have often been used.

The alumina-forming austenitic stainless steel Fe-20Cr-30Ni-2 Nb-5Al was given a solutionizing anneal at 1250 °C followed by anneals at 800 °C for 0, 2.4, 24, 240 h to produce B2 (ordered b.c.c.) and Laves phase precipitates of different sizes with different extents of grain boundary coverage. Both tensile tests and constant-stress (43 MPa) creep tests were performed on the heat-treated materials and on the as-cast alloy at 760 °C. The precipitates grew during the creep testing. In addition, L1 2 (ordered f.c.c.) precipitates nucleated and grew during the creep testing to similar particle sizes after 500 h independent of the prior heat treatment at 800 °C. The specimens given the shortest heat treatment of 2.4 h, which had the smallest initial particle sizes, showed both the highest yield strength and the smallest creep strain after 500 h. The extent of grain boundary coverage by precipitates did not appear to affect the creep rates. No grain boundary cracking or precipitate cracking was found in the heat-treated specimens after creep testing, but the as-cast material failed around 600 h.

The microstructure and mechanical properties studies of a series of two-phase f.c.c./B2 (ordered b.c.c.) lamellar-structured, high entropy alloys (HEA) Fe36Ni18Mn33Al13Tix with x up to 6 at. % Ti have been investigated. X-ray microanalysis in a TEM showed that the Ti resided mostly in the B2 phase. The lamellar spacing decreased significantly with increasing Ti content from 1.56 μm for the undoped alloy to 155 nm with an addition of 4 at. % Ti, leading to a sharp increase in room-temperature yield strength,σy, from 270 MPa to 953 MPa, but with a concomitant decrease in ductility from 22% elongation to 2.3%. Annealing at 1173 K for 20 h greatly increased the lamellar spacing of Fe36Ni18Mn33Al13Ti4 to 577 nm, producing a corresponding decrease in σy to 511 MPa. The yield strengths of all the doped alloys decreased significantly when tensile tested at 973 K with a concomitant increase in ductility due to softening of the B2 phase. The fracture mode changed from cleavage at room temperature to a ductile dimple-type rupture at 973 K. The results are discussed in terms of the Hall-Petch-type relationship.

Fe36Ni18Mn33Al13 is a lamellar two-phase alloy comprising a hard, Ni,Al-rich B2 phase measuring ~500 nm in width and a ductile, Fe,Mn-rich f.c.c. phase ~1 µm in width. Upon cold rolling and annealing, the as-cast microstructure is replaced by discrete, recrystallized ~1 µm-sized grains consisting of the f.c.c. phase and a 7R (14 M) martensite phase. The formation of the latter phase appears to be related to the change in composition of the phases upon recrystallization. Room-temperature tensile tests performed on 50 % cold-worked and annealed Fe36Ni18Mn33Al13 reveal that complete recrystallization does not occur until after 24 h of annealing at 900 °C, wherein the yield strength and elongation to fracture of the recrystallized alloy are ~443 MPa and 21 %, respectively—a change from the as-cast alloy’s values of ~352 MPa and ~28 %.

In the present study, a novel Fe40.2Ni11.3Mn30Al7.5Cr11 high entropy alloy displaying an excellent combination of high strength and high ductility has been developed. The b.c.c.+B2/f.c.c. dendritic-interdendritic microstructure was characterized using scanning electron microscopy, X-ray diffraction, and transmission electron microscopy, and the alloy’s mechanical properties were examined using Vickers hardness measurements and room-temperature tensile tests. The phase stability of Fe40.2Ni11.3Mn30Al7.5Cr11 was investigated by annealing the alloy between 1173 K–1273 K, and the presence of both Ni-rich, b.c.c. needle-shaped precipitates and Cr-rich, σ phase particles was observed for the 1173 K annealed specimen. The σ phase precipitates contributed to the rapid age-hardening effect in the material annealed at 1173 K. A further increase in ageing temperature to 1223 K and 1273 K led to the dissolution of the σ phase and a reduction in the volume fraction of the b.c.c./B2 dendrites, which led to a consequent drop in room-temperature yield strength from the as-cast value of ∼593 MPa–∼486 MPa and ∼228 MPa for the specimens annealed at 1223 K and 1273 K, respectively. An accompanying increase in ductility was observed from ∼22% for the as-cast alloy to ∼27% and ∼40% after annealing the material at 1223 K and 1273 K, respectively. Post-deformation transmission electron micrographs revealed that the f.c.c interdendrites accommodated plastic strain via wavy slip and moreover, deformed before the b.c.c. dendritic regions, which were reinforced by B2 particles and acted as obstacles to moving dislocations. The discovery of a multi-phase HEA that contains 11% Cr and good mechanical properties has relevant high-temperature structural applications especially in cases that require suitable corrosion resistance.

