AIM:To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus(T2DM) patients who have inadequate control with m...AIM:To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus(T2DM) patients who have inadequate control with metformin monotherapy.METHODS:Eligible patients were randomized to receive vildagliptin 100 mg qd or metformin(500 mg qd for 2 wk and then 500 mg bid) added to open label me tformin 500 mg bid for the 24 wk.The primary endpoi nt was baseline to endpoint hemoglobin A1c(HbA1c) change.RESULTS:The adjusted mean change from baseline in HbA1c at the 24th wk was-0.51% in the vildagliptin/metformin group(mean baseline HbA1c:7.4%) and-0.37% in the metformin monothera py group(mean baseline HbA1c:7.3%).The mean diffe rence was-0.14% with 95% Confidence Interval(-0.24%,-0.05%).As non-inf e riority(margin of 0.4%) was achieved,a test for superiority was performed.This test showed statistically significant superiority of the combination over monotherapy group(P = 0.002).Gastrointestinal(GI) adverse events were signif icantly more frequent in the metformin group than the combin ation group(21.0% vs 15.4%,P = 0.032).CONCLUSION:In patients with T2DM inadequately controlled with metformin up to 1000 mg daily,the addition of vildagliptin 100 mg daily achieved larger HbA1c reduction with fewer GI events than with increa sing the metformin dose.展开更多
Economic and environmental load dispatch aims to determine the amount of electricity generated from power plants to meet load demand while minimizing fossil fuel costs and air pollution emissions subject to operationa...Economic and environmental load dispatch aims to determine the amount of electricity generated from power plants to meet load demand while minimizing fossil fuel costs and air pollution emissions subject to operational and licensing requirements.These two scheduling problems are commonly formulated with non-smooth cost functions respectively considering various effects and constraints,such as the valve point effect,power balance and ramprate limits.The expected increase in plug-in electric vehicles is likely to see a significant impact on the power system due to high charging power consumption and significant uncertainty in charging times.In this paper,multiple electric vehicle charging profiles are comparatively integrated into a 24-hour load demand in an economic and environment dispatch model.Self-learning teaching-learning based optimization(TLBO)is employed to solve the non-convex non-linear dispatch problems.Numerical results onwell-known benchmark functions,as well as test systems with different scales of generation units show the significance of the new scheduling method.展开更多
Electric vehicles(EV)are proposed as a measure to reduce greenhouse gas emissions in transport and support increased wind power penetration across modern power systems.Optimal benefits can only be achieved,if EVs are ...Electric vehicles(EV)are proposed as a measure to reduce greenhouse gas emissions in transport and support increased wind power penetration across modern power systems.Optimal benefits can only be achieved,if EVs are deployed effectively,so that the exhaust emissions are not substituted by additional emissions in the electricity sector,which can be implemented using Smart Grid controls.This research presents the results of an EV roll-out in the all island grid(AIG)in Ireland using the long term generation expansion planning model called the Wien Automatic System Planning IV(WASP-IV)tool to measure carbon dioxide emissions and changes in total energy.The model incorporates all generators and operational requirements while meeting environmental emissions,fuel availability and generator operational and maintenance constraints to optimize economic dispatch and unit commitment power dispatch.In the study three distinct scenarios are investigated base case,peak and off-peak charging to simulate the impacts of EV’s in the AIG up to 2025.展开更多
Coronary artery disease(CAD) is a leading cause of death and disability worldwide. Cardiovascular magnetic resonance(CMR) is established in clinical practice guidelines with a growing evidence base supporting its use ...Coronary artery disease(CAD) is a leading cause of death and disability worldwide. Cardiovascular magnetic resonance(CMR) is established in clinical practice guidelines with a growing evidence base supporting its use to aid the diagnosis and management of patients with suspected or established CAD. CMR is a multi-parametric imaging modality that yields high spatial resolution images that can be acquired in any plane for the assessment of global and regional cardiac function, myocardial perfusion and viability, tissue characterisation and coronary artery anatomy, all within a single study protocol and without exposure to ionising radiation. Advances in technology and acquisition techniques continue to progress the utility of CMR across a wide spectrum of cardiovascular disease, and the publication of large scale clinical trials continues to strengthen the role of CMR in daily cardiology practice. This article aims to review current practice and explore the future directions of multi-parametric CMR imaging in the investigation of stable CAD.展开更多
