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The theoretical and political approach process involving the categories of culture and development engendered the conditions of possibility that enabled the development of economic and cultural policies. Such policies now occupy the center of the contemporary agenda for public cultural policies. The actions and programs that mobilize most discursive and material resources are directed to the so-called creative economy, whose concep- tual and political lexicon is spreading and consolidating in very diverse organizations. To understand the specificity of this process, it is necessary to explore the theoretical, political and institutional realm in which the categories of culture and development stood in sharp contrast between the years 1950 and 1980. This paper seeks to objectify the main sociological conditions responsible for the dissolution of that tension, whose practical effects have allowed the operation of certain cultural policies, such as financing the incubation cultural enterprises.

Hereditary congenital facial paresis type 1 (HCFP1) is an autosomal dominant disorder of absent or limited facial movement that maps to chromosome 3q21-q22 and is hypothesized to result from facial branchial motor neuron (FBMN) maldevelopment. In the present study, we report that HCFP1 results from heterozygous duplications within a neuron-specific GATA2 regulatory region that includes two enhancers and one silencer, and from noncoding single-nucleotide variants (SNVs) within the silencer. Some SNVs impair binding of NR2F1 to the silencer in vitro and in vivo and attenuate in vivo enhancer reporter expression in FBMNs. Gata2 and its effector Gata3 are essential for inner-ear efferent neuron (IEE) but not FBMN development. A humanized HCFP1 mouse model extends Gata2 expression, favors the formation of IEEs over FBMNs and is rescued by conditional loss of Gata3. These findings highlight the importance of temporal gene regulation in development and of noncoding variation in rare mendelian disease.

The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occur within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2+ fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2+ fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2+ myeloid cells, CCR7+ LAMP3+ dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2+ fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an in-depth view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.

BackgroundA standardized pathology management tool for melanocytic skin lesions may improve patient care by simplifying interpretation and categorization of the diverse terminology currently extant.ObjectiveTo assess an online educational intervention that teaches dermatopathologists to use the Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx), a schema collapsing multiple diagnostic terms into 5 classes ranging from benign to invasive melanoma.MethodsPracticing dermatopathologists (N = 149) from 40 US states participated in a 2-year educational intervention study (71% response rate). The intervention involved a brief tutorial followed by practice on 28 melanocytic lesions, with the goal of teaching pathologists how to correctly use the MPATH-Dx schema; competence using the MPATH-Dx tool 12-24 months postintervention was assessed. Participants' self-reported confidence using the MPATH-Dx tool was assessed preintervention and postintervention.ResultsAt preintervention, confidence using the MPATH-Dx tool was already high, despite 68% lacking prior familiarity with it, and confidence increased postintervention (P = .0003). During the intervention, participants used the MPATH-Dx tool correctly for 90% of their interpretations; postintervention, participants used the MPATH-Dx tool correctly for 88% of their interpretations.LimitationsFuture research should examine implementing a standardized pathology assessment schema in actual clinical practice.ConclusionDermatopathologists can be taught to confidently and competently use the MPATH-Dx schema with a simple educational tutorial followed by practice.

Poa pratensis, commonly known as Kentucky bluegrass, is a popular cool-season grass species used as turf in lawns and recreation areas globally. Despite its substantial economic value, a reference genome had not previously been assembled due to the genome's relatively large size and biological complexity that includes apomixis, polyploidy, and interspecific hybridization. We report here a fortuitous de novo assembly and annotation of a P. pratensis genome. Instead of sequencing the genome of a C4 grass, we accidentally sampled and sequenced tissue from a weedy P. pratensis whose stolon was intertwined with that of the C4 grass. The draft assembly consists of 6.09 Gbp with an N50 scaffold length of 65.1 Mbp, and a total of 118 scaffolds, generated using PacBio long reads and Bionano optical map technology. We annotated 256K gene models and found 58% of the genome to be composed of transposable elements. To demonstrate the applicability of the reference genome, we evaluated population structure and estimated genetic diversity in P. pratensis collected from three North American prairies, two in Manitoba, Canada and one in Colorado, USA. Our results support previous studies that found high genetic diversity and population structure within the species. The reference genome and annotation will be an important resource for turfgrass breeding and study of bluegrasses.

