bluuebunny/crossref_metadata_2025 huggingface dataset:
Shared features of transcription: mutational analysis of the eosinophil/basophil Charcot-Leyden crystal protein gene promoter
Authors: Dyer Kimberly D , Rosenberg Helene F
Published: January 2018

The lineage-specific Charcot-Leyden crystal (CLC) protein is found in human eosinophils and basophils where it comprises 7–10% of the cellular protein content. Previous work from our laboratory has identified the motif GGAGA[A/G] as a powerful enhancer of gene transcription in two eosinophil ribonuclease genes. To evaluate a potentially larger role for this motif in the transcriptional regulation of eosinophil genes, we have isolated 1504 nucleotides 5' to the transcriptional start site of the gene encoding CLC protein and identified a functionally active promoter that includes three distinct copies of the GGAGAA motif. Destruction of only one of the three motifs by site-directed mutagenesis resulted in loss of promoter activity (73 ± 6% reduction), suggesting that this core motif is necessary but not sufficient to support enhanced transcriptional activity. Sequence comparisons and site-specific mutagenesis has permitted further delineation of this enhancer element which, as a result of this work, is now defined as GGAGA[A/G]NNNA. Electromobility shift assays demonstrated specific binding of nuclear protein(s) from an eosinophilic clone-15 nuclear extract to this extended motif. Similar analysis of a GATA-1 binding site demonstrated enhancer activity, with mutagenesis resulting in a 94 ± 1.4% reduction in activity, whereas the AML1 site functioned as a gene silencer. J. Leukoc. Biol. 67: 691–698; 2000.
Transient infiltration of neutrophils into the thymus in association with apoptosis induced by whole-body X-irradiation
Authors: Uchimura Eiji , Watanabe Naoko , Niwa Otsura , Muto Masahiro , Kobayashi Yoshiro
Published: January 2018

Generally, the process of apoptosis does not cause leakage of noxious cytosolic contents and is therefore non-inflammatory. However, as previously shown, macrophages ingesting apoptotic CTLL-2 cells produced pro-inflammatory cytokines, particularly interleukin-8 (IL-8) and macrophage inflammatory protein-2 (MIP-2), a murine IL-8 homolog. This predicted that rapid and massive apoptosis may induce neutrophil accumulation in vivo. In this study, we tested this prediction by inducing apoptosis by whole-body X-irradiation in mice. After exposure to 4 Gy X-ray irradiation, mice exhibited considerable apoptosis of thymic cells, which was associated with transient infiltration of neutrophils as well as MIP-2 mRNA expression. In contrast, in p53-deficient mice in which irradiation-induced apoptosis was suppressed, as has been reported, infiltration of neutrophils into the thymus was less than that found in p53+/+ mice. Taken together, these results suggest that massive and rapid apoptosis can result in infiltration of neutrophils. J. Leukoc. Biol. 67: 780–784; 2000.
Exoenzyme S from Pseudomonas aeruginosa induces apoptosis in T lymphocytes
Authors: Bruno Tony F , Woods Donald E , Mody Christopher H
Published: January 2018

Exoenzyme S from Pseudomonas aeruginosa is a unique T cell mitogen; it is a powerful immunostimulus that activates a large proportion of T cells, but results in delayed and reduced lymphocyte proliferation. This study was performed to explain the discrepancy between early T cell activation and subsequent proliferation. Studies revealed that exoenzyme S induced rapid and unsustained surface expression of CD69, but could not induce interleukin-2 receptor α (IL-2Rα) up-regulation on T cells. IL-2 was undetectable in supernatants and addition of rIL-2 could not reverse the unresponsiveness, indicating that anergy was not involved. Exoenzyme S induced membrane phosphatidylserine translocation, DNA hypodip-loidy, and DNA fragmentation, implicating apoptosis as the mechanism for the unresponsiveness. Exoenzyme S-induced apoptosis shows features of both propriocidal and death by neglect, suggesting shared characteristics of an intermediate pathway. Thus, a Pseudomonas exoproduct induces T cell apoptosis, which may contribute to the pathogenesis of Pseudomonas infections in diseases such as cystic fibrosis. J. Leukoc. Biol. 67: 808–816; 2000.
Regulation of chemokine-induced transendothelial migration of T lymphocytes by endothelial activation: differential effects on naive and memory T cells
Authors: Ding Ziqiang , Xiong Ke , Issekutz Thomas B
Published: January 2018

Human T lymphocyte transendothelial migration (TEM) was examined in response to chemokines across cytokine-activated endothelium. Monocyte chemotactic protein-1 (MCP-1), RANTES, and macrophage inflammatory protein-1α (MIP-1α) induced TEM by memory T cells, while stromal cell-derived factor-1 (SDF-1) induced TEM by both naive and memory T cells. Tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) increased endothelial adhesion molecule (CAM) expression, whereas interferon-γ (IFN-γ) induced little up-regulation of CAM. However, both TNF-α and IFN-α strongly facilitated T cell migration, which was completely inhibited by pertussis toxin and both greatly increased TEM to RANTES, MIP-1α, and SDF-1 selectively of memory but not naive T cells. Thus, the dual selective effect on memory T cells of endothelial activation and these chemokines promotes the preferential recruitment of memory T cells to inflammatory sites. However, the enhanced chemokine-induced migration by memory T cells across activated endothelium appears to be independent of the increase in endothelial CAM expression. G-protein-linked stimuli may play an important part in T cell TEM across cytokine-activated endothelium. J. Leukoc. Biol. 67: 825–833; 2000.
Identifying and Treating Race‐Based Trauma in Counseling
Authors: Hemmings Carrie , Evans Amanda M.
Published: January 2018

This study investigated 106 counseling professionals’ experiences with identifying and treating race‐based trauma and the relationship between training and treatment. Competency was assessed with the Race‐Based Trauma Survey for Counselors. Although most participants reported working with clients who had symptoms associated with race‐based trauma, many had not received training in identifying and treating race‐based trauma among individuals of color. This finding highlights the disparities between health care and the provision of related services. Recommendations for counseling professionals and researchers are included.

