Targeting medication non-adherence behavior in selected autoimmune diseases: a systematic approach to digital health program development

Background 29 autoimmune diseases, including Rheumatoid Arthritis, gout, Crohn’s Disease, and Systematic Lupus Erythematosus affect 7.6-9.4% of the population. While effective therapy is available, many patients do not follow treatment or use medications as directed. Digital health and Web 2.0 interventions have demonstrated much promise in increasing medication and treatment adherence, but to date many Internet tools have proven disappointing. In fact, most digital interventions continue to suffer from high attrition in patient populations, are burdensome for healthcare professionals, and have relatively short life spans. Objective Digital health tools have traditionally centered on the transformation of existing interventions (such as diaries, trackers, stage-based or cognitive behavioral therapy programs, coupons, or symptom checklists) to electronic format. Advanced digital interventions have also incorporated attributes of Web 2.0 such as social networking, text messaging, and the use of video. Despite these efforts, there has not been little measurable impact in non-adherence for illnesses that require medical interventions, and research must look to other strategies or development methodologies. As a first step in investigating the feasibility of developing such a tool, the objective of the current study is to systematically rate factors of non-adherence that have been reported in past research studies. Methods Grounded Theory, recognized as a rigorous method that facilitates the emergence of new themes through systematic analysis, data collection and coding, was used to analyze quantitative, qualitative and mixed method studies addressing the following autoimmune diseases: Rheumatoid Arthritis, gout, Crohn’s Disease, Systematic Lupus Erythematosus, and inflammatory bowel disease. Studies were only included if they contained primary data addressing the relationship with non-adherence. Results Out of the 27 studies, four non-modifiable and 11 modifiable risk factors were discovered. Over one third of articles identified the following risk factors as common contributors to medication non-adherence (percent of studies reporting): patients not understanding treatment (44%), side effects (41%), age (37%), dose regimen (33%), and perceived medication ineffectiveness (33%). An unanticipated finding that emerged was the need for risk stratification tools (81%) with patient-centric approaches (67%). Conclusions This study systematically identifies and categorizes medication non-adherence risk factors in select autoimmune diseases. Findings indicate that patients understanding of their disease and the role of medication are paramount. An unexpected finding was that the majority of research articles called for the creation of tailored, patient-centric interventions that dispel personal misconceptions about disease, pharmacotherapy, and how the body responds to treatment. To our knowledge, these interventions do not yet exist in digital format. Rather than adopting a systems level approach, digital health programs should focus on cohorts with heterogeneous needs, and develop tailored interventions based on individual non-adherence patterns.

Using proxies to calculate the carbon impact of investment into electricity network assets

Replacement and upgrading of assets in the electricity network requires financial investment for the distribution and transmission utilities. The replacement and upgrading of network assets also represents an emissions impact due to the carbon embodied in the materials used to manufacture network assets. This paper uses investment and asset data for the GB system for 2015-2023 to assess the suitability of using a proxy with peak demand data and network investment data to calculate the carbon impacts of network investments. The proxies are calculated on a regional basis and applied to calculate the embodied carbon associated with current network assets by DNO region. The proxies are also applied to peak demand data across the 2015-2023 period to estimate the expected levels of embodied carbon that will be associated with network investment during this period. The suitability of these proxies in different contexts are then discussed, along with initial scenario analysis to calculate the impact of avoiding or deferring network investments through distributed generation projects. The proxies were found to be effective in estimating the total embodied carbon of electricity system investment in order to compare investment strategies in different regions of the GB network.

Estrogens and thyroid hormone: Non-genomic effects are coupled to transcription.

