Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial

BACKGROUND Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. METHODS We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. FINDINGS Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one-sided 95% CI 1·97%, p for non-inferiority <0·0004). No significant differences were noted in rates of definite stent thrombosis (9 [0·9%] vs 4 [0·4%], rate ratio [RR] 2·26, 95% CI 0·70-7·33, p=0·16). In pre-specified stratified analyses of the primary endpoint, biodegradable polymer sirolimus-eluting stents were associated with improved outcome compared with durable polymer everolimus-eluting stents in the subgroup of patients with ST-segment elevation myocardial infarction (7 [3·3%] vs 17 [8·7%], RR 0·38, 95% CI 0·16-0·91, p=0·024, p for interaction=0·014). INTERPRETATION In a patient population with minimum exclusion criteria and high adherence to dual antiplatelet therapy, biodegradable polymer sirolimus-eluting stents were non-inferior to durable polymer everolimus-eluting stents for the combined safety and efficacy outcome target lesion failure at 12 months. The noted benefit in the subgroup of patients with ST-segment elevation myocardial infarction needs further study. FUNDING Clinical Trials Unit, University of Bern, and Biotronik, Bülach, Switzerland.

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

BACKGROUND It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING The Medicines Company and Terumo.

Fine-grained Indoor Tracking by Fusing Inertial Sensor and Physical Layer Information in WLANs

Indoor positioning has become an emerging research area because of huge commercial demands for location-based services in indoor environments. Channel State Information (CSI) as a fine-grained physical layer information has been recently proposed to achieve high positioning accuracy by using range-based methods, e.g., trilateration. In this work, we propose to fuse the CSI-based ranges and velocity estimated from inertial sensors by an enhanced particle filter to achieve highly accurate tracking. The algorithm relies on some enhanced ranging methods and further mitigates the remaining ranging errors by a weighting technique. Additionally, we provide an efficient method to estimate the velocity based on inertial sensors. The algorithms are designed in a network-based system, which uses rather cheap commercial devices as anchor nodes. We evaluate our system in a complex environment along three different moving paths. Our proposed tracking method can achieve 1:3m for mean accuracy and 2:2m for 90% accuracy, which is more accurate and stable than pedestrian dead reckoning and range-based positioning.

Accuracy of tidal breathing measurement of FloRight compared to an ultrasonic flowmeter in infants.

INTRODUCTION Monitoring breathing pattern is especially relevant in infants with lung disease. Recently, a vest-based inductive plethysmograph system (FloRight®) has been developed for tidal breathing measurement in infants. We investigated the accuracy of tidal breathing flow volume loop (TBFVL) measurements in healthy term-born infants and infants with lung disease by the vest-based system in comparison to an ultrasonic flowmeter (USFM) with a face mask. We also investigated whether the system discriminates between healthy infants and those with lung disease. METHODS Floright® measures changes in thoracoabdominal volume during tidal breathing through magnetic field changes generated by current-carrying conductor coils in an elastic vest. Simultaneous TBFVL measurements by the vest-based system and the USFM were performed at 44 weeks corrected postmenstrual age during quiet unsedated sleep. TBFVL parameters derived by both techniques and within both groups were compared. RESULTS We included 19 healthy infants and 18 infants with lung disease. Tidal volume per body weight derived by the vest-based system was significantly lower with a mean difference (95% CI) of -1.33 ml/kg (-1.73; -0.92), P < 0.001. Respiratory rate and ratio of time to peak tidal expiratory flow over total expiratory time (tPTEF/tE) did not differ between the two techniques. Both systems were able to discriminate between healthy infants and those with lung disease using tPTEF/tE. CONCLUSION FloRight® accurately measures time indices and may discriminate between healthy infants and those with lung disease, but demonstrates differences in tidal volume measurements. It may be better suited to monitor breathing pattern than for TBFVL measurements.