Cold rolling followed by annealing was performed on the as-cast, two-phase (f.c.c. + B2), lamellar-structured high entropy alloy Fe28.2Ni18.8Mn32.9Al14.1Cr6. The cold-rolled Fe28.2Ni18.8Mn32.9Al14.1Cr6 showed a very high yield strength of 1422 MPa due to the high dislocation density (>1 × 1015 m−2), but only 2.3% elongation to failure. Annealing produced recrystallization, which caused the as-cast lamellar microstructure to be replaced by an equi-axed, duplex grain structure consisting of discrete B2 and f.c.c. grains with both different compositions and volume fractions. The recrystallized alloy showed a yield strength of ∼600 MPa and an elongation of ∼20%, which was only slightly different from the as-cast mechanical properties, a feature ascribed to the similarity in the scale (0.5 μm) of the microstructure in the two states. It was found that although initial plastic deformation takes place in the f.c.c. phase, specimens either cold-rolled or strained to failure showed that both phases plastically deformed.

This work demonstrates an improvement in the mechanical performance of the high entropy alloy Fe40.4Ni11.3Mn34.8Al7.5Cr6 containing 1.1 at. % carbon (CHEA) by hot-rolling followed by annealing at 1323 K. The microstructure was examined using scanning electron microscopy, electron backscatter diffraction, X-ray diffraction, and transmission electron microscopy. Room-temperature tensile tests were used to assess the alloy's mechanical properties. The presence of dense dislocation walls indicate that the alloy has not fully recrystallized and, moreover, the deformation substructure and the large fraction of Σ3 twin boundaries contribute to the high room temperature yield strength (~523 MPa). Despite the presence of substantial dislocation density, the annealed, hot-rolled CHEA displays an improvement in elongation to fracture (~33%) compared to the negligible ductility (

The journal impact factor (JIF) reported in journal citation reports has been used to represent the influence and prestige of a journal. Whereas the consideration of the stochastic nature of a statistic is a prerequisite for statistical inference, the estimation of JIF uncertainty is necessary yet unavailable for comparing the impact among journals. Using journals in the Database of Research in Science Education (DoRISE), the current study proposes bootstrap methods to estimate the JIF variability. The paper also provides a comprehensive exposition of the sources of JIF variability. The collections of articles in the year of interest and in the preceding years both contribute to JIF variability. In addition, the variability estimate differs depending on the way a database selects its journals for inclusion. In the bootstrap process, the nested structure of articles in a journal was accounted for to ensure that each bootstrap replication reflects the actual citation characteristics of articles in the journal. In conclusion, the proposed point and interval estimates of the JIF statistic are obtained and more informative inferences on the impact of journals can be drawn.

BACKGROUND: Concern about the process of identifying underlying competencies that contribute to effective nursing performance has been debated with a lack of consensus surrounding an approved measurement instrument for assessing clinical performance. Although a number of methodologies are noted in the development of competency-based assessment measures, these studies are not without criticism. RESEARCH AIM: The primary aim of the study was to develop and validate a Performance Based Scoring Rubric, which included both analytical and holistic scales. The aim included examining the validity and reliability of the rubric, which was designed to measure clinical competencies in the operating theatre. RESEARCH METHOD: The fieldwork observations of 32 nurse educators and preceptors assessing the performance of 95 instrument nurses in the operating theatre were used in the calibration of the rubric. The Rasch model, a particular model among Item Response Models, was used in the calibration of each item in the rubric in an attempt at improving the measurement properties of the scale. This is done by establishing the 'fit' of the data to the conditions demanded by the Rasch model. RESULTS: Acceptable reliability estimates, specifically a high Cronbach's alpha reliability coefficient (0.940), as well as empirical support for construct and criterion validity for the rubric were achieved. Calibration of the Performance Based Scoring Rubric using Rasch model revealed that the fit statistics for most items were acceptable. CONCLUSION: The use of the Rasch model offers a number of features in developing and refining healthcare competency-based assessments, improving confidence in measuring clinical performance. The Rasch model was shown to be useful in developing and validating a competency-based assessment for measuring the competence of the instrument nurse in the operating theatre with implications for use in other areas of nursing practice.

Lung volume reduction surgery (LVRS) is associated with weight gain in some patients, but the group that gains weight after LVRS and the mechanisms underlying this phenomenon have not been well characterized.To describe the weight change profiles of LVRS patients enrolled in the National Emphysema Treatment Trial (NETT) and to correlate alterations in lung physiological parameters with changes in weight.We divided 1,077 non-high-risk patients in the NETT into groups according to baseline body mass index (BMI): underweight (21 kg/m(2)), normal weight (21-25 kg/m(2)), overweight (25-30 kg/m(2)), and obese (30 kg/m(2)). We compared BMI groups and LVRS and medical groups within each BMI stratum with respect to baseline characteristics and percent change in BMI (%ΔBMI) from baseline. We examined patients with (ΔBMI ≥ 5%) and without (ΔBMI5%) significant weight gain at 6 months and assessed changes in lung function and ventilatory efficiency (Ve/Vco(2)).The percent change in BMI was greater in the LVRS arm than in the medical arm in the underweight and normal weight groups at all follow-up time points, and at 12 and 24 months in the overweight group. In the LVRS group, patients with ΔBMI ≥ 5% at 6 months had greater improvements in FEV(1) (11.53 ± 9.31 vs. 6.58 ± 8.68%; P0.0001), FVC (17.51 ± 15.20 vs. 7.55 ± 14.88%; P0.0001), residual volume (-66.20 ± 40.26 vs. -47.06 ± 39.87%; P0.0001), 6-minute walk distance (38.70 ± 69.57 vs. 7.57 ± 73.37 m; P0.0001), maximal expiratory pressures (12.73 ± 49.08 vs. 3.54 ± 32.22; P = 0.0205), and Ve/Vco(2) (-1.58 ± 6.20 vs. 0.22 ± 8.20; P = 0.0306) at 6 months than patients with ΔBMI5% at 6 months.LVRS leads to weight gain in nonobese patients, which is associated with improvement in lung function, exercise capacity, respiratory muscle strength, and ventilatory efficiency. These physiological changes may be partially responsible for weight gain in patients who undergo LVRS.

