Miracle-dz/UniFAR-FTUs huggingface dataset:
Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma.

PURPOSE To provide a more precise estimate of long-term survival observed for ipilimumab-treated patients with advanced melanoma, we performed a pooled analysis of overall survival (OS) data from multiple studies. METHODS The primary analysis pooled OS data for 1,861 patients from 10 prospective and two retrospective studies of ipilimumab, including two phase III trials. Patients were previously treated (n = 1,257) or treatment naive (n = 604), and the majority of patients received ipilimumab 3 mg/kg (n = 965) or 10 mg/kg (n = 706). We also conducted a secondary analysis of OS data (n = 4,846) with an additional 2,985 patients from an expanded access program. OS rates were estimated using the Kaplan-Meier method. RESULTS Among 1,861 patients, median OS was 11.4 months (95% CI, 10.7 to 12.1 months), which included 254 patients with at least 3 years of survival follow-up. The survival curve began to plateau around year 3, with follow-up of up to 10 years. Three-year survival rates were 22%, 26%, and 20% for all patients, treatment-naive patients, and previously treated patients, respectively. Including data from the expanded access program, median OS was 9.5 months (95% CI, 9.0 to 10.0 months), with a plateau at 21% in the survival curve beginning around year 3. CONCLUSION To our knowledge, this is the largest analysis of OS to date for ipilimumab-treated patients with advanced melanoma. We observed a plateau in the survival curve, beginning at approximately 3 years, which was independent of prior therapy or ipilimumab dose. These data add to the evidence supporting the durability of long-term survival in ipilimumab-treated patients with advanced melanoma.
L’apprentissage hybride en sciences de gestion : ce qu’en pensent les étudiants

Face a un environnement de plus en plus concurrentiel des ecoles et facultes de gestion, l’apprentissage hybride devient une strategie institutionnelle tres prisee. Ce constat nous a permis de concevoir et d’implanter durant quatre sessions des annees universitaires 2009 a 2011, un projet d’apprentissage hybride. Ce dispositif a ete deploye dans dix cours distincts pour un total de 27 classes. Nous avons recueilli les perceptions des 805 etudiants inscrits dans ce projet pilote, notamment pour connaitre leurs raisons de s’inscrire a un cours hybride, leurs appreciations des dispositifs pedagogiques hybrides ainsi que leurs points de vue des impacts sur les apprentissages. Les donnees colligees par questionnaire ont ete analysees dans l’optique d’une evaluation de l’innovation pedagogique et de sa possible institutionnalisation. L’article se termine par une serie de quatre propositions reliees a une conceptualisation emergente sur l’apprentissage hybride.
The Effects of CoCl2 on HIF-1α Protein under Experimental Conditions of Autoprogressive Hypoxia Using Mouse Models

It is well known that cobalt chloride (CoCl2) can enhance the stability of hypoxia-inducible factor (HIF)-1α. The aim of this study is to detect the effect of CoCl2 on the hypoxia tolerance of mice which were repeatedly exposed to autoprogressive hypoxia. Balb/c mice were randomly divided into groups of chemical pretreatment and normal saline (NS), respectively injected with CoCl2 and NS 3 h before exposure to hypoxia for 0 run (H0), 1 run (H1), and 4 runs (H4). Western Blot, electrophoretic mobility shift assay (EMSA), extracellular recordings population spikes in area cornus ammonis I (CA 1) of mouse hippocampal slices and real-time were used in this study. Our results demonstrated that the tolerance of mice to hypoxia, the changes of HIF-1α protein level and HIF-1 DNA binding activity in mice hippocampus, the mRNA level of erythropoietin (EPO) and vascular endothelial growth factor (VEGF), and the disappearance time of population spikes of hippocampal slices were substantially different between the control group and the CoCl2 group. Over-induction of HIF-1α by pretreatment with CoCl2 before hypoxia did not increase the hypoxia tolerance.
The north–south cleavage and political support in Kyrgyzstan

This contribution applies Easton's concept of political support to an analysis of north and south Kyrgyzstan. Testing alternative theories of geographical distribution of political support, the study seeks to understand the relationship between, on the one hand, political support for the regime and its institutions, and on the other, ethnicity, urbanization and region of residence. It rejects the hypothesis that the north tends to support the opposition and the south supports the president, arguing instead that the north is more pessimistic in general about the state and non-state institutions.
An Analysis and Evaluation of the Internal Validity of the Remote Associates Test: What Does it Measure?

