Miracle-dz/UniFAR-FTUs huggingface dataset:
Adaptation of the Manchester-Minneapolis Quality of Life instrument for use in the UK population

Introduction: The availability of health-related quality of life (HRQL) measures that are reliable, valid, brief and comprehensible and appropriate for use with UK children is limited. We report the validation of a HRQL measure suitable for UK use in healthy children, children with chronic disease conditions and socially disadvantaged children. Patients: A total of 1238 children took part in the study, including healthy children as controls (n = 824) and five exemplar groups: children diagnosed with asthma (n = 87), diabetes (n = 103) or inflammatory bowel disease (IBD; n = 69), children in remission from cancer (n = 68) and children in public care (n = 87). Methods: In phase I, the Manchester-Minneapolis Quality of Life instrument (MMQL) Child Form was translated into UK English. In phases II and III, the questionnaire was shortened and validated. Results: MMQL was anglicised and shortened to five components comprising 29 items. Good internal reliability was found with &agr; reaching at least 0.69 for all subscales. Construct validity was established through moderate correlations with comparable PedsQL subscales (Pearson’s r ranged from 0.38 to 0.58, p<0.01). Discriminant validity was also demonstrated in children with asthma and IBD, children in remission from cancer and children in public care, all of whom reported significantly lower HRQL than healthy children. Children with diabetes showed similar HRQL to their healthy peers. Good reproducibility and moderate responsiveness were demonstrated for the new measure. Conclusions: The anglicised and shortened MMQL was shown to be valid and reliable and could be a valuable new tool for the assessment of HRQL in children.
Risk for opportunistic disease and death after reinitiating continuous antiretroviral therapy in patients with HIV previously receiving episodic therapy: a randomized trial.

BACKGROUND Episodic use of antiretroviral therapy guided by CD4+ cell counts is inferior to continuous antiretroviral therapy. OBJECTIVE To determine whether reinitiating continuous antiretroviral therapy in patients who received episodic treatment reduces excess risk for opportunistic disease or death. DESIGN Randomized, controlled trial. SETTING Sites in 33 countries. PATIENTS 5472 HIV-infected individuals with CD4(+) cell counts greater than 0.350 x 10(9) cells/L enrolled from January 2002 to January 2006. INTERVENTION Episodic or continuous antiretroviral therapy initially, followed by continuous therapy in participants previously assigned to episodic treatment. MEASUREMENTS Opportunistic disease or death was the primary outcome. RESULTS Eighteen months after the recommendation to reinitiate continuous therapy, mean CD4+ cell counts were 0.152 x 10(9) cells/L (95% CI, 0.136 to 0.167 x 10(9) cells/L) less in participants previously assigned to episodic treatment (P < 0.001). The proportion of follow-up time spent with CD4+ cell counts of 0.500 x 10(9) cells/L or more and HIV RNA levels of 400 copies/mL or less was 29% for participants initially assigned to episodic therapy and 66% for those assigned to continuous therapy. Participants who reinitiated continuous therapy experienced rapid suppression of HIV RNA levels (89.7% with HIV RNA levels < or =400 copies/mL after 6 months), but CD4+ cell counts after 6 months remained 0.140 x 10(9) cells/L below baseline. The hazard ratio (episodic versus continuous treatment) for opportunistic disease or death decreased after the recommendation to reinitiate continuous therapy (from 2.5 [CI, 1.8 to 3.5] to 1.4 [CI, 1.0 to 2.0]; P = 0.033 for difference). The residual excess risk was attributable to failure to reinitiate therapy by some participants and slow recovery of CD4+ cell counts for those who reinitiated therapy. LIMITATION Follow-up was too short to assess the full effect of switching from episodic to continuous antiretroviral therapy. CONCLUSION Reinitiating continuous antiretroviral therapy in patients previously assigned to episodic treatment reduced excess risk for opportunistic disease or death, but excess risk remained. Episodic antiretroviral therapy, as used in the SMART study, should be avoided.
Identification of MHC class II and TCR binding residues in the type II collagen immunodominant determinant mediating collagen-induced arthritis.

