Miracle-dz/UniFAR-FTUs huggingface dataset:
The HLA profiles of mixed connective tissue disease differ distinctly from the profiles of clinically related connective tissue diseases.

OBJECTIVE The Norwegian nationwide MCTD cohort was established to obtain unbiased data on key disease issues, and thereby reappraise the concept of MCTD. In the current study, the aims were to obtain detailed HLA profile data on the large Norwegian MCTD cohort and compare these with the HLA profiles of ethnically matched healthy controls and related CTD controls. METHODS HLA profiles, determined by sequence-based typing of HLA-B* and DRB1*, were compared between four control groups of Norwegian ancestry, SLE (n = 96), SSc (n = 95), PM/DM (n = 84), healthy individuals (n = 282), the complete MCTD cohort (n = 155) and MCTD subsets defined by key clinical parameters. RESULTS HLA-B*08 [odds ratio (OR) 2.05, P = 1.31 × 10(-4)) and DRB1*04:01 (OR 2.82, P = 3.64 × 10(-8)) were identified as risk alleles for MCTD, while DRB1*04:04, DRB1*13:01 and DRB1*13:02 were protective. Risk alleles for SLE and PM/DM were B*08 and DRB1*03:01. SSc risk was associated with DRB1*08:01. Analyses of MCTD subsets identified B*18 [OR 3.32 (95% CI 1.38, 8.01)] and DRB1*03:01 [OR 1.83 (95% CI 1.03, 3.25)] as independent risk factors for lung fibrosis. CONCLUSION Novel HLA alleles associated with MCTD and disease subsets were identified and DRB1*04:01 was confirmed as a major risk allele. Altogether, the data reinforce the notion of MCTD as a disease entity distinct from SLE, SSc and PM/DM.
Linear Approaches to Characterization of Delayed Emissions of Methane

It is becoming more common to include the effects of delayed greenhouse gas emissions as an additional aspect in carbon footprinting. Although full dynamic assessment is the only accurate option to calculate those effects, the linear approach as outlined in, for example, the International Reference Life Cycle Data System (ILCD) Handbook, which is a popular reference. This approach overestimates the benefits of delayed emissions in all cases, but, for methane, the deviation is orders of magnitude. An alternative linear approach is proposed that does not start at t = 0. When using a time horizon of 100 years, an initial no‐accounting period of 75 years is found to be appropriate for delayed emissions of methane, in most cases. The difference between the two approaches, when applying the concept of temporary carbon storage or delayed emissions to landfill, is considerable.
Quantitative Assessment of Breast Parenchymal Uptake on 18F-FDG PET/CT: Correlation with Age, Background Parenchymal Enhancement, and Amount of Fibroglandular Tissue on MRI

Background parenchymal enhancement (BPE), and the amount of fibroglandular tissue (FGT) assessed with MRI have been implicated as sensitive imaging biomarkers for breast cancer. The purpose of this study was to quantitatively assess breast parenchymal uptake (BPU) on 18F-FDG PET/CT as another valuable imaging biomarker and examine its correlation with BPE, FGT, and age. Methods: This study included 129 patients with suspected breast cancer and normal imaging findings in one breast (BI-RADS 1), whose cases were retrospectively analyzed. All patients underwent prone 18F-FDG PET/CT and 3-T contrast-enhanced MRI of the breast. In all patients, interpreter 1 assessed BPU quantitatively using SUVmax. Interpreters 1 and 2 assessed amount of FGT and BPE in the normal contralateral breast by subjective visual estimation, as recommended by BI-RADS. Interpreter 1 reassessed all cases and repeated the BPU measurements. Statistical tests were used to assess correlations between BPU, BPE, FGT, and age, as well as inter- and intrainterpreter agreement. Results: BPU on 18F-FDG PET/CT varied among patients. The mean BPU SUVmax ± SD was 1.57 ± 0.6 for patients with minimal BPE, 1.93 ± 0.6 for mild BPE, 2.42 ± 0.5 for moderate BPE, and 1.45 ± 0.3 for marked BPE. There were significant (P < 0.001) moderate to strong correlations among BPU, BPE, and FGT. BPU directly correlated with both BPE and FGT on MRI. Patient age showed a moderate to strong indirect correlation with all 3 imaging-derived tissue biomarkers. The coefficient of variation for quantitative BPU measurements with SUVmax was 5.6%, indicating a high reproducibility. Interinterpreter and intrainterpreter agreement for BPE and FGT was almost perfect, with a κ-value of 0.860 and 0.822, respectively. Conclusion: The results of our study demonstrate that BPU varied among patients. BPU directly correlated with both BPE and FGT on MRI, and BPU measurements were highly reproducible. Patient age showed a strong inverse correlation with all 3 imaging-derived tissue biomarkers. These findings indicate that BPU may serve as a sensitive imaging biomarker for breast cancer prediction, prognosis, and risk assessment.
Claudin-2, a component of the tight junction, forms a paracellular water channel