It is shown that items constructed like those of Mednick's Remote Associates Test (1962) fall into distinct categories. These categories of items are shown to interact significantly with subjects and with subject groups determined on the basis of RAT performance. Furthermore, RAT performance is shown to be more related to performance on items containing idiomatic relationships between stimuli and targets than to performance on items in which such relationships are semantic in nature. It is suggested either that the RAT is measuring a loosely related group of subtraits, or that its item population is poorly specified. Some doubts are cast on the validity of the RAT.
Is sampled data sufficient for anomaly detection?

Sampling techniques are widely used for traffic measurements at high link speed to conserve router resources. Traditionally, sampled traffic data is used for network management tasks such as traffic matrix estimations, but recently it has also been used in numerous anomaly detection algorithms, as security analysis becomes increasingly critical for network providers. While the impact of sampling on traffic engineering metrics such as flow size and mean rate is well studied, its impact on anomaly detection remains an open question.This paper presents a comprehensive study on whether existing sampling techniques distort traffic features critical for effective anomaly detection. We sampled packet traces captured from a Tier-1 IP-backbone using four popular methods: random packet sampling, random flow sampling, smart sampling, and sample-and-hold. The sampled data is then used as input to detect two common classes of anomalies: volume anomalies and port scans. Since it is infeasible to enumerate all existing solutions, we study three representative algorithms: a wavelet-based volume anomaly detection and two portscan detection algorithms based on hypotheses testing. Our results show that all the four sampling methods introduce fundamental bias that degrades the performance of the three detection schemes, however the degradation curves are very different. We also identify the traffic features critical for anomaly detection and analyze how they are affected by sampling. Our work demonstrates the need for better measurement techniques, since anomaly detection operates on a drastically different information region, which is often overlooked by existing traffic accounting methods that target heavy-hitters.
Emotional labour and emotional exhaustion: Interpersonal and intrapersonal mechanisms

Abstract In some occupations, particularly in the service sector, dealing with patients or clients may require an employee to pretend to have emotions that they do not really have, or to actually experience required emotions. The regulation of emotion can be either automatic or controlled. This study extends research on the consequences and processes of emotional labour in two ways. First, it examines how the use of different emotion regulation strategies with patients relates to doctors’ emotional exhaustion. Second, it tests two mechanisms that may explain those relationships. A survey of 345 general practitioners (GPs) working in a large urban community in Spain was conducted for the study. Based on Côté's (2005) social interaction model, GP satisfaction with the responses of their patients was tested as a potential interpersonal mediator between their use of automatic, surface, and deep emotion regulation strategies and their emotional exhaustion. Psychological effort was tested as a potential intrapersonal mediator in the same pathway. Regression analysis indicated that emotion regulation was associated with GP emotional exhaustion when it was performed automatically, but that it had a positive and a neutral association when it was performed using surface and deep acting respectively. The mediating role of interpersonal and intrapersonal factors helped explain the differential associations between the GPs’ emotion regulation strategies and their emotional exhaustion.
INFLUENCE OF NON-ENZYMATIC ANTIOXIDANTS ON ANTIOXIDATION STATUS IN ACUTE HAEMORRHAGIC NECROTIZING PANCREATITIS IN RAT