Members of the Deaf New American community reported they arrived in the United States with no formal education, unable to read or write in their native language, and had zero fluency in English. Efforts to educate them have floundered, and the study aims to find out why and how to fix the problem. Interviews of eight Deaf New Americans yielded rich data that demonstrates how education policy in the form of the Individuals with Disabilities Education Act (IDEA) and other laws fail to address their needs, because these laws do not include them in their coverage. The study's main findings are the deleterious effect of the home country's failure to educate their Deaf citizens, America's failure to provide accessible and effective instruction, and the combined effect of these institutional failures on the ability of Deaf New Americans to master English and find gainful employment. This article is an argument for a change in education policy that recognizes the unique nature of this community and provides for a role of Deaf educators in teaching Deaf New Americans.

The potency of whole-cell pertussis (wP) vaccines is still determined by an intracerebral mouse protection test. To allow development of suitable in vitro alternatives to this test, insight into relevant parameters to monitor the consistency of vaccine quality is essential. To this end, a panel of experimental wP vaccines of varying quality was prepared by sulfate-mediated suppression of the BvgASR master virulence regulatory system of Bordetella pertussis during cultivation. This system regulates the transcription of a range of virulence proteins, many of which are considered important for the induction of effective host immunity. The protein compositions and in vivo potencies of the vaccines were BvgASR dependent, with the vaccine containing the highest amount of virulence proteins having the highest in vivo potency. Here, the capacities of these vaccines to stimulate human Toll-like receptors (hTLR) 2 and 4 and the role these receptors play in wP vaccine-mediated activation of antigen-presenting cells in vitro were studied. Prolonged BvgASR suppression was associated with a decreased capacity of vaccines to activate hTLR4. In contrast, no significant differences in hTLR2 activation were observed. Similarly, vaccine-induced activation of MonoMac-6 and monocyte-derived dendritic cells was strongest with the highest potency vaccine. Blocking of TLR2 and TLR4 showed that differences in antigen-presenting cell activation could be largely attributed to vaccine-dependent variation in hTLR4 signalling. Interestingly, this BvgASR-dependent decrease in hTLR4 activation coincided with a reduction in GlcN-modified lipopolysaccharides in these vaccines. Accordingly, expression of the lgmA-C genes, required for this glucosamine modification, was significantly reduced in bacteria exposed to sulfate. Together, these findings demonstrate that the BvgASR status of bacteria during wP vaccine preparation is critical for their hTLR4 activation capacity and suggest that including such parameters to assess consistency of newly produced vaccines could bring in vitro testing of vaccine quality a step closer.

Este artigo procura situar o advento e a operacionalização de uma formação discursiva responsável pela emergência de um novo universalismo global. Tal universalismo traz como imperativo ético-moral a defesa e a promoção de valores como a diversidade cultural. Para compreender as implicações políticas e culturais desse universalismo, este trabalho elege como eixo empírico a atuação da Organização das Nações Unidas Para Educação, a Ciência e a Cultura (UNESCO), destacando as ações dessa organização na coordenação e dinamização de um trânsito simbólico e discursivo transnacional envolvendo governos, organizações não-governamentais e grupos políticos.This article attempts to situate the emergence and development of a discursive formation responsible for the appearance of a new global universalism. The ethical and moral imperative of this universalism is the defense and promotion of values such as cultural diversity. To understand the political and cultural implications of this universalism, this article elects as its empirical axis the performance of the United Nations Educational, Scientific and Cultural Organization (UNESCO), highlighting the actions of the organization in coordinating and facilitating a symbolic and discursive transnational transit involving governments, nongovernmental organizations and political groups.

Implicit measures were initially assumed to assess stable individual differences, but other perspectives posit that they reflect context-dependent processes. This pre-registered research investigates whether the processes contributing to responses on the race Implicit Association Test are temporally stable and reliably measured using multinomial processing tree modeling. We applied two models-the Quad model and the Process Dissociation Procedure-to six datasets (N = 2,036), each collected over two occasions, examined the within-measurement reliability and between-measurement stability of model parameters, and meta-analyzed the results. Parameters reflecting accuracy-oriented processes demonstrate adequate stability and reliability, which suggests these processes are relatively stable within individuals. Parameters reflecting evaluative associations demonstrate poor stability but modest reliability, which suggests that associations are either context-dependent or stable but noisily measured. These findings suggest that processes contributing to racial bias on implicit measures differ in temporal stability, which has practical implications for predicting behavior using the Implicit Association Test.