Rocky Mountain spotted fever(RMSF)is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century.Along the US south-western border and across norther...Rocky Mountain spotted fever(RMSF)is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century.Along the US south-western border and across northern Mexico,the brown dog tick,Rhipicephalus sanguineus,is responsible for spreading the disease between dogs and humans.The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease.Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria,transmission dynamics between dogs and ticks are critical for understanding the epidemic.In this paper,we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America.We discovered that there is an extended lag—as much as two years—between introduction of the pathogen to a naïve population and epidemic-level transmission,suggesting that infected ticks could disseminate extensively before disease is detected.A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns.This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.展开更多
AIM: To assess the efficacy and safety of vildagliptin 50 mg bid as add-on therapy to insulin in Asian patients with type 2 diabetes mellitus(T2DM).METHODS: This was a post hoc analysis of a subgroup of Asian patients...AIM: To assess the efficacy and safety of vildagliptin 50 mg bid as add-on therapy to insulin in Asian patients with type 2 diabetes mellitus(T2DM).METHODS: This was a post hoc analysis of a subgroup of Asian patients from a multicenter,randomized,double-blind,placebo-controlled,parallel-group study in T2DM patients inadequately controlled by stable insulin therapy,with or without metformin.A total of 173 patients were randomized 1:1 to receive treatment with vildagliptin 50 mg bid(n = 87) or placebo(n = 86) for 24 wk.Changes in HbA1c and fasting plasma glucose(FPG),from baseline to study endpoint,were analyzed using an analysis of covariance model.Change from baseline to endpoint in body weight was summarized by treatment.Safety and tolerability of vildagliptin was also evaluated.RESULTS: After 24 wk,the difference in adjusted mean change in HbA1c between vildagliptin and placebo was 0.82%(8.96 mmol/mol;P < 0.001) in Asian subgroup,0.85%(9.29 mmol/mol;P < 0.001) in patients also receiving metformin,and 0.73%(7.98 mmol/mol;P < 0.001) in patients without metformin,all in favor of vildagliptin.There was no significant difference in the change in FPG between treatments.Weight was stable in both treatment groups(+0.3 kg and-0.2 kg,for vildagliptin and placebo,respectively).Overall,vildagliptin was safe and well tolerated with similarly low incidences of hypoglycemia(8.0% vs 8.1%) and no severe hypoglycemic events were experienced in either group.CONCLUSION: In Asian patients inadequately controlled with insulin(with or without concomitant metformin),insulin-vildagliptin combination treatment significantly reduced HbA1c compared with placebo,without an increase in risk of hypoglycemia or weight gain.展开更多
Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control o...Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.展开更多
There has been a lot written lately on the topic of sustainability in the industry,and it's not going away.Efforts are underway in many countries to reduce theworld's carbonfootprint.Of all the global sources ...There has been a lot written lately on the topic of sustainability in the industry,and it's not going away.Efforts are underway in many countries to reduce theworld's carbonfootprint.Of all the global sources of Carbon Dioxide(CO2),the transportation sector emits 13%of the overall greenhouse gases.Of this,10%comes from road vehicles and 1%from rail and shipping.展开更多
Electric vehicles (EVs) offer great potential to move from fossil fuel dependency in transport once some of the technical barriers related to battery reliability and grid integration are resolved. The European Union h...Electric vehicles (EVs) offer great potential to move from fossil fuel dependency in transport once some of the technical barriers related to battery reliability and grid integration are resolved. The European Union has set a target to achieve a 10% reduction in greenhouse gas emissions by 2020 relative to 2005 levels. This target is binding in all the European Union member states. If electric vehicle issues are overcome then the challenge is to use as much renewable energy as possible to achieve this target. In this paper, the impacts of electric vehicle charged in the all-Ireland single wholesale electricity market after the 2020 deadline passes is investigated using a power system dispatch model. For the purpose of this work it is assumed that a 10% electric vehicle target in the Republic of Ireland is not achieved, but instead 8% is reached by 2025 considering the slow market uptake of electric vehicles. Our experimental study shows that the increasing penetration of EVs could contribute to approach the target of the EU and Ireland government on emissions reduction, regardless of different charging scenarios. Furthermore, among various charging scenarios, the off-peak charging is the best approach, contributing 2.07% to the target of 10% reduction of Greenhouse gas emissions by 2025.展开更多