The aim of the work was to assess the influence of some non-enzymatic antioxidants (uric acid, blood urea, bilirubin) on the antioxidant status of rat’s organism during the experimental acute haemorrhagic necrotising pancreatitis. The experiment was carried out on male Wistar rats, body weight 280-320 g, which were divided randomly into control and experimental groups. The control group (n=8) underwent laparotomy. The experimental group (n=24) was injected into pancreatic duct with natrium taurocholate to induce acute pancreatitis – according to the Heinkel and Aho method. Total antioxidation status in plasma was assessed according to the Benzie method (FRAP); total bilirubin, urea, and uric acid in plasma were assessed as described elsewhere. These parameters were examined in each group 3 h, 24 h, and 48 h after the experiment started. Simultaneously α-amylase activity (indicator of pancreatitis severity) was assessed in plasma. The obtained results were analysed statistically. Pancreatitis achieved its maximum severity 24 h after the beginning of the experiment and then decreased. After 48 h αamylase activity was only 2 times higher than that in the control group. FRAP maximum was noticed just after 3 h, then became lower and 48 h after the experiment onset its minimal value was 2 times lower than that of the control. Uric acid and bilirubin plasma concentration grew up 24 h after experiment beginning and next decreased. Only plasma urea concentration increased stably to the maximum value which was observed 24 h after the operation and after 48 h only slight decrease in its concentration was noticed. This phenomenon may be the result of parenchymatous organs damage occurring in acute haemorrhagic necrotising pancreatitis. It leads to interlobular and periadenous tissue necrosis as a consequence of lipid peroxidation. The obtained results showed the booster effect of non-enzymatic antioxidant agents on total antioxidant status during experimental pancreatitis. This effect correlated with pancreatitis severity which was evidenced by an increased αamylase activity in plasma.
Accelerating the development of formal thinking in middle and high school students III: Testing the permanency of effects

Two years after the end of a two-year intervention program intended to promote formal operational thinking, the achievement of students initially 12 years of age was tested by their results in British National examinations, taken at age 16. The intervention methodology was set within the context of science learning, so the difference between experimental and control classes was examined first in terms of their science results. The boys achieved an average of 40% more grades of C or above than the controls. This grade is the minimum criterion for higher education in Britain. The achievement was not found equally in all students: About 40% of the boys and 25% of the girls showed effect sizes of two standard deviations in relation to comparable controls, whereas the others did not differ from the controls. Both boys and girls showed significantly higher achievement in English than comparable controls, with an effect size about half that for science. The boys—but not the girls—also showed higher achievement in mathematics. It is argued that this evidence supports the interpretation that the students' increased science achievement was caused by increased general intellectual capacity, and not just by improved domain-specific skills.
Visual Information Density Adjuster (VIDA)

We introduce a system that helps users construct interactive visualizations with constant information density. This work is an extension of the DataSplash database visualization environment. DataSplash is a direct manipulation system in which users can construct and navigate visualizations. DataSplash users place objects in a canvas using a paint program interface. They can pan and zoom above the resulting visualization. Objects in the canvas change as users zoom closer to or further away from the canvas. Users specify graphically the point at which these changes occur. Our experience with DataSplash indicates that users find it difficult to construct visualizations that display an appropriate amount of detail. In this paper, we introduce an extension to DataSplash based on the Principle of Constant Information Density. This system provides users feedback about the density of their visualizations (as defined by user-defined constraints) as they are creating them. We have performed an informal study of constant information density. We further introduce heuristics based on the Principle of Constant Information Density. We propose a system that uses these heuristics to evaluate DataSplash applications created by users and recommend specific improvements.
THE ACADEMIC LECTURE