Whether or not significant amounts of water pass the tight junction (TJ) of leaky epithelia is still unresolved, because it is difficult to separate transcellular water flux from TJ-controlled paracellular water flux. Using an approach without differentiating technically between the transcellular and paracellular route, we measured transepithelial water flux with and without selective molecular perturbation of the TJ to unequivocally attribute changes to the paracellular pathway. To this end, MDCK C7 cells were stably transfected with either claudin-2 or claudin-10b, two paracellular cation-channel-forming TJ proteins that are not endogenously expressed in this cell line. Claudin-2 is typical of leaky, water-transporting epithelia, such as the kidney proximal tubule, whereas claudin-10b is present in numerous epithelia, including water-impermeable segments of the loop of Henle. Neither transfection altered the expression of endogenous claudins or aquaporins. Water flux was induced by an osmotic gradient, a Na+ gradient or both. Under all conditions, water flux in claudin-2-transfected cells was elevated compared with vector controls, indicating claudin-2-mediated paracellular water permeability. Na+-driven water transport in the absence of an osmotic gradient indicates a single-file mechanism. By contrast, claudin-10b transfection did not alter water flux. We conclude that claudin-2, but not claudin-10b, forms a paracellular water channel and thus mediates paracellular water transport in leaky epithelia.
Oxytocin enhances processing of positive versus negative emotional information in healthy male volunteers

Abstract Animal studies have shown the role of oxytocin in affiliation and attachment, and recent evidence suggests that oxytocin is also involved in human models of approach behaviour, possibly by modulating the processing of emotionally valenced stimuli. Although oxytocin administration has been reported to decrease neural responses to facial emotional information, the effects on a wider range of behavioural measures of emotional processing shown to be sensitive to antidepressant manipulation have not been examined. The aim of this study was to investigate whether intranasally administered oxytocin affects the processing of positive and negative affective information in healthy male volunteers across tasks measuring attention, perception and memory. Twenty-nine male healthy volunteers were randomly allocated to receive a single dose of oxytocin nasal spray (24 UI) or placebo. 50 min later, participants completed a battery of psychological tests measuring emotional processing. A single dose of intranasally administered oxytocin slowed reaction time to correctly identify fearful facial expressions and reduced the misclassification of positive emotions as negative ones. These effects occurred in the absence of significant differences in subjective ratings of mood and anxiety. These results suggest that oxytocin modulates emotion processing in healthy male volunteers. This action may contribute to the emerging role of the neuropeptide in promoting affiliative and approach behaviours by reducing the salience of potentially ambiguous and threatening social stimuli.
Ameliorative Effects of Chloroform Fraction of Cocos nucifera L. Husk Fiber Against Cisplatin-induced Toxicity in Rats

