Exploring the potential role of allostatic load biomarkers in risk assessment of patients presenting with depressive symptoms

Background: Depression is a major health problem worldwide and the majority of patients presenting with depressive symptoms are managed in primary care. Current approaches for assessing depressive symptoms in primary care are not accurate in predicting future clinical outcomes, which may potentially lead to over or under treatment. The Allostatic Load (AL) theory suggests that by measuring multi-system biomarker levels as a proxy of measuring multi-system physiological dysregulation, it is possible to identify individuals at risk of having adverse health outcomes at a prodromal stage. Allostatic Index (AI) score, calculated by applying statistical formulations to different multi-system biomarkers, have been associated with depressive symptoms. Aims and Objectives: To test the hypothesis, that a combination of allostatic load (AL) biomarkers will form a predictive algorithm in defining clinically meaningful outcomes in a population of patients presenting with depressive symptoms. The key objectives were: 1. To explore the relationship between various allostatic load biomarkers and prevalence of depressive symptoms in patients, especially in patients diagnosed with three common cardiometabolic diseases (Coronary Heart Disease (CHD), Diabetes and Stroke). 2 To explore whether allostatic load biomarkers predict clinical outcomes in patients with depressive symptoms, especially in patients with three common cardiometabolic diseases (CHD, Diabetes and Stroke). 3 To develop a predictive tool to identify individuals with depressive symptoms at highest risk of adverse clinical outcomes. Methods: Datasets used: ‘DepChron’ was a dataset of 35,537 patients with existing cardiometabolic disease collected as a part of routine clinical practice. ‘Psobid’ was a research data source containing health related information from 666 participants recruited from the general population. The clinical outcomes for 3 both datasets were studied using electronic data linkage to hospital and mortality health records, undertaken by Information Services Division, Scotland. Cross-sectional associations between allostatic load biomarkers calculated at baseline, with clinical severity of depression assessed by a symptom score, were assessed using logistic and linear regression models in both datasets. Cox’s proportional hazards survival analysis models were used to assess the relationship of allostatic load biomarkers at baseline and the risk of adverse physical health outcomes at follow-up, in patients with depressive symptoms. The possibility of interaction between depressive symptoms and allostatic load biomarkers in risk prediction of adverse clinical outcomes was studied using the analysis of variance (ANOVA) test. Finally, the value of constructing a risk scoring scale using patient demographics and allostatic load biomarkers for predicting adverse outcomes in depressed patients was investigated using clinical risk prediction modelling and Area Under Curve (AUC) statistics. Key Results: Literature Review Findings. The literature review showed that twelve blood based peripheral biomarkers were statistically significant in predicting six different clinical outcomes in participants with depressive symptoms. Outcomes related to both mental health (depressive symptoms) and physical health were statistically associated with pre-treatment levels of peripheral biomarkers; however only two studies investigated outcomes related to physical health. Cross-sectional Analysis Findings: In DepChron, dysregulation of individual allostatic biomarkers (mainly cardiometabolic) were found to have a non-linear association with increased probability of co-morbid depressive symptoms (as assessed by Hospital Anxiety and Depression Score HADS-D≥8). A composite AI score constructed using five biomarkers did not lead to any improvement in the observed strength of the association. In Psobid, BMI was found to have a significant cross-sectional association with the probability of depressive symptoms (assessed by General Health Questionnaire GHQ-28≥5). BMI, triglycerides, highly sensitive C - reactive 4 protein (CRP) and High Density Lipoprotein-HDL cholesterol were found to have a significant cross-sectional relationship with the continuous measure of GHQ-28. A composite AI score constructed using 12 biomarkers did not show a significant association with depressive symptoms among Psobid participants. Longitudinal Analysis Findings: In DepChron, three clinical outcomes were studied over four years: all-cause death, all-cause hospital admissions and composite major adverse cardiovascular outcome-MACE (cardiovascular death or admission due to MI/stroke/HF). Presence of depressive symptoms and composite AI score calculated using mainly peripheral cardiometabolic biomarkers was found to have a significant association with all three clinical outcomes over the following four years in DepChron patients. There was no evidence of an interaction between AI score and presence of depressive symptoms in risk prediction of any of the three clinical outcomes. There was a statistically significant interaction noted between SBP and depressive symptoms in risk prediction of major adverse cardiovascular outcome, and also between HbA1c and depressive symptoms in risk prediction of all-cause mortality for patients with diabetes. In Psobid, depressive symptoms (assessed by GHQ-28≥5) did not have a statistically significant association with any of the four outcomes under study at seven years: all cause death, all cause hospital admission, MACE and incidence of new cancer. A composite AI score at baseline had a significant association with the risk of MACE at seven years, after adjusting for confounders. A continuous measure of IL-6 observed at baseline had a significant association with the risk of three clinical outcomes- all-cause mortality, all-cause hospital admissions and major adverse cardiovascular event. Raised total cholesterol at baseline was associated with lower risk of all-cause death at seven years while raised waist hip ratio- WHR at baseline was associated with higher risk of MACE at seven years among Psobid participants. There was no significant interaction between depressive symptoms and peripheral biomarkers (individual or combined) in risk prediction of any of the four clinical outcomes under consideration. Risk Scoring System Development: In the DepChron cohort, a scoring system was constructed based on eight baseline demographic and clinical variables to predict the risk of MACE over four years. The AUC value for the risk scoring system was modest at 56.7% (95% CI 55.6 to 57.5%). In Psobid, it was not possible to perform this analysis due to the low event rate observed for the clinical outcomes. Conclusion: Individual peripheral biomarkers were found to have a cross-sectional association with depressive symptoms both in patients with cardiometabolic disease and middle-aged participants recruited from the general population. AI score calculated with different statistical formulations was of no greater benefit in predicting concurrent depressive symptoms or clinical outcomes at follow-up, over and above its individual constituent biomarkers, in either patient cohort. SBP had a significant interaction with depressive symptoms in predicting cardiovascular events in patients with cardiometabolic disease; HbA1c had a significant interaction with depressive symptoms in predicting all-cause mortality in patients with diabetes. Peripheral biomarkers may have a role in predicting clinical outcomes in patients with depressive symptoms, especially for those with existing cardiometabolic disease, and this merits further investigation.

