(VIDEO) Characterizing the Exposome: Critical Analysis of Exposome-Wide Association Studies

Purpose: The exposome is a conceptual framework of all exposures encountered by an individual in his or her lifetime. Studying the exposome is thereby a monumental feat that may require extensive research, conceptualization, and proof-of-concept analyses. Researchers have begun studying the exposome by developing exposome- and environment-wide association studies (EWAS). Since EWAS is such a novel technique, this critical analysis of existing EWAS in the literature sought to determine whether the studies utilized common research methods, how the data were analyzed, and whether the analyses were similar. The analysis also sought to explore ways in which these studies could inform study of the exposome. Methods: The ProQuest Environmental Science Collection was queried for articles conducting exposome-wide association studies and environment-wide association studies. Only research articles were accepted for further analysis. These articles were examined following epidemiological study critical analysis guidelines. Results: Five research articles were returned through literature review. Methods analysis determined that the studies conducted similar regression analyses of extensive exposure variables with a single health outcome as the dependent variable. One study utilized an animal model and primarily studied metabolites, thereby supporting the concept that metabolomics may play a supporting role in study of the exposome. All studies utilized validation procedures and examined results using a false discovery rate. Conclusions: The EWAS articles examined in this critical analysis conducted extensive validation procedures to successfully demonstrate the statistical significance of large-scale linear and logistic regression. These procedures will likely make EWAS a valuable resource in future exposome studies

DESIGN THINKING AS ACTIVE TEACHING METHODOLOGY AT THE UNIVERSITY. COMPARATIVE STUDY BETWEEN COURSES

In a move to go beyond pedagogical concerns for engineering teaching and learning and expand to other higher education courses and other professionals, this study compared the use of Design Thinking as a tool to pedagogically mobilize courses in Business Administration, Design, Nursing and Pedagogy. The results showed that the same pedagogical concern of engineering was shared with the compared courses. The relationships between students were fundamental for solving problems, as proposed by Design Thinking, as well as the relationships between the classes of a given course with their concerns about the professional profile that is being formed.En un movimiento para ir más allá de las preocupaciones pedagógicas por la enseñanza y el aprendizaje de la ingeniería y expandirse a otros cursos de educación superior y otros profesionales, este estudio comparó el uso del Design Thinking como una herramienta para movilizar pedagógicamente los cursos de Administración de Empresas, Diseño, Enfermería y Pedagogía. Los resultados mostraron que la misma inquietud pedagógica de la ingeniería se comparte con los cursos comparados. Las relaciones entre los estudiantes fueron fundamentales para la resolución de problemas, tal y como propone Design Thinking, así como las relaciones entre las clases de un determinado curso con sus inquietudes sobre el perfil profesional que se está formando.Num movimento para ir além das preocupações pedagógicas para o ensino e aprendizagem da engenharia e expandir para outros cursos de ensino superior e outros profissionais, este estudo comparou o uso do Design Thinking como uma ferramenta para mobilizar pedagogicamente os cursos de Administração de Empresas, Design, Enfermagem e a Pedagogia. Os resultados mostraram que a mesma preocupação pedagógica da engenharia foi compartilhada com os cursos comparados. As relações entre os alunos foram fundamentais para a resolução de problemas, conforme proposto pelo Design Thinking, assim como as relações entre as turmas de um determinado curso com suas preocupações quanto ao perfil profissional que se está formando

2010-2011 A Salute to Gershwin

https://spiral.lynn.edu/conservatory_philharmonia/1101/thumbnail.jp

Ultrasensitive microfluidic electrochemical immunosensor based on electrodeposited nanoporous gold for SOX-2 determination

An ultrasensitive and portable microfluidic electrochemical immunosensor for SOX-2 cancer biomarker determination was developed. The selectivity and sensitivity of the sensor were improved by modifying the microfluidic channel. This was accomplished through a physical-chemical treatment to produce a hydrophilic surface, with an increased surface to volume/ratio, where the anti-SOX-2 antibodies can be covalently immobilized. A sputtered gold electrode was used as detector and its surface was activated by using a dynamic hydrogen bubble template method. As a result, a gold nanoporous structure (NPAu) with outstanding properties, like high specific surface area, large pore volume, uniform nanostructure, good conductivity, and excellent electrochemical activity was obtained. SOX-2 present in the sample was bound to the anti-SOX-2 immobilized in the microfluidic channel, and then was labeled with a second antibody marked with horseradish peroxidase (HRP-anti-SOX-2) like a sandwich immunoassay. Finally, an H2O2 + catechol solution was added, and the enzymatic product (quinone) was reduced on the NPAu electrode at +0.1 V (vs. Ag). The current obtained was directly proportional to the SOX-2 concentration in the sample. The detection limit achieved was 30 pg mL−1, and the coefficient of variation was less than 4.75%. Therefore, the microfluidic electrochemical immunosensor is a suitable clinical device for in situ SOX-2 determination in real samples.Fil: Regiart, Daniel Matias Gaston. Universidade de Sao Paulo; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto de Química de San Luis. Universidad Nacional de San Luis. Facultad de Química, Bioquímica y Farmacia. Instituto de Química de San Luis; ArgentinaFil: Gimenez, Alba Marina. Universidade de Sao Paulo; BrasilFil: Lopes, Alexandre T.. Universidade de Sao Paulo; BrasilFil: Carreño, Marcelo Nelson Paéz. Universidade de Sao Paulo; BrasilFil: Bertotti, Mauro. Universidade de Sao Paulo; Brasi