Este estudio investigó las experiencias de 106 profesionales en consejería con la identificación y el tratamiento de traumas basados en la raza, así como la relación entre la capacitación y el tratamiento. La competencia se evaluó usando la Encuesta para Consejeros sobre Traumas Basados en la Raza. A pesar de que la mayoría de participantes informó que había trabajado con clientes que tenían síntomas asociados con traumas basados en la raza, muchos no habían recibido capacitación para identificar y tratar traumas basados en la raza en personas de color. Este hallazgo resalta las disparidades entre la atención sanitaria y la provisión de servicios relacionados. Se incluyen recomendaciones para profesionales en consejería e investigadores.
Privilege and Oppression in Counselor Education: An Intersectionality Framework
Authors: Chan Christian D. , Cor Deanna N. , Band Monica P.
Published: January 2018

Multiculturalism and social justice are considered major forces in the counseling profession, revolutionizing the complexity of social identity, cultural identity, and diversity. Although these major forces have influenced the profession, many challenges exist with their implementation within counselor education curriculum and pedagogy. A major challenge is the complex dynamics of privilege and oppression that both counselor educators and counseling students face. This article discusses the use of intersectionality to approach counselor education pedagogy and practice.

El multiculturalismo y la justicia social están considerados como fuerzas importantes con las que la profesión de la consejería está revolucionando la complejidad de la identidad social, la identidad cultural y la diversidad. Aunque estas fuerzas importantes han influido en la profesión, existen desafíos relacionados con su implementación en los planes curriculares y pedagogía de la educación de consejeros. Un desafío significativo es la compleja dinámica entre privilegio y opresión que enfrentan tanto los formadores de consejeros como los estudiantes de consejería. Este artículo discute el uso de la interseccionalidad para enfocar la pedagogía de la educación de consejeros y la práctica.
Analysis of trace levels of impurities and hydrogen isotopes in helium purge gas using gas chromatography for tritium extraction system of an Indian lead lithium ceramic breeder test blanket module
Authors: Devi V. Gayathri , Sircar Amit , Yadav Deepak , Parmar Jayraj
Published: January 2018

In the fusion fuel cycle, the accurate analysis and understanding of the chemical composition of any gas mixture is of great importance for the efficient design of a tritium extraction and purification system or any tritium handling system. Methods like laser Raman spectroscopy and gas chromatography with thermal conductivity detector have been considered for hydrogen isotopes analyses in fuel cycles. Gas chromatography with a cryogenic separation column has been used for the analysis of hydrogen isotopes gas mixtures in general due to its high reliability and ease of operation. Hydrogen isotopes gas mixture analysis with cryogenic columns has been reported earlier using different column materials for percentage level composition. In the present work, trace levels of hydrogen isotopes (∼100 ppm of H2 and D2) have been analyzed with a Zeolite 5A and a modified γ‐Al2O3 column. Impurities in He gas (∼10 ppm of H2, O2, and N2) have been analyzed using a Zeolite 13‐X column. Gas chromatography with discharge ionization detection has been utilized for this purpose. The results of these experiments suggest that the columns developed were able to separate ppm levels of the desired components with a small response time (<6 min) and good resolution in both cases.
Ionic liquid chemically bonded basalt fibers for in‐tube solid‐phase microextraction
Authors: Feng Juanjuan , Mao Huijun , Wang Xiuqin , Tian Yu , Luo Chuannan , Sun Min
Published: January 2018

Ionic liquids have been widely used in different fields by advantage of their specific properties. In this work, 1‐methyl‐3‐(3‐trimethoxysilyl propyl)imidazolium chloride was prepared and chemically bonded onto basalt fibers for in‐tube solid‐phase microextraction. Through combining in‐tube extraction device with high‐performance liquid chromatography equipped with a diode array detector, an online enrichment and analysis method for eight polycyclic aromatic hydrocarbons was established under the optimum conditions. A good enrichment factor (52–814), good linearity (0.10–15 and 0.20–15 μg/L), low limits of detection (0.03–0.05 μg/L), and low limits of quantitation (0.10–0.20 μg/L) were achieved using a sample volume of 50 mL. Analysis method was applied to the real samples including the groundwater and wastewater from a chemical industry park, some target analytes were detected and the relative recoveries were in the range of 80.4–116.8%.
Saddle point equilibrium under uncertain environment
Authors: Sun Yun , Ding Chunxiao , Zhu Yuanguo
Published: January 2018