We consider the response of a test subject upon a skin area being heated with an electromagnetic wave or a contact surface. When the specifications of the electromagnetic beam are fixed, the stimulus is solely describ...We consider the response of a test subject upon a skin area being heated with an electromagnetic wave or a contact surface. When the specifications of the electromagnetic beam are fixed, the stimulus is solely described by the heating duration. The binary response of a subject, escape or no escape, is determined by the stimulus and a subjective threshold that varies among test realizations. We study four methods for inferring the median subjective threshold in psychophysical experiments: 1) sample median, 2) maximum likelihood estimation (MLE) with 2 variables, 3) MLE with 1 variable, and 4) adaptive Bayesian method. While methods 1 - 3 require samples of time to escape measured in the method of limits, method 4 utilizes binary outcomes observed in the method of constant stimuli. We find that a) the adaptive Bayesian method converges and is as efficient as the sample median even when the assumed model distribution is incorrect;b) this robust convergence is lost if we infer the mean instead of the median;c) for the optimal performance in an uncertain situation, it is best to use a wide model distribution;d) the predicted error from the posterior standard deviation is unreliable, dominated by the assumed model distribution.展开更多
Minerals are critical in maintaining health and physiological function in wildlife. Geographic variation in soil and forage mineral concentration may predispose wildlife to mineral imbalances, where a common symptom i...Minerals are critical in maintaining health and physiological function in wildlife. Geographic variation in soil and forage mineral concentration may predispose wildlife to mineral imbalances, where a common symptom is restricted somatic growth. We investigated if mineral imbalances could explain localized differences in morphology of white-tailed deer (Odocoileus virginianus) occurring in geographically proximate sites with similar management, climate, and habitat. We collected serum samples and morphological measurements from free-ranging white-tailed deer captured during 2011-2019 from coastal and inland rangeland sites in South Texas, USA. We measured mineral concentrations in serum from captured deer at each location. Asymptotic deer body mass and antler size averaged 8% - 20% smaller for deer at the coastal compared to the inland site. The proportion of deer with deficient levels of serum copper was greater at the coastal site (66% versus 14%). Our results suggest regional mineral deficiencies in deer may limit antler and body development. Wildlife managers should be aware of all aspects of wildlife nutrition and the importance of considering nutrients beyond energy and protein.展开更多
We document the first record of Borrelia americana in Canada. This Borrelia was detected in an avian coast tick, Ixodes auritulus (Acari: Ixodidae), collected from a Varied Thrush, Ixoreus naevius, along coastal Briti...We document the first record of Borrelia americana in Canada. This Borrelia was detected in an avian coast tick, Ixodes auritulus (Acari: Ixodidae), collected from a Varied Thrush, Ixoreus naevius, along coastal British Columbia. Using real-time PCR and DNA sequencing of the flagellin gene, we determined that the borrelial amplicon from the I. auritulus nymph was 99% homologous with B. americana type strain SCW-41. Because patients infected with B. americana can be seronegative for Lyme disease, medical professionals should be willing to pursue molecular analyses and consider treatment for patients with Lyme disease-like symptoms.展开更多
Uterine atony remains the major cause of postpartum hemorrhage, and of death from postpartum hemorrhage in the United States. While existing guidelines outlining a general approach to postpartum hemorrhage are useful,...Uterine atony remains the major cause of postpartum hemorrhage, and of death from postpartum hemorrhage in the United States. While existing guidelines outlining a general approach to postpartum hemorrhage are useful, recent data suggest that greater specificity may be necessary to significantly impact mortality. We present a highly specific and methodical approach to the management of uterine atony, which addresses what we believe to be the most common cause of preventable maternal hemorrhagic death in the US—lack of an intensive, focused approach to atony and perseverance with therapies that are not working. This protocol should result in cessation of hemorrhage by medical or surgical means within 1 hour of diagnosis. We then apply this protocol to a number of illustrative cases of maternal death due to atony. An approach involving the active management of uterine atony may assist clinicians in avoiding severe morbidity and mortality from uterine atony.展开更多
<strong>Background:</strong> Plain radiography usual method to detect degeneration in the subtalar and talonavicluar joints. MRI is a better way to fully characterise non-ossified structures, such as artic...