Fine-grained Indoor Tracking by Fusing Inertial Sensor and Physical Layer Information in WLANs

Indoor positioning has become an emerging research area because of huge commercial demands for location-based services in indoor environments. Channel State Information (CSI) as fine-grained physical layer information has been recently proposed to achieve high positioning accuracy by using range based methods, e.g., trilateration. In this work, we propose to fuse the CSI-based ranging and velocity estimated from inertial sensors by an enhanced particle filter to achieve highly accurate tracking. The algorithm relies on some enhanced ranging methods and further mitigates the remaining ranging errors by a weighting technique. Additionally, we provide an efficient method to estimate the velocity based on inertial sensors. The algorithms are designed in a network-based system, which uses rather cheap commercial devices as anchor nodes. We evaluate our system in a complex environment along three different moving paths. Our proposed tracking method can achieve 1.3m for mean accuracy and 2.2m for 90% accuracy, which is more accurate and stable than pedestrian dead reckoning and range-based positioning.

The in vivo and in vitro formation of sticky DNA and the GAA.TTC trinucleotide repeat associated with Friedreich's ataxia

Friedreich's ataxia is caused by the expansion of the GAA•TTC trinucleotide repeat sequence located in intron 1 of the frataxin gene. The long GAA•TTC repeats are known to form several non-B DNA structures including hairpins, triplexes, parallel DNA and sticky DNA. Therefore it is believed that alternative DNA structures play a role in the loss of mRNA transcript and functional frataxin protein in FRDA patients. We wanted to further elucidate the characteristics for formation and stability of sticky DNA by evaluating the structure in a plasmid based system in vitro and in vivo in Escherichia coli. The negative supercoil density of plasmids harboring different lengths of GAA•TTC repeats, as well as either one or two repeat tracts were studied in E. coli to determine if plasmids containing two long tracts (≥60 repeats) in a direct repeat orientation would have a different topological effect in vivo compared to plasmids that harbored only one GAA•TTC tract or two tracts of < 60 repeats. The experiments revealed that, in fact, sticky DNA forming plasmids had a lower average negative supercoil density (-σ) compared to all other control plasmids used that had the potential to form other non-B DNA structures such as triplexes or Z-DNA. Also, the requirements for in vitro dissociation and reconstitution of the DNA•DNA associated region of sticky DNA were evaluated. Results conclude that the two repeat tracts associate in the presence of negative supercoiling and MgCl 2 or MnCl2 in a time and concentration-dependent manner. Interaction of the repeat sequences was not observed in the absence of negative supercoiling and/or MgCl2 or in the presence of other monovalent or divalent cations, indicating that supercoiling and quite specific cations are needed for the association of sticky DNA. These are the first experiments studying a more specific role of supercoiling and cation influence on this DNA conformation. To support our model of the topological effects of sticky DNA in plasmids, changes in sticky DNA band migration was measured with reference to the linear DNA after treatment with increasing concentrations of ethidium bromide (EtBr). The presence of independent negative supercoil domains was confirmed by this method and found to be segregated by the DNA-DNA associated region. Sequence-specific polyamide molecules were used to test the effect of binding of the ligands to the GAA•TTC repeats on the inhibition of sticky DNA. The destabilization of the sticky DNA conformation in vitro through this binding of the polyamides demonstrated the first conceptual therapeutic approach for the treatment of FRDA at the DNA molecular level. ^ Thus, examining the properties of sticky DNA formed by these long repeat tracts is important in the elucidation of the possible role of sticky DNA in Friedreich's ataxia. ^

Use of Echogenic Immunoliposomes for Delivery of both Drug and Stem Cells for Inhibition of Atheroma Progression