The saddle point equilibrium problem is of great importance in differential game theory. In this paper, an optimistic value model for the saddle point equilibrium problem under uncertain environment is investigated. The equilibrium equation for the proposed model is presented. Then a linear quadratic model is discussed. Finally, a counter terror problem is analyzed by the results obtained in the paper.
Optimal feedback strategies for bacterial growth with degradation, recycling, and effect of temperature
Authors: Yegorov Ivan , Mairet Francis , Gouzé Jean‐Luc
Published: January 2018

Mechanisms of bacterial adaptation to environmental changes are of great interest for both fundamental biology and engineering applications. In this work, we consider a continuous‐time dynamic problem of resource allocation between metabolic and gene expression machineries for a self‐replicating prokaryotic cell population. In compliance with evolutionary principles, the criterion is to maximize the accumulated structural biomass. In the model, we include both the degradation of proteins into amino acids and the recycling of the latter (ie, using as precursors again). On the basis of the analytical investigation of our problem by Pontryagin's maximum principle, we develop a numerical method to approximate the switching curve of the optimal feedback control strategy. The obtained field of extremal state trajectories consists of chattering arcs and 1 steady‐state singular arc. The constructed feedback control law can serve as a benchmark for comparing actual bacterial strategies of resource allocation. We also study the influence of temperature, whose increase intensifies protein degradation. While the growth rate suddenly decreases with the increase in temperature in a certain range, the optimal control synthesis appears to be essentially less sensitive.
Surface modification of poly(2‐hydroxyethyl methacrylate) hydrogel for contact lens application
Authors: Kazemi Ashtiani Mohammad , Zandi Mojgan , Shokrollahi Parvin , Ehsani Morteza , Baharvand Hossein
Published: January 2018

The present study examined poly(2‐hydroxyethyl methacrylate) (PHEMA)‐based hydrogels that have been extensively used in biomedical applications, including contact lens. In this research, we aimed to reduce adsorption of protein components from tears and bacterial deposition by surface modification of the hydrogel with different functional groups that included carboxylic acid, primary amine, and quaternary ammonium. The PHEMA was treated with a solution of sulfuric acid for partial hydrolysis of the HEMA ester groups to induce acid groups on the surface of the hydrogel. Carboxylic acid groups of the modified PHEMA were converted to primary amine and quaternary ammonium groups via carbodiimide chemistry. The surface physical and chemical properties of different samples were investigated by atomic force microscopy and X‐ray photoelectron spectroscopy, respectively. We conducted the bicinchoninic acid assay to evaluate protein deposition from artificial tear fluid on samples. Antibacterial properties of the modified hydrogels were investigated with a culture of Staphylococcus aureus, one of the major causes of eye infections. Our data showed that positively charged amine and ammonium groups efficiently resisted protein adsorption and bacterial deposition compared to alcohol and carboxylic acid groups.
Composites of poly(L‐lactide‐trimethylene carbonate‐glycolide) and surface modified SBA‐15 as bone repair material
Authors: Wang Jielin , Du Beibei , Fan Zhongyong , Li Suming , Yun Peng , Su Feng
Published: January 2018

This work aims to develop novel composites from a poly(L‐lactide‐co‐trimethylene carbonate‐co‐glycolide) (PLTG) terpolymer and mesoporous silica (SBA‐15) nanofillers surface modified by post‐synthetic functionalization. SBA‐15 first reacts with a silane coupling agent, γ‐aminopropyl‐trimethoxysilane to introduce ammonium group. PLLA chains were then grafted on the surface of SBA‐15 through ammonium initiated ring‐opening polymerization of L‐lactide. Composites were prepared via solution mixing of PLTG terpolymer and surface modified SBA‐15. The structures and properties of pure SBA‐15, γ‐aminopropyl‐trimethoxysilane modified SBA‐15 (H2N‐SBA‐15), PLLA modified SBA‐15 (PLLA‐NH‐SBA‐15), and PLTG/PLLA‐NH‐SBA‐15 composites were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, X‐ray diffraction, scanning electron microscopy, energy‐dispersive X‐ray spectroscopy, transmission electron microscopy, N2 adsorption‐desorption, differential scanning calorimetry, contact angle measurement, and mechanical testing. The results demonstrated that PLLA chains were successfully grafted onto the surface of SBA‐15 with grafting amounts up to 16 wt.%. The PLTG/PLLA‐NH‐SBA‐15 composites exhibit good mechanical properties. The tensile strength, Young's modulus, and elongation at break of the composite containing 5 wt.% of PLLA‐NH‐SBA‐15 were 39.9 MPa, 1.3 GPa, and 273.6%, respectively, which were all higher than those of neat PLTG or of the composite containing 5 wt.% of pure SBA‐15. Cytocompatibility tests showed that the composites present very low cytotoxicity.
Effect of polystyrenes with different architectures on the β‐nucleating efficiency and toughening of isotactic polypropylene
Authors: Liu Jingru , Li Chen , Hu Fangming
Published: January 2018