<strong>Background:</strong> Plain radiography usual method to detect degeneration in the subtalar and talonavicluar joints. MRI is a better way to fully characterise non-ossified structures, such as articular cartilage, marrow tissue and synovial fluid and therefore detect changes of arthritis. The motivation behind this study was to develop a quantitative way to score arthritic changes to the subtalar and talonavicular joints using MRI. The developed system will then be used as a research tool and in the close assessment and monitoring of patients with hindfoot degenerative disease. <strong>Methods:</strong> The MRI scans of thirty consecutive subjects with foot and ankle pain were retrospectively evaluated. Images were interpreted independently by three musculoskeletal radiologists in order to determine intra-observer reliability as well as the inter-observer reliability of the score. Five features of osteoarthritis were scored in the Subtalar joint and the Talonavicular joint. These were cartilage morphology, subarticular marrow, subarticular cyst, marginal osteophytes and synovitis. <strong>Results:</strong> For the 30 MRI scans the mean score for the Subtalar joint ranged from 11.7 to 14.4 and for the Talonavicular joint ranged from 3.7 to 5.6. The inter-observer correlation for the Subtalar joint between the three readers ranged between 0.53 and 0.83 for the individual features but overall was excellent at 0.76. For the Talonavicular joint the total correlation was good at 0.67. The inter-observer ICC for the total score was 0.75 which showed excellent agreement between the three readers. The total intra-observer correlation was excellent. <strong>Conclusions:</strong> The current work has shown excellent reliability for the scoring system. It will be a useful tool to diagnose and monitor disease progression of the Subtalar and Talonavicluar joints.展开更多
We consider the psychophysical experiments in which the test subject’s binary reaction is determined by the prescribed exposure duration to a stimulus and a random variable subjective threshold. For example, when a s...We consider the psychophysical experiments in which the test subject’s binary reaction is determined by the prescribed exposure duration to a stimulus and a random variable subjective threshold. For example, when a subject is exposed to a millimeter wave beam for a prescribed duration, the occurrence of flight action is binary (yes or no). In experiments, in addition to the binary outcome, the actuation time of flight action is also recorded if it occurs;the delay from the initiation time to the actuation time of flight action is the human reaction time, which is not measurable. In this study, we model the random subjective threshold as a Weibull distribution and formulate an inference method for estimating the human reaction time, from data of prescribed exposure durations, binary outcomes and actuation times of flight action collected in a sequence of tests. Numerical simulations demonstrate that the inference of human reaction time based on the Weibull distribution converges to the correct value even when the underlying true model deviates from the inference model. This robustness of the inference method makes it applicable to real experimental data where the underlying true model is unknown.展开更多
We consider the problem of inducing withdrawal reflex on a test subject via exposure to a millimeter wave beam. In our physical model, there are 10 physical parameters affecting the occurrence of withdrawal reflex. Ou...We consider the problem of inducing withdrawal reflex on a test subject via exposure to a millimeter wave beam. In our physical model, there are 10 physical parameters affecting the occurrence of withdrawal reflex. Our goal is to pinpoint the roles of these physical parameters in inducing withdrawal reflex. We first carry out non-dimensionalization to reduce the model to a non-dimensional system of only 3 composite parameters: non-dimensional beam power density, non-dimensional beam radius, and non-dimensional exposure time. If the beam power is kept on and steady, withdrawal reflex occurs eventually;the shortest exposure time for inducing withdrawal reflex corresponds to the smallest energy consumption at the given power density and beam radius. In the 2D space of power density and beam radius, the overall minimum energy occurs at the corner of very large power density and very small beam radius, which also produces a very large value of maximum skin temperature and a long time to withdrawal reflex. To reduce the burn injury risk, we introduce a cap on the maximum skin temperature. At each given total beam power, we carry out optimizations with respect to the beam radius, constrained by the prescribed temperature cap. The energy consumption varies negatively with the prescribed temperature cap: a lower temperature cap can be accommodated only with a higher energy consumption via the venue of a larger beam radius. The energy consumption is relatively flat with respect to the total beam power and attains a minimum at a moderately large total beam power. The time to withdrawal reflex is approximately inversely proportional to the total beam power. Our analysis demonstrates that a moderately large total beam power is a good compromise to achieve both low energy consumption and short time to withdrawal reflex.展开更多
The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex proc...The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex process, driven by a lack of normal immune homeostatic functions and excessive production of proinflammatory cytokines, which leads to multi-organ failure. The Toll-like receptor(TLR) family, one of whose members was initially discovered in Drosophila, performs an important role in the recognition of microbial pathogens. These pattern recognition receptors(PRRs), upon sensing invading microorganisms, activate intracellular signal transduction pathways. NOD signaling is also involved in the recognition of bacteria and acts synergistically with the TLR family in initiating an efficient immune response for the eradication of invading microbial pathogens. TLRs and NOD1/NOD2 respond to different pathogenassociated molecular patterns(PAMPs). Modulation of both TLR and NOD signaling is an area of research that has prompted much excitement and debate as a therapeutic strategy in the management of sepsis. Molecules targeting TLR and NOD signaling pathways exist but regrettably thus far none have proven efficacy from clinical trials.展开更多
Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructu...Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructural changes within brain tissue are expected to precede this volumetric decline.The tissue microstructure can be assayed non-invasively using diffusion MRI,which also allows a tractographic analysis of brain connectivity.Methods:We here used ex vivo diffusion MRI(11.7 T)to measure microstructural changes in different brain regions of end-stage(14 weeks of age)wild type and R6/2 mice(male and female)modeling Huntington's disease.To probe the microstructure of different brain regions,reduce partial volume effects and measure connectivity between different regions,a 100μm isotropic voxel resolution was acquired.Results:Although fractional anisotropy did not reveal any difference between wild-type controls and R6/2 mice,mean,axial,and radial diffusivity were increased in female R6/2 mice and decreased in male R6/2 mice.Whole brain streamlines were only reduced in male R6/2 mice,but streamline density was increased.Region-to-region tractography indicated reductions in connectivity between the cortex,hippocampus,and thalamus with the striatum,as well as within the basal ganglia(striatum—globus pallidus—subthalamic nucleus—substantia nigra—thalamus).Conclusions:Biological sex and left/right hemisphere affected tractographic results,potentially reflecting different stages of disease progression.This proof-of-principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions.In a translation setting,these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models,as well as patients with Huntington's disease.展开更多
基金Supported by Novartis Pharmaceuticals Corporation, NC-T00396357
文摘AIM:To evaluate the efficacy and safety of the addition of vildagliptin to low-dose metformin and compare it to an uptitration of metformin in type 2 diabetes mellitus(T2DM) patients who have inadequate control with metformin monotherapy.METHODS:Eligible patients were randomized to receive vildagliptin 100 mg qd or metformin(500 mg qd for 2 wk and then 500 mg bid) added to open label me tformin 500 mg bid for the 24 wk.The primary endpoi nt was baseline to endpoint hemoglobin A1c(HbA1c) change.RESULTS:The adjusted mean change from baseline in HbA1c at the 24th wk was-0.51% in the vildagliptin/metformin group(mean baseline HbA1c:7.4%) and-0.37% in the metformin monothera py group(mean baseline HbA1c:7.3%).The mean diffe rence was-0.14% with 95% Confidence Interval(-0.24%,-0.05%).As non-inf e riority(margin of 0.4%) was achieved,a test for superiority was performed.This test showed statistically significant superiority of the combination over monotherapy group(P = 0.002).Gastrointestinal(GI) adverse events were signif icantly more frequent in the metformin group than the combin ation group(21.0% vs 15.4%,P = 0.032).CONCLUSION:In patients with T2DM inadequately controlled with metformin up to 1000 mg daily,the addition of vildagliptin 100 mg daily achieved larger HbA1c reduction with fewer GI events than with increa sing the metformin dose.
基金The authors would also like to thank UK EPSRC under grant EP/L001063/1 and China NSFC under grants 51361130153 and 61273040.
文摘Economic and environmental load dispatch aims to determine the amount of electricity generated from power plants to meet load demand while minimizing fossil fuel costs and air pollution emissions subject to operational and licensing requirements.These two scheduling problems are commonly formulated with non-smooth cost functions respectively considering various effects and constraints,such as the valve point effect,power balance and ramprate limits.The expected increase in plug-in electric vehicles is likely to see a significant impact on the power system due to high charging power consumption and significant uncertainty in charging times.In this paper,multiple electric vehicle charging profiles are comparatively integrated into a 24-hour load demand in an economic and environment dispatch model.Self-learning teaching-learning based optimization(TLBO)is employed to solve the non-convex non-linear dispatch problems.Numerical results onwell-known benchmark functions,as well as test systems with different scales of generation units show the significance of the new scheduling method.
基金Dr Aoife FOLEY would like to thank UK Engineering and Physical Sciences Research Council(EPSRC)under grant EP/L001063/1the National Natural Science Foundation of China under grants 51361130153 and 61273040 and the Shanghai Rising Star programme 12QA1401100 for financial supporting this research.Dr Aoife FOLEY and Dr Brian O´GALLACHO´IR would also like to thank the Irish Environmental Protection Agency(EPA)Climate Change Research Programme under grant CCRP-09-FS-7-2.Dr FOLEY also acknowledges Dr Jianhui WANG,Vladimir KORITAROV,Dr Aidun BOTTERUD,Guenter CONZELMANN at Argonne National Energy Laboratory,Illinois,USA.