Estrogens and thyroid hormones are regulators of important diverse physiological processes such as reproduction, thermogenesis, neural development, neural differentiation and cardiovascular functions. Both are ligands for receptors in the nuclear receptor superfamily, which act as ligand-dependent transcription factors, regulating transcription. However, estrogens and thyroid hormones also rapidly (within minutes or seconds) activate kinase cascades and calcium increases, presumably initiated at the cell membrane. We discuss the relevance of both modes of hormone action, including the membrane estrogen receptor, to physiology, with particular reference to lordosis behavior. We first showed that estrogen restricted to the membrane can, in fact, lead to subsequent increases in transcription from a consensus estrogen response element-based reporter in the neuroblastoma cell line, SK-N-BE(2)C. Using a novel hormonal paradigm, we also showed that the activation of protein kinase A, protein kinase C, mitogen activated protein kinase and increases in calcium were important in the ability of the membrane-limited estrogen to potentiate transcription. We discuss the source of calcium important in transcriptional potentiation. Since estrogens and thyroid hormones have common effects on neuroprotection, cognition and mood, we also hypothesized that crosstalk could occur between the rapid actions of thyroid hormones and the genomic actions of estrogens. In neural cells, we showed that triiodothyronine acting rapidly via MAPK can increase transcription by the nuclear estrogen receptor ERa from a consensus estrogen response element, possibly by the phosphorylation of the ERa. Novel mechanisms that link signals initiated by hormones from the membrane to the nucleus are physiologically relevant and can achieve neuroendocrine integration

Review of current in vivo measurement techniques for quantifying enteric methane emission from ruminants

Ruminant husbandry is a major source of anthropogenic greenhouse gases (GHG). Filling knowledge gaps and providing expert recommendation are important for defining future research priorities, improving methodologies and establishing science-based GHG mitigation solutions to government and non-governmental organisations, advisory/extension networks, and the ruminant livestock sector. The objectives of this review is to summarize published literature to provide a detailed assessment of the methodologies currently in use for measuring enteric methane (CH4) emission from individual animals under specific conditions, and give recommendations regarding their application. The methods described include respiration chambers and enclosures, sulphur hexafluoride tracer (SF6) technique, and techniques based on short-term measurements of gas concentrations in samples of exhaled air. This includes automated head chambers (e.g. the GreenFeed system), the use of carbon dioxide (CO2) as a marker, and (handheld) laser CH4 detection. Each of the techniques are compared and assessed on their capability and limitations, followed by methodology recommendations. It is concluded that there is no ‘one size fits all’ method for measuring CH4 emission by individual animals. Ultimately, the decision as to which method to use should be based on the experimental objectives and resources available. However, the need for high throughput methodology e.g. for screening large numbers of animals for genomic studies, does not justify the use of methods that are inaccurate. All CH4 measurement techniques are subject to experimental variation and random errors. Many sources of variation must be considered when measuring CH4 concentration in exhaled air samples without a quantitative or at least regular collection rate, or use of a marker to indicate (or adjust) for the proportion of exhaled CH4 sampled. Consideration of the number and timing of measurements relative to diurnal patterns of CH4 emission and respiratory exchange are important, as well as consideration of feeding patterns and associated patterns of rumen fermentation rate and other aspects of animal behaviour. Regardless of the method chosen, appropriate calibrations and recovery tests are required for both method establishment and routine operation. Successful and correct use of methods requires careful attention to detail, rigour, and routine self-assessment of the quality of the data they provide.

The non-coding RNA BC1 is down-regulated in the hippocampus of Wistar Audiogenic Rat (WAR) strain after audiogenic kindling

The aim of this study was to identify molecular pathways involved in audiogenic seizures in the epilepsy-prone Wistar Audiogenic Rat (WAR). For this, we used a suppression-subtractive hybridization (SSH) library from the hippocampus of WARs coupled to microarray comparative gene expression analysis, followed by Northern blot validation of individual genes. We discovered that the levels of the non-protein coding (npc) RNA BC1 were significantly reduced in the hippocampus of WARs submitted to repeated audiogenic seizures (audiogenic kindling) when compared to Wistar resistant rats and to both naive WARs and Wistars. By quantitative in situ hybridization, we verified lower levels of BC1 RNA in the GD-hilus and significant signal ratio reduction in the stratum radiatum and stratum pyramidale of hippocampal CA3 subfield of audiogenic kindled animals. Functional results recently obtained in a BC1-/- mouse model and our current data are supportive of a potential disruption in signaling pathways, upstream of BC1, associated with the seizure susceptibility of WARs. (C) 2010 Elsevier B.V. All rights reserved.