The effect of polystyrenes (PSs) with different architectures (three‐arm star‐shaped polystyrene (sPS), comb‐like branched polystyrene (cPS) and linear polystyrene) on their β‐nucleating efficiency for isotactic polypropylene (iPP) during crystallization and final impact and the tensile properties of iPP/PS blends were investigated by dynamic rheological measurements, SEM, DSC, polarized optical microscopy, wide angle X‐ray diffraction and mechanical property measurements. The results show that the architecture of PS has marked influence on its dispersibility in iPP and β‐nucleating efficiency. For iPP/cPS blend, plenty of short side chains reduce the probability of cPS chain entanglements, facilitating the interdiffusion between iPP and cPS chains. A favorable interfacial interaction results in good dispersibility, high β nucleating efficiency and an excellent toughening effect of cPS on iPP. However, the relatively high chain entanglement degree of sPS may not be in favor of chain diffusion between iPP and sPS and therefore relatively poor dispersibility and toughening effect are obtained. The elongation at break and impact strength of iPP were dramatically improved, especially with the addition of 1 wt% cPS. The toughening mechanism of PS on iPP is the dissipated energy caused by cavitation and the β‐nucleating effect of PS. © 2018 Society of Chemical Industry
Facile preparation of silver/reduced graphene oxide/chitosan colloid and application of the nanocomposite in antibacterial and catalytic activity
Authors: An Jing , Guo Guizhen , Yin Rong , Luo Qingzhi , Li Xueyan , Liu Fan , Wang Desong
Published: January 2018

Reduced graphene oxide (RGO) decorated with silver nanoparticles (AgNPs) was synthesized by a facile solution‐based approach in chitosan (CS) solution. The morphology and elemental composition of as‐prepared Ag/RGO/CS colloid were characterized by SEM and energy dispersive X‐ray spectroscopy, respectively. TEM images show that most of the AgNPs are uniformly dispersed in the CS matrix while the other nanoparticles are decorated on the RGO nanosheets. XRD indicates that the interlayer distance of RGO is between 0.34 and 1.87 nm while the diameter of face‐centered cubic AgNPs is no more than 30 nm. Fourier transform infrared spectroscopy of the Ag/RGO/CS colloid confirms the formation of AgNPs and RGO. X‐ray photoelectron spectroscopy proves that both the Ag − O bond and the C − N bond exist in the nanocomposite. Antimicrobial assays were performed using the most common species of Gram bacteria. The inhibitory effect indicates that the incorporation of AgNPs and RGO significantly improves the antimicrobial activity of CS colloid. In addition, the nanocomposite colloid exhibits significant catalytic activity toward the reduction of 4‐nitrophenol by NaBH4. © 2018 Society of Chemical Industry
A Review of the Literature: The Needs of Nontraditional Students in Postsecondary Education
Authors: MacDonald Kris
Published: January 2018

Nontraditional students, or adult learners, are the new majority in the classroom in any sector of higher education according to the National Center for Education Statistics. These students are considered nontraditional if they identify with at least one of the following criteria: be at least 25 years old, attend school part‐time, work full‐time, be a veteran, have children, wait at least one year after high school before entering college, have a GED instead of a high school diploma, being a first‐generation student (FGS), are enrolled in nondegree programs, or have reentered a college program. This population also tends to be predominantly female. As this population trend grows exponentially in higher education, it is imperative for administrators and instructors to learn how to work with these students, as they deal with far different struggles to stay in school than their traditional counterparts. This review of the current literature will explore the best practices for what nontraditional students need based on the varied issues they face in reentering a classroom. A lack of knowledge about this population has led to low enrollment rates and high attrition rates, leaving some schools especially in the for‐profit sector, struggling to stay afloat. It is imperative that as populations shift, so do pedagogical and supportive approaches within postsecondary institutions in order to retain these students and ensure their academic success.
Enhanced surface free energy of UHMWPE fibers and its interfacial adhesion behavior to PI resins
Authors: He Runqin , Chang Qiuxiang , Huang Xinjun , Li Jian
Published: January 2018

Mechanical properties of composites made up of ultra‐high‐molecular‐weight polyethylene (UHMWPE) fiber, polyimide (PI), and TiO2 particles were investigated. The hybrid composite of 20 vol% of UHMWPE fiber with TiO2 showed tensile strength greater than UHMWPE fiber/PI composite. A positive hybrid effect in tensile strength is obtained. It is observed that addition of small amount of TiO2 to UHMWPE fiber/PI increased the tensile strength of the composite by 28%. With increase in TiO2 loading to 1 to 3 vol%, the impact strength of the hybrid composite is increased from 55 KJ/m2 to 69 KJ/m2. This maximum value is more than one and a half times greater than the impact strength of neat UHMWPE fiber/PI composite.
Surface interaction of H2O and H2S onto Ca12O12 nanocluster: Quantum‐chemical analyses
Authors: Rad Ali Shokuhi , Aghaei Sadegh Mehdi , Pazoki Hossein , Binaeian Ehsan , Mirzaei Mahmoud
Published: January 2018

To find the selectivity of H2S, we explicate the adsorption properties of water (H2O) and hydrogen sulfide (H2S) molecules on the external surfaces of free Ca12O12 nanocages using the density functional theory method. More specifically, binding energies, natural bond orbital charge transfer, dipole moment, molecular electrostatic potential, frontier molecular orbitals, density of states, and global indices of activities are calculated to deeply understand the impacts of the aforementioned molecules on the electronic and chemical properties of Ca12O12 nanocages. Our theoretical findings indicate that although H2O seems to be adsorbed in molecular form, the H2S molecule is fully dissociated during the adsorption process because of the weak bond between sulfur and hydrogen atoms of the molecule. Interestingly, the highest occupied molecular orbital–lowest unoccupied molecular orbital energy gap of the nanocage is decreased by 1.87 eV upon H2S adsorption, indicating that the electrical conductivity of the nanocage is strongly increased by the dissociation process. In addition, the values of softness and electrophilicity for the H2S‐Ca12O12 complex are higher than those for the free nanocage. Our results suggest that Ca12O12 nanoclusters show promise in the adsorption/dissociation of H2S molecules, which can be used further for designing its selective sensor.
Relationship style and glycaemic control in women with type 2 diabetes: The mediating role of psychological distress
Authors: Braizat Omar , Feinn Richard , Abbott Gina , Wagner Julie
Published: January 2018