文摘Electric vehicles(EV)are proposed as a measure to reduce greenhouse gas emissions in transport and support increased wind power penetration across modern power systems.Optimal benefits can only be achieved,if EVs are deployed effectively,so that the exhaust emissions are not substituted by additional emissions in the electricity sector,which can be implemented using Smart Grid controls.This research presents the results of an EV roll-out in the all island grid(AIG)in Ireland using the long term generation expansion planning model called the Wien Automatic System Planning IV(WASP-IV)tool to measure carbon dioxide emissions and changes in total energy.The model incorporates all generators and operational requirements while meeting environmental emissions,fuel availability and generator operational and maintenance constraints to optimize economic dispatch and unit commitment power dispatch.In the study three distinct scenarios are investigated base case,peak and off-peak charging to simulate the impacts of EV’s in the AIG up to 2025.
文摘Coronary artery disease(CAD) is a leading cause of death and disability worldwide. Cardiovascular magnetic resonance(CMR) is established in clinical practice guidelines with a growing evidence base supporting its use to aid the diagnosis and management of patients with suspected or established CAD. CMR is a multi-parametric imaging modality that yields high spatial resolution images that can be acquired in any plane for the assessment of global and regional cardiac function, myocardial perfusion and viability, tissue characterisation and coronary artery anatomy, all within a single study protocol and without exposure to ionising radiation. Advances in technology and acquisition techniques continue to progress the utility of CMR across a wide spectrum of cardiovascular disease, and the publication of large scale clinical trials continues to strengthen the role of CMR in daily cardiology practice. This article aims to review current practice and explore the future directions of multi-parametric CMR imaging in the investigation of stable CAD.
基金This project was funded by the Pacific Southwest Regional Center of Excellence for Vector-borne Diseases funded by the US Centers for Disease Control and Prevention(Cooperative Agreement 1U01CK000649).
文摘Rocky Mountain spotted fever(RMSF)is a fatal tick-borne zoonotic disease that has emerged as an epidemic in western North America since the turn of the 21st century.Along the US south-western border and across northern Mexico,the brown dog tick,Rhipicephalus sanguineus,is responsible for spreading the disease between dogs and humans.The widespread nature of the disease and the ongoing epidemics contrast with historically sporadic patterns of the disease.Because dogs are amplifying hosts for the Rickettsia rickettsii bacteria,transmission dynamics between dogs and ticks are critical for understanding the epidemic.In this paper,we developed a compartment metapopulation model and used it to explore the dynamics and drivers of RMSF in dogs and brown dog ticks in a theoretical region in western North America.We discovered that there is an extended lag—as much as two years—between introduction of the pathogen to a naïve population and epidemic-level transmission,suggesting that infected ticks could disseminate extensively before disease is detected.A single large city-size population of dogs was sufficient to maintain the disease over a decade and serve as a source for disease in surrounding smaller towns.This model is a novel tool that can be used to identify high risk areas and key intervention points for epidemic RMSF spread by brown dog ticks.
文摘AIM: To assess the efficacy and safety of vildagliptin 50 mg bid as add-on therapy to insulin in Asian patients with type 2 diabetes mellitus(T2DM).METHODS: This was a post hoc analysis of a subgroup of Asian patients from a multicenter,randomized,double-blind,placebo-controlled,parallel-group study in T2DM patients inadequately controlled by stable insulin therapy,with or without metformin.A total of 173 patients were randomized 1:1 to receive treatment with vildagliptin 50 mg bid(n = 87) or placebo(n = 86) for 24 wk.Changes in HbA1c and fasting plasma glucose(FPG),from baseline to study endpoint,were analyzed using an analysis of covariance model.Change from baseline to endpoint in body weight was summarized by treatment.Safety and tolerability of vildagliptin was also evaluated.RESULTS: After 24 wk,the difference in adjusted mean change in HbA1c between vildagliptin and placebo was 0.82%(8.96 mmol/mol;P < 0.001) in Asian subgroup,0.85%(9.29 mmol/mol;P < 0.001) in patients also receiving metformin,and 0.73%(7.98 mmol/mol;P < 0.001) in patients without metformin,all in favor of vildagliptin.There was no significant difference in the change in FPG between treatments.Weight was stable in both treatment groups(+0.3 kg and-0.2 kg,for vildagliptin and placebo,respectively).Overall,vildagliptin was safe and well tolerated with similarly low incidences of hypoglycemia(8.0% vs 8.1%) and no severe hypoglycemic events were experienced in either group.CONCLUSION: In Asian patients inadequately controlled with insulin(with or without concomitant metformin),insulin-vildagliptin combination treatment significantly reduced HbA1c compared with placebo,without an increase in risk of hypoglycemia or weight gain.