Collagen-induced arthritis (CIA), an autoimmune arthritis model, is elicited by the immunization of genetically susceptible strains of mice with type II collagen (CII). We have analyzed the molecular interactions that occur during the presentation of the immunodominant determinant within CII(257-270) by the murine class II susceptibility allele, I.Aq. Utilizing a soluble I-A binding assay and clonally distinct CII-specific T cells, we have identified the residues that control the ability of the CII(257-270) peptide to bind to I-Aq and those that interact with the TCR. In competitive binding assays with a panel of analog peptides, only two residues within CII(257-270) were found to participate in the binding of this peptide to I-Aq, residues 260 (Ile) and 263 (Phe). When these substitutions were combined into a single peptide, no binding of the peptide to I-Aq could be detected. Although no other substitutions decreased the binding affinity of the peptides, substitution of several amino acid residues lying outside of the determinant core increased the peptide's affinity for I-Aq and in some instances greatly enhanced the potency of the peptide in stimulating T cells. In antigen presentation assays, clonotypic variation in the recognition of several analog peptides indicated that residues 261, 262, 264, 266, and 267 are likely TCR contact sites. Since residue 266 interacts with the TCR and is the only residue in this determinant that differs between chick/bovine CII and mouse CII, these data indicate that immunity to the autoantigen may play a role in this model.
Circe: A grammar-based oracle for testing Cross-site scripting in web applications

Security is a crucial concern, especially for those applications, like web-based programs, that are constantly exposed to potentially malicious environments. Security testing aims at verifying the presence of security related defects. Security tests consist of two major parts, input values to run the application and the decision if the actual output matches the expected output, the latter is known as the “oracle”. In this paper, we present a process to build a security oracle for testing Cross-site scripting vulnerabilities in web applications. In the learning phase, we analyze web pages generated in safe conditions to learn a model of their syntactic structure. Then, in the testing phase, the model is used to classify new test cases either as “safe tests” or as “successful attacks”. This approach has been implemented in a tool, called Circe, and empirically assessed in classifying security test cases for two real world open source web applications.
Evaluation of Item Candidates: The PROMIS Qualitative Item Review

One of the PROMIS (Patient-Reported Outcome Measurement Information System) network’s primary goals is the development of a comprehensive item bank for patient-reported outcomes of chronic diseases. For its first set of item banks, PROMIS chose to focus on pain, fatigue, emotional distress, physical function, and social function. An essential step for the development of an item pool is the identification, evaluation, and revision of extant questionnaire items for the core item pool. In this work, we also describe the systematic process wherein items are classified for subsequent statistical processing by the PROMIS investigators. Six phases of item development are documented: identification of extant items, item classification and selection, item review and revision, focus group input on domain coverage, cognitive interviews with individual items, and final revision before field testing. Identification of items refers to the systematic search for existing items in currently available scales. Expert item review and revision was conducted by trained professionals who reviewed the wording of each item and revised as appropriate for conventions adopted by the PROMIS network. Focus groups were used to confirm domain definitions and to identify new areas of item development for future PROMIS item banks. Cognitive interviews were used to examine individual items. Items successfully screened through this process were sent to field testing and will be subjected to innovative scale construction procedures.
Insomnia Characterization: From Hypnogram to Graph Spectral Theory