This study examined whether depressive symptoms and/or diabetes distress mediate the association between relationship style and glycaemic control in women with diabetes. Seventy‐five women with type 2 diabetes completed the Relationship Questionnaire. Participants endorsing “secure” or “preoccupied” adult attachment were combined into the interactive relationship style and “dismissing/avoidant” or “fearful” adult attachment were combined into the independent relationship style. Glycaemic control was a latent variable composed of A1c and 48‐hr continuously measured glucose. Diabetes distress was assessed with the Problem Areas in Diabetes scale and depressive symptoms with the Center for Epidemiological Studies Depression scale. A parallel multiple mediation model with relationship style as the independent variable, glycaemic control as the dependent variable, and Problem Areas in Diabetes and Center for Epidemiological Studies Depression scale as mediators, tested indirect effects. Bias‐corrected bootstrap with 10,000 replications was used to construct 95% confidence intervals. The indirect association of relationship style with glycaemic control through diabetes distress was significant (effect = −0.09, p = .036, 95CI = −0.19–0.01), but through depressive symptoms was not. A model testing the indirect association of relationship style with diabetes distress through glycaemic control was not significant. Results suggest that relationship style is associated with glycaemic control through diabetes distress in women with type 2 diabetes.
Production of Esterified Starches with Increased Resistant Starch Content by an α‐Hydroxy Acid‐Catalyzed Route
Authors: Tupa Maribel V. , Arroyo Silvana , Herrera María L. , Foresti María L.
Published: January 2018

Resistant starch (RS) refers to the portion of starch that is not broken down by human enzymes in the small intestine, and thus reaches the large bowel of healthy individuals. In the large bowel RS is fermented by colonic microflora producing short chain fatty acids (SCFA) – predominantly acetate, propionate, and butyrate – that are known to contribute substantially to large bowel health. Currently, there is an increasing interest in obtaining RS by esterification of starch with target SCFA, due to its capacity to deliver significant quantities of the particular esterified SCFA to the colon. In the current contribution an α‐hydroxy acid‐catalyzed methodology, which has recently proven useful for esterifying starch, was used to produce acetylated, propionylated, and butyrylated corn starch samples with varying degree of substitution (DS) (0.05–0.75). Results showed the suitability of the route to produce the RS4 starch type, with RS contents that increased with DS as a consequence of a larger steric hindrance effect caused by a higher number of ester groups introduced. Data also indicated that the DS conferred to starch was the key factor conditioning its resistance, whereas RS content showed to be independent of the resulting esterified starch structure and the type of ester group introduced.
Correction to: Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders
Authors: Posset Roland , Garcia‐Cazorla Angeles , Valayannopoulos Vassili , Leão Teles Elisa , Dionisi‐Vici Carlo , Brassier Anaïs , Burlina Alberto B. , Burgard Peter , Cortès‐Saladelafont Elisenda , Dobbelaere Dries , Couce Maria L. , Sykut‐Cegielska Jolanta , Häberle Johannes , Lund Allan M. , Chakrapani Anupam , Schiff Manuel , Walter John H. , Zeman Jiri , Vara Roshni , Kölker Stefan ,   Additional individual contributors of the E‐IMD consortium
Published: January 2018

Due to an unfortunate error during the typesetting process, the collaborators were presented incorrectly.
Temporal unfolding of declining episodic memory on the Free and Cued Selective Reminding Test in the predementia phase of Alzheimer's disease: Implications for clinical trials
Authors: Grober Ellen , Veroff Amy E. , Lipton Richard B.
Published: January 2018

Introduction

Free and Cued Selective Reminding Test (FCSRT) performance identifies patients with preclinical disease at elevated risk for developing Alzheimer's dementia, predicting diagnosis better than other memory tests.

Methods

Based on literature mapping FCSRT performance to clinical outcomes and biological markers, and on longitudinal preclinical data from the Baltimore Longitudinal Study of Aging, we developed the Stages of Objective Memory Impairment (SOMI) model. Five sequential stages of episodic memory decline are defined by Free Recall (FR) and Total Recall (TR) score ranges and years prior to dementia diagnosis. We sought to replicate the SOMI model using longitudinal assessments of 142 Einstein Aging Study participants who developed AD over 10 years.

Results

Average time to diagnosis was seven years if FR was intact, four years if TR was intact, and two years if TR was impaired, consistent with SOMI model predictions. The SOMI identified incipient dementia with excellent sensitivity and specificity.

