Search

Background Head and neck squamous cell cancer (HNSCC) occurs at higher rates among persons with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared with HNSCC patients without HIV. Methods Patient data from HNSCC individuals were collected at a single academic hospital center between 2002 and 2018. Forty-eight patients with HIV (HIV-HNSCC) and 2894 HNSCC patients without HIV were included. Multivariate analysis determined predictors of survival using Cox proportional hazards regression model. HIV-positive and -negative tumors were analyzed by quantitative immunofluorescence for expression of CD4, CD8, CD20 and PD-L1. Results HIV-HNSCC patients had a lower median overall survival than HNSCC patients without HIV (34 [18–84] vs 94 [86–103] months; P < .001). In multivariate analysis that included age, sex, race/ethnicity, stage, site, tobacco use, time to treatment initiation, and insurance status, HIV was an independent predictor of poorer survival, with a hazard ratio of 1.98 (95% CI: 1.32–2.97; P < .001). PWH with human papillomavirus (HPV)–positive oropharyngeal tumors also had worse prognosis than HPV-positive oropharyngeal tumors in the population without HIV (P < .001). The tumor microenvironment among HIV-HNSCC patients revealed lower intratumoral CD8 infiltration among HIV+ HPV+ tumors compared with HIV– HPV+ tumors (P = .04). Conclusions HIV-HNSCC patients had worse prognosis than the non-HIV population, with HIV being an independent predictor of poor clinical outcomes when accounting for important sociodemographic and clinicopathologic factors. Our findings highlight differences in tumor biology that require further detailed characterization in large cohorts and increased inclusion of PWH in immunotherapy trials.

Head and neck squamous cell cancer (HNC) occurs at higher rates among people with HIV (PWH). This study compares the impact of sociodemographic and clinicopathologic characteristics on outcomes among PWH-HNSCC compared to Uninfected- HNSCC patients.Patient data from individuals with HNSCC were collected at a single academic hospital center between 2002 and 2018. 48 patients with HIV infection (HIV-HNSCC) and 2894 uninfected patients (Uninfected-HNSCC) were included. Multivariate analysis determined predictors of survival using Cox proportional hazards regression model. HIV + and HIV- tumors were analyzed by quantitative immunofluorescence for expression of CD4, CD8, CD20 and PD-L1.HIV-HNSCC patients had lower median overall survival compared to Uninfected-HNSCC patients (34 [18-84] vs. 94 [86-103] months, p 0.001). In a multivariate analysis that included age, sex, race/ethnicity, stage, site, tobacco use, time to treatment initiation, and insurance status, HIV infection was an independent predictor of poorer survival with a hazard ratio of 1.98 (95% CI 1.32-2.97, p 0.001). PWH with HPV + oropharyngeal tumors also had worse prognosis compared to HPV + oropharyngeal tumors in the HIV-Uninfected population(p 0.001). The tumor microenvironment among HIV-HNSCC patients revealed lower intra-tumoral CD8 infiltration among HIV + HPV + tumors compared to HIV-HPV + tumors (p = 0.04).HNSCC patients with HIV had worse prognosis compared to the general population, with HIV being an independent predictor of poor clinical outcomes when accounting for important sociodemographic and clinicopathologic factors. Our findings highlight differences in tumor biology that require further detailed characterization in large cohorts and increased inclusion of PWH in immunotherapy trials.

Musculoskeletal ultrasound (MSUS) has been extensively studied by rheumatologists in Europe and the Americas, but less is known about MSUS use in Asia. Our hypothesis is that MSUS use is less prevalent in China as compared with its Western counterparts. This study reports the most up-to-date recommendations for MSUS use in rheumatology globally and is also the first study to characterize the current practices, training, and perceptions regarding MSUS of rheumatologists in China. A 43-question survey was designed and distributed via mobile application to members of the Chinese Rheumatology Association, primarily to investigate the current prevalence and utilization of MSUS in China. Statistical analyses included the use of chi-square tests and independent-samples t tests, with p values less than 0.05 considered statistically significant. The results showed low rates of MSUS training (129/528, 24%) and current MSUS use (89/524, 17%) in China. However, there was a high level of interest in learning MSUS, especially among younger respondents. Lack of access to training programs and user variability in skill were seen as significant barriers to the uptake of MSUS. Despite low rates of MSUS training and utilization, the vast majority of respondents believe that MSUS should become a standard clinical tool in rheumatology, and there was great interest in undergoing training. Importantly, lack of access to MSUS training programs and user variability in skill were seen as significant obstacles to the more widespread use of MSUS, which suggests a need for more standardized, high-quality MSUS training in China.