Fibroblast growth factor 21 (FGF21) mitigates many of the pathogenic features of type 2 diabetes, despite a short circulating half-life. PEGylation is a proven approach to prolonging the duration of action while enhancing biophysical solubility and stability. However, in the absence of a specific protein PEGylation site, chemical conjugation is inherently heterogeneous and commonly leads to dramatic loss in bioactivity. This work illustrates a novel means of specific PEGylation, producing FGF21 analogs with high specific activity and salutary biological activities. Using homology modeling and structure-based design, specific sites were chosen in human FGF21 for site-specific PEGylation to ensure that receptor binding regions were preserved. The in vitro activity of the PEGylated FGF21 ana-logs corresponded with the site of PEG placement within the binding model. Site-specific PEGylated analogs demonstrated dramatically increased circulating half-life and enhanced efficacy in db/db mice. Twice-weekly dosing of an optimal FGF21 analog reduced blood glucose, plasma lipids, liver triglycerides, and plasma glucagon and enhanced pancreatic insulin content, islet number, and glucose-dependent insulin secretion. Restoration of insulin sensitivity was demonstrated by the enhanced ability of insulin to induce Akt/protein kinase B phosphorylation in liver, muscle, and adipose tissues. PEGylation of human FGF21 at a specific and preferred site confers superior metabolic pharmacology.

In large-scale assessments, such as state-wide testing programs, national sample-based assessments, and international comparative studies, there are many steps involved in the measurement and reporting of student achievement. There are always sources of inaccuracies in each of the steps. It is of interest to identify the source and magnitude of the errors in the measurement process that may threaten the validity of the final results. Assessment designers can then improve the assessment quality by focusing on areas that pose the highest threats to the results.This paper discusses the relative magnitudes of three main sources of error with reference to the objectives of assessment programs: measurement error, sampling error, and equating error. A number of examples from large-scale assessments are used to illustrate these errors and their impact on the results. The paper concludes by making a number of recommendations that could lead to an improvement of the accuracies of large-scale assessment results.

Background CT scan measures of emphysema and airway disease have been correlated with lung function in cohorts of subjects with a range of COPD severity. The contribution of CT scan-assessed airway disease to objective measures of lung function and respiratory symptoms such as dyspnea in severe emphysema is less clear. Methods Using data from 338 subjects in the National Emphysema Treatment Trial (NETT) Genetics Ancillary Study, densitometric measures of emphysema using a threshold of −950 Hounsfield units (%LAA-950) and airway wall phenotypes of the wall thickness (WT) and the square root of wall area (SRWA) of a 10-mm luminal perimeter airway were calculated for each subject. Linear regression analysis was performed for outcome variables FEV 1 and percent predicted value of FEV 1 with CT scan measures of emphysema and airway disease. Results In univariate analysis, there were significant negative correlations between %LAA-950 and both the WT ( r = −0.28, p = 0.0001) and SRWA ( r = −0.19, p = 0.0008). Airway wall thickness was weakly but significantly correlated with postbronchodilator FEV 1 % predicted (R = −0.12, p = 0.02). Multivariate analysis showed significant associations between either WT or SRWA (β = −5.2, p = 0.009; β = −2.6, p = 0.008, respectively) and %LAA-950 (β = −10.6, p = 0.03) with the postbronchodilator FEV 1 % predicted. Male subjects exhibited significantly thicker airway wall phenotypes (p = 0.007 for WT and p = 0.0006 for SRWA). Conclusions Airway disease and emphysema detected by CT scanning are inversely related in patients with severe COPD. Airway wall phenotypes were influenced by gender and associated with lung function in subjects with severe emphysema.