The interaction factor as a challenge for foreign language learning in the technology based education: a pedagogical reflection

The author carries out a pedagogical reflection on how the technology driven distance learning repeatedly neglects the scientific achievements of Second Language Acquisition and Language Pedagogy. Seeing communicative competence as a major goal of a language classroom, she presents the main challenges that the communicative approach poses to distance learning. To this end, a general distance learning theory by Moore is adapted to the needs of language education, through a distinction between three aspects of learner interaction – with the teacher, with other learners and with content. In this three-dimensional paradigm the learner is seen as the main actor of the process, the teacher as a facilitator, the text as a main source of communicative data and the learner autonomy as the fundament of the process.

Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction

Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10 years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1 year, median 371 days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD = 1.5, 95% confidence interval 1.1 to 2.1, p = 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD = 1.8, 95% confidence interval 1.2 to 2.6, p = 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p = 0.016). HGF showed a complementary value over NT-proBNP (p = 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.

Dentists’ actions about oral health of individuals with Down Syndrome

Aim: To investigate the knowledge and actions of dentists for treatment of individuals with Down syndrome. Methods: A questionnaire was applied to all the dentists (n=90) working at the FHS (Family Health Strategy) modules in the urban limits of Parnaíba, PI, Brazil. Four of the questions in the questionnaire were written according to the Theory of Planned Behavior Table and Likert scale (questions 6,7,9 and 15), in order to analyze the professionals’ intentions. Sixteen objective questions were elaborated with the purpose of collecting information about the degree of the dentists’ knowledge as regards the intention of attending courses in the patients with special needs area including DS, and interaction with other professionals and families. The option was to use a questionnaire applied to the dentists of the region, from August to November 2014. Results: It was found that most professionals were women and they considered themselves able to identify these patients. Among the professionals, 70% showed they had no difficulty in identifying the patient with DS, and 5.2% had no opinion about the subject. Only 6.6% of the professionals showed to be certain about their aptitude to attend to these patients; 70% were partially apt, that is, they were not absolutely sure about their aptness. There was a statistical relationship between the variables understanding and difficulty in the treatment. There was no statistical relationship between the variable capacity to identify, understanding of the needs and fitness variable in attendance. Conclusions: Patients with Down syndrome need more attention and care of dentists, they must also be involved in a multidisciplinary approach. Most of the professionals do not follow the procedures laid down by the Ministry of Health, but showed interest in attending a course in this area and there is a low number of SD patients being cared in Parnaíba, PI.

