Evaluating Methods for Mapping Historical Redlining to Census Tracts for Health Equity Research.

Neighborhood characteristics including housing status can profoundly influence health. Recently, increasing attention has been paid to present-day impacts of "redlining," or historic area classifications that indicated less desirable (redlined) areas subject to decreased investment. Scholarship of redlining and health is emerging; limited guidance exists regarding optimal approaches to measuring historic redlining in studies of present-day health outcomes. We evaluated how different redlining approaches (map alignment methods) influence associations between redlining and health outcomes. We first identified 11 existing redlining map alignment methods and their 37 logical extensions, then merged these 48 map alignment methods with census tract life expectancy data to construct 9696 linear models of each method and life expectancy for all 202 redlined cities. We evaluated each model's statistical significance and R2 values and compared changes between historical and contemporary geographies and populations using Root Mean Squared Error (RMSE). RMSE peaked with a normal distribution at 0.175, indicating persistent difference between historical and contemporary geographies and populations. Continuous methods with low thresholds provided higher neighborhood coverage. Weighting methods had more significant associations, while high threshold methods had higher R2 values. In light of these findings, we recommend continuous methods that consider contemporary population distributions and mapping overlap for studies of redlining and health. We developed an R application {holcmapr} to enable map alignment method comparison and easier method selection.

MOSAIC: a joint modeling methodology for combined circadian and non-circadian analysis of multi-omics data.

MOTIVATION: Circadian rhythms are approximately 24-h endogenous cycles that control many biological functions. To identify these rhythms, biological samples are taken over circadian time and analyzed using a single omics type, such as transcriptomics or proteomics. By comparing data from these single omics approaches, it has been shown that transcriptional rhythms are not necessarily conserved at the protein level, implying extensive circadian post-transcriptional regulation. However, as proteomics methods are known to be noisier than transcriptomic methods, this suggests that previously identified arrhythmic proteins with rhythmic transcripts could have been missed due to noise and may not be due to post-transcriptional regulation. RESULTS: To determine if one can use information from less-noisy transcriptomic data to inform rhythms in more-noisy proteomic data, and thus more accurately identify rhythms in the proteome, we have created the Multi-Omics Selection with Amplitude Independent Criteria (MOSAIC) application. MOSAIC combines model selection and joint modeling of multiple omics types to recover significant circadian and non-circadian trends. Using both synthetic data and proteomic data from Neurospora crassa, we showed that MOSAIC accurately recovers circadian rhythms at higher rates in not only the proteome but the transcriptome as well, outperforming existing methods for rhythm identification. In addition, by quantifying non-circadian trends in addition to circadian trends in data, our methodology allowed for the recognition of the diversity of circadian regulation as compared to non-circadian regulation. AVAILABILITY AND IMPLEMENTATION: MOSAIC's full interface is available at https://github.com/delosh653/MOSAIC. An R package for this functionality, mosaic.find, can be downloaded at https://CRAN.R-project.org/package=mosaic.find. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

ECHO: an application for detection and analysis of oscillators identifies metabolic regulation on genome-wide circadian output.

MOTIVATION: Time courses utilizing genome scale data are a common approach to identifying the biological pathways that are controlled by the circadian clock, an important regulator of organismal fitness. However, the methods used to detect circadian oscillations in these datasets are not able to accommodate changes in the amplitude of the oscillations over time, leading to an underestimation of the impact of the clock on biological systems. RESULTS: We have created a program to efficaciously identify oscillations in large-scale datasets, called the Extended Circadian Harmonic Oscillator application, or ECHO. ECHO utilizes an extended solution of the fixed amplitude oscillator that incorporates the amplitude change coefficient. Employing synthetic datasets, we determined that ECHO outperforms existing methods in detecting rhythms with decreasing oscillation amplitudes and in recovering phase shift. Rhythms with changing amplitudes identified from published biological datasets revealed distinct functions from those oscillations that were harmonic, suggesting purposeful biologic regulation to create this subtype of circadian rhythms. AVAILABILITY AND IMPLEMENTATION: ECHO's full interface is available at https://github.com/delosh653/ECHO. An R package for this functionality, echo.find, can be downloaded at https://CRAN.R-project.org/package=echo.find. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Transsexuality and health demands: representations of nursing students.