Use of Echogenic Immunoliposomes for Delivery of both Drug and Stem Cells for Inhibition of Atheroma Progression By Ali K. Naji B.S. Advisor: Dr. Melvin E. Klegerman PhD Background and significance: Echogenic liposomes can be used as drug and cell delivery vehicles that reduce atheroma progression. Vascular endothelial growth factor (VEGF) is a signal protein that induces vasculogenesis and angiogenesis. VEGF functionally induces migration and proliferation of endothelial cells and increases intracellular vascular permeability. VEGF activates angiogenic transduction factors through VEGF tyrosine kinase domains in high-affinity receptors of endothelial cells. Bevacizumab is a humanized monoclonal antibody specific for VEGF-A which was developed as an anti-tumor agent. Often, anti-VEGF agents result in regression of existing microvessels, inhibiting tumor growth and possibly causing tumor shrinkage with time. During atheroma progression neovasculation in the arterial adventitia is mediated by VEGF. Therefore, bevacizumab may be effective in inhibiting atheroma progression. Stem cells show an ability to inhibit atheroma progression. We have previously demonstrated that monocyte derived CD-34+ stem cells that can be delivered to atheroma by bifunctional-ELIP ( BF-ELIP) targeted to Intercellular Adhesion Molecule-1 (ICAM-1) and CD-34. Adhesion molecules such as ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) are expressed by endothelial cells under inflammatory conditions. Ultrasound enhanced liposomal targeting provides a method for stem cell delivery into atheroma and encapsulated drug release. This project is designed to examine the ability of echogenic liposomes to deliver bevacizumab and stem cells to inhibit atheroma progression and neovasculation with and without ultrasound in vitro and optimize the ultrasound parameters for delivery of bevacizumab and stem cells to atheroma. V Hypotheses: Previous studies showed that endothelial cell VEGF expression may relate to atherosclerosis progression and atheroma formation in the cardiovascular system. Bevacizumab-loaded ELIP will inhibit endothelial cell VEGF expression in vitro. Bevacizumab activity can be enhanced by pulsed Doppler ultrasound treatment of BEV-ELIP. I will also test the hypothesis that the transwell culture system can serve as an in vitro model for study of US-enhanced targeted delivery of stem cells to atheroma. Monocyte preparations will serve as a source of CD34+ stem cells. Specific Aims: Induce VEGF expression using PKA and PKC activation factors to endothelial cell cultures and use western blot and ELISA techniques to detect the expressed VEGF.  Characterize the relationship between endothelial cell proliferation and VEGF expression to develop a specific EC culture based system to demonstrate BEV-ELIP activity as an anti-VEGF agent. Design a cell-based assay for in vitro assessment of ultrasound-enhanced bevacizumab release from echogenic liposomes.  Demonstrate ultrasound delivery enhancement of stem cells by applying different types of liposomes on transwell EC culture using fluorescently labeled monocytes and detect the effect on migration and attachment rate of these echogenic liposomes with and without ultrasound in vitro.

Ideología étnica durante el período amarniano : ¿límite o contacto con la otredad?

Durante el Reino Nuevo se produjo una ampliación de las fronteras y una fuerte centralización y estabilidad interna; es insoslayable resaltar al respecto el control por parte de la monarquía de los territorios conquistados y el mantenimiento de su posición en el Levante mediterráneo frente a la presión de mitanios e hititas. Particularmente, nos centraremos en el período amarniano, que tradicionalmente ha tenido una visión peyorativa basada en el supuesto de la 'incapacidad' real de intervención en asuntos políticos, como así también las grandes 'dificultades' en mantener el efectivo dominio del territorio.Sin embargo, diversos fueron los mecanismos de legitimación desarrollados por el poder regio en este contexto. Centrándonos en la postura fenomenológico-hermenéutica del historiador de las religiones rumano Mircea Eliade (1957) y basándonos también en los aportes de Fredrik Barth (1976), Jan Assmann (2005) y Pascal Vernus (2011), será nuestro objetivo analizar las implicaciones simbólico-religiosas de la concepción egipcia de los pueblos extranjeros y de las interacciones políticas con ellos bajo el período de gobierno de Akhenatón.