Background: Cisplatin (Cis) is used in the treatment of solid tumors and is known to elicit serious side effects. Objective: The present study investigated the protective effects of chloroform fraction of Cocos nucifera husk fiber (CFCN) against Cis-induced organs' damage and chromosomal defect in rats. Quercetin (QUE), standard antioxidant, served as positive control. Materials and Methods: Thirty male Wistar rats were assigned into six groups and treated with corn oil (control), Cis alone, Cis + CFCN, CFCN alone, Cis + QUE, and QUE alone. QUE and CFCN were given at 50 and 200 mg/kg/day, respectively, by oral gavage for 7 days before the rats were exposed to a single dose of Cis (10 mg/kg, intraperitoneal) at the last 36 h of study. Results: Administration of Cis alone caused a significant (P < 0.05) increase in the levels of serum creatinine and urea by 72% and 70%, respectively, when compared with the control. The activity of serum aspartate aminotransferase was significantly (P < 0.05) increased while alanine aminotransferase and alkaline phosphatase were insignificantly (P > 0.05) affected in Cis-treated rats. Furthermore, the activities of hepatic and renal catalase, superoxide dismutase, glutathione S-transferase, glutathione peroxidase, and levels of reduced glutathione were significantly (P < 0.05) decreased in Cis-treated rats with concomitant elevation of malondialdehyde. Cis exposure increased the frequency of micro nucleated polychromatic erythrocytes (mPCE) by 92%. Pretreatment with CFCN inhibited lipid peroxidation, enhanced the activities of some antioxidative enzymes and reduced the frequency of mPCE. Conclusions: Chloroform fraction of CFCN may protect against organs damage by Cis. Further studies are required to determine the component of the plant responsible for this activity.
Purification of Cytochrome P‐450 Enzymes

Among the liver P‐450 xenobiotic‐metabolizing enzymes, P450‐2E1 is of interest because of its activation of potent carcinogens, and P‐450 1A2 is of interest because of its role in oxidation of drugs and carcinogens. This unit describes column chromatography protocols for purification of recombinant forms of these enzymes expressed in a bacterial expression system.
Innovation and Entrepreneurship: A Model Based on Entrepreneur Development

This article proposes a person-centered model for entrepreneurship, rather than one based on an idea or business plan. It analyzes the characteristics of entrepreneurship development programs worldwide and presents a representative sample of best practices. On the basis of the main findings and lessons learned, this paper defines the characteristics and components of a new model for entrepreneur development and presents recommendations as to how to deploy the model in Latin America and the Caribbean.
Children's Schooling in Sub-Saharan Africa: The Role of Fathers, Mothers, and Others

Multinomial logistic regression techniques are used to estimate personal and familial determinants of childrens participation and progress in school in seven sub-Saharan African countries. Data are obtained from Demographic and Health Surveys for Kenya and Tanzania Cameroon and Niger and Malawi Namibia and Zambia. Findings indicate that most 10-14 year olds were currently enrolled in school with the exception of Niger. However few in this age group completed the first four years of primary education. Four conclusions are drawn. 1) Family and household characteristics in particular education of the head and living standard determined whether a child was enrolled and how rapidly the child advanced by grade level. Both factors were important but education of the head appeared to be the most important factor in explaining current enrollment rates and the timing of school entry. Standard of living was associated with the widest differences in attainment of four grade levels. 2) The chances of enrollment and progress in school appeared to be unrelated to the survival of parents. 3) Children benefitted educationally more from female headed households when compared to male headed households at the same resource level. 4) Specific gender differences varied by country. Family and household circumstances did not operate systematically across countries to the advantage of boys or girls. The proportion of children aged 10 years currently attending school who were at the appropriate grade level ranged from 96% in Tanzania to 59% in Malawi. By the age of 14 years the respective proportions were from 56% to 25%. The drop was attributed in part to grade repetition. The proportion who completed grade 4 by age 14 out of the ever-enrolled was 79% in Kenya 74% in Zambia 73% in Tanzania 68% in Cameroon 58% in Namibia 44% in Malawi and 23% in Niger.
Fertility considerations and preservation in haemato‐oncology patients undergoing treatment