Insulin analogs have been developed to treat diabetes with focus primarily on improving the time action profile without affecting ligand-receptor interaction or functional selectivity. As a result, inherent liabilities (e.g. hypoglycemia) of injectable insulin continue to limit the true therapeutic potential of related agents. Insulin dimers were synthesized to investigate whether partial agonism of the insulin receptor (IR) tyrosine kinase is achievable, and to explore the potential for tissue-selective systemic insulin pharmacology. The insulin dimers induced distinct IR conformational changes compared to native monomeric insulin and substrate phosphorylation assays demonstrated partial agonism. Structurally distinct dimers with differences in conjugation sites and linkers were prepared to deliver desirable IR partial agonist (IRPA). Systemic infusions of a B29-B29 dimer in vivo revealed sharp differences compared to native insulin. Suppression of hepatic glucose production and lipolysis were like that attained with regular insulin, albeit with a distinctly shallower dose-response. In contrast, there was highly attenuated stimulation of glucose uptake into muscle. Mechanistic studies indicated that IRPAs exploit tissue differences in receptor density and have additional distinctions pertaining to drug clearance and distribution. The hepato-adipose selective action of IRPAs is a potentially safer approach for treatment of diabetes.

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.

Introduction: Incidence of non-AIDS-defining cancers, including head and neck cancer (HNC), is rising among people living with HIV (PLWH). This study compares outcomes of HIV+ and Uninfected HNC patients at a single institution. Methods: Yale Tumor Registry query identified 3,488 HNC patients, including 50 with HIV, for analysis (Clinical Cohort, 2002-2018). Quantitative immunofluorescence (QIF) was performed on tumor tissue among 22 HIV+ and 75 matched Uninfected patients. Results: Within our clinical cohort, HIV+ HNC patients were younger compared to Uninfected patients (55.5 vs. 62.0, p Conclusion: HNC patients with HIV were significantly younger compared to the general HNC population, and experienced lower 1-yr survival with early stage disease. CD8 T cell infiltration, which is associated with improved outcomes, appears lower among PLWH. Further evaluation of HIV-HNC subgroups, with detailed analysis of tumor site, HPV status and treatment disparities, is warranted to better delineate differences in outcome. Citation Format: Syim Salahuddin, Margaret Wu, Javier Perez Irizarry, Teresita Vega, Natalia Isaeva, Kurt Schalper, Wendell G. Yarbrough, Brinda Emu. Lower survival among HIV-infected head and neck cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 418.

Rationale: Asthma in children generally starts as being mild but may progress to being severe and may stay severe for unknown reasons. Objectives: To identify factors in childhood that predict the persistence of severe asthma in late adolescence and early adulthood. Methods: The CAMP (Childhood Asthma Management Program) is, to our knowledge, the largest and longest asthma trial to date; it includes 1,041 children aged 5–12 years with mild to moderate asthma. We evaluated 682 program participants with analyzable data in late adolescence (age, 17–19 yr) and early adulthood (age, 21–23 yr). Measurements and Main Results: To best capture the cases of severe asthma, a status of severe asthma was defined by using criteria from the American Thoracic Society and the National Asthma Education and Prevention Program. Logistic regression with stepwise elimination was used to analyze the clinical features, biomarkers, and lung function that are predictive of the persistence of severe asthma. In late adolescence and early adulthood, 12% and 19% of the participants had severe asthma, respectively; only 6% at both time points had severe cases. For every 5% decrease in the postbronchodilator FEV(1)/FVC ratio in childhood, the odds of the persistence of severe asthma increased by 2.36-fold (95% confidence interval [CI], 1.70–3.28; P