Integrable maps with non-trivial topology: application to divertor configurations

We explore a method for constructing two-dimensional area-preserving, integrable maps associated with Hamiltonian systems, with a given set of fixed points and given invariant curves. The method is used to find an integrable Poincare map for the field lines in a large aspect ratio tokamak with a poloidal single-null divertor. The divertor field is a superposition of a magnetohydrodynamic equilibrium with an arbitrarily chosen safety factor profile, with a wire carrying an electric current to create an X-point. This integrable map is perturbed by an impulsive perturbation that describes non-axisymmetric magnetic resonances at the plasma edge. The non-integrable perturbed map is applied to study the structure of the open field lines in the scrape-off layer, reproducing the main transport features obtained by integrating numerically the magnetic field line equations, such as the connection lengths and magnetic footprints on the divertor plate.

Study of sodium tellurite glass using the thermally stimulated depolarization current technique (TSDC)

In order to have a better understanding of the role of the structure and the defects involved in the polarization processes in an 85TeO(2)-15Na(2)O mol% glass, we used the thermally stimulated depolarization currents (TSDC technique). The TSDC of the non-irradiated sample presented a strong negative peak of current at the temperature of 340 K, preceded by a relatively weak positive peak at about 300 K. after different d.c. voltages of 1200, 1500 and 2000 V were applied. No response was obtained with 1000 V. but the peak intensity increased considerably for voltages above 1200 V. After gamma-irradiation of 25 and 50 KGy doses, a depolarization of the negative peak was observed in the sample submitted to 25 KGy, whereas for the sample irradiated with 50 KGy, six TSDC peaks appeared at regular intervals of 5 KGy, in the temperature range of 100 and 300 K. Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved.

Low cost BIST techniques for linear and non-linear analog circuits

With the ever increasing demands for high complexity consumer electronic products, market pressures demand faster product development and lower cost. SoCbased design can provide the required design flexibility and speed by allowing the use of IP cores. However, testing costs in the SoC environment can reach a substantial percent of the total production cost. Analog testing costs may dominate the total test cost, as testing of analog circuits usually require functional verification of the circuit and special testing procedures. For RF analog circuits commonly used in wireless applications, testing is further complicated because of the high frequencies involved. In summary, reducing analog test cost is of major importance in the electronic industry today. BIST techniques for analog circuits, though potentially able to solve the analog test cost problem, have some limitations. Some techniques are circuit dependent, requiring reconfiguration of the circuit being tested, and are generally not usable in RF circuits. In the SoC environment, as processing and memory resources are available, they could be used in the test. However, the overhead for adding additional AD and DA converters may be too costly for most systems, and analog routing of signals may not be feasible and may introduce signal distortion. In this work a simple and low cost digitizer is used instead of an ADC in order to enable analog testing strategies to be implemented in a SoC environment. Thanks to the low analog area overhead of the converter, multiple analog test points can be observed and specific analog test strategies can be enabled. As the digitizer is always connected to the analog test point, it is not necessary to include muxes and switches that would degrade the signal path. For RF analog circuits, this is specially useful, as the circuit impedance is fixed and the influence of the digitizer can be accounted for in the design phase. Thanks to the simplicity of the converter, it is able to reach higher frequencies, and enables the implementation of low cost RF test strategies. The digitizer has been applied successfully in the testing of both low frequency and RF analog circuits. Also, as testing is based on frequency-domain characteristics, nonlinear characteristics like intermodulation products can also be evaluated. Specifically, practical results were obtained for prototyped base band filters and a 100MHz mixer. The application of the converter for noise figure evaluation was also addressed, and experimental results for low frequency amplifiers using conventional opamps were obtained. The proposed method is able to enhance the testability of current mixed-signal designs, being suitable for the SoC environment used in many industrial products nowadays.

Life Cycle Models, Heterogeneity of Initial Assets,and Wealth Inequality

Life cycle general equilibrium models with heterogeneous agents have a very hard time reproducing the American wealth distribution. A common assumption made in this literature is that all young adults enter the economy with no initial assets. In this article, we relax this assumption – not supported by the data - and evaluate the ability of an otherwise standard life cycle model to account for the U.S. wealth inequality. The new feature of the model is that agents enter the economy with assets drawn from an initial distribution of assets, which is estimated using a non-parametric method applied to data from the Survey of Consumer Finances. We found that heterogeneity with respect to initial wealth is key for this class of models to replicate the data. According to our results, American inequality can be explained almost entirely by the fact that some individuals are lucky enough to be born into wealth, while others are born with few or no assets.