Discussion

The SOMI model provides an efficient approach for clinical trial cognitive screening in advance of more costly biomarker studies and ultimately in clinical practice, and provides a vocabulary for understanding AD biomarker patterns and for re‐analysis of existing clinical trial data.
OP22 Societal Perspective On Cost Drivers For Health Technology Assessment
Authors: Khowaja Asif , Mitton Craig , Qureshi Rahat , Bryan Stirling , Magee Laura , von Dadelszen Peter , Bhutta Zulfiqar
Published: January 2018

INTRODUCTION:

Understanding cost drivers and estimating societal costs are important challenges for economic evaluation of health technologies in low-and-middle-income countries (LMICs) (1). This study assessed community experiences of health resource utilization and perceived cost drivers from a societal perspective to inform the design of an economic model for the Community Level Interventions for Pre-eclampsia (CLIP) trials (2).

METHODS:

Qualitative research was undertaken alongside the CLIP trial in two districts of Sindh province, Pakistan. Nine focus groups were conducted with a wide range of stakeholders, including pregnant women, mothers-in-law, husbands, fathers-in-law, healthcare providers at community and health facility-levels, and health decision-/policy-makers at the district-level. The societal perspective included out-of-pocket (OOP), health system, and program implementation costs related to CLIP. Thematic analysis was performed using NVivo software.

RESULTS:

Most pregnant women and male decision makers reported a large burden of OOP costs for in- and out-patient care, informal care from traditional healers, self-medication, childbirth, newborn care, transport to health facility, and missed wages by caretakers. Many healthcare providers identified health system costs associated with human resources for hypertension risk assessment, transport, and communication about patient referrals. Health decision-/policy-makers recognized program implementation costs (such as the mobile health infrastructure, staff training, and monitoring/supervision) as major investments for the health system.

CONCLUSIONS:

Our investigation of care-seeking practices revealed financial implications for families of pregnant women, and program implementation costs for the health system. The societal perspective provided comprehensive knowledge of cost drivers to guide an economic appraisal of the CLIP trial in Sindh, Pakistan.
OP33 Developing A Public Version Of A Health Technology Assessment Report
Authors: Fearns Naomi , Riches Emma , Kelly Joanna , Macpherson Karen
Published: January 2018

INTRODUCTION:

As the Health Technology Assessment (HTA) community moves towards greater levels of Patient and Public Involvement (PPI), the need to communicate with the public about the results and impact of HTA, and of PPI itself, is also increasing. DECIDE was a European Commission funded collaborative project arising from the GRADE working group, which developed and evaluated strategies for effectively communicating the recommendations from clinical guidelines to a multiple stakeholders. The Scottish Intercollegiate Guidelines Network (SIGN) led the work stream on patients and the public (1, 2). We extended the findings to develop a patient/public version of an HTA on Antimicrobial Wound Dressings (AWDs). The clinical and cost effectiveness evidence was inconclusive (3) which increased the importance of engagement with clinical and patient/public stakeholders.

METHODS:

A literature review, and a series of focus groups and user testing informed the development of a set of principles for designing patient versions of guidelines (1,2). Using these principles developed by the DECIDE collaboration, a patient version of the HTA was developed, in partnership with public volunteers and a standing public communications advisory group.

RESULTS:

We incorporated key facilitators of usability, such as distinct branding as material for the public, a clearly communicated purpose, and the layering of information. Other facilitators included a “friendly” and accessible tone which was achieved by the use of colour, icons, simple language and charts, and brief chunked text. While feedback about clarity, design and usefulness was generally positive, some public reviewers were concerned by the level of uncertainty and complexity in the findings.

CONCLUSIONS:

Using the principles from the DECIDE project, it is feasible and useful to develop public versions of an HTA report. The patient version is currently informing the development of educational material for patients/public about chronic wounds and AWDs by the Scottish Government. However, it remains a challenge to balance the complexity and uncertainty underlying evidence-based recommendations, with the need to provide accessible, understandable, and yet accurate information about them for the public.
OP70 Economic Impact Of Macular Edema Diseases, A Retrospective Study
Authors: Mennini Francesco , Fabiano Gianluca , Russo Simone , Marcellusi Andrea , Cerri Luca , Ricci Federico
Published: January 2018

INTRODUCTION:

Inhibitors of Vascular Endothelial Growth Factor (VEGF) have made possible the treatment of the Retinal Vascular Diseases (RVD) for which there were limited therapeutic resources. The aim of this work was to estimate annual direct costs of major macular edema diseases in Italy in particular Choroidal Neovascularization (CNV), Diabetic Macular Edema (DME) and Retinal Vein Occlusions (RVO) from the hospital perspectives.

METHODS:

This descriptive study was aimed at quantifying direct costs incurred by five hospitals in Italy. Administrative and clinical databases of Policlinico Tor Vergata in Rome were analyzed for a 6-year period. In this context, it was possible to stratify patients depending on the disease and number of eyes treated. From these results, a survey with structured questionnaires was developed involving four other hospitals in Italy. Thanks to that, direct costs (drugs and specialist) were estimated from the hospitals perspective in 2016.