The computer paradigm in vocational guidance

The technological advances in last decades have transformed the external resources of Vocational Counseling, Occupational Information and assessment of clients. Most computer systems follow a behaviorist-cognitive approach. However, the use of vocational counseling software is not exclusive to one conceptual approach. Computers are introduced in education from primary school; counselors and other educators are expected to use those systems. The attitude of counselors ranges from enthusiastic acceptance to complete refusal. Many counselors fear that computers will replace them. An underlying theory holds that counseling is based on the counselor-client interaction. A computer- client interaction cannot be considered vocational counseling. Counseling has five basic aims: prevention, assistance, education and development, service of diverse groups and research. The most relevant trends in computer-based counseling are: tests and questionnaires based on computers, adaptive development, computarized information, vocational counseling systems and research. Basic aims and the potential role of computers in achieving them are discussed. Present vocational counselors can use the technology of computers to link the past of our profession to its promising future. In view of these premises we have developed two computer systems that assist the vocational counseling process: "Professional Interests Questionnaire, Computer Version", and "Computer-based System of Vocational Counseling".

Ideología étnica durante el período amarniano : ¿límite o contacto con la otredad?

Durante el Reino Nuevo se produjo una ampliación de las fronteras y una fuerte centralización y estabilidad interna; es insoslayable resaltar al respecto el control por parte de la monarquía de los territorios conquistados y el mantenimiento de su posición en el Levante mediterráneo frente a la presión de mitanios e hititas. Particularmente, nos centraremos en el período amarniano, que tradicionalmente ha tenido una visión peyorativa basada en el supuesto de la 'incapacidad' real de intervención en asuntos políticos, como así también las grandes 'dificultades' en mantener el efectivo dominio del territorio.Sin embargo, diversos fueron los mecanismos de legitimación desarrollados por el poder regio en este contexto. Centrándonos en la postura fenomenológico-hermenéutica del historiador de las religiones rumano Mircea Eliade (1957) y basándonos también en los aportes de Fredrik Barth (1976), Jan Assmann (2005) y Pascal Vernus (2011), será nuestro objetivo analizar las implicaciones simbólico-religiosas de la concepción egipcia de los pueblos extranjeros y de las interacciones políticas con ellos bajo el período de gobierno de Akhenatón.

The computer paradigm in vocational guidance

The technological advances in last decades have transformed the external resources of Vocational Counseling, Occupational Information and assessment of clients. Most computer systems follow a behaviorist-cognitive approach. However, the use of vocational counseling software is not exclusive to one conceptual approach. Computers are introduced in education from primary school; counselors and other educators are expected to use those systems. The attitude of counselors ranges from enthusiastic acceptance to complete refusal. Many counselors fear that computers will replace them. An underlying theory holds that counseling is based on the counselor-client interaction. A computer- client interaction cannot be considered vocational counseling. Counseling has five basic aims: prevention, assistance, education and development, service of diverse groups and research. The most relevant trends in computer-based counseling are: tests and questionnaires based on computers, adaptive development, computarized information, vocational counseling systems and research. Basic aims and the potential role of computers in achieving them are discussed. Present vocational counselors can use the technology of computers to link the past of our profession to its promising future. In view of these premises we have developed two computer systems that assist the vocational counseling process: "Professional Interests Questionnaire, Computer Version", and "Computer-based System of Vocational Counseling".

Ideología étnica durante el período amarniano : ¿límite o contacto con la otredad?