Transmission heterogeneity, whereby a disproportionate fraction of pathogen transmission events result from a small number of individuals or geographic locations, is an inherent property of many, if not most, infectious disease systems. For vector-borne diseases, transmission heterogeneity is inferred from the distribution of the number of vectors per host, which could lead to significant bias in situations where vector abundance and transmission risk at the household do not correlate, as is the case with dengue virus (DENV). We used data from a contact tracing study to quantify the distribution of DENV acute infections within human activity spaces (AS), the collection of residential locations an individual routinely visits, and quantified measures of virus transmission heterogeneity from two consecutive dengue outbreaks (DENV-4 and DENV-2) that occurred in the city of Iquitos, Peru. Negative-binomial distributions and Pareto fractions showed evidence of strong overdispersion in the number of DENV infections by AS and identified super-spreading units (SSUs): i.e. AS where most infections occurred. Approximately 8% of AS were identified as SSUs, contributing to more than 50% of DENV infections. SSU occurrence was associated more with DENV-2 infection than with DENV-4, a predominance of inapparent infections (74% of all infections), households with high Aedes aegypti mosquito abundance, and high host susceptibility to the circulating DENV serotype. Marked heterogeneity in dengue case distribution, and the role of inapparent infections in defining it, highlight major challenges faced by reactive interventions if those transmission units contributing the most to transmission are not identified, prioritized, and effectively treated.

Diagnostic error can be defined as deviation from a gold standard diagnosis, typically defined in terms of expert opinion, although sometimes in terms of unexpected events that might occur in follow-up (such as progression and death from disease). Although diagnostic error does exist for melanoma, deviations from gold standard diagnosis, certainly among appropriately trained and experienced practitioners, are likely to be the result of uncertainty and lack of specific criteria, and differences of opinion, rather than lack of diagnostic skills. In this review, the concept of diagnostic error will be considered in relation to diagnostic uncertainty, and the concept of overdiagnosis in melanoma will be presented and discussed.

ImportanceA standardized pathology classification system for melanocytic lesions is needed to aid both pathologists and clinicians in cataloging currently existing diverse terminologies and in the diagnosis and treatment of patients. The Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis (MPATH-Dx) has been developed for this purpose.ObjectiveTo revise the MPATH-Dx version 1.0 classification tool, using feedback from dermatopathologists participating in the National Institutes of Health-funded Reducing Errors in Melanocytic Interpretations (REMI) Study and from members of the International Melanoma Pathology Study Group (IMPSG).Evidence reviewPracticing dermatopathologists recruited from 40 US states participated in the 2-year REMI study and provided feedback on the MPATH-Dx version 1.0 tool. Independently, member dermatopathologists participating in an IMPSG workshop dedicated to the MPATH-Dx schema provided additional input for refining the MPATH-Dx tool. A reference panel of 3 dermatopathologists, the original authors of the MPATH-Dx version 1.0 tool, integrated all feedback into an updated and refined MPATH-Dx version 2.0.FindingsThe new MPATH-Dx version 2.0 schema simplifies the original 5-class hierarchy into 4 classes to improve diagnostic concordance and to provide more explicit guidance in the treatment of patients. This new version also has clearly defined histopathological criteria for classification of classes I and II lesions; has specific provisions for the most frequently encountered low-cumulative sun damage pathway of melanoma progression, as well as other, less common World Health Organization pathways to melanoma; provides guidance for classifying intermediate class II tumors vs melanoma; and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as neoplasms lacking criteria for melanoma.Conclusions and relevanceThe implementation of the newly revised MPATH-Dx version 2.0 schema into clinical practice is anticipated to provide a robust tool and adjunct for standardized diagnostic reporting of melanocytic lesions and management of patients to the benefit of both health care practitioners and patients.