Optimization of quantum states for signaling across an arbitrary qubit noise channel with minimum-error detection

International audience

O conhecimento profissional do professor e as investigações matemáticas na sala de aula: Um estudo nos 1º e 2º ciclos do ensino básico

Este estudo tem como objetivo contribuir para a compreensão do conhecimento profissional do professor de Matemática envolvido no desenvolvimento de tarefas de investigação na sala de aula, focando-se em quatro questões orientadoras: (i) como é que os professores colocam em prática as tarefas de investigação, considerando a planificação e condução das aulas? (ii) que dificuldades sentem os professores no desenvolvimento de tarefas de investigação na sala de aula? (iii) como é que o conhecimento didático dos professores influencia o desenvolvimento de tarefas de investigação? (iv) como é que o conhecimento didático dos professores é influenciado pelo desenvolvimento de tarefas de investigação? A fundamentação teórica assenta sobre as duas grandes temáticas do estudo: o conhecimento profissional do professor, sendo discutida a sua natureza, estrutura e conteúdo, e as tarefas de investigação, das quais se aprofunda a natureza e a utilização em sala de aula. Apresenta-se ainda investigação empírica referente ao conhecimento profissional do professor envolvido no desenvolvimento de tarefas de investigação. O estudo assumiu uma abordagem interpretativa, concretizando-se através dois estudos de caso, um de uma professora de 1. ° Ciclo e outro de um professor de Matemática do 2. ° Ciclo do Ensino Básico. Estes professores trabalharam em colaboração com a investigadora sobre tarefas de investigação, que até aí não conheciam, planificando, lecionado e refletindo acerca de um conjunto de aulas com tarefas desta natureza. Foram recolhidos dados durante as sessões de trabalho referidas, bem como nas aulas e ainda em entrevistas realizadas a cada um dos professores. Uma leitura transversal dos casos permite retirar algumas conclusões. A possibilidade de enquadramento nos conteúdos programáticos parece ser o principal critério de seleção das tarefas por parte dos professores. Na planificação, é a inventariação dos conteúdos que a tarefa mobiliza a principal prioridade, na busca da redução do grau de incerteza relacionado com as eventuais reações dos alunos. Quanto à condução de tarefas de investigação, a fase de introdução foi a mais breve, tendo servido o objetivo de conduzir à compreensão do propósito da tarefa por parte dos alunos e também reforçar alguns aspetos metodológicos do trabalho investigativo. A fase de desenvolvimento da tarefa foi aquela a que o professor de 2. ° Ciclo atribuiu maior importância, embora também valorizada pela professora de 1. ° Ciclo. Aqui, os professores consideram que o seu papel é acompanhar e orientar o trabalho dos alunos, ajudando a ultrapassar possíveis obstáculos, mantendo uma atitude questionadora. Quanto à fase de discussão, a grande preocupação dos professores é garantir a compreensão das ideias apresentadas pelos alunos. No entanto, existem duas estratégias distintas: enquanto a professora de 1. ° Ciclo, que muito valorizou esta fase, estimula a interação aluno-aluno, atribuindo-lhes a responsabilidade de validar/rejeitar as conjeturas apresentadas, o professor de 2. ° Ciclo centra em si toda esta fase, assumindo a responsabilidade de corrigir as ideias apresentadas. O desenvolvimento de tarefas de investigação é influenciado pelo conhecimento didático, revelando-se determinantes o conhecimento dos alunos e da forma como aprendem e o conhecimento do processo instrucional. O desenvolvimento de tarefas de investigação influencia várias componentes do conhecimento didático do professor, permitindo-lhe fortalecer o seu conhecimento matemático, desenvolver um conhecimento mais completo dos alunos e da forma como aprendem. Por último, a prática letiva com tarefas de investigação fornece ao professor dados importantes de como planificar e conduzir tarefas de natureza aberta, de forma a tirar o máximo partido das suas potencialidades. ABSTRACT: This study’s aim is to contribute to the understanding of the professional knowledge of the Maths teacher, involved in the development of investigative tasks in the classroom, focusing four guiding questions: (i) how do teachers give practical way to the investigative tasks, having in mind the lesson plans and lesson execution? (ii) Which difficulties do the teachers face when developing the investigative tasks in the classroom? (iii) How does the teachers' didactical knowledge influence the development of the investigative tasks? (iv) How is the teachers' didactical knowledge influenced by the development of the investigative tasks? The theorical framework is based on two broad themes of the study: teacher's professional knowledge (discussing its nature, structure and contents) and the investigative tasks (whose nature and use in the classroom is deepened). Besides, empirical research in what concerns to the professional knowledge of the teacher involved in the development of investigative tasks is also added. The study assumed an interpretative approach, materialised through two case studies, one of a primary school teacher, the other of a preparatory school Maths teacher. The teachers worked in cooperation with the researcher on the investigative tasks, which, until then, they weren't familiar with, planning, teaching and thinking about a set of lessons with tasks of this kind. Data were collected during the work meetings, as well as in the lessons and also in interviews to each one of the teachers. A transversal appreciation of the cases allows us to draw some conclusions. The possibility of integrating the programmatic contents seems to be the main criteria for the selection of the tasks by the teachers. ln the planning, the main priority of the task is the inventory of contents, aiming to reduce the level of uncertainty in what concerns to eventual reactions of the students. ln what concerns to the conduction of the investigative tasks, the introduction phase was the shortest, fulfilling the aim of leading to the understanding of the proposal of the task by the students and also to reinforce some methodological aspects of the investigative work. The task's development phase was the one the preparatory school teacher dedicated more importance, though it was also valued by the primary school teacher. ln this aspect, the teachers consider that their role is to follow and lead the students’ work, helping them to overtake eventual obstacles, keeping the questioning attitude. ln what concerns the discussion phase, the big concern of the teachers is to reassure the understanding of the ideas presented by the students. However, there are two different strategies: while the primary school teacher, who really valued this phase, stimulates the student-student interaction, giving them the responsibility of validating/rejecting the presented conjectures; the preparatory school teacher centers around himself all this phase, assuming the responsibilities of correcting the presented ideas. The development of the investigative tasks is influenced by the didactical knowledge, and it is determinant the knowledge about the students and about the way they learn and the instructional knowledge. The development of the investigative tasks influences several components of the didactical knowledge of the teacher, allowing him/her to reinforce his mathematical knowledge, developing a more complete knowledge about the students and the way they learn. Finally, the lessons execution with investigative tasks provides the teacher with important data about how to plan and conduct open nature tasks, in order to take the biggest advantage of their potential.