OBJECTIVE: To analyze the social representations of nursing students about transsexuality and the health demands of transsexual people. METHODS: Qualitative, descriptive research with undergraduate nursing students from a public university in Rio de Janeiro/Brazil. The data came from a semi-structured interview and lexical analysis using Alceste 2012 software. RESULTS: Transsexuality was represented as a transgression, with the transsexual person being objectified as unnatural because they do not identify with their biological sex. Hormone therapy and sex reassignment surgeries were understood as the main demands, being anchored in a pathologizing and medicalizing health sphere. However, the theme is not addressed during graduation, generating unpreparedness for professional life. FINAL CONSIDERATIONS: The need to update the academic curriculum, as well as the way of thinking about the care of transsexual people, is essential and urgent for an integral and equitable care.

The PAICE suite reveals circadian posttranscriptional timing of noncoding RNAs and spliceosome components in Mus musculus macrophages.

Circadian rhythms broadly regulate physiological functions by tuning oscillations in the levels of mRNAs and proteins to the 24-h day/night cycle. Globally assessing which mRNAs and proteins are timed by the clock necessitates accurate recognition of oscillations in RNA and protein data, particularly in large omics data sets. Tools that employ fixed-amplitude models have previously been used to positive effect. However, the recognition of amplitude change in circadian oscillations required a new generation of analytical software to enhance the identification of these oscillations. To address this gap, we created the Pipeline for Amplitude Integration of Circadian Exploration suite. Here, we demonstrate the Pipeline for Amplitude Integration of Circadian Exploration suite's increased utility to detect circadian trends through the joint modeling of the Mus musculus macrophage transcriptome and proteome. Our enhanced detection confirmed extensive circadian posttranscriptional regulation in macrophages but highlighted that some of the reported discrepancy between mRNA and protein oscillations was due to noise in data. We further applied the Pipeline for Amplitude Integration of Circadian Exploration suite to investigate the circadian timing of noncoding RNAs, documenting extensive circadian timing of long noncoding RNAs and small nuclear RNAs, which control the recognition of mRNA in the spliceosome complex. By tracking oscillating spliceosome complex proteins using the PAICE suite, we noted that the clock broadly regulates the spliceosome, particularly the major spliceosome complex. As most of the above-noted rhythms had damped amplitude changes in their oscillations, this work highlights the importance of the PAICE suite in the thorough enumeration of oscillations in omics-scale datasets.

ENCORE: A Visualization Tool for Insight into Circadian Omics.

Circadian rhythms are 24-hour biological cycles that control daily molecular rhythms in many organisms. The cellular elements that fall under the regulation of the clock are often studied through the use of omics-scale data sets gathered over time to determine how circadian regulation impacts cellular physiology. Previously, we created the ECHO (Extended Circadian Harmonic Oscillator) tool to identify rhythms in these data sets. Using ECHO, we found that circadian oscillations widely undergo a change in amplitude over time and that these amplitude changes have a biological function in the cell. However, ECHO does not align gene ontologies with the identified oscillating genes to give functional context. Thus, we created ENCORE (ECHO Native Circadian Ontological Rhythmicity Explorer), a novel visualization tool which combines the disparate databases of Gene Ontologies, protein-protein interactions, and auxiliary information to uncover the meaning of circadianly-regulated genes. This freely-available tool performs automatic enrichment and creates publication-worthy visualizations which we used to extend previously-gathered data on circadian regulation of physiology from published omics-scale studies in three circadian model organisms: mouse, fruit fly, and Neurospora crassa.

Identifying Windows of Susceptibility by Temporal Gene Analysis.