Dengue virus (DENV) transmission from humans to mosquitoes is a poorly documented, but critical component of DENV epidemiology. Magnitude of viremia is the primary determinant of successful human-to-mosquito DENV transmission. People with the same level of viremia, however, can vary in their infectiousness to mosquitoes as a function of other factors that remain to be elucidated. Here, we report on a field-based study in the city of Iquitos, Peru, where we conducted direct mosquito feedings on people naturally infected with DENV and that experienced mild illness. We also enrolled people naturally infected with Zika virus (ZIKV) after the introduction of ZIKV in Iquitos during the study period. Of the 54 study participants involved in direct mosquito feedings, 43 were infected with DENV-2, two with DENV-3, and nine with ZIKV. Our analysis excluded participants whose viremia was detectable at enrollment but undetectable at the time of mosquito feeding, which was the case for all participants with DENV-3 and ZIKV infections. We analyzed the probability of onward transmission during 50 feeding events involving 27 participants infected with DENV-2 based on the presence of infectious virus in mosquito saliva 7-16 days post blood meal. Transmission probability was positively associated with the level of viremia and duration of extrinsic incubation in the mosquito. In addition, transmission probability was influenced by the day of illness in a non-monotonic fashion; i.e., transmission probability increased until 2 days after symptom onset and decreased thereafter. We conclude that mildly ill DENV-infected humans with similar levels of viremia during the first two days after symptom onset will be most infectious to mosquitoes on the second day of their illness. Quantifying variation within and between people in their contribution to DENV transmission is essential to better understand the biological determinants of human infectiousness, parametrize epidemiological models, and improve disease surveillance and prevention strategies.

BACKGROUND: Evidence exists that escalating melanoma incidence is due in part to overdiagnosis, the diagnosis of lesions that will not lead to symptoms or death. The authors aimed to characterize subsets of melanoma patients with very-low risk of death that may be contributing to overdiagnosis. METHODS: Melanoma patients diagnosed in 2010 and 2011 with stage I lesions ≤1.0 mm thick and negative clinical lymph nodes from the Surveillance, Epidemiology, and End Results database were selected. Classification and regression tree and logistic regression models were developed and validated to identify patients with very-low risk of death from melanoma within 7 years. Logistic models were also used to identify patients at higher risk of death among this group of stage I patients. RESULTS: Compared to an overall 7-year mortality from melanoma of 2.5% in these patients, a subset comprising 25% had a risk below 1%. Younger age at diagnosis and Clark level II were associated with low risk of death in all models. Breslow thickness below 0.4 mm, absence of mitogenicity, absence of ulceration, and female sex were also associated with lower mortality. A small subset of high-risk patients with >20% risk of death was also identified. CONCLUSION: Patients with very-low risk of dying from melanoma within 7 years of diagnosis were identified. Such cases warrant further study and consensus discussion to develop classification criteria, with the potential to be categorized using an alternative term such as melanocytic neoplasms of low malignant potential. LAY SUMMARY: Although melanoma is the most serious skin cancer, most melanoma patients have high chances of survival. There is evidence that some lesions diagnosed as melanoma would never have caused symptoms or death, a phenomenon known as overdiagnosis. In this study, we used cancer registry data to identify a subset of early-stage melanoma patients with almost no melanoma deaths. Using two statistical approaches, we identified patients with

Introduction: Incident delirium in older patients is associated with prolonged hospitalization and mortality. A recent study suggested an association between emergency department (ED) length of stay (LOS), time in ED hallways, and incident delirium. In this study we further evaluated the emerging association between incident delirium with ED LOS, time in ED hallways, and number of non-clinical patient moves in the ED.Methods: We performed this retrospective cohort study at a single, urban, academic medical center. All data were extracted from the electronic health record. We included patients aged ≥65 years presenting to the ED and admitted to family or internal medicine services over a two-year period . Patients admitted to any other service, transferred from another hospital, discharged from the ED, or who underwent procedural sedation were excluded. The primary outcome was incident delirium, defined as a positive delirium screen, receipt of sedative medications, or use of physical restraints. Multivariable logistic regression models including age, gender, language, history of dementia, Elixhauser Comorbidity Index, number of non-clinical patient moves within the ED, total time spent in the ED hallway, and ED LOS were fitted.Results: We studied 5,886 patients ≥65 years of age; median age was 77 (69-83) years; 3,031 (52%) were female, and 1,361 (23%) reported a history of dementia. Overall, 1,408 (24%) patients experienced incident delirium. In multivariable models, ED LOS was associated with development of delirium (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.03, per hour), while non-clinical patient moves [OR 0.97, (95% CI 0.91-1.04) and ED hallway time [OR 0.99, 95% CI 0.98-1.01, per hour) was not associated with development of delirium.Conclusion: In this single-center study, ED length of stay was associated with incident delirium in older adults, while non-clinical patient moves and ED hallway time in the ED were not. Health systems should systemically limit time in the ED for admitted older adults.