Rationale: In studies that address health-related quality of life (QoL) and survival, subjects who die are usually censored from QoL assessments. This practice tends to inflate the apparent benefits of interventions with a high risk of mortality. Assessing a composite QoL-death outcome is a potential solution to this problem. Objectives:Todeterminetheeffectoflungvolumereductionsurgery (LVRS) on a composite endpoint consisting of the occurrence of deathoraclinicallymeaningfuldeclineinQoLdefinedasanincrease of at leasteight points in the St. George’s Respiratory Questionnaire total score from the National Emphysema Treatment Trial. Methods:Inpatientswithchronicobstructivepulmonarydiseaseand emphysema randomized to receive medical treatment (n 5 610) or LVRS(n 5608),weanalyzedthesurvivaltothecompositeendpoint, thehazardfunctionsandconstructedpredictionmodelsoftheslope of QoL decline. Measurements and Main Results: The time to the composite endpoint was longer in the LVRS group (2 years) than the medical treatment group (1 year) (P , 0.0001). It was even longer in the subsets of patients undergoing LVRS without a high risk for perioperative death and with upper-lobe-predominant emphysema. The hazard for the composite event significantly favored the LVRS group, although it was most significant in patients with predominantly upper-lobe emphysema. The beneficial impact of LVRS on QoL decline was most significant during the 2 years after LVRS. Conclusions: LVRS has a significant effect on the composite QoLsurvival endpoint tested, indicating its meaningful palliative role, particularly in patients with upper-lobe‐predominant emphysema.

This study compares the Programme for International Student Assessment (PISA) 2003 Mathematics results with the Trends in International Mathematics and Science Study (TIMSS) 2003 Grade 8 mathematics results, using country mean scores for 22 participants of both studies. It is found that Western countries generally performed better in PISA than in TIMSS, and Eastern European and Asian countries generally performed better in TIMSS than in PISA. Furthermore, two factors, content balance and years of schooling, can account for 93% of the variation between the differential performance of countries in PISA and TIMSS. Consequently, the rankings of countries in the two studies can be reconciled to a reasonable degree of accuracy.

This research examined students’ responses to mathematics problem-solving tasks and applied a general multidimensional IRT model at the response category level. In doing so, cognitive processes were identified and modelled through item response modelling to extract more information than would be provided using conventional practices in scoring items. More specifically, the study consisted of two parts. The first part involved the development of a mathematics problem-solving framework that was theoretically grounded, drawing upon research in mathematics education and cognitive psychology. The framework was then used as the basis for item development. The second part of the research involved the analysis of the item response data. It was demonstrated that multidimensional IRT models were powerful tools for extracting information from a limited number of item responses. A problem-solving profile for each student could be constructed from the results of IRT scaling.

Purpose: Limited data exist describing risk factors for mortality in patients having predominantly emphysema. Subjects and Methods: A total of 609 patients with severe emphysema (ages 40–83 yr; 64.2% male) randomized to the medical therapy arm of the National Emphysema Treatment Trial formed the study group. Cox proportional hazards regression analysis was used to investigate risk factors for all-cause mortality. Risk factors examined included demographics, body mass index, physiologic data, quality of life, dyspnea, oxygen utilization, hemoglobin, smoking history, quantitative emphysema markers on computed tomography, and a modification of a recently described multifunctional index (modified BODE). Results: Overall, high mortality was seen in this cohort (12.7 deaths per 100 person-years; 292 total deaths). In multivariate analyses, increasing age (p = 0.001), oxygen utilization (p = 0.04), lower total lung capacity % predicted (p = 0.05), higher residual volume % predicted (p = 0.04), lower maximal cardiopulmonary exercise testing workload (p = 0.002), greater proportion of emphysema in the lower lung zone versus the upper lung zone (p = 0.005), and lower upper-to-lower-lung perfusion ratio (p = 0.007), and modified BODE (p = 0.02) were predictive of mortality. FEV1 was a significant predictor of mortality in univariate analysis (p = 0.005), but not in multivariate analysis (p = 0.21). Conclusion: Although patients with advanced emphysema experience significant mortality, subgroups based on age, oxygen utilization, physiologic measures, exercise capacity, and emphysema distribution identify those at increased risk of death.

This open-label, randomized, placebo-controlled, incomplete-block, 3-period crossover pilot study investigated the effects of peroxisome proliferator-activated receptor alpha- and gamma-agonists on biomarkers of lipid and glucose metabolism in 12 nondiabetic subjects. Plasma samples were collected before and after each 14-day treatment with placebo, fenofibrate (201 mg/d), rosiglitazone (4 mg twice daily), and combined fenofibrate (201 mg/d) plus rosiglitazone (4 mg twice daily). Except for triglycerides (P < .042) and free fatty acids (P < .074), no significant interaction was demonstrated between fenofibrate and rosiglitazone; thus, the effect due to each drug alone was evaluated (presence/absence of drug). Fenofibrate significantly (P < .050) increased lipoprotein lipase activity (35%) and decreased apolipoproteins B (13%) and C-III (20%). Rosiglitazone significantly (P < .050) decreased fasting glucose (7.3%) and increased apolipoprotein C-III (19%) and adiponectin (137%). Fenofibrate and rosiglitazone also produced effects on triglycerides and free fatty acids, but it was not possible to determine if these effects were synergistic in nature.