The improved survival rates among patients with haematological malignancies, such as lymphoma and leukaemia, are shifting areas of focus towards understanding and preventing treatment‐induced sequelae. Of these, infertility is one of the most devastating consequences for patients with reproductive potential. The degree of treatment‐induced gonadal dysfunction depends on age and gender‐related differences, the type and dosage of chemotherapy used and the field and cumulative dose of abdomino‐pelvic irradiation. There is also the interesting phenomenon of reduced pre‐treatment fertility among male lymphoma patients. At present, the only established methods of fertility preservation are cryopreservation of sperm, oocytes and embryos, as well as gonadal shielding and transposition of ovaries during irradiation. Several other methods, such as cryopreservation and subsequent transplantation of gonadal tissue and the gonadoprotective role of hormonal suppression, are under investigation. Pre‐pubertal patients present a unique constellation of fertility considerations, especially as embryo and sperm cryopreservation are not applicable to this age group.
Bending bureaucracy: leadership and multi-level governance

About the book: Bureaucracy is often used as short-hand for the dysfunctions of organizations. Its reform or abolition is continually demanded or promised. This book highlights the positive attributes of bureaucracy and shows why bureaucratic organization should be valued, both by those engaged in business and commerce, and those responsible for running states and delivering public services.
Diagnostic orphans: adolescents with alcohol symptom who do not qualify for DSM-IV abuse or dependence diagnoses.

OBJECTIVE Little is known about the validity of the DSM-IV criteria for alcohol use disorders when applied to adolescents. This report describes a group of "diagnostic orphans," adolescents with one or two DSM-IV alcohol dependence symptoms who do not meet the DSM-IV criteria for alcohol abuse or alcohol dependence. METHOD The study included 199 male and 173 female subjects aged 13-19 years. All subjects were regular drinkers, recruited from community sources and alcohol treatment programs. At baseline and at 1-year follow-up, DSM-IV alcohol use disorders were assessed with a version of the Structured Clinical Interview for DSM-III-R, modified for DSM-IV criteria. RESULTS Diagnostic orphans represented 31% of the drinkers without an alcohol use disorder. The orphans were similar to the alcohol abusers and dissimilar to the other drinkers in alcohol and substance use patterns and in the course of alcohol problems over 1 year. CONCLUSIONS The results indicate limitations of the DSM-IV criteria for alcohol use disorders when applied to adolescents. Diagnostic orphans should be considered separately from other drinkers in research and treatment efforts.
Exploiting the Task-Pipelined Parallelism of Stream Programs on Many-Core GPUs

By exploiting data-level parallelism, Graphics Processing Units (GPUs) have become a high-throughput, general purpose computing platform. Many real-world applications especially those following a stream processing pattern, however, feature interleaved task-pipelined and data parallelism. Current GPUs are ill equipped for such applications due to the insufficient usage of computing resources and/or the excessive offchip memory traffic. In this paper, we focus on microarchitectural enhancements to enable task-pipelined execution of data-parallel kernels on GPUs. We propose an efficient adaptive dynamic scheduling mechanism and a moderately modified L2 design. With minor hardware overhead, our techniques orchestrate both task-pipeline and data parallelisms in a unified manner. Simulation results derived by a cycle-accurate simulator on real-world applications prove that the proposed GPU microarchitecture improves the computing throughput by 18% and reduces the overall accesses to off-chip GPU memory by 13%. key words: GPU, task-pipeline, dynamic scheduling, load balance, L2 cache
An Analysis of the Forecast Error Impact of Alternative Beta Adjustment Techniques and Risk Classes

THE PURPOSE OF THIS paper is to examine empirically the relationships among the stability of security and portfolio betas and (1) beta adjustment techniques, (2) beta risk classes, and (3) the length of the sample periods used to calculate betas. The beta coefficient of the familiar market model has emerged in recent years as an important tool for assessing the risk associated with individual securities and portfolios. The usefulness of an ex post beta for measuring the ex ante risk of an investment depends, however, upon the temporal stability of the asset's beta coefficient. While there have been numerous studies concerned with an empirical examination of beta stability [1, 2, 3, 6, 7, 8, 10], there has been no examination of forecast error components associated with different beta groups classified according to beta magnitude or with different beta estimation and prediction period lengths. ' Typically, studies have used a single length beta estimation and prediction period [2, 3, 5, 6, 7], and if the lengths of the beta estimation and prediction periods were varied, the two period lengths were always equal for each comparison [1, 8]. Alternative estimation and prediction period lengths are used in this study to examine the impact of beta adjustment techniques, risk classes, and portfolio size on the beta forecast error and its components. The results of this study indicate that beta forecast errors may be substantially reduced when (1) beta adjustment procedures are utilized, (2) portfolio size is increased, and (3) the estimation or prediction period is increased. When securities or portfolios are grouped into risk classes, adjustment techniques are very effective in reducing the size of the inefficiency and bias components of the forecast error, but they show little impact on the random error components. Furthermore, for more extreme risk classes, the primary source of error is bias for portfolios when no adjustments are made, while random error is the major source of forecast error for single securities for longer estimation periods.
Thromboembolism in children with acute lymphoblastic leukaemia treated on Dana‐Farber Cancer Institute protocols: effect of age and risk stratification of disease