Current knowledge of dengue virus (DENV) transmission provides only a partial understanding of a complex and dynamic system yielding a public health track record that has more failures than successes. An important part of the problem is that the foundation for contemporary interventions includes a series of longstanding, but untested, assumptions based on a relatively small portion of the human population; i.e., people who are convenient to study because they manifest clinically apparent disease. Approaching dengue from the perspective of people with overt illness has produced an extensive body of useful literature. It has not, however, fully embraced heterogeneities in virus transmission dynamics that are increasingly recognized as key information still missing in the struggle to control the most important insect-transmitted viral infection of humans. Only in the last 20 years have there been significant efforts to carry out comprehensive longitudinal dengue studies. This manuscript provides the rationale and comprehensive, integrated description of the methodology for a five-year longitudinal cohort study based in the tropical city of Iquitos, in the heart of the Peruvian Amazon. Primary data collection for this study was completed in 2019. Although some manuscripts have been published to date, our principal objective here is to support subsequent publications by describing in detail the structure, methodology, and significance of a specific research program. Our project was designed to study people across the entire continuum of disease, with the ultimate goal of quantifying heterogeneities in human variables that affect DENV transmission dynamics and prevention. Because our study design is applicable to other Aedes transmitted viruses, we used it to gain insights into Zika virus (ZIKV) transmission when during the project period ZIKV was introduced and circulated in Iquitos. Our prospective contact cluster investigation design was initiated by detecttion of a person with a symptomatic DENV infection and then followed that person's immediate contacts. This allowed us to monitor individuals at high risk of DENV infection, including people with clinically inapparent and mild infections that are otherwise difficult to detect. We aimed to fill knowledge gaps by defining the contribution to DENV transmission dynamics of (1) the understudied majority of DENV-infected people with inapparent and mild infections and (2) epidemiological, entomological, and socio-behavioral sources of heterogeneity. By accounting for factors underlying variation in each person's contribution to transmission we sought to better determine the type and extent of effort needed to better prevent virus transmission and disease.

BackgroundLatina women are less likely to report engaging in leisure-time physical activity (PA) than non-Latina white women. This study evaluated the 24-month impact of a faith-based PA intervention targeting Latinas.MethodsThe study is a cluster randomized controlled trial of a PA intervention or cancer screening comparison condition, with churches as the randomization unit. A total of 436 Latinas (aged 18-65 years) from 16 churches who engaged in low levels of self-report and accelerometer-based PA were enrolled. The experimental condition was a 24-month PA intervention, with in-person classes, social support, and environmental changes, led by community health workers (i.e., promotoras). At baseline, 12-, and 24 months, we assessed changes in accelerometer-based and self-reported moderate to vigorous physical activity (MVPA; primary outcomes). Secondary outcomes were light intensity activity, sedentary time, body mass index (BMI), and waist circumference.ResultsAfter adjusting for sociodemographic factors, a mixed effects analysis found significant increases in self-reported leisure time MVPA (p

This article details a model for research and practice using video data for multidimensional purposes as part of a professional development school (PDS) partnership. The research methods described situate practitioners as leaders in a school working toward more inclusive school reform with support from PDS partners, including two Professors-in-Residence (PIRs) and PDS teacher co-liaisons. The purpose of sharing this methodological model is to: (a) explore how video research can foster reflective opportunities; (b) highlight professional leaders; (c) (re)construct student competence from a strengths-based perspective; (d) contribute to a video bank of best practices, all as part of collaborative work toward more inclusive schools.

Technology continues to form an important part of the educational landscape, although the value of portable devices as learning tools is still being explored and debated. In light of the technology-based teaching methods suddenly brought into effect in response to the COVID-19 pandemic, the deliberate use of technology for learning is increasingly significant. The purpose of this article is to highlight student perspectives of learning with portable devices to inform the use of portable technology in the Canadian school system going forward. To gather student perceptions, the research team surveyed 704 students in Grades 6 to 9 about their use of iPads in the classroom during a 1:1 technology initiative. While students were enthusiastic about the presence of portable technology, they also shared mixed feelings about the use of such technology as a learning tool. Key themes fell into three categories--engagement, inclusivity, and learning--as students shared their insight into the academic, social, and physical barriers that exist as a result of the technology. In the discussion, we identify lessons learned, especially in the area of self-regulation, and make recommendations on how to harness the power of this multi-faceted learning tool and minimize the chaos it can create when not utilized deliberately and carefully.