In large-scale assessment programs such as NAEP, TIMSS and PISA, students' achievement data sets provided for secondary analysts contain so-called plausible values. Plausible values are multiple imputations of the unobservable latent achievement for each student. In this article it has been shown how plausible values are used to: (1) address concerns with bias in the estimation of certain population parameters when point estimates of latent achievement are used to estimate those population parameters; (2) allow secondary data analysts to employ standard techniques and tools (e.g., SPSS, SAS procedures) to analyse achievement data that contains substantial measurement error components; and (3) facilitate the computation of standard errors of estimates when the sample design is complex. The advantages of plausible values have been illustrated by comparing the use of maximum likelihood estimates and plausible values (PV) for estimating a range of population statistics.

Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.

Background. The Child and Adolescent Trial for Cardiovascular Health (CATCH), a multisite field trial, tested the effectiveness of multiple interventions for cardiovascular disease risk behaviors in children in third through fifth grades. This paper reports the tracking of physiologic variables through eighth grade. Methods. The cohort began with 5,106 third grade students from diverse ethnic backgrounds: 69% Caucasian, 14% Hispanic, 13% African American, and 4% other. Seventy-two percent of students were remeasured. Measures described are serum lipids, blood pressure, and body anthropometrics. Tracking was examined across three time points (third, fifth, and eighth grades) with a scaled Kendall concordance coefficient and percentage retention within quintiles across time. Results. For the overall sample, tacking was strongest for body mass index (BMI) (Kendall coefficient = 0.86) and weight (0.86), followed by skinfold thicknesses (0.72–0.78), serum lipids (0.67–0.72), and blood pressure (0.45–0.51). For BMI, 96% of students stayed within ±1 quintile from third to fifth grades; 90% stayed within this range from third to eighth grades. Conclusions. There were small but noticeable gender and ethnic differences: tracking was stronger among boys and African American students. These results demonstrate that the children's relative level of cardiovascular risk remained stable over a 6-year period.

In this article we show how certain analytic problems that arise when one attempts to use latent variables as outcomes in regression analyses can be addressed by taking a multilevel perspective on item response modeling. Under a multilevel, or hierarchical, perspective we cast the item response model as a within-student model and the student population distribution as a between-student model. Taking this perspective leads naturally to an extension of the student population model to include a range of student-level variables, and it invites the possibility of further extending the models to additional levels so that multilevel models can be applied with latent outcome variables. In the two-level case, the model that we employ is formally equivalent to the plausible value procedures that are used as part of the National Assessment of Educational Progress (NAEP), but we present the method for a different class of measurement models, and we use a simultaneous estimation method rather than two-step estimation. In our application of the models to the appropriate treatment of measurement error in the dependent variable of a between-student regression, we also illustrate the adequacy of some approximate procedures that are used in NAEP.

This paper examines the residual-based fit statistics commonly used in Rasch measurement. In particular, the paper analytically examines some of the theoretical properties of the residual-based fit statistics with a view to establishing the inferences that can be made using these fit statistics. More specifically, the relationships between the distributional properties of the fit statistics and sample size are discussed; some research that erroneously concludes that residual-based fit statistics are unstable is reviewed; and finally, it is analytically illustrated that, for dichotomous items, residual-based fit statistics provide a measure of the relative slope of empirical item characteristic curves. With a clear understanding of the theoretical properties of the fit statistics, the use and limitations of these statistics can be placed in the right light.

The Child and Adolescent Trial for Cardiovascular Health (CATCH) is an elementary school cardiovascular health education field trial in progress in San Diego, California, New Orleans, Louisiana, Minneapolis, Minnesota, and Austin, Texas. Because a significant part of a child's health behaviors are shaped within the home, CATCH is evaluating whether the effects of the school-based program are enhanced by the inclusion of a home-based program. A 7 x 7 x 10 randomized design with 7 school-only and 7 school-plus-family intervention schools, along with 10 control schools is implemented at each site. The CATCH family intervention is implemented during Grades 3 through 5 and consists of home-based curricula and Family Fun Nights focusing on healthier eating and increased physical activity during Grades 3 and 4, along with a smoking prevention curriculum in Grade 5. CATCH is examining the effectiveness of family (household) involvement through changes in students' dietary intake of fat and sodium. This paper describes the process evaluation methods used to document the extent of participation in the family program. Data reported for the third-grade Family Fun Nights held in the 28 family schools across all sites reflected an average student participation rate of 67%. The average family member to student ratio was approximately 2:1. Participation by all third-grade teachers and the majority of physical education specialists was observed.