Since its debut a century ago, insulin therapies have saved many lives and are now routinely used by patients with diabetes to manage hyperglycemia. Exemplary early studies of insulin molecular pathways led to the realization of the critical roles of signaling transduction in mediating its pleiotropic actions. Multiple insulin analogs have been developed in the last few decades primarily focused on improving the time action profile without affecting ligand-receptor interaction or functional selectivity in downstream signaling. As a result, inherent liabilities of injectable insulins continue to limit insulin’s true therapeutic potential. For example, fear of hypoglycemia often leads to underdosing and inadequate glycemic control and, as a consequence, continued risk of diabetic complications. Efforts to develop hepatic targeted basal insulin analogs lead to reduced effect on skeletal muscle and lower hypoglycemic risk but failed to adequately suppress lipolysis. To achieve both functional selectivity and a more desirable pharmacological profile, we evaluated a series of covalent insulin dimers that act in cellular assays as insulin receptor partial agonists (IRPA). Structural studies revealed distinct insulin receptor interactions compared to insulin analogs. Furthermore, IRPAs were shown to induce biased signaling in cellular assays that supports the potential for reduced mitogenic and atherosclerotic activities compared to regular insulin. In vivo, IRPAs exhibit tissue preferential action that attenuates stimulation of skeletal muscle glucose uptake while retaining hepatic and adipose actions to regulate glucose production and lipolysis, respectively. These attributes are expected to significantly reduce the hypoglycemic risk while achieving similar glycemic control and less body weight gain relative to comparator insulin analogs in animal models. Furthermore, IRPA lessens receptor internalization resulting in a slower clearance and long duration of action across species, an optimal feature for a basal insulin. In summary, IRPA possesses the desired molecular features that are required to reduce the hypoglycemic risk while maintaining the broad metabolic benefits of insulin therapy and as such represents a potential transformative therapy for patients with diabetes.

e18080 Background: Incidence of non-AIDS-defining cancers, including head and neck cancer (HNC), is rising among people with HIV (PWH) in the combination antiretroviral therapy (cART) era. The following study compares demographics, clinical outcomes, and the tumor microenvironment of HIV+ and Uninfected HNC patients at a single institution. Methods: Yale Tumor Registry query identified 3,356 HNC patients from 2002 to 2018 for analysis, including 50 PWH. In addition, quantitative immunofluorescence (QIF) was performed on tumor tissue from 22 PWH and 75 matched Uninfected patients. HPV status was based on p16 staining done universally among oropharyngeal squamous cell carcinomas (OPSCC) after 2010. Results: PWH were younger at cancer presentation compared to Uninfected patients (55.5 vs. 62.0, p < 0.001), with differences in race/ethnicity and insurance status (p < 0.001 for both). Biologic sex, tobacco use, alcohol consumption, anatomic site, stage at presentation, stage-specific treatment, and time to initiation of treatment were comparable between HIV+ and Uninfected cohorts. 89% of the PWH were on cART, with 79% achieving viral loads ≤200 copies/mL and a median CD4 count of 341 cells/mm³. Median survival among PWH was 39.1 months, compared to 100.8 months among Uninfected patients (p < 0.001). In a multivariate (MV) analysis that included age, sex, race/ethnicity, tobacco use, anatomic site, stage, time to treatment initiation and insurance status, HIV was an independent predictor of poor outcome (HR 1.88 with 95% CI: 1.25-2.81). Difference in survival was noted particularly in early stage (stages 0, I, II) cancer, with a median survival of 73.8 months in PWH compared to 141.9 months in Uninfected patients (p = 0.001). Survival was comparable among late stage (stages III, IV) HNC patients. Among PWH, increased HIV viral load was associated with poor outcome in a MV analysis (p = 0.03). Among HPV-associated OPSCC, PWH had decreased survival compared to Uninfected patients (p < 0.001). In our study of the tumor microenvironment by QIF, tumors of PWH had lower tumoral CD8 T cell infiltration (p = 0.04) and lower PD-L1 expression in tumor, stroma, and combined compartments (CPS) (p = 0.01, p = 0.03, and p = 0.01, respectively) compared to Uninfected patients. Conclusions: In our single institution study, HNC patients living with HIV experienced decreased overall survival, with HIV serving as an independent predictor of poor outcome in a multivariate analysis which included insurance status and treatment approaches. Difference in outcome was significant among early stage tumors and among HPV+ OPSCC. CD8 T cell infiltration and PD-L1 expression, both associated with improved outcomes in the general population, are decreased within the TME of PWH. Our data suggest that HIV-associated HNC is associated with poorer outcomes and highlight differences in tumor biology that require further detailed characterization in large cohorts.