Increased understanding of developmental disorders of the brain has shown that genetic mutations, environmental toxins and biological insults typically act during developmental windows of susceptibility. Identifying these vulnerable periods is a necessary and vital step for safeguarding women and their fetuses against disease causing agents during pregnancy and for developing timely interventions and treatments for neurodevelopmental disorders. We analyzed developmental time-course gene expression data derived from human pluripotent stem cells, with disease association, pathway, and protein interaction databases to identify windows of disease susceptibility during development and the time periods for productive interventions. The results are displayed as interactive Susceptibility Windows Ontological Transcriptome (SWOT) Clocks illustrating disease susceptibility over developmental time. Using this method, we determine the likely windows of susceptibility for multiple neurological disorders using known disease associated genes and genes derived from RNA-sequencing studies including autism spectrum disorder, schizophrenia, and Zika virus induced microcephaly. SWOT clocks provide a valuable tool for integrating data from multiple databases in a developmental context with data generated from next-generation sequencing to help identify windows of susceptibility.

Transsexuality and health demands: representations of nursing students / Transexualidad y demandas de salud: representaciones de estudiantes de enfermería / Transexualidade e demandas de saúde: representações de graduandos de Enfermagem

ABSTRACT Objective: To analyze the social representations of nursing students about transsexuality and the health demands of transsexual people. Methods: Qualitative, descriptive research with undergraduate nursing students from a public university in Rio de Janeiro/Brazil. The data came from a semi-structured interview and lexical analysis using Alceste 2012 software. Results: Transsexuality was represented as a transgression, with the transsexual person being objectified as unnatural because they do not identify with their biological sex. Hormone therapy and sex reassignment surgeries were understood as the main demands, being anchored in a pathologizing and medicalizing health sphere. However, the theme is not addressed during graduation, generating unpreparedness for professional life. Final considerations: The need to update the academic curriculum, as well as the way of thinking about the care of transsexual people, is essential and urgent for an integral and equitable care.

RESUMEN Objetivo: Analizar las representaciones sociales de estudiantes de enfermería sobre la transexualidad y las demandas de salud de las personas transexuales. Métodos: Investigación cualitativa, descriptiva con estudiantes de graduación en enfermería de una universidad pública de Río de Janeiro/Brasil. Los datos provinieron de una entrevista semiestructurada y análisis léxico utilizando el software Alceste 2012. Resultados: La transexualidad fue representada como una transgresión, siendo objetivada la persona transexual como antinatural porque no se identifica con su sexo biológico. La terapia hormonal y las cirugías de reasignación de sexo fueron entendidas como las principales demandas, ancladas en un ámbito patologizante. ymedicalizando la salud. Sin embargo, el tema no es abordado durante la graduación, generando despreparación para la vida profesional. Consideraciones finales: La necesidad de actualizar el currículo académico, así como la forma de pensar la atención a las personas transexuales, es fundamental y urgente para una atención integral y equitativa.

RESUMO Objetivo: Analisar as representações sociais dos graduandos de enfermagem acerca da transexualidade e as demandas de saúde das pessoas transexuais. Métodos: Pesquisa qualitativa, descritiva, com 28 graduandos em enfermagem de uma universidade pública do Rio de Janeiro/Brasil. Realizou-se uma entrevista semiestruturada, no período de novembro de 2017 a março de 2018, e análise tipo lexical com auxílio do software Alceste 2012. Resultados: A transexualidade foi representada como uma transgressão, sendo a pessoa transexual objetivada como antinatural por não se identificar com seu sexo biológico. Terapia hormonal e cirurgias de redesignação sexual foram entendidas como as principais demandas, sendo ancoradas numa esfera patologizante e medicalizadora da saúde. A temática não é abordada durante a graduação, gerando despreparo para vida profissional. Considerações finais: Faz-se necessário ampliar as discussões sobre gênero na academia, tendo como propósito a transposição do imperativo da heteronormatividade, para que futuros enfermeiros estejam aparelhados para fornecer um cuidado integral e equânime.