Rationale: The predictive value of longitudinal change in BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise capacity) index has received limited attention. We hypothesized that decrease in a modified BODE (mBODE) would predict survival in National Emphysema Treatment Trial (NETT) patients. Objectives: To determine how the mBODE score changes in patients with lung volume reduction surgery versus medical therapy and correlations with survival. Methods: Clinical data were recorded using standardized instruments. The mBODE was calculated and patient-specific mBODE trajectories during 6, 12, and 24 months of follow-up were estimated using separate regressions for each patient. Patients were classified as having decreasing, stable, increasing, or missing mBODE based on their absolute change from baseline. The predictive ability of mBODE change on survival was assessed using multivariate Cox regression models. The index of concordance was used to directly compare the predictive ability of mBODE and its separate components. Measurements and Main Results: The entire cohort (610 treated medically and 608 treated surgically) was characterized by severe airflow obstruction, moderate breathlessness, and increased mBODE at baseline. A wide distribution of change in mBODE was seen at follow-up. An increase in mBODE of more than 1 point was associated with increased mortality in surgically and medically treated patients. Surgically treated patients were less likely to experience death or an increase greater than 1 in mBODE. Indices of concordance showed that mBODE change predicted survival better than its separate components. Conclusions: The mBODE demonstrates short- and intermediate-term responsiveness to intervention in severe chronic obstructive pulmonary disease. Increase in mBODE of more than 1 point from baseline to 6, 12, and 24 months of follow-up was predictive of subsequent mortality. Change in mBODE may prove a good surrogate measure of survival in therapeutic trials in severe chronic obstructive pulmonary disease. Clinical trial registered with www.clinicaltrials.gov (NCT 00000606).

Purpose: To evaluate two generic and two disease-specific measures of health-related quality of life (QOL) using prerandomization data from the National Emphysema Treatment Trial (NETT). Method: The analyses used data collected from the 1,218 subjects who were randomized in the NETT. Patients completed evaluations before and after completion of the prerandomization phase of the NETT pulmonary rehabilitation program. Using data obtained prior to participation in the rehabilitation program, QOL measures were evaluated against physiologic and functional criteria using correlational analysis. The physiologic criteria included estimates of emphysema severity based on FEV 1 and measures of Pa o 2 obtained with the subject at rest and breathing room air. Functional measures included the 6-min walk distance (6MWD), maximum work, and hospitalizations in the prior 3 months. Results: Correlation coefficients between QOL measures ranged from −0.31 to 0.70. In comparison to normative samples, scores on general QOL measures were low, suggesting that the NETT participants were quite ill. All QOL measures were modestly but significantly correlated with FEV 1 , maximum work, and 6MWD. Patients who had stayed overnight in a hospital in the prior 3 months reported lower QOL on average than those who had not been hospitalized. There were significant improvements for all QOL measures following the rehabilitation program, and improvements in QOL were correlated with improvements in 6MWD. Comment: The disease-specific and general QOL measures used in the NETT were correlated. Analyses suggested that these measures improved significantly following the rehabilitation phase of the NETT.

BACKGROUND Antiinflammatory therapies, such as inhaled corticosteroids or nedocromil, are recommended for children with asthma, although there is limited information on their long-term use. METHODS We randomly assigned 1041 children from 5 through 12 years of age with mild-to-moderate asthma to receive 200 microg of budesonide (311 children), 8 mg of nedocromil (312 children), or placebo (418 children) twice daily. We treated the participants for four to six years. All children used albuterol for asthma symptoms. RESULTS There was no significant difference between either treatment and placebo in the primary outcome, the degree of change in the forced expiratory volume in one second (FEV1, expressed as a percentage of the predicted value) after the administration of a bronchodilator. As compared with the children assigned to placebo, the children assigned to receive budesonide had a significantly smaller decline in the ratio of FEV1 to forced vital capacity (FVC, expressed as a percentage) before the administration of a bronchodilator (decline in FEV1:FVC, 0.2 percent vs. 1.8 percent). The children given budesonide also had lower airway responsiveness to methacholine, fewer hospitalizations (2.5 vs. 4.4 per 100 person-years), fewer urgent visits to a caregiver (12 vs. 22 per 100 person-years), greater reduction in the need for albuterol for symptoms, fewer courses of prednisone, and a smaller percentage of days on which additional asthma medications were needed. As compared with placebo, nedocromil significantly reduced urgent care visits (16 vs. 22 per 100 person-years) and courses of prednisone. The mean increase in height in the budesonide group was 1.1 cm less than in the placebo group (22.7 vs. 23.8 cm, P=0.005); this difference was evident mostly within the first year. The height increase was similar in the nedocromil and placebo groups. CONCLUSIONS In children with mild-to-moderate asthma, neither budesonide nor nedocromil is better than placebo in terms of lung function, but inhaled budesonide improves airway responsiveness and provides better control of asthma than placebo or nedocromil. The side effects of budesonide are limited to a small, transient reduction in growth velocity.