Prognostic performance of computerized tomography scoring systems in civilian penetrating traumatic brain injury : an observational study

Background The prognosis of penetrating traumatic brain injury (pTBI) is poor yet highly variable. Current computerized tomography (CT) severity scores are commonly not used for pTBI prognostication but may provide important clinical information in these cohorts. Methods All consecutive pTBI patients from two large neurotrauma databases (Helsinki 1999-2015, Stockholm 2005-2014) were included. Outcome measures were 6-month mortality and unfavorable outcome (Glasgow Outcome Scale 1-3). Admission head CT scans were assessed according to the following: Marshall CT classification, Rotterdam CT score, Stockholm CT score, and Helsinki CT score. The discrimination (area under the receiver operating curve, AUC) and explanatory variance (pseudo-R-2) of the CT scores were assessed individually and in addition to a base model including age, motor response, and pupil responsiveness. Results Altogether, 75 patients were included. Overall 6-month mortality and unfavorable outcome were 45% and 61% for all patients, and 31% and 51% for actively treated patients. The CT scores' AUCs and pseudo-R(2)s varied between 0.77-0.90 and 0.35-0.60 for mortality prediction and between 0.85-0.89 and 0.50-0.57 for unfavorable outcome prediction. The base model showed excellent performance for mortality (AUC 0.94, pseudo-R-2 0.71) and unfavorable outcome (AUC 0.89, pseudo-R-2 0.53) prediction. None of the CT scores increased the base model's AUC (p > 0.05) yet increased its pseudo-R-2 (0.09-0.15) for unfavorable outcome prediction. Conclusion Existing head CT scores demonstrate good-to-excellent performance in 6-month outcome prediction in pTBI patients. However, they do not add independent information to known outcome predictors, indicating that a unique score capturing the intracranial severity in pTBI may be warranted.Peer reviewe

Early antenatal prediction of gestational diabetes in obese women: development of prediction tools for targeted intervention

All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0–18+6 weeks’ gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68–0.74). This increased to 0.77 (95%CI 0.73–0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74–0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most

Gene expression of the IGF pathway family distinguishes subsets of gastrointestinal stromal tumors wild type for KIT and PDGFRA

Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal (ICCs) and are the most common mesenchymal neoplasm of the gastrointestinal tract. While the majority of GISTs harbor activating mutations in either the v-kit Hardy-Zuckerman feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha (PDGFRA) tyrosine kinases, approximately 10–15% of adult GISTs and 85% of pediatric GISTs lack such mutations. These “wild-type” GISTs have been reported to express high levels of the insulin-like growth factor 1 receptor (IGF1R), and IGF1R-targeted therapy of wild-type GISTs is being evaluated in clinical trials. However, it is not clear that all wild-type GISTs express IGF1R, because studies to date have predominantly focused on a particular subtype of gastric wild-type GIST that is deficient in the mitochondrial succinate dehydrogenase (SDH) complex. This study of a series of 136 GISTs, including 72 wild-type specimens, was therefore undertaken to further characterize wild-type GIST subtypes based on the relative expression of transcripts encoding IGF1R. Additional transcripts relevant to GIST biology were also evaluated, including members of the IGF-signaling pathway (IGF1, IGF2, and insulin receptor [INSR]), neural markers (CDH2[CDH: Cadherin], neurofilament, light polypeptide, LHX2 [LHX: LIM homeobox], and KIRREL3 [KIRREL: kin of IRRE like]), KIT, PDGFRA, CD34, and HIF1A. Succinate dehydrogenase complex, subunit B protein expression was also assessed as a measure of SDH complex integrity. In addition to the previously described SDH-deficient, IGF1Rhigh wild-type GISTs, other SDH-intact wild-type subpopulations were defined by high relative expression of IGF1R, neural markers, IGF1 and INSR, or low IGF1R coupled with high IGF2. These results underscore the complexity and heterogeneity of wild-type GISTs that will need to be factored into molecularly-targeted therapeutic strategies