Circadian Proteomic Analysis Uncovers Mechanisms of Post-Transcriptional Regulation in Metabolic Pathways.

Transcriptional and translational feedback loops in fungi and animals drive circadian rhythms in transcript levels that provide output from the clock, but post-transcriptional mechanisms also contribute. To determine the extent and underlying source of this regulation, we applied newly developed analytical tools to a long-duration, deeply sampled, circadian proteomics time course comprising half of the proteome. We found a quarter of expressed proteins are clock regulated, but >40% of these do not arise from clock-regulated transcripts, and our analysis predicts that these protein rhythms arise from oscillations in translational rates. Our data highlighted the impact of the clock on metabolic regulation, with central carbon metabolism reflecting both transcriptional and post-transcriptional control and opposing metabolic pathways showing peak activities at different times of day. The transcription factor CSP-1 plays a role in this metabolic regulation, contributing to the rhythmicity and phase of clock-regulated proteins.

Circadian Rhythms in Neurospora Exhibit Biologically Relevant Driven and Damped Harmonic Oscillations.

Circadian rhythms are endogenous cycles of approximately 24 hours reinforced by external cues such as light. These cycles are typically modeled as harmonic oscillators with fixed amplitude peaks. Using experimental data measuring global gene transcription in Neurospora crassa over 48 hours in the dark (i.e. with external queues removed), we demonstrate that many circadian genes frequently exhibit either damped harmonic oscillations, in which the peak amplitudes decrease each day, or driven harmonic oscillations, in which the peak amplitudes increase each day. By fitting extended harmonic oscillator models which include a damping ratio coefficient, we detected additional circadian genes that were not identified by the current standard tools that use fixed amplitude waves as reference, e.g. JTK_CYCLE. Functional Catalogue analysis confirms that our identified damped or driven genes exhibit distinct biological functions. The application of extended damped/driven harmonic oscillator models thus can elucidate, not only previously unidentified circadian genes, but also characterize gene subsets with expression patterns of biological relevance. Thus, expanded harmonic oscillators provide a powerful new tool for circadian system biology.

Intervening to enhance collaboration in translational research: A relational coordination approach.

INTRODUCTION: A core challenge of a multidisciplinary and multi-organizational translational research enterprise such as a Clinical and Translational Research Award (CTSA) is coordinating and integrating the work of individuals, workgroups, and organizations accustomed to working independently and autonomously. Tufts Clinical and Translational Science Institute (CTSI) undertook and studied a multifacted intervention to address this challenge and to create a culture of systems thinking, process awareness, responsive to others' needs, and shared decision-making. INTERVENTION: The intervention, based on relational coordination, included 1) relational interventions, in three staff retreats and a diagnostic survey to provide feedback on the current quality of relational coordination, and 2) structural interventions, in the launching of five new cross-functional teams with regular meeting structures. METHODS: A mixed-methods evaluation yielded quantitative data via two types of team surveys and qualitative data via interviews and meeting observations. RESULTS: The findings suggest that interventions to improve relational coordination are feasible for CTSAs, including good fidelity to the model and staff/physician engagement. Survey and interview data suggest model improvements in coordination and alignment. Further research about their optimal design is warranted.

Cryptosporidium spp. and Giardia spp. in feces and water and the associated exposure factors on dairy farms.