We sought to determine whether depressive or anxiety symptoms are associated with chronic obstructive pulmonary disease (COPD) hospitalization or mortality. These data were collected as part of the National Emphysema Treatment Trial (NETT), a randomized controlled trial of lung volume reduction surgery vs continued medical treatment conducted at 17 clinics across the United States between January 29, 1998, and July 31, 2002.Prospective cohort study among participants in the NETT with emphysema and severe airflow limitation who were randomized to medical therapy. Primary outcomes were 1- and 3-year mortality, as well as COPD or respiratory-related hospitalization or emergency department visit during the 1-year follow-up period. Of 610 patients randomized to medical therapy, complete data on hospitalization and mortality were available for 3 years of follow-up for 603 patients (98.9%).Depressive symptoms were assessed using the Beck Depression Inventory (BDI) questionnaire, and anxiety was assessed using the State-Trait Anxiety Inventory. Among 610 subjects, 40.8% had at least mild to moderate depressive symptoms. Patients in the highest quintile of BDI score (BDI score,or=15) had an increased risk of respiratory hospitalization in unadjusted analysis compared with patients in the lowest quintile (BDI score,5) (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.30-3.93). After adjustment for disease severity, this relationship was no longer statistically significant. The adjusted risk of 3-year mortality was increased among those in the highest quintile of BDI score (OR, 2.74; 95% CI, 1.42-5.29) compared with those in the lowest quintile. Anxiety was not associated with hospitalization or mortality in this population.Depressive symptoms are common in patients with severe COPD and are treated in few subjects. Depressive symptoms are associated with increased risk for 3-year mortality but not 1-year mortality or hospitalization.

Objective To assess differences through grade 8 in diet, physical activity, and related health indicators of students who participated in the Child and Adolescent Trial for Cardiovascular Health (CATCH) school and family intervention from grades 3 through 5. Design Follow-up of the 4-center, randomized, controlled field trial with 56 intervention and 40 control elementary schools. Participants We studied 3714 (73%) of the initial CATCH cohort of 5106 students from ethnically diverse backgrounds in California, Louisiana, Minnesota, and Texas at grades 6, 7, and 8. Results Self-reported daily energy intake from fat at baseline was virtually identical in the control (32.7%) and intervention (32.6%) groups. At grade 5, the intake for controls remained at 32.2%, while the intake for the intervention group declined to 30.3% ( P P =.01). Intervention students maintained significantly higher self-reported daily vigorous activity than control students ( P =.001), although the difference declined from 13.6 minutes in grade 5 to 11.2, 10.8, and 8.8 minutes in grades 6, 7, and 8, respectively. Significant differences in favor of the intervention students also persisted at grade 8 for dietary knowledge and dietary intentions, but not for social support for physical activity. No impact on smoking behavior or stages of contemplating smoking was detected at grade 8. No significant differences were noted among physiologic indicators of body mass index, blood pressure, or serum lipid and cholesterol levels. Conclusion The original CATCH results demonstrated that school-level interventions could modify school lunch and school physical education programs as well as influence student behaviors. This 3-year follow-up without further intervention suggests that the behavioral changes initiated during the elementary school years persisted to early adolescence for self-reported dietary and physical activity behaviors.

grade intervention including school food service modifications, enhanced physical education (PE), and classroom health curricula. Twenty-eight additional schools received these components plus family education. Main Outcome Measures.\p=m-\Atthe school level, the two primary end points were changes in the fat content of food service lunch offerings and the amount of moderate-to-vigorous physical activity in the PE programs. At the level of the individual student, serum cholesterol change was the primary end point and was used for power calculations for the study. Individual level secondary end points included psychosocial factors, recall measures of eating and physical activity patterns, and other physiologic measures. Results.\p=m-\Inintervention school lunches, the percentage of energy intake from fat fell significantly more (from 38.7% to 31.9%) than in control lunches (from 38.9% to 36.2%)(P

Objective To characterize mortality in persons diagnosed with primary pulmonary hypertension and to investigate factors associated with survival. Design Registry with prospective follow-up. Setting Thirty-two clinical centers in the United States participating in the Patient Registry for the Characterization of Primary Pulmonary Hypertension supported by the National Heart, Lung, and Blood Institute. Patients Patients (194) diagnosed at clinical centers between 1 July 1981 and 31 December 1985 and followed through 8 August 1988. Measurements At diagnosis, measurements of hemodynamic variables, pulmonary function, and gas exchange variables were taken in addition to information on demographic variables, medical history, and life-style. Patients were followed for survival at 6-month intervals. Main results The estimated median survival of these patients was 2.8 years (95% Cl, 1.9 to 3.7 years). Estimated single-year survival rates were as follows: at 1 year, 68% (Cl, 61% to 75%); at 3 years, 48% (Cl, 41% to 55%); and at 5 years, 34% (Cl, 24% to 44%). Variables associated with poor survival included a New York Heart Association (NYHA) functional class of III or IV, presence of Raynaud phenomenon, elevated mean right atrial pressure, elevated mean pulmonary artery pressure, decreased cardiac index, and decreased diffusing capacity for carbon monoxide (DLCO). Drug therapy at entry or discharge was not associated with survival duration. Conclusions Mortality was most closely associated with right ventricular hemodynamic function and can be characterized by means of an equation using three variables: mean pulmonary artery pressure, mean right atrial pressure, and cardiac index. Such an equation, once validated prospectively, could be used as an adjunct in planning treatment strategies and allocating medical resources.

