General Architecture for Development of Virtual Coaches for Healthy Habits Monitoring and Encouragement.

Good health is the result of a healthy lifestyle, where caring about physical activity and nutrition are key concerns. However, in today's society, nutritional disorders are becoming increasingly frequent, affecting children, adults, and elderly people, mainly due to limited nutrition knowledge and the lack of a healthy lifestyle. A commonly adopted therapy to these imbalances is to monitor physical activity and daily habits, such as recording exercise or creating custom meal plans to count the amount of macronutrients and micronutrients acquired in each meal. Nowadays, many health tracking applications (HTA) have been developed that, for instance, record energy intake as well as users' physiological parameters, or measure the physical activity during the day. However, most existing HTA do not have a uniform architectural design on top of which to build other applications and services. In this manuscript, we present system architecture intended to serve as a reference architecture for building HTA solutions. In order to validate the proposed architecture, we performed a preliminary evaluation with 15 well recognized experts in systems and software architecture from different entities around world and who have estimated that our proposal can generate architecture for HTA that is adequate, reliable, secure, modifiable, portable, functional, and with high conceptual integrity. In order to show the applicability of the architecture in different HTA, we developed two telemonitoring systems based on it, targeted to different tasks: nutritional coaching (Food4Living) and physical exercise coaching (TrainME). The purpose was to illustrate the kind of end-user monitoring applications that could be developed.

Platelet cytochrome c oxidase activity and quantity in septic patients.

OBJECTIVE: The cytopathic hypoxia theory proposes that there is an impaired cellular oxygen utilization during sepsis. Respiratory complex IV, or cytochrome c oxidase, was only previously studied in muscle biopsies of 16 surviving and 12 nonsurviving septic patients. We hypothesized that higher activities and quantities of this enzyme complex could be associated with septic patient survival. The objective was to evaluate the relationship between cytochrome c oxidase activities and quantities and 6-month survival in a larger series of septic patients using a less invasive method (circulating platelets). DESIGN: Prospective, multicenter, observational study. SETTING: The study was carried out in six Spanish intensive care units. PATIENTS: We included 96 septic patients. INTERVENTIONS: We determined the cytochrome c oxidase activity per citrate synthase activity ratio and cytochrome c oxidase quantity per citrate synthase activity ratio in circulating platelets at the time of diagnosis and related them to 6-month survival. The written informed consent from the family members was obtained. MEASUREMENTS AND MAIN RESULTS: Survivor patients (n = 54) showed higher cytochrome c oxidase activity per citrate synthase activity ratio (p = .04) and cytochrome c oxidase quantity per citrate synthase activity ratio (p = .006) than nonsurvivors (n = 42). Logistic regression analyses confirmed that the cytochrome c oxidase activity per citrate synthase activity ratio (p = .04) and cytochrome c oxidase quantity per citrate synthase activity ratio (p = .02) were independent predictors of 6-month survival. The area under the curve to predict 6-month survival was 0.62 (95% confidence interval 0.51-0.74; p = .04) for the cytochrome c oxidase activity per citrate synthase activity ratio and 0.67 (95% confidence interval 0.56-0.76; p = .003) for the cytochrome c oxidase quantity per citrate synthase activity ratio. A negative correlation was found between the cytochrome c oxidase quantity per citrate synthase activity ratio and Sepsis-Related Organ Failure Assessment score (p = .04). CONCLUSIONS: Platelet cytochrome c oxidase activity and quantity were independent predictors of 6-month survival and could be used as biomarkers of sepsis mortality. This is a rapid, easy, and less invasive protocol to assess mitochondrial function. Patients with lower cytochrome c oxidase activity and quantity could benefit from drugs that improve mitochondrial function.

Genome-wide association filtering using a highly locus-specific transmission/disequilibrium test.