Made available in DSpace on 2019-10-06T17:15:07Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-26 American Diabetes Association American Heart Association Ben B. and Iris M. Margolis Foundation Diabetes Research Center, University of Washington Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Preeclampsia Research Laboratories U.S. Department of Agriculture Juvenile Diabetes Research Foundation United Kingdom Agricultural Research Service National Institutes of Health Norges Idrettshøgskole Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders. Department of Nutrition and Integrative Physiology Diabetes and Metabolism Research Center University of Utah Merck Research Laboratories Merck School of Dentistry São Paulo State University (UNESP) Department of Biochemistry and the Diabetes and Metabolism Research Center University of Utah Baker IDI Heart and Diabetes Institute Faculty of Science University of Brunei Darussalam Sciex Howard Hughes Medical Institute Bristol Myers Squibb Morphic Therapeutic Johnson and Johnson School of Dentistry São Paulo State University (UNESP) FAPESP: 2014/17619-6 U.S. Department of Agriculture: 2019-67018-29250 Juvenile Diabetes Research Foundation United Kingdom: 3-SRA-2019-768-A-B Agricultural Research Service: 5T32DK091317 National Institutes of Health: DK108833 National Institutes of Health: DK112826 National Institutes of Health: DK115824 National Institutes of Health: DK116450 Norges Idrettshøgskole: P30DK020579

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.

Musculoskeletal ultrasound (MSUS) has been extensively studied by rheumatologists in Europe and the Americas, but less is known about MSUS use in Asia. Our hypothesis is that MSUS use is less prevalent in China as compared with its Western counterparts. This study reports the most up-to-date recommendations for MSUS use in rheumatology globally and is also the first study to characterize the current practices, training, and perceptions regarding MSUS of rheumatologists in China.A 43-question survey was designed and distributed via mobile application to members of the Chinese Rheumatology Association, primarily to investigate the current prevalence and utilization of MSUS in China. Statistical analyses included the use of chi-square tests and independent-samples t tests, with p values less than 0.05 considered statistically significant.The results showed low rates of MSUS training (129/528, 24%) and current MSUS use (89/524, 17%) in China. However, there was a high level of interest in learning MSUS, especially among younger respondents. Lack of access to training programs and user variability in skill were seen as significant barriers to the uptake of MSUS.Despite low rates of MSUS training and utilization, the vast majority of respondents believe that MSUS should become a standard clinical tool in rheumatology, and there was great interest in undergoing training. Importantly, lack of access to MSUS training programs and user variability in skill were seen as significant obstacles to the more widespread use of MSUS, which suggests a need for more standardized, high-quality MSUS training in China. Key Points • A low percentage of Chinese rheumatologists (17%) currently use MSUS. • Chinese rheumatologists expressed a high level of interest in obtaining MSUS training. • The greatest perceived obstacle to more widespread MSUS use is the lack of training programs.

[Image: see text] We report new SSTR5 antagonists with enhanced potency, subtype selectivity, and minimal off-target activities as compared to previously reported compounds. Starting from the reported SSTR5 antagonist 1, we systematically surveyed changes in the central core and head piece while maintaining the diphenyl tail group constant. From this study the azaspirodecanone 10 emerged as a new highly potent and selective SSTR5 antagonist. Compound 10 lowered glucose excursion by 94% in an oral glucose tolerance test (OGTT) in mice following a 3 mg/kg oral dose. The compound increased both total and active circulating incretin hormone GLP-1 levels in mice at a dose of 10 mg/kg. A synergistic effect was also demonstrated when compound 10 was coadministered with a DPP-4 inhibitor, substantially increasing circulating active GLP-1[7–36] amide and insulin in response to a glucose challenge.

