Quantifying audience experience in the wild

Measuring the experience of audience of arts events is essential in the “experience economy” of this day and age, but it is a difficult task. The value of such information goes beyond evaluating the impact of the arts, as it can provide insights and feedback to enhance the work of artists and the experiences of other audience members. Through in-depth understanding of the needs of the providers and consumers of the arts, we progressively developed a biosensor infrastructure that was deployed in theaters. Over the years, we identified the challenges and issues related to developing and deploying a biosensor infrastructure in theaters. These collective experiences and identified issues were categorized into three main areas: processes, data, and system. A total of seven heuristics are developed across the three main areas. Processes place the stakeholders and audiences at the core of the research; data provides guidelines for data validity, collecting a variety of data, and supporting real-time data gathering; and systems covers the concurrency, scalability, deployment and feedback of the infrastructure. We believe that this set of heuristics forms the foundation for an adequate infrastructure to measure audience experience in the wild and it is a valuable source of guideline for future work

A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival

The hypomethylating agent azacitidine can prolong overall survival (OS) in patients with higher risk-myelodysplastic syndromes (HR-MDS) compared to conventional regimens. However, outcomes differ largely between studies, making it challenging to determine the contribution of novel therapies added to azacitidine. Further, a discrepancy is seen between complete (CR) or partial (PR) response rates and OS improvement with azacitidine, making it challenging to rely on earlier endpoints than OS. We conducted a systematic literature search and study-level systematic review of 237 clinical studies to better understand outcomes for HR-MDS patients treated with azacitidine. Pooled marrow CR was 9% (N = 2654; 95% CI: 6-13 %), CR rate was 17 % (N = 6943; 95% CI: 15-20 %), and median OS (mOS) was 18.6 months (N = 2820; 95% CI: 15.3-21.9). A weak correlation to mOS was detected with CR rate (207 patient cohorts, Pearson\u27s r = 0.315; P \u3c 0.0005), and a much stronger correlation with median progression-free survival (mPFS) (r=0.88, P = 3 × 1

Estudo de seguimento por dois anos de idosos residentes em São Paulo, Brasil: metodologia e resultados preliminares

INTRODUCTION: Previous cross-sectional studies have shown a high prevalence of chronic disease and disability among the elderly. Given Brazil s rapid aging process and the obvious consequences of the growing number of old people with chronic diseases and associated disabilities for the provision of health services, a need was felt for a study that would overcome the limitations of cross-sectional data and shed some light on the main factors determining whether a person will live longer and free of disabling diseases, the so-called successful aging. The methodology of the first follow-up study of elderly residents in Brazil is presented. METHOD: The profile of the initial cohort is compared with previous cross-sectional data and an in-depth analysis of nonresponse is carried out in order to assess the validity of future longitudinal analysis. The EPIDOSO ( Epidemiologia do Idoso ) Study conducted a two-year follow-up of 1,667 elderly people (65+), living in S. Paulo. The study consisted of two waves, each consisting of household, clinical, and biochemical surveys. RESULTS AND CONCLUSIONS: In general, the initial cohort showed a similar profile to previous cross-sectional samples in S. Paulo. There was a majority of women, mostly widows, living in multigenerational households, and a high prevalence of chronic illnesses, psychiatric disturbances, and physical disabilities. Despite all the difficulties inherent in follow-up studies, there was a fairly low rate of nonresponse to the household survey after two years, which did not actually affect the representation of the cohort at the final household assessment, making unbiased longitudinal analysis possible. Concerning the clinical and blood sampling surveys, the respondents tended to be younger and less disabled than the nonrespondents, limiting the use of the clinical and laboratory data to longitudinal analysis aimed at a healthier cohort. It is worth mentioning that gender, education, family support, and socioeconomic status were not important determinants of nonresponse, as is often the case.INTRODUÇÃO: Estudos transversais recentes mostraram alta prevalência de doenças crônicas e incapacidades físicas entre idosos. Considerando o rápido processo de envelhecimento do Brasil e as conseqüências que esse aumento de idosos com doenças crônicas e incapacidades associadas acarretará para o sistema de saúde, fazia-se necessário estudo que pudesse superar as limitações dos dados transversais, permitindo determinar quais os fatores determinantes de uma vida longa e livre de doenças incapacitantes, o chamado envelhecimento bem sucedido. É apresentada a metodologia do primeiro estudo epidemiológico longitudinal com idosos residentes na comunidade, no Brasil. MÉTODO: O perfil do cohorte inicial é comparado com dados de estudos anteriores a com o perfil dos não respondentes para avaliar a validade de análises longitudinais futuras.O projeto EPIDOSO (Epidemiologia do Idoso) seguiu por dois anos 1.667 idosos (65+), residentes em São Paulo. Consistiu de duas ondas, cada qual com três inquéritos: domiciliar, clínico e laboratorial. RESULTADOS E CONCLUSÕES: O perfil da população não diferiu de estudos anteriores, mostrando maioria de mulheres, viúvas, vivendo em domicílios multigeracionais, com uma alta prevalência de doenças crônicas, distúrbios psiquiátricos e incapacidades físicas. A despeito de todas as dificuldades inerentes a um estudo longitudinal, o grupo de não-respondentes ao segundo inquérito domiciliar não diferiu significativamente dos respondentes, assegurando análises longitudinais livres desse tipo de viés. Em relação aos inquéritos clínico e laboratorial, os não-respondentes mostraram-se mais velhos e mais incapacitados que os respondentes, limitando o uso dos dados clínicos e laboratoriais a análises pertinentes a uma cohorte mais jovem e saudável. Sexo, educação, apoio familiar e nível socioeconômico não influenciaram de forma significativa a taxa de não - resposta, ao contrário do que se costuma verificar.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

