Aggregate Risk Score Based on Markers of Inflammation, Cell Stress, and Coagulation Is an Independent Predictor of Adverse Cardiovascular Outcomes

Objectives: This study sought to determine an aggregate, pathway-specific risk score for enhanced prediction of death and myocardial infarction (MI). Background Activation of inflammatory, coagulation, and cellular stress pathways contribute to atherosclerotic plaque rupture. We hypothesized that an aggregate risk score comprised of biomarkers involved in these different pathways - high-sensitivity C-reactive protein (CRP), fibrin degradation products (FDP), and heat shock protein 70 (HSP70) levels - would be a powerful predictor of death and MI. Methods: Serum levels of CRP, FDP, and HSP70 were measured in 3,415 consecutive patients with suspected or confirmed coronary artery disease (CAD) undergoing cardiac catheterization. Survival analyses were performed with models adjusted for established risk factors. Results: Median follow-up was 2.3 years. Hazard ratios (HRs) for all-cause death and MI based on cutpoints were as follows: CRP ≥3.0 mg/l, HR: 1.61; HSP70 >0.625 ng/ml, HR; 2.26; and FDP ≥1.0 μg/ml, HR: 1.62 (p < 0.0001 for all). An aggregate biomarker score between 0 and 3 was calculated based on these cutpoints. Compared with the group with a 0 score, HRs for all-cause death and MI were 1.83, 3.46, and 4.99 for those with scores of 1, 2, and 3, respectively (p for each: <0.001). Annual event rates were 16.3% for the 4.2% of patients with a score of 3 compared with 2.4% in 36.4% of patients with a score of 0. The C statistic and net reclassification improved (p < 0.0001) with the addition of the biomarker score. Conclusions: An aggregate score based on serum levels of CRP, FDP, and HSP70 is a predictor of future risk of death and MI in patients with suspected or known CAD

The population history of northeastern Siberia since the Pleistocene.

Northeastern Siberia has been inhabited by humans for more than 40,000 years but its deep population history remains poorly understood. Here we investigate the late Pleistocene population history of northeastern Siberia through analyses of 34 newly recovered ancient genomes that date to between 31,000 and 600 years ago. We document complex population dynamics during this period, including at least three major migration events: an initial peopling by a previously unknown Palaeolithic population of 'Ancient North Siberians' who are distantly related to early West Eurasian hunter-gatherers; the arrival of East Asian-related peoples, which gave rise to 'Ancient Palaeo-Siberians' who are closely related to contemporary communities from far-northeastern Siberia (such as the Koryaks), as well as Native Americans; and a Holocene migration of other East Asian-related peoples, who we name 'Neo-Siberians', and from whom many contemporary Siberians are descended. Each of these population expansions largely replaced the earlier inhabitants, and ultimately generated the mosaic genetic make-up of contemporary peoples who inhabit a vast area across northern Eurasia and the Americas

Combination of multiple alignment analysis and surface mapping paves a way for a detailed pathway reconstruction—The case of VHL (von Hippel-Lindau) protein and angiogenesis regulatory pathway

Using the tumor suppressor VHL protein as an example, we show that detailed analysis of conservation versus variation pattern in the multiple alignment can be coupled with the genomic pathway/complex conservation analysis to provide a more complete picture of the entire interaction/regulatory network. Results from the present study have allowed us to hypothesize that two additional proteins are involved in the VHL-mediated regulation of angiogenesis. Detailed modeling also has led to a prediction of the possible interaction mode between the known and the proposed parts of the VHL complex. To aid in an analysis of the VHL protein regulation of HIF-1α degradation, an important and only partially understood process that directly influences angiogenesis, we performed a comprehensive search for the orthologs of the VHL as well as for VHL-interacting proteins in all the available eukaryotic genomes. Analysis of a multiple alignment of thus identified VHL orthologs reveals an unusually high degree of conservation of the surface amino acid residues that almost exactly correspond to positions mutated in the VHL disease-associated tumors. In addition, these positions form well-defined clusters in three-dimensional space, and presence or absence of individual clusters correlates with the presence or absence of pathway elements in different genomes. We have also shown that relation trees derived from the multiple sequence alignment, functional surface-mapping, and HIF-1α degradation pathway structure are in complete agreement, linking the functional and structural evolution of the VHL protein and VHL-dependent HIF-1α degradation complex