基金financially supported by the Science Foundation Ireland (SFI) Frontiers for the Future 2019 call (No.19/FFP/6522)the National Natural Science Foundation of China (NSFC)(No.51873179)Irish Research Council (IRC) Government of Ireland Postdoctoral Fellowship (No.GOIPD/2022/209)。
文摘Copper(0)-mediated reversible-deactivation radical polymerization(Cu(0)-mediated RDRP) of the water-soluble monomer Nisopropylacrylamide(NIPAM) has been challenging with the problems of high dispersity, poor control over the molecular weights(MWs) or complex or multi reaction steps, etc. In this work, we report the well-controlled polymerization of NIPAM in water via a facile one-pot and one-step Cu(0)-mediated RDRP. The results of this approach show that the key for kicking off the Cu(0)-mediated NIPAM RDRPs is to ensure sufficient Cu~I at the very beginning, and the key to achieve a well-controlled chain growth is to provide adequate deactivation strength during the polymerization process. For NIPAM, which has a high propagation rate constant, the deactivation control can be effectively enhanced by extra adding deactivator(i.e., Cu~II) to the system. Moreover, a low reaction temperature(4 ℃) is necessary in the controlled synthesis of higher MW poly(Nisopropylacrylamide)(PNIPAM) to avoid the compromise in control caused by the phase transition from its lower critical solution temperature(LCST). Through this new kinetically controlled strategy, PNIPAMs with well-defined structure, narrow molecular weight distributions(MWDs) and varied MWs were successfully achieved.
文摘There has been a lot written lately on the topic of sustainability in the industry,and it's not going away.Efforts are underway in many countries to reduce theworld's carbonfootprint.Of all the global sources of Carbon Dioxide(CO2),the transportation sector emits 13%of the overall greenhouse gases.Of this,10%comes from road vehicles and 1%from rail and shipping.
文摘Electric vehicles (EVs) offer great potential to move from fossil fuel dependency in transport once some of the technical barriers related to battery reliability and grid integration are resolved. The European Union has set a target to achieve a 10% reduction in greenhouse gas emissions by 2020 relative to 2005 levels. This target is binding in all the European Union member states. If electric vehicle issues are overcome then the challenge is to use as much renewable energy as possible to achieve this target. In this paper, the impacts of electric vehicle charged in the all-Ireland single wholesale electricity market after the 2020 deadline passes is investigated using a power system dispatch model. For the purpose of this work it is assumed that a 10% electric vehicle target in the Republic of Ireland is not achieved, but instead 8% is reached by 2025 considering the slow market uptake of electric vehicles. Our experimental study shows that the increasing penetration of EVs could contribute to approach the target of the EU and Ireland government on emissions reduction, regardless of different charging scenarios. Furthermore, among various charging scenarios, the off-peak charging is the best approach, contributing 2.07% to the target of 10% reduction of Greenhouse gas emissions by 2025.
文摘We consider the response of a test subject upon a skin area being heated with an electromagnetic wave or a contact surface. When the specifications of the electromagnetic beam are fixed, the stimulus is solely described by the heating duration. The binary response of a subject, escape or no escape, is determined by the stimulus and a subjective threshold that varies among test realizations. We study four methods for inferring the median subjective threshold in psychophysical experiments: 1) sample median, 2) maximum likelihood estimation (MLE) with 2 variables, 3) MLE with 1 variable, and 4) adaptive Bayesian method. While methods 1 - 3 require samples of time to escape measured in the method of limits, method 4 utilizes binary outcomes observed in the method of constant stimuli. We find that a) the adaptive Bayesian method converges and is as efficient as the sample median even when the assumed model distribution is incorrect;b) this robust convergence is lost if we infer the mean instead of the median;c) for the optimal performance in an uncertain situation, it is best to use a wide model distribution;d) the predicted error from the posterior standard deviation is unreliable, dominated by the assumed model distribution.
文摘Minerals are critical in maintaining health and physiological function in wildlife. Geographic variation in soil and forage mineral concentration may predispose wildlife to mineral imbalances, where a common symptom is restricted somatic growth. We investigated if mineral imbalances could explain localized differences in morphology of white-tailed deer (Odocoileus virginianus) occurring in geographically proximate sites with similar management, climate, and habitat. We collected serum samples and morphological measurements from free-ranging white-tailed deer captured during 2011-2019 from coastal and inland rangeland sites in South Texas, USA. We measured mineral concentrations in serum from captured deer at each location. Asymptotic deer body mass and antler size averaged 8% - 20% smaller for deer at the coastal compared to the inland site. The proportion of deer with deficient levels of serum copper was greater at the coastal site (66% versus 14%). Our results suggest regional mineral deficiencies in deer may limit antler and body development. Wildlife managers should be aware of all aspects of wildlife nutrition and the importance of considering nutrients beyond energy and protein.