Objective: To quantify and differentiate control and insomnia sleep onset patterns through biomedical signal processing of overnight polysomnograms. Methods: The approach consisted of three tandem modules: 1) biosignal processing module, which used state-space time-varying autoregressive moving average (TVARMA) processes with recursive particle filter, 2) hypnogram generation module that implemented a fuzzy inference system (F'S), and 3) insomnia characterization module that discriminated between control and subjects with insomnia using a logistic regression model trained with a set of similarity measures (d1, d2, d3, d4). The study employed sleep onset periods from 16 control and 16 subjects with insomnia. Results: Statespaced TVARMA processes with recursive particle filtering provided resilience to nonlinear, nonstationary, and non-Gaussian conditions of biosignals. F'S managed automated sleep scoring robust to intersubjects' and interraters' variability. The similarity distances quantified in a scalar measure the transitions amongst sleep onset stages, computed from expert and automated hypnograms. A statistical set of unpaired two-tailed t-tests suggested that distances d1, d2, and d3 had larger statistical significance (pd1 <; 6.5 × 10-5, pd2 <; 2.1 × 10-4, pd3 <; 4.5 × 10-7) to characterize sleeping patterns. The logistic regression model classified control and subjects with insomnia with sensitivity 87%, specificity 75%, and accuracy 81%. Conclusion: Our approach can perform a supportive role in either biosignal processing, sleep staging, insomnia characterization, or all the previous, coping with time-consuming procedures and massive data volumes of standard protocols. Significance: The introduction of graph spectral theory and logistic regression for the diagnosis of insomnia represents a novel concept, attempting to describe complex sleep dynamics throughout transitions networks and scalar measures.
A promoter polymorphism in the ALDH2 gene affects its basal and acetaldehyde/ethanol-induced gene expression in human peripheral blood leukocytes and HepG2 cells.

AIMS To assess the effect of the -360G/A polymorphism in the promoter region of the human aldehyde dehydrogenase-2 (ALDH2) gene on its transcription, basal and acetaldehyde/ethanol-induced gene expression was examined by in vivo and in vitro experiments. METHODS Human peripheral blood leukocytes were collected before and after alcohol ingestion (0.4 g/kg body weight) in 21 healthy young Japanese volunteers with a deficient phenotype of ALDH2 ((487)Glu/Lys), and the levels of ALDH2 mRNA were quantified by real-time RT-PCR. The transcriptional activity of the ALDH2 promoter was investigated by a reporter assay using HepG2 cells in the presence or absence of acetaldehyde/ethanol. RESULTS The basal level of ALDH2 mRNA was significantly higher in -360A heterozygous subjects than in -360G homozygous subjects. In all subjects, regardless of the genotype, ALDH2 mRNA increased following ethanol ingestion. The promoter activity of a reporter plasmid for -360G was significantly lower than that of a reporter plasmid for -360A. Exposure to acetaldehyde induced a significant increase in the transcriptional activity of the -360G reporter, but not the -360A reporter. CONCLUSIONS In vivo and in vitro experiments showed that the -360G allele has lower basal transcriptional activity than the -360A allele, whereas acetaldehyde/ethanol-induced gene expression, in general, seems to be more enhanced in individuals homozygous for the -360G allele than in those with the -360A allele. Thus, the promoter polymorphism may be involved in individual differences in acetaldehyde elimination.
Stabilizing the System of Mortgage Finance in the United States

It has been over a decade since the peak of house prices in the US was attained, and while there has been a concerted regulatory response to the subsequent collapse, the two Government Sponsored Enterprises (GSEs) remain in conservatorship. While this action served to forestall a deeper crisis at the time, over the past several years risks related to the system of mortgage finance can be seen building across several dimensions that need to be addressed. While reforms to the GSEs are an important part of dealing with these concerns, this paper argues that broader changes need to be made across the entire mortgage landscape to stabilize the system, even before the final state of the GSEs is fully determined.
Pharmacokinetics and tolerance of intravenous and intramuscular recombinant alpha2 interferon in patients with malignancies

Fifteen patients with advanced hematopoietic and other malignancies were treated with recombinant DNA produced Alpha2 Interferon (IFN) (Schering) by intravenous (IV) and intramuscular (IM) routes at weekly intervals in escalating doses from 1 × 106 IU to 100 × 106 IU in order to determine the tolerance and pharmacokinetics. The most common side effects included fever, chills, myalgia, and arthralgia. At doses of 60 × 106 or above, severe but reversible hypotension was observed in five patients receiving interferon by intravenous route. Patients receiving interferon by intramuscular route had fever, chills, and myalgias but did not develop hypotension at the same dosage. Two patients with non‐Hodgkin lymphoma showed objective evidence of regression. Our data suggest a biphasic pattern of elimination with terminal half‐life ranging from 1.9 to 2.9 hours and peak titer of 16,000 units and under for IV interferon, and terminal half‐life of 6 hours with peak titers of 600 units for intramuscular interferon. However, interpatient variability precludes a definite conclusion.
Endoscopic Anatomy of the Pediatric Middle Ear