The aims of this study were to verify the prevalence of Cryptosporidium spp. and Giardia spp. in animal feces and drinking water on dairy farms and to identify a possible relation between the exposure factors and the presence of these parasites. Fecal samples from cattle and humans and water samples were collected on dairy farms in Paraná, Brazil. Analysis of (oo)cysts in the feces was performed by the modified Ziehl-Neelsen staining and centrifugal flotation in zinc sulfate. Test-positive samples were subjected to nested PCR amplification of the 18SSU ribosomal RNA gene for identification of Cryptosporidium and Giardia and of the gp60 gene for subtyping of Cryptosporidium. Microbiological analysis of water was carried out by the multiple-tube method and by means of a chromogenic substrate, and parasitological analysis was performed on 31 samples by direct immunofluorescence and nested PCR of the genes mentioned above. Identification of the species of Cryptosporidium was performed by sequencing and PCR with analysis of restriction fragment length polymorphisms. The prevalence of Giardia and Cryptosporidium was higher in calves than in adults. Among the samples of cattle feces, Cryptosporidium parvum was identified in 41 (64%), C. ryanae in eight (12.5%), C. bovis in four (6.3%), C. andersoni in five (7.8%), and a mixed infection in 20 samples (31.3%). These parasites were not identified in the samples of human feces. Thermotolerant coliform bacteria were identified in 25 samples of water (45.5%). Giardia duodenalis and C. parvum were identified in three water samples. The gp60 gene analysis of C. parvum isolates revealed the presence of two strains (IIaA20G1R1 and IIaA17G2R2) in the fecal samples and one (IIaA17G2R1) in the water samples. The presence of coliforms was associated with the water source, structure and degradation of springs, rain, and turbidity. The prevalence of protozoa was higher in calves up to six months of age. C. parvum and G. duodenalis were identified in the water of dairy farms, as were thermotolerant coliforms; these findings point to the need for guidance on handling of animals, preservation of water sources, and water treatment.

An outbreak of caprine toxoplasmosis - investigation and case report / Surto de toxoplasmose caprina - investigação e relato de caso

ABSTRACT: The present study aimed to investigate an abortion outbreak in a dairy goat herd in the municipality of Arapoti, Parana, Brazil. At the beginning of the outbreak, blood samples were collected from 33 goats with clinical signs; later, of the whole goat herd, two cats and two dogs. Milk samples were collected from 78 lactating goats. Four environmental soil samples and four samples of feed residue from goat feeders were collected too. Immunofluorescence antibody test (IFA) was used for serodiagnosis, the molecular analysis was conducted by means of the polymerase chain reaction (PCR), for the isolation of the etiological agent the bioassay was used. The results of the IFA revealed that 76.53% (137/179) of the goats, two dogs and two cats were seropositive for Toxoplasma gondii. Bioassay revealed one buffy coat and two milk sample having viable T. gondii. In the PCR, 11 whole blood samples, eight milk, three feeder troughs, and all soil samples were positive. The findings of the present study confirmed an outbreak caused by environmental contamination (of soil and feed) with T. gondii oocysts that could have been shed by kittens that lived on the farm and had access to the stock of goat food, facilitating this contamination, which reinforces the need for veterinary assistance and good management practices on farms.

RESUMO: O presente estudo teve como objetivo investigar um surto de aborto em um rebanho de cabras leiteiras no município de Arapoti, Paraná, Brasil. No início do surto, foram coletadas amostras de sangue de 33 cabras com sinais clínicos; mais tarde, de todo o rebanho caprino, dois gatos e dois cachorros. Foram obtidas amostras de leite das 78 cabras em lactação. Quatro amostras ambientais de solo e quatro de resíduos de comedouro também foram coletadas. O teste de imunofluorescência (IFI) foi utilizado para o sorodiagnóstico, a análise molecular foi conduzida por meio da reação em cadeia da polimerase (PCR), para isolamento do agente etiológico utilizou-se o bioensaio. Os resultados da IFI revelaram que 76,53% (137/179) das cabras, todos os cães e gatos eram soropositivos para Toxoplasma gondii. O bioensaio revelou uma amostra de camada leucocitária e duas de leite contaminadas com T. gondii viável. Na PCR, 11 amostras de sangue total, oito de leite, três resíduos alimentares e todas as amostras de solo foram positivas. Os resultados do presente estudo confirmaram um surto causado por contaminação ambiental (de solo e alimentos) com oocistos de T. gondii que, provavelmente, foram eliminados por gatos que permaneceram na fazenda e tinham acesso ao estoque de alimento dos caprinos, reforçando a necessidade de assistência técnica veterinária e boas práticas de manejo.