MEMS Sensors Bias Thermal Profiles Classification Using Machine Learning

The paper describes the methodology and experimental results for revealing similarities in thermal dependencies of biases of accelerometers and gyroscopes from 250 inertial MEMS chips (MPU-9250). Temperature profiles were measured on an experimental setup with a Peltier element for temperature control. Classification of temperature curves was carried out with machine learning approach. A perfect sensor should not have thermal dependency at all. Thus, only sensors inside the clusters with smaller dependency (smaller total temperature slopes) might be pre-selected for production of high accuracy inertial navigation modules. It was found that no unified thermal profile (“family” curve) exists for all sensors in a production batch. However, obviously, sensors might be grouped according to their parameters. Therefore, the temperature compensation profiles might be regressed for each group. 12 slope coefficients on 5 degrees temperature intervals from 0°C to +60°C were used as the features for the k-means++ clustering algorithm. The minimum number of clusters for all sensors to be well separated from each other by bias thermal profiles in our case is 6. It was found by applying the elbow method. For each cluster a regression curve can be obtained

Measurement Analysis of Multiple MEMS Sensor Array

The low cost and small size of MEMS inertial sensors allows their combination into a multi sensor module in order to improve performance. However the different linear accelerations measured on different places on a rotating rigid body have to be considered for the proper fusion of the measurements. The errors in measurement of MEMS inertial sensors include deterministic imperfection, but also random noise. The gain in accuracy of using multiple sensors depends strongly on the correlation between these errors from the different sensors. Although for sensor fusion it usually assumed that the measurement errors of different sensors are uncorrelated, estimation theory shows that for the combination of the same type of sensors actually a negative correlation will be more beneficial. Therefore we describe some important and often neglected considerations for the combination of several sensors and also present some preliminary results with regard to the correlation of measurements from a simple multi sensor setup

Експериментальне обґрунтування можливості застосування композитних матеріалів на основі хітозану та фосфатів кальцію для заміщення кісткових дефектів

A number of chitosane/hydroxyl apatite composite materials were synthesized from aqueous solutions of a biopolymer and soluble salts-precursors. The composites were obtained in the dense and porous variants. The examinations conducted by the methods of X-ray diffraction analysis and infrared spectroscopy showed that apatite crystals in the composites had structural characteristics similar to those of biogenic apatite. Cylindrical rods, made of chitosane/hydroxyl apatite composite materials, were experimentally implanted into the tibial bone of linear laboratory rats in vivo. Histological and histomorphological studies for assessing osteoconductivity were performed 5, 10, 15 and 24 days after the implantation. The specimens were examined by the method of scanning electronic microscopy with X-ray microanalysis for comparing the elemental composition and morphological characteristics of the implant and bone during the integration. The results of the tests make it possible to conclude that chitosane/hydroxyl apatite composites are bioinert and biocompatible. The porous specimens also demonstrated satisfactory osteoconductive properties and were experimentally replaced in vivo by a newly formed bone tissue.Проведен синтез ряда хитозан/гидроксилапатитных композитных материалов из водных растворов биополимера и растворимых солей-прекурсоров. Композитные материалы были получены в плотном и пористом вариантах. Проведенные исследования методами рентгенодифракционного анализа и ИК-спектроскопии показали, что кристаллы апатита в композитах обладают структурными характеристиками, близкими к характеристикам биогенного апатита. В экспериментах in vivo в большеберцовую кость линейных лабораторных крыс имплантировали цилиндрические стержни, изготовленные из хитозан/апатитных композитных материалов. На 5, 10, 15 и 24 сутки после имплантации проводили гистологические и гистоморфологические исследования для оценки остеокондуктивности. Образцы исследовали методом растровой электронной микроскопии с рентгеновским микроанализом для сравнения элементного состава и морфологических характеристик имплантата и кости в течение интеграции. По результатам тестов можно заключить, что хитозан/гидроксилапатитные материалы являются биоинертными и биосовместимыми. Пористые образцы показали также удовлетворительные остеокондуктивные свойства, будучи замещены в экспериментах in vivo новосформированной костной тканью.Проведено синтез ряду хітозан/гідроксилапа-титних композитних матеріалів з водних розчинів біополімеру та розчинних солей-прекурсорів. Композитні матеріали було одержано у щільному та пористому варіантах. Проведені дослідження методом рентгенодифракційного аналізу та ІЧ-спектроскопії показали, що кристали апатиту в композитах мають структурні характеристики, близькі до характеристик біогенного апатиту. В експериментах in vivo у великогомілкову кістку лінійних лабораторних щурів імплантували циліндричні стержні, виготовлені з хітозан/апатитних композитних матеріалів. На 5, 10, 15 та 24 добу після імплантації проводили гістологічні та гістоморфологічні дослідження для оцінки остеокондуктивності. Зразки досліджували методом растрової електронної мікроскопії з рентгенівським мікроаналізом для порівняння елементного складу та морфологічних характеристик імплантата й кістки впродовж інтеграції. За результатами тестів можна зробити висновок, що хітозан/гідроксилапатитні матеріали є біоінертними та біосумісними. Пористі зразки показали також задовільні остеокондуктивні властивості, оскільки були заміщені в експериментах in vivo новоутвореною кістковою тканиною