RESULTS:

Interviews included 7,356 individuals of which 1,860 were treated in both eyes. Within the considered five hospitals, 64 percent of treated patients had CNV, 21 percent DME, and 15 percent RVOs. The average annual administration rate of anti-VEGF treatment resulted in 4.03 (Standard Deviation, SD 3.46) per patient eye: 4.69 (SD 1.75) for cases enrolled for less than one year (naïve) and 3.38 (SD 0.82) per patients treated for more than one year (experienced). Naïve patients had a mean per capita annual cost of EUR2,368 per eye (EUR2,536 for CNV; EUR2,280 RVO; EUR1,986 DME) of which EUR2,952 was related to the administration of on-label drugs mainly Eylea, Lucentis, Macugen, Ozurdex and EUR49 due to off-labels such as Avastin. Experienced patients average annual cost per eye was EUR1,689: EUR2.179 for the on-label drugs, EUR34 due to off-labels (EUR1,839 for CNV; EUR1,327 RVO; EUR1,399 DME). The average rate of the specialist annual visit was four times; the most frequent types were Optical Coherence Tomography (OCT), Angiography, and Fundus Photography (FP).

CONCLUSIONS:

This is a first attempt to study direct costs incurred from the hospital perspective associated with RVD with overexpression of VEGF in Italy. This might represent a first step for further analysis assessing the burden of RVD diseases from the Italian National Health System perspective globally.
OP83 Value Assessment Framework: Evidence-Informed Deliberative Processes
Authors: Tummers Marcia , Baltussen Rob , Jansen Maarten , Bijlmakers Leon , Grutters Janneke , Kluytmans Anouck , Reuzel Rob , van der Wilt Gert Jan
Published: January 2018

INTRODUCTION:

Priority setting in health care has been long recognized as an intrinsically complex and value-laden process. Yet, Health Technology Assessment (HTA) agencies presently employ value assessment frameworks that are ill-fitted to capture the range and diversity of stakeholder values, and thereby risk to compromise the legitimacy of their recommendations. We propose ‘evidence-informed deliberative processes’ as an alternative framework with the aim to enhance this legitimacy.

METHODS:

The framework is based on an integration of two increasingly popular and complementary frameworks for priority setting: multi-criteria decision analysis (MCDA) and accountability for reasonableness (A4R), Evidence-informed deliberative processes are, on the one hand, based on early, continued stakeholder deliberation to learn about the importance of relevant social values. On the other hand, they are based on rational decision-making – through evidence-informed evaluation of the identified values.

RESULTS:

The framework has important implications for how HTA agencies should ideally organize their processes. Firstly, HTA agencies should take the responsibility to organize stakeholder involvement. Second, agencies are advised to integrate their assessment and appraisal phase, allowing for the timely collection of evidence on values that are considered relevant. Third, HTA agencies should subject their specification of decision-making criteria to public scrutiny. Fourth, agencies are advised to use a checklist of potentially relevant criteria, and to provide argumentation how each criterion affected the recommendation. Fifth, HTA agencies must publish their argumentation and install options for appeal.

CONCLUSIONS:

Adopting ‘evidence-informed deliberative processes’ as a value assessment framework could be an important step forward for HTA agencies to optimize the legitimacy of their priority setting decisions. Agencies can incorporate elements according to their needs and affordances.
OP101 Do We Need To Extend Health Technology Assessment To Health Enhancement Assessment?
Authors: Hofmann Bjørn
Published: January 2018

INTRODUCTION:

Several health technologies used for therapy can also be used for health enhancement. Drugs stimulating cognitive abilities are but one example. Health Technology Assessment (HTA) has not been developed for assessing enhancements. This raises the question of how HTA should address the blurred distinction between therapy and enhancement. Should we (i) carve out a distinction between therapy and enhancement and limit HTA to therapy, (ii) use HTA for both therapy and enhancement (with some modifications), or (iii) should we develop a separate health enhancement assessment (HEA)?

METHODS:

A literature search of the medical, philosophical, and bioethical literature was conducted for debates, arguments, and suggested solutions to the issue of therapy versus enhancement.

RESULTS:

The same improvement in health may be therapeutic in one patient, but an enhancement in another. Moreover, both therapy and enhancement share the same goal: increased health and wellbeing. A wide range of arguments try to establish a difference between therapy and enhancement. They refer to naturalness, rehabilitation, normality, species-typical functioning/potential, disease, sustainability, and responsibility. On closer scrutiny few of these arguments do the job in bolstering the therapy-enhancement distinction. We already use a wide range of means to extend human abilities. Moreover, the therapy-enhancement distinction raises a wide range of ethical issues that are relevant for the assessment of a number of emerging health technologies.

CONCLUSIONS:

Existing HTA methodology can address a wide range of non-therapeutic health enhancements. However, a series of broader issues related to the goal of health care and responsibility for altering human evolution may not be addressed within traditional HTA frameworks. Specific HEAs may therefore be helpful.
PP053 A Case Study: Collective Individual Basis For The Judiciary Debate
Authors: Melo Daniela , Trindade Evelinda , Oliveira Daniel , Martins Patricia , Ribeiro Lúcia
Published: January 2018

INTRODUCTION:

The volume of lawsuits for drugs has increased in Brazil. The scientific evidence basis consideration by the Brazilian judiciary system is being debated. In the State of São Paulo, the drug with the highest number of lawsuits is insulin glargine. Between January and August 2016, the São Paulo State Department of Health lost 264 insulin glargine lawsuits requiring supply for adult patients (>18 years old). Insulin glargine has already been submitted and unfavorably assessed by the Health Ministry SUS Technology Incorporation National Commission (CONITEC), so is not available in the Brazilian public system.