Traditionally, otologists have aimed to produce a clean, dry, safe ear with the best possible hearing result. More recently, “less invasively” has been added to this list of goals. The development of small-diameter, high-quality rigid endoscopes and high-definition video systems has made totally endoscopic, transcanal surgery a reality in adult otology and a possibility in pediatric otology. This article reviews the anatomy of the pediatric middle ear and its surrounding airspaces and structures based on the work of dozens of researchers over the past 50 years. It will focus on the developmental changes in ear anatomy from birth through the first decade, when structure and function change most rapidly. Understanding the limits and possibilities afforded by new endoscopic technologies, the pediatric otologist can strive for results matching or exceeding those achieved by more invasive surgical approaches.
Significance of β‐catenin and pRB pathway components in malignant ovarian germ cell tumours: INK4A promoter CpG island methylation is associated with cell proliferation

To clarify the mechanisms underlying cell cycle promotion in malignant germ cell tumours of the ovary (MGCTOs), β‐catenin and components of the pRB pathway, cyclin D1 and p16, were analysed in relation to cell proliferation. Immunohistochemically, p16 protein was not expressed in a number of MGCTOs (9 of 42 tumours: 21.4%) and was associated with p16 gene (INK4A) promoter 5′‐CpG islands methylation. Amplification of the cyclin D1 gene (CCND1) was detected in a small number of MGCTOs (5 of 42 tumours: 13.5%). Reduced expression of p16 due to promoter methylation correlated significantly with increased cell proliferation as evidenced by Ki‐67 labelling index (p < 0.001) and mitotic index (p < 0.01). In some tumour types, nuclear localization of β‐catenin has been reported to be associated with β‐catenin gene (CTNNB1) mutation, cyclin D1 overexpression, and increased cell proliferation. Nuclear localization of β‐catenin, which was observed in MGCTOs other than dysgerminoma, was not associated with cyclin D1 expression and increased cell proliferation, but appeared to be related to tumour differentiation. Furthermore, CTNNB1 mutations were not detected in any of the MGCTOs examined. Our results suggest that reduced expression of p16 due to INK4A promoter methylation is one of the principal factors that promote cell proliferation in MGCTOs. Thus, p16 may be a novel target for gene therapies to treat MGCTOs. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance*

The receptor deleted in colorectal cancer (DCC) mediates the attraction of growing axons to netrin-1 during brain development. In response to netrin-1 stimulation, DCC becomes a signaling platform to recruit proteins that promote axon outgrowth and guidance. The Ras GTPase-activating protein (GAP) p120RasGAP inhibits Ras activity and mediates neurite retraction and growth cone collapse in response to repulsive guidance cues. Here we show an interaction between p120RasGAP and DCC that positively regulates netrin-1-mediated axon outgrowth and guidance in embryonic cortical neurons. In response to netrin-1, p120RasGAP is recruited to DCC in growth cones and forms a multiprotein complex with focal adhesion kinase and ERK. We found that Ras/ERK activities are elevated aberrantly in p120RasGAP-deficient neurons. Moreover, the expression of p120RasGAP Src homology 2 (SH2)-SH3-SH2 domains, which interact with the C-terminal tail of DCC, is sufficient to restore netrin-1-dependent axon outgrowth in p120RasGAP-deficient neurons. We provide a novel mechanism that exploits the scaffolding properties of the N terminus of p120RasGAP to tightly regulate netrin-1/DCC-dependent axon outgrowth and guidance.
Interdependence of Endomembrane Trafficking and Actin Dynamics during Polarized Growth of Arabidopsis Pollen Tubes1[C][W][OA]