President Gerty’s invitation to address this assembly of the future leaders of our Association was one of the great pleasures and honors of my life. I can well remember my excitement when, in company with my father and my teacher Ernest Southard, I attended my first annual meeting-the 75th anniversary. This was 40 years ago, here in Philadelphia. I think I have missed only one meeting since then. In those days we were a small, intimate, informal group of a few hundred; everyone knew everyone. The program was simple, the entertainment lavish and the whole meeting a kind of family reunion. Southard and father and many others are gone now-but there are new elements of a family affair for my brother Will and myself of which we are proud. In the years since then there has been a vast development in the numbers and complexity of our organization. I am glad to have had a part in the planning for its re-structuring, even though the immediate impact of the suggestions made by the Committee on Reorganization was a shock reaction. That 14 of our 18 recommendations have been put into effect is gratifying. But I find the greatest satisfaction in the emphasis which the program committees and officers have placed on our continued self-improvement, on psychiatric education, on, for example, academic lectures! it is from a background of teaching that the topic which I propose to discuss emerged. I would like to warn you not to expect a scientific analysis of it along conventional lines. The subject does not permit of that; we don’t yet know enough about it, and it would be presumptuous to make the attempt. I am not reporting a
A doença crônica orgânica na infância e as práticas educativas maternas

Estudos apontam que a presenca de doenca cronica orgânica na infância pode se constituir num importante fator de mediacao da qualidade da interacao mae-crianca. Entretanto, poucos estudos investigam as praticas educativas maternas em criancas portadoras de doenca cronica. Os cuidados diarios exigidos pelo tratamento da enfermidade, bem como a fragilidade fisica e emocional da crianca podem afetar as praticas educativas maternas. Participaram do estudo 40 maes, metade das quais eram maes de criancas portadoras de doenca cronica orgânica e as demais de criancas sem doenca cronica. As criancas eram de ambos os sexos e tinham entre 03 e 05 anos de idade. Os participantes foram recrutados em hospitais e pre-escolas publicas. Uma entrevista semi-estruturada foi utilizada para se investigar as praticas educativas maternas, examinadas atraves de analise de conteudo. Os resultados revelaram uma tendencia marginalmente significativa no grupo com doenca cronica a utilizar um numero menor de praticas coercitivas. Alem disso, houve uma diferenca significativa entre os grupos quanto ao uso de punicao fisica e privacao/castigo, indicando que as maes de criancas com doenca cronica utilizaram com menor frequencia este tipo de pratica. Os resultados apoiam a expectativa inicial de que as maes de criancas com doenca cronica seriam menos coercitivas quando comparadas as maes do outro grupo.
Using social robots to studyabnormal social development

Social robots recognize and respond to human social cues with appropriate behaviors. Social robots, and the technology used in their construction, can be unique tools in the study of abnormal social development. Autism is a pervasive developmental disorder that is characterized by social and communicative impairments. Based on three years of integration and immersion with a clinical research group which performs more than 130 diagnostic evaluations of children for autism per year, this paper discusses how social robots will make an impact on the ways in which we diagnose, treat, and understand autism.
Modelling of emotional facial expressions during speech in synthetic talking heads using a hybrid approach

Talking heads and virtual characters, able to commu nicate complex information with human-like expressiveness and naturalness, should be able to display emotional fa cial expressions. In recent years several works, both ru le-based and statistical, have obtained important results in the modelling of emotional facial expressions to be use d in synthetic Talking Heads. However, most of the rulebased systems suffer from the drawback of static generati on, due to the fact that the set of rules and their combinatio ns are limited. On the other hand, most of works on synthe sis using statistical approaches are restricted to speech and lip movements. This paper presents a modelling of the dynamics of emotional facial expressions based on a hybrid statistical/machine learning approach. This approac h combines Hidden Markov Models (HMMs) and Recurrent Neural Networks (RNNs), aiming at benefiting from t he advantages of both paradigms and overcoming their o wn limitations.
Examining the Transcriptional Response in Wheat Fhb1 Near‐Isogenic Lines to Fusarium graminearum Infection and Deoxynivalenol Treatment