Low cost non-intrusive home energy monitoring

This thesis presents a low cost non-intrusive home energy monitor built on top of Non-Intrusive Load Monitoring (NILM) concepts and techniques. NILM solutions are already considered low cost alternatives to the big majority of existing commercial energy monitors but the goal here is to make its cost even lower by using a mini netbook as a whole in one solution. The mini netbook is installed in the homes main circuit breaker and computes power consumption by reading current and voltage from the built-in sound card. At the same time, feedback to the users is provided using the 11’’ LCD screen as well as other built-in I/O modules. Our meter is also capable of detecting changes in power and tries to find out which appliance lead to that change and it is being used as part of an eco-feedback platform that was build to study the long terms of energy eco-feedback in individuals. In this thesis the steps that were taken to come up with such a system are presented, from the basics of AC power measurements to the implementation of an event detector and classifier that was used to disaggregate the power load. In the last chapter results from some validation tests that have been performed are presented in order to validate the experiment. It is believed that such a system will not only be important as an energy monitor, but also as an open system than can be easily changed to accommodate and test new or existing nonintrusive load monitoring techniques.

Incidence of non-01 Vibrio cholerae and Aeromonas spp. in fresh water in Araraquara, Brazil

The occurrence of Aeromonas spp., Vibrio cholerae, and Plesiomonas shigelloides in fresh water from various sources in Araraquara, State of São Paulo, Brazil was determined. Samples from ten distinct irrigation systems used in vegetable cultivation, from five distinct streams, from two reservoirs, from one artificial lake, and from three distinct springs were analyzed. All isolates were serotyped and tested for hemolysin, cytotoxin, heat-stable (ST) and heat-labile (LT) enterotoxins production; presence of plasmid; autoagglutination and drug resistance. V. cholerae isolates were also tested for cholera enterotoxin (CT) production, and Aeromonas isolates for suicide phenomenon. No P. shigelloides was found. V. cholerae non 01 was found in five irrigation water samples and in three stream samples. Aeromonas sp. were isolated in two samples of irrigation water, in three streams, and in one reservoir. All the V. cholerae and Aeromonas isolates were positive for P-hemolysin production, and all Aeromonas isolates were positive for suicide phenomenon; cytotoxic activities were observed in two Aeromonas strains. Cholera enterotoxin was not found in eight V. cholerae non-01 isolates tested by the Y-1 mouse adrenal cell. All isolates were also negative for the other virulence markers. Ii cholelerae isolates were found to be sensitive to the majority of drugs tested, while Aeromonas strains presented multiple drug resistance..

Conventional and microwave sintering of CaCu(3)Ti(4)O(12)/CaTiO(3) ceramic composites: non-ohmic and dielectric properties

The non-ohmic and dielectric properties as well as the dependence on the microstructural features of CaCu(3)Ti(4)O(12)/CaTiO(3) ceramic composites obtained by conventional and microwave sintering were investigated. It was demonstrated that the non-ohmic and dielectric properties depend strongly on the sintering conditions. It was found that the non-linear coefficient reaches values of 65 for microwave-sintered samples and 42 for samples sintered in a conventional furnace when a current density interval of 1-10 mA cm(-2) is considered. The non-linear coefficient value of 65 is equivalent to 1500 for samples sintered in the microwave if a current interval of 5-30 mA is considered as is shortly discussed by Chung et al (2004 Nature Mater. 3 774). Due to a high non-linear coefficient and a low leakage current (90 mu A) under both processing conditions, these samples are promising for varistor applications. The conventionally sintered samples exhibit a higher relative dielectric constant at 1 kHz (2960) compared with the samples sintered in the microwave furnace (2100). At high frequencies, the dielectric constant is also larger in the samples sintered in the conventional furnace. Depending on the application, one or another synthesis methodology is recommended, that is, for varistor applications sintered in a microwave furnace and for dielectric application sintered in a conventional furnace.

Comparison of non-Ohmic accelerated ageing of the ZnO- and SnO2-based voltage dependent resistors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The influence of area/volume ratio on microstructure and non-Ohmic properties of SnO2-based varistor ceramic blocks

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Vibration energy harvesting using piezoelectric transducer and non-controlled rectifiers circuits

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)