Insulin-induced hypoglycemia in diabetes is associated with impaired glucagon secretion. In this study, we tested whether stimulation of GPR119, a G-protein–coupled receptor expressed in pancreatic islet as well as enteroendocrine cells and previously shown to stimulate insulin and incretin secretion, might enhance glucagon secretion during hypoglycemia. In the study, GPR119 agonists were applied to isolated islets or perfused pancreata to assess insulin and glucagon secretion during hypoglycemic or hyperglycemic conditions. Insulin infusion hypoglycemic clamps were performed with or without GPR119 agonist pretreatment to assess glucagon counterregulation in healthy and streptozotocin (STZ)-induced diabetic rats, including those exposed to recurrent bouts of insulin-induced hypoglycemia that leads to suppression of hypoglycemia-induced glucagon release. Hypoglycemic clamp studies were also conducted in GPR119 knockout (KO) mice to evaluate whether the pharmacological stimulatory actions of GPR119 agonists on glucagon secretion during hypoglycemia were an on-target effect. The results revealed that GPR119 agonist-treated pancreata or cultured islets had increased glucagon secretion during low glucose perfusion. In vivo, GPR119 agonists also significantly increased glucagon secretion during hypoglycemia in healthy and STZ-diabetic rats, a response that was absent in GPR119 KO mice. In addition, impaired glucagon counterregulatory responses were restored by a GPR119 agonist in STZ-diabetic rats that were exposed to antecedent bouts of hypoglycemia. Thus, GPR119 agonists have the ability to pharmacologically augment glucagon secretion, specifically in response to hypoglycemia in diabetic rodents. Whether this effect might serve to diminish the occurrence and severity of iatrogenic hypoglycemia during intensive insulin therapy in patients with diabetes remains to be established.

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.

GPR40 and GPR120 are fatty acid sensors that play important roles in glucose and energy homeostasis. GPR40 potentiates glucose-dependent insulin secretion and demonstrated in clinical studies robust glucose lowering in type 2 diabetes. GPR120 improves insulin sensitivity in rodents, albeit its mechanism of action is not fully understood. Here, we postulated that the antidiabetic efficacy of GPR40 could be enhanced by coactivating GPR120. A combination of GPR40 and GPR120 agonists in db/db mice, as well as a single molecule with dual agonist activities, achieved superior glycemic control compared with either monotherapy. Compared with a GPR40 selective agonist, the dual agonist improved insulin sensitivity in ob/ob mice measured by hyperinsulinemic-euglycemic clamp, preserved islet morphology, and increased expression of several key lipolytic genes in adipose tissue of Zucker diabetic fatty rats. Novel insights into the mechanism of action for GPR120 were obtained. Selective GPR120 activation suppressed lipolysis in primary white adipocytes, although this effect was attenuated in adipocytes from obese rats and obese rhesus, and sensitized the antilipolytic effect of insulin in rat and rhesus primary adipocytes. In conclusion, GPR120 agonism enhances insulin action in adipose tissue and yields a synergistic efficacy when combined with GPR40 agonism.

Climate variability and man-made impacts have severely damaged forests around the world in recent years, which calls for an urgent need of restoration aiming toward long-term sustainability for the forest environment. This paper proposes a new three-level decision tree (TLDT) approach to map forest, shadowy, bare and low-vegetated lands sequentially by integrating three spectral indices. TLDT requires neither image normalization nor atmospheric correction, and improves on the other methods by introducing more levels of decision tree classification with inputs from the same multispectral imagery. This approach is validated by comparing the results obtained from aerial orthophotos (25 cm) that were acquired at approximately the same time in which the Formosa-2 images (8 m) were being taken. The overall accuracy is as high as 96.8% after excluding the deviations near the boundary of each class caused by the different resolutions. With TLDT, the effectiveness of forest restoration at 30 sites are assessed using all available multispectral Formosat-2 images acquired between 2005 and 2016. The distinction between natural regeneration and regrowth enhanced by restoration efforts were also made by using the existing dataset and TLDT developed in this research. This work supports the use of multitemporal remote sensing imagery as a reliable source of data for assessing the effectiveness of forest restoration on a regular basis. This work also serves as the basis for studying the global trend of forest restoration in the future.

This abstract was not presented at the symposium.

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.

OBJECTIVES: GPR142, which is highly expressed in pancreatic islets, has recently been deorphanized as a receptor for aromatic amino acids; however, its physiological role and pharmacological potential is unclear.METHODS AND RESULTS: We find that GPR142 is expressed not only in β- but also in α-cells of the islets as well as in enteroendocrine cells, and we confirm that GPR142 is a highly selective sensor of essential aromatic amino acids, in particular Trp and oligopeptides with N-terminal Trp. GPR142 knock-out mice displayed a very limited metabolic phenotype but demonstrated that L-Trp induced secretion of pancreatic and gut hormones is mediated through GPR142 but that the receptor is not required for protein-induced hormone secretion. A synthetic GPR142 agonist stimulated insulin and glucagon as well as GIP, CCK, and GLP-1 secretion. In particular, GIP secretion was sensitive to oral administration of the GPR142 agonist an effect which in contrast to the other hormones was blocked by protein load. Oral administration of the GPR142 agonist increased [3H]-2-deoxyglucose uptake in muscle and fat depots mediated through insulin action while it lowered liver glycogen conceivably mediated through glucagon, and, consequently, it did not lower total blood glucose. Nevertheless, acute administration of the GPR142 agonist strongly improved oral glucose tolerance in both lean and obese mice as well as Zucker fatty rat. Six weeks in-feed chronic treatment with the GPR142 agonist did not affect body weight in DIO mice, but increased energy expenditure and carbohydrate utilization, lowered basal glucose, and improved insulin sensitivity.CONCLUSIONS: GPR142 functions as a sensor of aromatic amino acids, controlling GIP but also CCK and GLP-1 as well as insulin and glucagon in the pancreas. GPR142 agonists could have novel interesting potential in modifying metabolism through a balanced action of gut hormones as well as both insulin and glucagon.