Fusarium head blight (FHB) is a disease caused predominantly by the fungal pathogen Fusarium graminearum that affects wheat and other small‐grain cereals and can lead to severe yield loss and reduction in grain quality. Trichothecene mycotoxins, such as deoxynivalenol (DON), accumulate during infection and increase pathogen virulence and decrease grain quality. The Fhb1 locus on wheat chromosome 3BS confers Type II resistance to FHB and resistance to the spread of infection on the spike and has been associated with resistance to DON accumulation. To gain a better genetic understanding of the functional role of Fhb1 and resistance or susceptibility to FHB, we examined DON and ergosterol accumulation, FHB resistance, and the whole‐genome transcriptomic response using RNA‐seq in a near‐isogenic line (NIL) pair carrying the resistant and susceptible alleles for Fhb1 during F. graminearum infection and DON treatment. Our results provide a gene expression atlas for the resistant and susceptible wheat–F. graminearum interaction. The DON concentration and transcriptomic results show that the rachis is a key location for conferring Type II resistance. In addition, the wheat transcriptome analysis revealed a set of Fhb1‐responsive genes that may play a role in resistance and a set of DON‐responsive genes that may play a role in trichothecene resistance. Transcriptomic results from the pathogen show that the F. graminearum genome responds differently to the host level of resistance. The results of this study extend our understanding of host and pathogen responses in the wheat–F. graminearum interaction.
Overrelaxation of the fast iterative shrinkage/thresholding algorithm for fast signal recovery

In this paper, we propose an overrelaxation scheme of FISTA and its monotone variant MFISTA. FISTA and MFISTA minimize the sum of a smooth and a nonsmooth convex function by iteratively applying a forward-backward splitting step. This problem setting arises naturally in the context of signal and image processing. The stepsize in the forward-backward splitting step of these methods is restricted to a constant value chosen from an interval that is determined by the Lipschitz constant of the gradient of the smooth function. The proposed scheme admits a variable stepsize that can be chosen from a larger interval than FISTA/MFISTA while keeping the same convergence rate as FISTA/MFISTA. A numerical example demonstrates the effectiveness of the proposed relaxations by showing that the proposed scheme outperforms the original FISTA and MFISTA in terms of speed of convergence.
Kinetic Validation of the Models for P-Glycoprotein ATP Hydrolysis and Vanadate-Induced Trapping. Proposal for Additional Steps

P-Glycoprotein, a member of the ATP-binding cassette (ABC) superfamily, is a multidrug transporter responsible for cellular efflux of hundreds of structurally unrelated compounds, including natural products, many clinically used drugs and anti-cancer agents. Expression of P-glycoprotein has been linked to multidrug resistance in human cancers. ABC transporters are driven by ATP hydrolysis at their two cytoplasmic nucleotide-binding domains, which interact to form a closed ATP-bound sandwich dimer. Intimate knowledge of the catalytic cycle of these proteins is clearly essential for understanding their mechanism of action. P-Glycoprotein has been proposed to hydrolyse ATP by an alternating mechanism, for which there is substantial experimental evidence, including inhibition of catalytic activity by trapping of ortho-vanadate at one nucleotide-binding domain, and the observation of an asymmetric occluded state. Despite many studies of P-glycoprotein ATPase activity over the past 20 years, no comprehensive kinetic analysis has yet been carried out, and some puzzling features of its behaviour remain unexplained. In this work, we have built several progressively more complex kinetic models, and then carried out simulations and detailed analysis, to test the validity of the proposed reaction pathway employed by P-glycoprotein for ATP hydrolysis. To establish kinetic parameters for the catalytic cycle, we made use of the large amount of published data on ATP hydrolysis by hamster P-glycoprotein, both purified and in membrane vesicles. The proposed kinetic scheme(s) include a high affinity priming reaction for binding of the first ATP molecule, and an independent pathway for ADP binding outside the main catalytic cycle. They can reproduce to varying degrees the observed behavior of the protein's ATPase activity and its inhibition by ortho-vanadate. The results provide new insights into the mode of action of P-glycoprotein, and some hypotheses about the nature of the occluded nucleotide-bound state.