Multimarker transmission/disequilibrium tests (TDTs) are powerful association and linkage tests used to perform genome-wide filtering in the search for disease susceptibility loci. In contrast to case/control studies, they have a low rate of false positives for population stratification and admixture. However, the length of a region found in association with a disease is usually very large because of linkage disequilibrium (LD). Here, we define a multimarker proportional TDT (mTDT ( P )) designed to improve locus specificity in complex diseases that has good power compared to the most powerful multimarker TDTs. The test is a simple generalization of a multimarker TDT in which haplotype frequencies are used to weight the effect that each haplotype has on the whole measure. Two concepts underlie the features of the metric: the 'common disease, common variant' hypothesis and the decrease in LD with chromosomal distance. Because of this decrease, the frequency of haplotypes in strong LD with common disease variants decreases with increasing distance from the disease susceptibility locus. Thus, our haplotype proportional test has higher locus specificity than common multimarker TDTs that assume a uniform distribution of haplotype probabilities. Because of the common variant hypothesis, risk haplotypes at a given locus are relatively frequent and a metric that weights partial results for each haplotype by its frequency will be as powerful as the most powerful multimarker TDTs. Simulations and real data sets demonstrate that the test has good power compared with the best tests but has remarkably higher locus specificity, so that the association rate decreases at a higher rate with distance from a disease susceptibility or disease protective locus.

GeneOnEarth: fitting genetic PC plots on the globe.

Principal component (PC) plots have become widely used to summarize genetic variation of individuals in a sample. The similarity between genetic distance in PC plots and geographical distance has shown to be quite impressive. However, in most situations, individual ancestral origins are not precisely known or they are heterogeneously distributed; hence, they are hardly linked to a geographical area. We have developed GeneOnEarth, a user-friendly web-based tool to help geneticists to understand whether a linear isolation-by-distance model may apply to a genetic data set; thus, genetic distances among a set of individuals resemble geographical distances among their origins. Its main goal is to allow users to first apply a by-view Procrustes method to visually learn whether this model holds. To do that, the user can choose the exact geographical area from an on line 2D or 3D world map by using, respectively, Google Maps or Google Earth, and rotate, flip, and resize the images. GeneOnEarth can also compute the optimal rotation angle using Procrustes analysis and assess statistical evidence of similarity when a different rotation angle has been chosen by the user. An online version of GeneOnEarth is available for testing and using purposes at http://bios.ugr.es/GeneOnEarth.

Increasing power by using haplotype similarity in a multimarker transmission/disequilibrium test.

It is already known that power in multimarker transmission/disequilibrium tests may improve with the number of markers as some associations may require several markers to be captured. However, a mechanism such as haplotype grouping must be used to avoid incremental complexity with the number of markers. 2G, a state-of-the-art transmission/disequilibrium test, implements this mechanism to its maximum extent by grouping haplotypes into only two groups, high and low-risk haplotypes, so that the test has only one degree of freedom regardless of the number of markers. The test checks whether those haplotypes more often transmitted from parents to offspring are truly high-risk haplotypes. In this paper we use haplotype similarity as prior knowledge to classify haplotypes as high or low risk ones and start with those haplotypes in which the prior will have lower impact i.e. those with the largest differences between transmission and non-transmission counts. If their counts are very different, the prior knowledge has little effect and haplotypes are classified as low or high risk as 2G does. We show a substantial gain in power achieved by this approach, in both simulation and real data sets.

Sample reproducibility of genetic association using different multimarker TDTs in genome-wide association studies: characterization and a new approach.

Multimarker Transmission/Disequilibrium Tests (TDTs) are very robust association tests to population admixture and structure which may be used to identify susceptibility loci in genome-wide association studies. Multimarker TDTs using several markers may increase power by capturing high-degree associations. However, there is also a risk of spurious associations and power reduction due to the increase in degrees of freedom. In this study we show that associations found by tests built on simple null hypotheses are highly reproducible in a second independent data set regardless the number of markers. As a test exhibiting this feature to its maximum, we introduce the multimarker 2-Groups TDT (mTDT(2G)), a test which under the hypothesis of no linkage, asymptotically follows a χ2 distribution with 1 degree of freedom regardless the number of markers. The statistic requires the division of parental haplotypes into two groups: disease susceptibility and disease protective haplotype groups. We assessed the test behavior by performing an extensive simulation study as well as a real-data study using several data sets of two complex diseases. We show that mTDT(2G) test is highly efficient and it achieves the highest power among all the tests used, even when the null hypothesis is tested in a second independent data set. Therefore, mTDT(2G) turns out to be a very promising multimarker TDT to perform genome-wide searches for disease susceptibility loci that may be used as a preprocessing step in the construction of more accurate genetic models to predict individual susceptibility to complex diseases.