Dynamic Image Precompensation for Improving Visual Performance of Computer Users with Ocular Aberrations

With the progress of computer technology, computers are expected to be more intelligent in the interaction with humans, presenting information according to the user's psychological and physiological characteristics. However, computer users with visual problems may encounter difficulties on the perception of icons, menus, and other graphical information displayed on the screen, limiting the efficiency of their interaction with computers. In this dissertation, a personalized and dynamic image precompensation method was developed to improve the visual performance of the computer users with ocular aberrations. The precompensation was applied on the graphical targets before presenting them on the screen, aiming to counteract the visual blurring caused by the ocular aberration of the user's eye. A complete and systematic modeling approach to describe the retinal image formation of the computer user was presented, taking advantage of modeling tools, such as Zernike polynomials, wavefront aberration, Point Spread Function and Modulation Transfer Function. The ocular aberration of the computer user was originally measured by a wavefront aberrometer, as a reference for the precompensation model. The dynamic precompensation was generated based on the resized aberration, with the real-time pupil diameter monitored. The potential visual benefit of the dynamic precompensation method was explored through software simulation, with the aberration data from a real human subject. An "artificial eye'' experiment was conducted by simulating the human eye with a high-definition camera, providing objective evaluation to the image quality after precompensation. In addition, an empirical evaluation with 20 human participants was also designed and implemented, involving image recognition tests performed under a more realistic viewing environment of computer use. The statistical analysis results of the empirical experiment confirmed the effectiveness of the dynamic precompensation method, by showing significant improvement on the recognition accuracy. The merit and necessity of the dynamic precompensation were also substantiated by comparing it with the static precompensation. The visual benefit of the dynamic precompensation was further confirmed by the subjective assessments collected from the evaluation participants.

