Suchergebnisse

Abstract

Aims
Excessive consumption of alcoholic beverages is associated with cardiac remodeling and cardiomyopathy. We examined the possible association of alcohol use, common Asian genetic variants in genes involved in alcohol metabolism, and cardiac structures/functions alterations.


Methods
A prospective, community-dwelling survey among individuals with available complete echocardiography examined the associations of alcohol use, cardiac structure/functions, and three common alcohol metabolizing genetic variants, including aldehyde dehydrogenase 2 (ALDH2), alcohol dehydrogenase 1B (ADH1B) and cytochrome P450 (CYP) isoform 2E1 (CYP2E1).


Results
Among 1577 participants (mean age: 53 ± 9, 59.7% female), we observed that in subjects with more frequent weekly ethanol intake showed greater left ventricle (LV) mass, more impaired diastolic functions, and reduced global longitudinal strain (GLS), systolic (SRs) and early diastolic strain rates (SRe) (P<0.05). After propensity matching for clinical confounders (n = 330:30 for frequent users and non-users), frequent alcohol use and subjects carrying ALDH2 (A/G or A/A), ADH1B (A/A) or CYP2E1(T/C or T/T) polymorphisms were all associated with worse GLSRs and GLSRe, with combined alcohol use and any given genetic variant aggravated these associations (all P < 0.05). Finally, we observed Gene–Gene synergistic effects on LV functional decline in frequent alcohol users by using linear mixed effect model (all interaction P < 0.05).


Conclusions
Among East Asians, even moderate alcohol consumption can confer subclinical adverse effects on cardiac systolic functions, which was most pronounced in subjects carrying common variants in alcohol metabolizing genes. These findings challenge the notion of beneficial influences of less heavy ethanol consumption on the heart, especially among East Asians.


Short summary
This study evaluated the association of level of alcohol consumption and genetic variants in genes involved in alcohol metabolism with changes in cardiac function in East Asians. Even moderate alcohol use conferred subclinical adverse effects on cardiac systolic functions, which were most pronounced in subjects carrying common alcohol metabolizing genes.

Background : Supported by the International Society for Translational Medicine (ISTM), Wenzhou Medical College and the First Affiliated Hospital of Wenzhou Medical College, the International Conference on Translational Medicine (ICTM) was held on October 22–23, 2011 in Wenzhou, China. Nearly 800 registrants attended the meeting, primarily representing institutes and hospitals in Europe, The United States of America, And Asia, and China. The meeting was chaired and organized by Dr. Xiangdong Wang, Xiaoming Chen, Richard Coico, Jeffrey M. Drazen, Richard Horton, Francesco M. Marincola, Laurentiu M. Popescu, Jia Qu and Aamir Shahzad. Findings : The meeting focused on the communication of the need to foster translational medicine (TM) by building and broadening bridges between basic research and clinical studies at the international level. The meeting included distinguished TM experts from academia, the pharmaceutical and diagnostics industries, government agencies, regulators, and clinicians and provided the opportunity to identify shared interests and efforts for collaborative approaches utilizing cutting edge technologies, innovative approaches and novel therapeutic interventions. The meeting defined the concept of TM in its two-way operational scheme and emphasized the need for bed to bench efforts based directly on clinical observation. Conclusions : It was the meeting participants' realization that the shared main goals of TM include breaking the separation between clinic practice and basic research, establishing positive feedback by understanding the basis of expected and unexpected clinical outcomes and accelerating basic research relevant to human suffering. The primary objectives of the meeting were two-fold: to accelerate the two-way translation by informing the participants representing the different disciplines about the state of art activities around TM approaches; and to identify areas that need to be supported by redirecting limited resources as well as identifying new sources of funding. This report summarizes key concepts presented during the meeting representing the state-of-art translational research and salient aspects of the ensuing discussions.

Currently, there are no harmonized guidelines which govern skin banking in the Asia Pacific region. Therefore, skin banks are either unregulated or rely on their nation's legislation or international accreditation to uphold their quality standards. A new set of skin banking guidelines was developed through a comprehensive review and collation of best international practices for the Asia Pacific Burn Association (APBA) members, from donor screening and testing, to skin recovery, processing, storage and distribution, and quality assurance. National regulatory requirements reviewed include the European directives, Australia's Therapeutic Goods Administration and Singapore's tissue banking standards. Further technical and quality management recommendations are referenced from the American Association of Tissue Banks (AATB), the United States Food and Drug Administration standards and guidance documents, various relevant European guides, Japanese Society of Tissue Transplantation guidelines and the Asia Pacific Association of Surgical Tissue Banking. Adapted mainly from the AATB standards, the new Asia Pacific Burn Association Guidelines for Skin Banking in Therapeutic Applications offer a comprehensive manual, addressing: governance and contracts; staff responsibilities; quality management; facilities, equipment and supplies management; donor consent and testing; and recommendations of good practices pertaining to skin recovery, processing, storage and distribution. Besides complementing current generic regulations, they provide technical specifications of major aspects unaddressed in most legislations. This inaugural set of new regional skin banking guidelines would be a start for regional members of the APBA to adopt, and will hopefully culminate in a set of standards so that, in the long run, skin allografts from this region can be of similar quality, which can simplify import process and facilitate the exchange of allografts between members.