STAT3 can be activated through paracrine signaling in breast epithelial cells

<p>Abstract</p> <p>Background</p> <p>Many cancers, including breast cancer, have been identified with increased levels of phosphorylated or the active form of Signal Transducers and Activators of Transcription 3 (STAT3) protein. However, whether the tumor microenvironment plays a role in this activation is still poorly understood.</p> <p>Methods</p> <p>Conditioned media, which contains soluble factors from MDA-MB-231 and MDA-MB-468 breast cancer cells and breast cancer associated fibroblasts, was added to MCF-10A breast epithelial and MDA-MB-453 breast cancer cells. The stimulation of phosphorylated STAT3 (p-STAT3) levels by conditioned media was assayed by Western blot in the presence or absence of neutralized IL-6 antibody, or a JAK/STAT3 inhibitor, JSI-124. The stimulation of cell proliferation in MCF-10A cells by conditioned media in the presence or absence of JSI-124 was subjected to MTT analysis. IL-6, IL-10, and VEGF levels were determined by ELISA analysis.</p> <p>Results</p> <p>Our results demonstrated that conditioned media from cell lines with constitutively active STAT3 are sufficient to induce p-STAT3 levels in various recipients that do not possess elevated p-STAT3 levels. This signaling occurs through the JAK/STAT3 pathway, leading to STAT3 phosphorylation as early as 30 minutes and is persistent for at least 24 hours. ELISA analysis confirmed a correlation between elevated levels of IL-6 production and p-STAT3. Neutralization of the IL-6 ligand or gp130 was sufficient to block increased levels of p-STAT3 (Y705) in treated cells. Furthermore, soluble factors within the MDA-MB-231 conditioned media were also sufficient to stimulate an increase in IL-6 production from MCF-10A cells.</p> <p>Conclusion</p> <p>These results demonstrate STAT3 phosphorylation in breast epithelial cells can be stimulated by paracrine signaling through soluble factors from both breast cancer cells and breast cancer associated fibroblasts with elevated STAT3 phosphorylation. The induction of STAT3 phosphorylation is through the IL-6/JAK pathway and appears to be associated with cell proliferation. Understanding how IL-6 and other soluble factors may lead to STAT3 activation via the tumor microenvironment will provide new therapeutic regimens for breast carcinomas and other cancers with elevated p-STAT3 levels.</p

Genome wide linkage study, using a 250K SNP map, of Plasmodium falciparum infection and mild malaria attack in a Senegalese population

Multiple factors are involved in the variability of host's response to P. falciparum infection, like the intensity and seasonality of malaria transmission, the virulence of parasite and host characteristics like age or genetic make-up. Although admitted nowadays, the involvement of host genetic factors remains unclear. Discordant results exist, even concerning the best-known malaria resistance genes that determine the structure or function of red blood cells. Here we report on a genomewide linkage and association study for P. falciparum infection intensity and mild malaria attack among a Senegalese population of children and young adults from 2 to 18 years old. A high density single nucleotide polymorphisms (SNP) genome scan (Affimetrix GeneChip Human Mapping 250K-nsp) was performed for 626 individuals: i.e. 249 parents and 377 children out of the 504 ones included in the follow-up. The population belongs to a unique ethnic group and was closely followed-up during 3 years. Genome-wide linkage analyses were performed on four clinical and parasitological phenotypes and association analyses using the family based association tests (FBAT) method were carried out in regions previously linked to malaria phenotypes in literature and in the regions for which we identified a linkage peak. Analyses revealed three strongly suggestive evidences for linkage: between mild malaria attack and both the 6p25.1 and the 12q22 regions (empirical p-value = 5 x 10(-5) and 96 x 10(-5) respectively), and between the 20p11q11 region and the prevalence of parasite density in asymptomatic children (empirical p-value = 1.5 x 10(-4)). Family based association analysis pointed out one significant association between the intensity of plasmodial infection and a polymorphism located in ARHGAP26 gene in the 5q31-q33 region (p-value = 3.7 x 10(-5)). This study identified three candidate regions, two of them containing genes that could point out new pathways implicated in the response to malaria infection. Furthermore, we detected one gene associated with malaria infection in the 5q31-q33 region

Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation

BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection

Lynx Mission Concept Status

Lynx is a concept under study for prioritization in the 2020 Astrophysics Decadal Survey. Providing orders of magnitude increase in sensitivity over Chandra, Lynx will examine the first black holes and their galaxies, map the large-scale structure and galactic halos, and shed new light on the environments of young stars and their planetary systems. In order to meet the Lynx science goals, the telescope consists of a high-angular resolution optical assembly complemented by an instrument suite that may include a High Definition X-ray Imager, X-ray Microcalorimeter and an X-ray Grating Spectrometer. The telescope is integrated onto the spacecraft to form a comprehensive observatory concept. Progress on the formulation of the Lynx telescope and observatory configuration is reported in this paper