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 article considers the role played by policy makers, government organisations, and research institutes (sometimes labelled “think tanks”) in the analysis, use and reporting of PISA data for the purposes of policy advice and advocacy. It draws on the ideas of Rizvi and Lingard (Globalizing Education Policy, 2010), Bogdandy and Goldmann (Governance by Indicators/ Global Power through Quantification and Rankings, 2012) and others to explore the ways in which such “agents of change” can interpret, manipulate and disseminate the results of data arising from large scale assessment survey programs such as PISA to influence and determine political and/or educational research agendas. This article illustrates this issue by highlighting the uncertainty surrounding the PISA data that have been used by a number of prominent, high profile agents of change to defend policy directions and advice. The final section of this paper highlights the need for policy makers and their advisors to become better informed of the technical limitations of using international achievement data if such data are to be used to inform policy development and educational reforms.

Hypoglycemia is commonly associated with insulin therapy, limiting both its safety and efficacy. The concept of modifying insulin to render its glucose-responsive release from an injection depot (of an insulin complexed exogenously with a recombinant lectin) was proposed approximately 4 decades ago but has been challenging to achieve. Data presented here demonstrate that mannosylated insulin analogs can undergo an additional route of clearance as result of their interaction with endogenous mannose receptor (MR), and this can occur in a glucose-dependent fashion, with increased binding to MR at low glucose. Yet, these analogs retain capacity for binding to the insulin receptor (IR). When the blood glucose level is elevated, as in individuals with diabetes mellitus, MR binding diminishes due to glucose competition, leading to reduced MR-mediated clearance and increased partitioning for IR binding and consequent glucose lowering. These studies demonstrate that a glucose-dependent locus of insulin clearance and, hence, insulin action can be achieved by targeting MR and IR concurrently.

Insulin has a narrow therapeutic index, reflected in a small margin between a dose that achieves good glycemic control and one that causes hypoglycemia. Once injected, the clearance of exogenous insulin is invariant regardless of blood glucose, aggravating the potential to cause hypoglycemia. We sought to create a “smart” insulin, one that can alter insulin clearance and hence insulin action in response to blood glucose, mitigating risk for hypoglycemia. The approach added saccharide units to insulin to create insulin analogs with affinity for both the insulin receptor (IR) and mannose receptor C-type 1 (MR), which functions to clear endogenous mannosylated proteins, a principle used to endow insulin analogs with glucose responsivity. Iteration of these efforts culminated in the discovery of MK-2640, and its in vitro and in vivo preclinical properties are detailed in this report. In glucose clamp experiments conducted in healthy dogs, as plasma glucose was lowered stepwise from 280 mg/dL to 80 mg/dL, progressively more MK-2640 was cleared via MR, reducing by ∼30% its availability for binding to the IR. In dose escalations studies in diabetic minipigs, a higher therapeutic index for MK-2640 (threefold) was observed versus regular insulin (1.3-fold).

Australia has declared its ambition to be within the ‘top five’ in the Programme for International Student Assessment (PISA) by 2025. So serious is it about this ambition, that the Australian Government has incorporated it into the Australian Education Act, 2013. Given this focus on PISA results and rankings, we go beyond average scores to take a close look at Australia's performance in PISA, examining rankings by different geographical units, by item content and by test completion. Based on this analysis and using data from interviews with measurement and policy experts, we show how uninformative and even misleading the ‘average performance scores’, on which the rankings are based, can be. We explore how a more nuanced understanding would point to quite different policy actions. After considering the PISA data and Australia's ‘top five’ ambition closely, we argue that neither the rankings nor such ambitions should be given much credence.