The article presents the latest status of the Maidanak 1 m telescope, instruments and the related facilities of the Observatory as well as the science projects. The renovation of the 1 m telescope of Carl Zeiss (Germany) at the Maidanak observatory of the Ulug Bek Astronomical Institute (UBAI) AS of Uzbekistan has been made. All systems of the telescope were completely modernized based on modern standards, the main results of modernization are also described. All modernization works, as well as scientific research on this project are carried out in close cooperation of UBAI with the National Astronomical Observatories of the Academy of Sciences of the PRC in framework of the Agreement on cooperation between these organizations. The FOV has been enlarged and new CCD camera is mounted. The related facilities, like the observing circumstance monitoring system and the photovoltaic station, are also built for the observing support. The telescope and new camera will be tested and used for the science projects of the 1 m telescope. According to the collaboration agreement, a large-scale scientific project on a full survey of the northern sky in special photometric system - Stellar Abundance and Galactic Evolution (SAGE) survey will be carried out with the upgraded 1 m telescope. The main goal of the project is to measure the stellar atmospheric parameters for more than 500 million FGK stars. As other projects, the time domain science, like GRB, SNe searching, variable stars, also will be performed.

We demonstrate four-and two-terminal perovskite-perovskite tandem solar cells with ideally matched band gaps. We develop an infrared-absorbing 1.2-electron volt band-gap perovskite, FA(0.75)Cs(0.25)Sn(0.5)Pb(0.5)I(3), that can deliver 14.8% efficiency. By combining this material with a wider-band gap FA(0.83)Cs(0.17)Pb(I0.5Br0.5)(3) material, we achieve monolithic two-terminal tandem efficiencies of 17.0% with > 1.65-volt open-circuit voltage. We also make mechanically stacked four-terminal tandem cells and obtain 20.3% efficiency. Notably, we find that our infrared-absorbing perovskite cells exhibit excellent thermal and atmospheric stability, not previously achieved for Sn-based perovskites. This device architecture and materials set will enable "all-perovskite" thin-film solar cells to reach the highest efficiencies in the long term at the lowest costs. ; We thank M. T. Horantner for performing the Shockley-Queisser calculation. The research leading to these results has received funding from the Graphene Flagship (Horizon 2020 grant no. 696656 - GrapheneCore1), the Leverhulme Trust (grant RL-2012-001), the UK Engineering and Physical Sciences Research Council (grant EP/J009857/1 and EP/M020517/1), and the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement nos. 239578 (ALIGN) and 604032 (MESO). T.L. is funded by a Marie Sklodowska Curie International Fellowship under grant agreement H2O2IF-GA-2015-659225. A.B. is financed by IMEC (Leuven) in the framework of a joint Ph.D. program with Hasselt University. B.C. is a postdoctoral research fellow of the Research Fund Flanders (FWO). We also acknowledge the U.S. Office of Naval Research for support. We acknowledge the use of the University of Oxford Advanced Research Computing (ARC) facility (http://dx.doi.org/10.5281/zenodo.22558) and the ARCHER UK National Super-computing Service under the "AMSEC" Leadership project. We thank the Global Climate and Energy Project (GCEP) at Stanford University. All data pertaining to the conclusions of this work can be found in the main paper and the supplementary materials.

This project explores participatory planning and community design methodologies (i.e. pattern language design, placemaking, community planning charrettes, planning-in-situ, open planning and peer to peer urbanism) to revitalize a service alleyway in downtown Montreal. The objective of this project is to democratize planning and urban design practices and to engage ordinary citizens in the planning of their own spaces. After a series of visioning workshops, brainstorming sessions and a community planning charrette, this project incorporates inputs from stakeholders, students and ordinary citizens into a collaborative urban design project. The project proposes interventions such as a woonerf, a planning committee, a cubic/fractal scaffolding structure, art murals and wall projections (among others). With the objective of encouraging future adaptations and transformations, this project is published under a Creative Commons license. Adopt and adapt these ideas (but cite and acknowledge accordingly).