During polarized growth of pollen tubes, endomembrane trafficking and actin polymerization are two critical processes that establish membrane/wall homeostasis and maintain growth polarity. Fine-tuned interactions between these two processes are therefore necessary but poorly understood. To better understand such cross talk in the model plant Arabidopsis (Arabidopsis thaliana), we first established optimized concentrations of drugs that interfere with either endomembrane trafficking or the actin cytoskeleton, then examined pollen tube growth using fluorescent protein markers that label transport vesicles, endosomes, or the actin cytoskeleton. Both brefeldin A (BFA) and wortmannin disturbed the motility and structural integrity of ARA7- but not ARA6-labeled endosomes, suggesting heterogeneity of the endosomal populations. Disrupting endomembrane trafficking by BFA or wortmannin perturbed actin polymerization at the apical region but not in the longitudinal actin cables in the shank. The interference of BFA/wortmannin with actin polymerization was progressive rather than rapid, suggesting an indirect effect, possibly due to perturbed endomembrane trafficking of certain membrane-localized signaling proteins. Both the actin depolymerization drug latrunculin B and the actin stabilization drug jasplakinolide rapidly disrupted transport of secretory vesicles, but each drug caused distinct responses on different endosomal populations labeled by ARA6 or ARA7, indicating that a dynamic actin cytoskeleton was critical for some steps in endomembrane trafficking. Our results provide evidence of cross talk between endomembrane trafficking and the actin cytoskeleton in pollen tubes.
Financial Literacy; Strategies and Concepts in Understanding the Financial Planning With Self-EfficacyTheory and Goal SettingTheory of Motivation Approach

This article discusses the strategies and concepts in understanding the financial literacy with the approach of self-efficacy theory and goal setting theory of motivation. The discussion begins with the concept of behavioral finance that discusses links between financial concepts to the behavior, and then proceed with the concept and measurement of financial literacy of individuals altogether with some approaches and factors that may affect it. Self-efficacy theory and goal setting theory of motivation is proposed to be a predictive factor of the level of financial literacy with relevant constructs, there are two propositions proposed to predict the level of financial literacy: (1) Self-efficacy theory, in this case the motivational construct (manage finances, use credit cards less, and control debt), and (2) goal setting theory of motivation, in this case the goal commitment and goal specificity construct (financial planning).
Pride and physical activity: Behavioural regulations as a motivational mechanism?

Objectives: The purpose of this study was to examine the association between fitness-related pride and moderate-to-vigorous physical activity (MVPA). A secondary aim was to examine behavioural regulations consistent with organismic integration theory (OIT) as potential mechanisms of the pride-MVPA relationship. Design: This study used a cross-sectional design. Methods: Young adults (N = 465; Mage = 20.55; SDage = 1.75 years) completed self-report instruments of fitness-related pride, motivation and MVPA. Results: Both authentic and hubristic fitness-related pride demonstrated a moderate positive relationship with MVPA, as well as positive associations to more autonomous regulations. Behavioural regulations mediated the relationship between both facets of pride and MVPA with specific indirect effects noted for identified regulation and intrinsic motivation. Conclusion: Overall, these findings demonstrate the association between experiencing fitness-related pride and increased engagement in MVPA. The tenability of OIT was also demonstrated for offering insight into explaining the association between pride and physical activity engagement.
Impact of Collective Rights-based Fisheries Management: Evidence from the New England Groundfish Fishery

This article uses a trip-level dataset to analyze the impact of a collective rights-based management system (“sectors”) introduced in the New England groundfish fishery in 2010. We examine the change of a number of outcome variables, including effort, species diversity, and location diversity. We then examine whether participation in sectors led to shifts in the production frontier and/or changes in technical efficiency using stochastic frontier models. Our results suggest that participation in sectors appears to have impacted trawl vessels more than gillnet vessels, likely due to the different ways in which the effort regulations in place under the common-pool regime impacted these vessel types. In addition, sector participation appears to have an impact on behavioral responses (i.e., changes in effort and diversity of species and locations) rather than technical efficiency, despite some evidence that sector participation led to shifts in the production frontiers of both vessel types.