Antagonism of somatostatin subtype receptor 3 (sstr3) has emerged as a potential treatment of Type 2 diabetes. Unfortunately, the development of our first preclinical candidate, MK-4256, was discontinued due to a dose-dependent QTc (QT interval corrected for heart rate) prolongation observed in a conscious cardiovascular (CV) dog model. As the fate of the entire program rested on resolving this issue, it was imperative to determine whether the observed QTc prolongation was associated with hERG channel (the protein encoded by the human Ether-à-go-go-Related Gene) binding or was mechanism-based as a result of antagonizing sstr3. We investigated a structural series containing carboxylic acids to reduce the putative hERG off-target activity. A key tool compound, 3A, was identified from this SAR effort. As a potent sstr3 antagonist, 3A was shown to reduce glucose excursion in a mouse oGTT assay. Consistent with its minimal hERG activity from in vitro assays, 3A elicited little to no effect in an anesthetized, vagus-intact CV dog model at high plasma drug levels. These results afforded the critical conclusion that sstr3 antagonism is not responsible for the QTc effects and therefore cleared a path for the program to progress.

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 (

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.

The Rasch rating (or partial credit) model is a widely applied item response model that is used to model ordinal observed variables that are assumed to collectively reflect a common latent variable. In the application of the model there is considerable controversy surrounding the assessment of fit. This controversy is most notable when the set of parameters that are associated with the categories of an item have estimates that are not ordered in value in the same order as the categories. Some consider this disordering to be inconsistent with the intended order of the response categories in a variable and often term it reversed deltas. This article examines a variety of derivations of the model to illuminate the controversy. The examination of the derivations shows that the so-called parameter disorder and order of the response categories are separate phenomena. When the data fit the Rasch rating model the response categories are ordered regardless of the (order of the) values of the parameter estimates. In summary, reversed deltas are not necessarily evidence of a problem. In fact the reversed deltas phenomenon is indicative of specific patterns in the relative numbers of respondents in each category. When there are preferences about such relative numbers in categories, the patterns of deltas may be a useful diagnostic.

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.

Wu（2009）的研究曾將2003 年「國際學生能力評量計畫」（Programme for International Student Assessment, PISA）的數學表現，與「國際數學與科學教育成就趨勢調查」（Trends in International Mathematics and Science Study, TIMSS）八年級學生的數學表現做一比較，結果發現，西方國家在PISA 的表現大致上比在TIMSS的表現為佳。本研究則將TIMSS公開的題目分為兩組，一組與PISA 的架構相符，另一組則不相符。其中，TIMSS評比有很多幾何與代數的題目是屬於「純粹的數學」題（即未以真實生活情境作為背景的數學題），而這些題目並未出現在PISA 評比之中。本研究檢視六個國家在這兩組題目表現上的差異，藉此反映出西方與亞洲國家的相對強項與弱點，接著再將這些強項與弱點連結到PISA與TIMSS評比的內容上。有證據顯示，西方與亞洲國家在PISA 與TIMSS的差異表現可歸因於兩評比題目種類的不同。 A study was carried out that compared Programme for International Student Assessment (PISA) 2003 Mathematics results with Trends in International Mathematics and Science Study (TIMSS) 2003 Grade 8 Mathematics results (Wu, 2009). It was 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. In this paper, TIMSS released items are divided into two sets: one that fits the PISA framework and one that does not. In particular, many geometry and algebra items in TIMSS are “inner mathematics” (mathematics without a real-life context), and such items do not appear in the PISA test. Differential performances of six countries on each set of items are examined. In this way, the relative strengths and weaknesses of Western and Asian countries are identified. These strengths and weaknesses are then linked back to the contents of the PISA and TIMSS tests. There is strong evidence that differential performance between Western and Asian countries in PISA and TIMSS can be directly attributed to the types of items in the respective tests.