The field of digital signal processing grew out of the flexibility afforded by the use of digital computers in implementing signal processing algorithms and systems. It has since broadened into the use of a variety of both digital and analog technologies, spanning a broad range of applications, bandwidths, and realizations. The Digital Signal Processing group carries out research on algorithms for signal processing and their applications. Current application areas of interest include signal enhancement and active noise cancellation; speech, audio and underwater acoustic signal processing; advanced beamforming for radar and sonar systems; and signal processing and coding for wireless and broadband multiuser communication networks. In some of our recent work, we have developed new methods for signal enhancement and noise cancellation with single or multisensor measurements. We have also been developing new methods for representing and analyzing fractal signals. This class of signals arises in a wide variety of physical environments and also has potential in problems involving signal design. We are also exploring potential uses of nonlinear dynamics and chaos theory of signal design and analysis. Another emphasis is on structuring algorithms for approximate processing and successive refinement. In other research, we are investigating applications of signal and array processing to ocean and structural acoustics and geophysics. These problems require the combination of digital signal processing tools with a knowledge of wave propagation to develop systems for short time spectral analysis, wavenumber spectrum estimation, source localization, and matched field processing. We emphasize the use of real-world data from laboratory and field experiments such as the Heard Island Experiment for Acoustic Monitoring of Global Warming and several Arctic acoustic experiments conducted on the polar ice cap. A major application focus of the group involves signal processing and coding for wireless multiuser systems and broadband communication networks. Specific interests include commercial and military mobile radio networks, wireless local area networks and personal communication systems, digital audio and television broadcast systems, and multimedia networks. Along with a number of other directions, we are currently exploring new code-division multiple- access (CDMA) strategies, new techniques for exploiting antenna arrays in wireless systems, and new methods for modeling and management of traffic in high-speed packet-switched networks. Much of our work involves close collaboration with the Woods Hole Oceanographic Institution, MIT Lincoln Laboratory, and a number of high technology companies in the Boston area. ; Sanders, a Lockheed-Martin Corporation ; US Army Research Laboratory ; US Navy - ONR ; National Science Foundation ; National Defense Science and Engineering Fellowship ; US Air Force Office of Scientific Research ; National Science Foundation Graduate Research Fellowship ; AT&T Bell Laboratories Graduate Research Fellowship ; Contract BZ4962 (Sanders) ; Contract DAAL01-96-2-0001 (USARL) Contract DAAL01-96-2-0002 ; Grant N00014-93-1-0686 (ONR) Grant N00014-96-1-0930 Grant N00014-95-1-0362 ; Grant MIP 95-02885 (NSF) ; Grant F49620-96-1-0072 (USAF-OSR)

Background: In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013–2025. Methods: We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Results: Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. Conclusion: These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed ; publishedVersion

BackgroundIn 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025.MethodsWe used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts.ResultsNine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour.ConclusionThese findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.

In 2013, an estimated 2.8 million newborns died and 2.7 million were stillborn. A much greater number suffer from long term impairment associated with preterm birth, intrauterine growth restriction, congenital anomalies, and perinatal or infectious causes. With the approaching deadline for the achievement of the Millennium Development Goals (MDGs) in 2015, there was a need to set the new research priorities on newborns and stillbirth with a focus not only on survival but also on health, growth and development. We therefore carried out a systematic exercise to set newborn health research priorities for 2013-2025. We used adapted Child Health and Nutrition Research Initiative (CHNRI) methods for this prioritization exercise. We identified and approached the 200 most productive researchers and 400 program experts, and 132 of them submitted research questions online. These were collated into a set of 205 research questions, sent for scoring to the 600 identified experts, and were assessed and scored by 91 experts. Nine out of top ten identified priorities were in the domain of research on improving delivery of known interventions, with simplified neonatal resuscitation program and clinical algorithms and improved skills of community health workers leading the list. The top 10 priorities in the domain of development were led by ideas on improved Kangaroo Mother Care at community level, how to improve the accuracy of diagnosis by community health workers, and perinatal audits. The 10 leading priorities for discovery research focused on stable surfactant with novel modes of administration for preterm babies, ability to diagnose fetal distress and novel tocolytic agents to delay or stop preterm labour. These findings will assist both donors and researchers in supporting and conducting research to close the knowledge gaps for reducing neonatal mortality, morbidity and long term impairment. WHO, SNL and other partners will work to generate interest among key national stakeholders, governments, NGOs, and research institutes in these priorities, while encouraging research funders to support them. We will track research funding, relevant requests for proposals and trial registers to monitor if the priorities identified by this exercise are being addressed.

WOS: 000471758500010 ; PubMed ID: 31209238 ; The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. ; AstraZenecaAstraZeneca; European Union Horizon 2020 research [668858 PrECISE]; Joint Research Center for Computational Biomedicine (Bayer AG); National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences; Wellcome TrustWellcome Trust [102696, 206194] ; We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194).

The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca's large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells. ; AstraZeneca ; European Union Horizon 2020 research [668858 PrECISE] ; Joint Research Center for Computational Biomedicine (Bayer AG) ; National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences ; Wellcome Trust [102696, 206194] ; We thank the Genomics of Drug Sensitivity in Cancer and COSMIC teams at the Wellcome Trust Sanger Institute for help with the preparation of the molecular data, Denes Turei for help with Omnipath, and Katjusa Koler for help with matching drug names across combination screens. We thank AstraZeneca for funding and provision of data to the DREAM Consortium to run the challenge, and funding from the European Union Horizon 2020 research (under grant agreement No 668858 PrECISE to J.S.R.), the Joint Research Center for Computational Biomedicine (which is partially funded by Bayer AG) to J.S.R., National Institute for Health Research (NIHR) Sheffield Biomedical Research Center, Premium Postdoctoral Fellowship Program of the Hungarian Academy of Sciences. M.G lab is supported by Wellcome Trust (102696 and 206194).