Recent findings in several laboratories have demonstrated the important interactions of platelet-activating factor (PAF) with vascular endothelial cells, and thus the potential role of this lipid mediator in the pathophysiology of the cardiovascular system. PAF potently and specifically stimulates the in situ and in vivo release of tissue-type plasminogen activator from the vascular endothelium [Emeis and Kluft, 1985]. Several lines of evidence indicate that PAF may play a critical role in the neutrophil adhesion to endothelial cells stimulated with thrombin or leukotrienes [Zimmerman et al., 1985]. PAF is a potent stimulator of Ca+2 efflux from endothelial cells, which thus might be an early step in the suspected involvement of the endothelium in in vivo responses to PAF, such as hypotension and increased vascular permeability [Brock and Gimbrone, 1986]. In our own laboratory, we have developed a specific and potent PAF receptor antagonist, L-652,731, in order to determine the role of PAF in different animal models of disease. Utilizing this receptor antagonist as well as other criteria, PAF is indicated to be a major mediator of the endotoxin-induced hypotension in rats and soluble immune complex-induced hypotension and extravasation, also in rats. The immune complex-induced increased plasma glucosaminidase is partially mediated by PAF, whereas the immediate and complete neutropenia is not indicated to involve PAF.

Two-sample rank tests for survival data in the presence of arbitrary right censoring are considered. We distinguish between administrative censoring, arising because survival study participants do not enter as a cohort, and censoring due to “loss to follow-up.” We show how conditionally distribution-free tests can be constructed in certain situations. Conditional versions of the generalized Wilcoxon and Mantel statistics are shown to be asymptotically normal in the conditional reference set, but with modified means and variances. Efficiency of these tests relative to asymptotically distribution-free competitors is unity, providing the censoring distributions are discrete, the same for both samples, and providing loss-to-follow-up (LFU) distributions are the same for the two samples. When these assumptions do not hold, efficiency can deteriorate considerably, being poorest, other things being equal, when the censoring distribution is continuous.

SummaryBackgroundIn COPD patients, hyperinflation impairs cardiac function. We examined whether lung deflation improves oxygen pulse, a surrogate marker of stroke volume.MethodsIn 129 NETT patients with cardiopulmonary exercise testing (CPET) and arterial blood gases (ABG substudy), hyperinflation was assessed with residual volume to total lung capacity ratio (RV/TLC), and cardiac function with oxygen pulse (O2 pulse=VO2/HR) at baseline and 6 months. Medical and surgical patients were divided into “deflators” and “non-deflators” based on change in RV/TLC from baseline (∆RV/TLC). We defined deflation as the ∆RV/TLC experienced by 75% of surgical patients. We examined changes in O2 pulse at peak and similar (iso-work) exercise. Findings were validated in 718 patients who underwent CPET without ABGs.ResultsIn the ABG substudy, surgical and medical deflators improved their RV/TLC and peak O2 pulse (median ∆RV/TLC −18.0% vs. −9.3%, p=0.0003; median ∆O2 pulse 13.6% vs. 1.8%, p=0.12). Surgical deflators also improved iso-work O2 pulse (0.53mL/beat, p=0.04 at 20W). In the validation cohort, surgical deflators experienced a greater improvement in peak O2 pulse than medical deflators (mean 18.9% vs. 1.1%). In surgical deflators improvements in O2 pulse at rest and during unloaded pedaling (0.32mL/beat, p

Background Anxiety in patients with chronic obstructive pulmonary disease (COPD) is associated with self-reported disability. The purpose of this study is to determine whether there is an association between anxiety and functional measures, quality of life and dyspnea. Methods Data from 1828 patients with moderate to severe emphysema enrolled in the National Emphysema Treatment Trial (NETT), collected prior to rehabilitation and randomization, were used in linear regression models to test the association between anxiety symptoms, measured by the Spielberger State Trait Anxiety Inventory (STAI) and: (a) six-minute walk distance test (6 MWD), (b) cycle ergometry peak workload, (c) St. Georges Respiratory Questionnaire (SRGQ), and (d) UCSD Shortness of Breath Questionnaire (SOBQ), after controlling for potential confounders including age, gender, FEV1 (% predicted), DLCO (% predicted), and the Beck Depression Inventory (BDI). Results Anxiety was significantly associated with worse functional capacity [6 MWD (B = -0.944, p < .001), ergometry peak workload (B = -.087, p = .04)], quality of life (B = .172, p < .001) and shortness of breath (B = .180, p < .001). Regression coefficients show that a 10 point increase in anxiety score is associated with a mean decrease in 6 MWD of 9 meters, a 1 Watt decrease in peak exercise workload, and an increase of almost 2 points on both the SGRQ and SOBQ. Conclusion In clinically stable patients with moderate to severe emphysema, anxiety is associated with worse exercise performance, quality of life and shortness of breath, after accounting for the influence of demographic and physiologic factors known to affect these outcomes. Trail Registration ClinicalTrials.gov NCT00000606