Durante el Reino Nuevo se produjo una ampliación de las fronteras y una fuerte centralización y estabilidad interna; es insoslayable resaltar al respecto el control por parte de la monarquía de los territorios conquistados y el mantenimiento de su posición en el Levante mediterráneo frente a la presión de mitanios e hititas. Particularmente, nos centraremos en el período amarniano, que tradicionalmente ha tenido una visión peyorativa basada en el supuesto de la 'incapacidad' real de intervención en asuntos políticos, como así también las grandes 'dificultades' en mantener el efectivo dominio del territorio.Sin embargo, diversos fueron los mecanismos de legitimación desarrollados por el poder regio en este contexto. Centrándonos en la postura fenomenológico-hermenéutica del historiador de las religiones rumano Mircea Eliade (1957) y basándonos también en los aportes de Fredrik Barth (1976), Jan Assmann (2005) y Pascal Vernus (2011), será nuestro objetivo analizar las implicaciones simbólico-religiosas de la concepción egipcia de los pueblos extranjeros y de las interacciones políticas con ellos bajo el período de gobierno de Akhenatón.

The computer paradigm in vocational guidance

The technological advances in last decades have transformed the external resources of Vocational Counseling, Occupational Information and assessment of clients. Most computer systems follow a behaviorist-cognitive approach. However, the use of vocational counseling software is not exclusive to one conceptual approach. Computers are introduced in education from primary school; counselors and other educators are expected to use those systems. The attitude of counselors ranges from enthusiastic acceptance to complete refusal. Many counselors fear that computers will replace them. An underlying theory holds that counseling is based on the counselor-client interaction. A computer- client interaction cannot be considered vocational counseling. Counseling has five basic aims: prevention, assistance, education and development, service of diverse groups and research. The most relevant trends in computer-based counseling are: tests and questionnaires based on computers, adaptive development, computarized information, vocational counseling systems and research. Basic aims and the potential role of computers in achieving them are discussed. Present vocational counselors can use the technology of computers to link the past of our profession to its promising future. In view of these premises we have developed two computer systems that assist the vocational counseling process: "Professional Interests Questionnaire, Computer Version", and "Computer-based System of Vocational Counseling".

How Blended Learning Reduce Underachievement in Higher Education: An Experience in Teaching Computer Sciences.

This paper presents a blended learning approach and a study evaluating instruction in a software engineering-related course unit as part of an undergraduate engineering degree program in computing. In the past, the course unit had a lecture-based format. In view of student underachievement and the high course unit dropout rate, a distance-learning system was deployed, where students were allowed to choose between a distance-learning approach driven by a moderate constructivist instructional model or a blended-learning approach. The results of this experience are presented, with the aim of showing the effectiveness of the teaching/learning system deployed compared to the lecture-based system previously in place. The grades earned by students under the new system, following the distance-learning and blended-learning courses, are compared statistically to the grades attained in earlier years in the traditional face-to-face classroom (lecture-based) learning.

Automatic Categorization for Improving Spanish into Spanish Sign Language Machine Translation

This paper describes a preprocessing module for improving the performance of a Spanish into Spanish Sign Language (Lengua de Signos Espanola: LSE) translation system when dealing with sparse training data. This preprocessing module replaces Spanish words with associated tags. The list with Spanish words (vocabulary) and associated tags used by this module is computed automatically considering those signs that show the highest probability of being the translation of every Spanish word. This automatic tag extraction has been compared to a manual strategy achieving almost the same improvement. In this analysis, several alternatives for dealing with non-relevant words have been studied. Non-relevant words are Spanish words not assigned to any sign. The preprocessing module has been incorporated into two well-known statistical translation architectures: a phrase-based system and a Statistical Finite State Transducer (SFST). This system has been developed for a specific application domain: the renewal of Identity Documents and Driver's License. In order to evaluate the system a parallel corpus made up of 4080 Spanish sentences and their LSE translation has been used. The evaluation results revealed a significant performance improvement when including this preprocessing module. In the phrase-based system, the proposed module has given rise to an increase in BLEU (Bilingual Evaluation Understudy) from 73.8% to 81.0% and an increase in the human evaluation score from 0.64 to 0.83. In the case of SFST, BLEU increased from 70.6% to 78.4% and the human evaluation score from 0.65 to 0.82.