Children with acute lymphoblastic leukaemia (ALL) are at increased risk for thromboembolism (TE). Identification of a susceptible population is crucial for effective thromboprophylaxis. However, the risk factors for ALL‐associated TE are unclear. Concomitant asparaginase (ASP) and steroid therapy has been shown to increase the incidence of TE. Dana‐Farber Cancer Institute (DFCI)‐ALL protocols use a combination of ASP and steroids during the postinduction intensification phase when high‐risk (HR) patients receive thrice the steroid‐dose given to standard‐risk (SR) patients. We studied prospectively assembled cohorts of children treated on two consecutive DFCI‐ALL protocols to define the risk factors for symptomatic TE. Ten (11%) of 91 patients developed symptomatic TE; eight (seven HR) during intensification. Seven (44%) of 16 older patients (≥10 years) compared with three of 75 (4%) younger patients developed TE (P < 0·0001). Nine of 35 (26%) HR and one of 56 (2%) SR patients developed TE (P = 0·0006). Gender, ALL‐immunophenotype, steroid‐type or ASP dosing schedule did not alter the risk but older age and HR‐disease were factors predisposing to TE associated with DFCI‐ALL protocols. Age‐related risk may partly reflect the effect of ALL‐risk stratification. Higher dose steroids combined with ASP may lead to an increased risk of TE in HR patients.
Innovation strategy in the US: top executives offer their views

Purpose – The USA is the world’s largest economy, but is it a leading innovation nation? As economies mature and slow in growth, innovation will prove to be a key driver in maintaining transient advantage. This article presents a pulse on innovation in the USA as F1000 C-suite executives weigh in on their organization’s innovation health. It also compares the US score with proxy benchmark measures in other countries, and provides operational and strategic considerations to advance innovation platforms in US organizations. Managers will gain insight into common hurdles faced by some of America’s most prominent companies, as well as how to improve innovation practices in their own organization. Design/methodology/approach – This current article reports on findings of innovation health in the USA based on responses from 1,127 F1000 executives (manager level and higher). F1000 executives report their innovation culture through completion of an innovation culture model survey developed by the authors. The F100.
Party system and media in Poland after 1989

Th e importance of the media for the party system formation in Poland in the transforma- tion is unarguable. Th is signifi cance resulted from the lack of developed party structures that could be involved in process of communication between party elites and electorate. Hence, media became the only possible instrument that might have been used in arousing electorate's interest. However, the interdependence between party system and media means also that the parties had their infl uence on the legal framework of the media and sometimes ideological profi le as well.
Irreversibilidad e incertidumbre de las decisiones financieras en i&d

The traditional methods for the valuation of investments are based on the possibility of calculating discount cash flows. The present paper analyses the problem associated to investments on innovative products, which require an important demand of R&D. The mentioned investments present irreversibility, flexibility and uncertainty characteristics. Therefore, it is proposed the Real Options methodology. To carry it out, investigations processes and their relationship with the financial market are described, with the aim of dealing with the irreversibility and the possibilities of making flexible a project. Finally, the different valuation methods are reviewed, focusing on the Black & Scholes formula to consider the options to wait, abandon, expand and suspend. It is necessary to take into account that the mentioned criteria does not replace the traditional valuation methods (especially NPV), but it should be incorporated to them, to appropriately treat the current context.