METHODS:

Random analysis of 153 (58 percent) lawsuits were carried out on digital court records. Data collected from legal proceedings were: the type of diabetes (1, 2 or unspecified); age of the patient; origin of the order; specialty of the prescriber and the reason described for the request. Each record was structured with variables data within a matrix in Microsoft Excel© software. Analysis of frequencies, absolute and relative distribution of quantitative variables, as well as conceptual clusters in the qualitative textual analysis are presented.

RESULTS:

The mean age of the 153 patients was 49±17 years. The majority of patients requested insulin glargine to achieve glycemic control (n = 116; 76 percent): because -“diabetes is uncontrolled and the analogous insulin is essential to get it” (n = 106; 69 percent); or -“patient claims to have obtained glycemic control with insulin glargine but there are none of the mandatory laboratory tests results in lawsuits” (n = 7; 5 percent); or -“ask replacement of insulin detemir with glargine for glycemic control” (n = 3; 2 percent). Only 87 (57 percent) lawsuits reported the patients diabetes type: type 1 (n = 42; 28% percent or 2 (n = 45; 29 percent). Most of this judicialization came from private outpatient clinics (n = 116; 76 percent) and 99 (65 percent) were prescribed by endocrinologists.

CONCLUSIONS:

Judicial decisions are still insufficiently underpinned by scientific evidence (only the patients drug needs claim has been recorded to justify supply) and are incomplete regarding objective diagnostic variables. Also, the judges awareness of interdisciplinary measures to achieve diabetic patients glycemic control, besides complementary drugs, may improve the Brazilian judicialization burden.
PP059 National Survey Of Current United Kingdom Ambulance Service Transient Ischemic Attack Referral Pathways
Authors: Hampton Chelsey , Porter Alison , Bulger Jenna , Jones Charlene , Rees Nigel , Seagrove Anne , Snooks Helen
Published: January 2018

INTRODUCTION:

Patients presenting to emergency ambulance services with Transient Ischemic Attack (TIA) are usually conveyed to the Emergency Department (ED) with subsequent referral to specialist assessment at a TIA clinic within one week if at low risk of stroke. There is opportunity for paramedics to refer patients with TIA at low risk of recurrent stroke directly to a specialist TIA clinic, avoiding the transportation and care at the ED however evidence is lacking about current practice, safety and effectiveness of this intervention.

We aimed to describe current service developments across the United Kingdom (UK) for the pre-hospital emergency care of patients with TIA, to inform the development of an intervention for testing.

METHODS:

We surveyed all UK Ambulance Trusts (n = 13) by email, asking them to identify initiatives related to the management of TIA, and followed up services reporting an alternative TIA pathway by telephone to gather further details.

RESULTS:

Twelve ambulance services responded to our survey. Eight reported that they had not developed or implemented TIA referral pathways. Three reported currently using a TIA referral pathway; one had discontinued their pathway due to service reconfiguration. All (4/4) pathways used the FAST test and ABCD2 tool to screen patients, in line with national guidelines, and classified patients as low risk if the ABCD2 score was ≤3. All indicated that eligible low-risk TIA patients should be referred by paramedics to specialist care, 2/4 by telephone, and 2/4 by fax.

Although protocol compliance was audited in an initial pilot in one service, no formal evaluation of effectiveness was reported.

CONCLUSIONS:

Several UK ambulance services have introduced similar referral pathways for low risk TIA patients, avoiding transportation of patients to the ED. Existing initiatives can inform the development of an intervention for evaluation in a randomized trial.
PP089 Health Technology Assessment Of An Automated Compounding Of Parenteral Nutrition
Authors: Faggiano Francesco , Andellini Martina , Sabusco Francesca , De Vivo Liliana , Derrico Pietro , Ritrovato Matteo
Published: January 2018

INTRODUCTION:

Pediatric parenteral nutrition is mainly used in neonatal intensive care units (NICU) and requires close collaboration with the hospital pharmacy, especially for manufacturing time, application, preparation and delivery (1). In this context, a Health Technology Assessment (HTA) to evaluate an automatic system compared with a manual system was carried out.

METHODS:

The Decision-oriented HTA (DoHTA) method (2), coordinated by Bambino Gesù Children's Hospital (BGCH) HTA Unit, was applied to carefully assess the technology. It was developed starting from the European Network for HTA (EUnetHTA) Core Model® and integrated with the Analytic Hierarchy Process (AHP). Its purpose is to identify all the relevant assessment aspects of automatic system integrating the evidence from the scientific literature with experts’ judgments and the specific context analysis for BGCH: an evaluation scheme inherent safety, clinical effectiveness, technical and organizational aspects (represented by a decision tree at three levels: dimensions of evaluation, I and II level indicators) was subsequently created. A weight was finally associated to each identified element and the alternatives’ ranking was defined.

RESULTS:

The study results show a “performance value” associated with the automatic system greater than about thirty-two percentage points compared to the manual system.

CONCLUSIONS:

At the current state of the scientific evidence and the results of analysis carried out by the working group, it is believed that the choice should be made to introduce the automatic system is available in BGCH.

More specifically, from the point of view of safety, automatic system is safer for both patient and operators; about clinical effectiveness, the system improves the nutritional intake, allows a reduction of post-infusional adverse events and the use of antibiotic therapy; concerning economic aspects, the analysis of available data shows a substantial equivalence between the alternatives considered; the technical-functional aspects show an improvement according to almost all indicators; organizational aspects show a slight improvement in the working and in process management and finally the legal aspects indicate a slight advantage for the automatic system.