大型調查研究常採用多階段分層叢集抽樣，檢視臺灣學生歷年來參與TIMSS 研究的結果顯示，其平均表現之標準誤常較他國稍大。應TIMSS 專責抽樣之單位要求，本研究旨在推導設計二階段分層叢集抽樣時即可預估標準誤的公式，以利選擇較佳分層架構，達減少標準誤的目標，並進行三個分析檢查其有效性。分析一將30 個參與TIMSS 2007 的國家資料，用該公式與《TIMSS 技術手冊》建議之刀切重複取樣法，分別估算各國學生平均科學成績之標準誤，發現兩者之線性相關達 .98。分析二以29 個連續參加TIMSS 2003和2007 的國家資料，論述利用該公式與現有輔助變項預估將要進行調查的誤差之實用性。分析三探討當叢集的分層輔助變項為連續量時，不同分層數與二階段分層叢集抽樣誤差間的關係，以預估臺灣學生在TIMSS 2011 平均科學成績之標準誤。文後尚提出四階段的評估流程，供相關研究預估主要依變項平均值之標準誤時做參考。 Most large-scale educational surveys utilize a multi-stage stratified cluster sampling design. Past findings revealed that the standard errors of Taiwan students’ mean performances were slightly larger than other countries’. In response to the request by the institute in charge of TIMSS sampling, this study was launched to derive a formula that could estimate the standard error of population mean prior to conducting a two-stage stratified cluster sampling design. This formula could then be used to select an optimal stratification framework that could reduce the size of standard error to an acceptable level. Its validity was investigated in three subsequent studies. In the first study, standard errors for 30 TIMSS 2007 participating countries were estimated according to the newly derived formula as well as by the jackknife replication. The correlation between the two sets of standard errors amounted to 0.98. The second study investigated the practicality of using the new formula in addition to auxiliary variables for predicting standard errors on the data of 29 countries that participated in both TIMSS 2003 and 2007. The third study explored the relationship between the number of stratum and the standard errors under a two-stage stratified cluster sampling design when the auxiliary variables for stratification were continuous. This paper closed by suggesting a four-step procedure to facilitate researchers in estimating standard errors of means during the planning stage of sampling design.

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.

Objective: To investigate the impact of reduced adipocyte fatty acid-binding protein 4 (FABP4) in control of body weight, glucose and lipid homeostasis in diet-induced obese (DIO) mice. Methods: We applied RNA interference (RNAi) technology to generate FABP4 germline knockdown mice to investigate their metabolic phenotype. Results: RNAi-mediated knockdown reduced FABP4 mRNA expression and protein levels by almost 90% in adipocytes of standard chow-fed mice. In adipocytes of DIO mice, RNAi reduced FABP4 expression and protein levels by 70 and 80%, respectively. There was no increase in adipocyte FABP5 expression in FABP4 knockdown mice. The knockdown of FABP4 significantly increased body weight and fat mass in DIO mice. However, FABP4 knockdown did not affect plasma glucose and lipid homeostasis in DIO mice; nor did it improve their insulin sensitivity. Conclusion: Our data indicate that robust knockdown of FABP4 increases body weight and fat mass without improving glucose and lipid homeostasis in DIO mice.

In 2001 and 2007 Vietnam conducted its first and second surveys of student achievement at primary school level in two key subject areas: literacy and mathematics. In order to track the progress of grade 5 students at the system level, the 2001 and 2007 tests were linked using common items. This paper presents the process used to link the two literacy tests. Several issues arose in the equating process of the two tests. This paper discusses these issues and the implications for assessment design and analysis to enable reliable and valid measures of student progress in longitudinal large-scale studies.

This article was migrated. The article was marked as recommended. B ackground: Structured feedback is an important component of learning and assessment and is highly valued by candidates. Unfortunately, item specific feedback is generally not feasible for high stakes professional assessments due to the high cost of item development and the need to maintain stable assessment performance characteristics. In a high stakes assessment of fetal surveillance knowledge, we sought to use graphical item mapping to allow informative candidate feedback without compromising the item bank. Met h ods: We developed Graphical Item Maps (GIMs) to display individual candidate performance in the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) Fetal Surveillance Education Program (FSEP) multiple-choice question assessment. GIMs use item and person parameter estimates from Item Response Theory (IRT) models to map the interaction between a test taker and assessment tasks of varying difficulty. Results: It is both feasible and relatively simple to provide GIMs for individual candidate feedback. Operational examples are presented from the RANZCOG FSEP assessment. This paper demonstrates how test takers and educators might use GIMs as a form of assessment feedback. Conclusions: Graphical Item Maps are a useful and insightful assessment feedback tool for clinical practitioners partaking in a high stakes professional education and assessment program. They might be usefully employed in similar healthcare professional assessments to inform directed learning.

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.