User interaction monitoring and analysis framework

An overview is given of a user interaction monitoring and analysis framework called BaranC. Monitoring and analysing human-digital interaction is an essential part of developing a user model as the basis for investigating user experience. The primary human-digital interaction, such as on a laptop or smartphone, is best understood and modelled in the wider context of the user and their environment. The BaranC framework provides monitoring and analysis capabilities that not only records all user interaction with a digital device (e.g. smartphone), but also collects all available context data (such as from sensors in the digital device itself, a fitness band or a smart appliances). The data collected by BaranC is recorded as a User Digital Imprint (UDI) which is, in effect, the user model and provides the basis for data analysis. BaranC provides functionality that is useful for user experience studies, user interface design evaluation, and providing user assistance services. An important concern for personal data is privacy, and the framework gives the user full control over the monitoring, storing and sharing of their data.

A service-oriented user interaction analysis framework supporting adaptive applications

A comprehensive user model, built by monitoring a user's current use of applications, can be an excellent starting point for building adaptive user-centred applications. The BaranC framework monitors all user interaction with a digital device (e.g. smartphone), and also collects all available context data (such as from sensors in the digital device itself, in a smart watch, or in smart appliances) in order to build a full model of user application behaviour. The model built from the collected data, called the UDI (User Digital Imprint), is further augmented by analysis services, for example, a service to produce activity profiles from smartphone sensor data. The enhanced UDI model can then be the basis for building an appropriate adaptive application that is user-centred as it is based on an individual user model. As BaranC supports continuous user monitoring, an application can be dynamically adaptive in real-time to the current context (e.g. time, location or activity). Furthermore, since BaranC is continuously augmenting the user model with more monitored data, over time the user model changes, and the adaptive application can adapt gradually over time to changing user behaviour patterns. BaranC has been implemented as a service-oriented framework where the collection of data for the UDI and all sharing of the UDI data are kept strictly under the user's control. In addition, being service-oriented allows (with the user's permission) its monitoring and analysis services to be easily used by 3rd parties in order to provide 3rd party adaptive assistant services. An example 3rd party service demonstrator, built on top of BaranC, proactively assists a user by dynamic predication, based on the current context, what apps and contacts the user is likely to need. BaranC introduces an innovative user-controlled unified service model of monitoring and use of personal digital activity data in order to provide adaptive user-centred applications. This aims to improve on the current situation where the diversity of adaptive applications results in a proliferation of applications monitoring and using personal data, resulting in a lack of clarity, a dispersal of data, and a diminution of user control.

Impacto del Programa de Alimentación Escolar en el Trabajo Infantil: Una aproximación desde la toma de decisiones familiares

Esta investigación analiza el impacto del Programa de Alimentación Escolar en el trabajo infantil en Colombia a través de varias técnicas de evaluación de impacto que incluyen emparejamiento simple, emparejamiento genético y emparejamiento con reducción de sesgo. En particular, se encuentra que este programa disminuye la probabilidad de que los escolares trabajen alrededor de un 4%. Además, se explora que el trabajo infantil se reduce gracias a que el programa aumenta la seguridad alimentaria, lo que consecuentemente cambia las decisiones de los hogares y anula la carga laboral en los infantes. Son numerosos los avances en primera infancia llevados a cabo por el Estado, sin embargo, estos resultados sirven de base para construir un marco conceptual en el que se deben rescatar y promover las políticas públicas alimentarias en toda la edad escolar.

Growth and symbiosis of plants with arbuscular mycorrhizal fungi in soil submitted to biochar application.

Arbuscular mycorrhizal fungi (AMF), which is intrinsically present or may be introduced in soils by inoculation, is an example of natural and renewable resource to increase plant nutrient uptake. This kind of fungi produces structures (hyphae, arbuscles and sometimes vesicles) inside the plant root cortex. This mutualistic relationship promotes plant gains in terms of water and nutrient absorption (mainly phosphorus). Biochar can benefit plant interaction with AMF, however, it can contain potentially toxic compounds such as heavy metals and organic compounds (e.g. dioxins, furans and polycyclic aromatic hydrocarbons), depending on the feedstock and pyrolysis conditions, which may damage organisms. For these reasons, the present work will approach the impacts of biochar application on soil attributes, AMF-plant symbiosis and its responses in plant growth and phosphorus uptake. Eucalyptus biochar produced at high temperatures increases sorghum growth; symbiosis with AMF; and enhances spore germination. Enhanced plant growth in the presence of high temperature biochar and AMF is a response of root branching stimulated by an additive effect between biochar characteristics and root colonization. Biochar obtained at low temperature reduces AMF spore germination; however it does not affect plant growth and symbiosis in soil.