文摘We document the first record of Borrelia americana in Canada. This Borrelia was detected in an avian coast tick, Ixodes auritulus (Acari: Ixodidae), collected from a Varied Thrush, Ixoreus naevius, along coastal British Columbia. Using real-time PCR and DNA sequencing of the flagellin gene, we determined that the borrelial amplicon from the I. auritulus nymph was 99% homologous with B. americana type strain SCW-41. Because patients infected with B. americana can be seronegative for Lyme disease, medical professionals should be willing to pursue molecular analyses and consider treatment for patients with Lyme disease-like symptoms.
文摘Uterine atony remains the major cause of postpartum hemorrhage, and of death from postpartum hemorrhage in the United States. While existing guidelines outlining a general approach to postpartum hemorrhage are useful, recent data suggest that greater specificity may be necessary to significantly impact mortality. We present a highly specific and methodical approach to the management of uterine atony, which addresses what we believe to be the most common cause of preventable maternal hemorrhagic death in the US—lack of an intensive, focused approach to atony and perseverance with therapies that are not working. This protocol should result in cessation of hemorrhage by medical or surgical means within 1 hour of diagnosis. We then apply this protocol to a number of illustrative cases of maternal death due to atony. An approach involving the active management of uterine atony may assist clinicians in avoiding severe morbidity and mortality from uterine atony.
文摘<strong>Background:</strong> Plain radiography usual method to detect degeneration in the subtalar and talonavicluar joints. MRI is a better way to fully characterise non-ossified structures, such as articular cartilage, marrow tissue and synovial fluid and therefore detect changes of arthritis. The motivation behind this study was to develop a quantitative way to score arthritic changes to the subtalar and talonavicular joints using MRI. The developed system will then be used as a research tool and in the close assessment and monitoring of patients with hindfoot degenerative disease. <strong>Methods:</strong> The MRI scans of thirty consecutive subjects with foot and ankle pain were retrospectively evaluated. Images were interpreted independently by three musculoskeletal radiologists in order to determine intra-observer reliability as well as the inter-observer reliability of the score. Five features of osteoarthritis were scored in the Subtalar joint and the Talonavicular joint. These were cartilage morphology, subarticular marrow, subarticular cyst, marginal osteophytes and synovitis. <strong>Results:</strong> For the 30 MRI scans the mean score for the Subtalar joint ranged from 11.7 to 14.4 and for the Talonavicular joint ranged from 3.7 to 5.6. The inter-observer correlation for the Subtalar joint between the three readers ranged between 0.53 and 0.83 for the individual features but overall was excellent at 0.76. For the Talonavicular joint the total correlation was good at 0.67. The inter-observer ICC for the total score was 0.75 which showed excellent agreement between the three readers. The total intra-observer correlation was excellent. <strong>Conclusions:</strong> The current work has shown excellent reliability for the scoring system. It will be a useful tool to diagnose and monitor disease progression of the Subtalar and Talonavicluar joints.
文摘We consider the psychophysical experiments in which the test subject’s binary reaction is determined by the prescribed exposure duration to a stimulus and a random variable subjective threshold. For example, when a subject is exposed to a millimeter wave beam for a prescribed duration, the occurrence of flight action is binary (yes or no). In experiments, in addition to the binary outcome, the actuation time of flight action is also recorded if it occurs;the delay from the initiation time to the actuation time of flight action is the human reaction time, which is not measurable. In this study, we model the random subjective threshold as a Weibull distribution and formulate an inference method for estimating the human reaction time, from data of prescribed exposure durations, binary outcomes and actuation times of flight action collected in a sequence of tests. Numerical simulations demonstrate that the inference of human reaction time based on the Weibull distribution converges to the correct value even when the underlying true model deviates from the inference model. This robustness of the inference method makes it applicable to real experimental data where the underlying true model is unknown.
文摘We consider the problem of inducing withdrawal reflex on a test subject via exposure to a millimeter wave beam. In our physical model, there are 10 physical parameters affecting the occurrence of withdrawal reflex. Our goal is to pinpoint the roles of these physical parameters in inducing withdrawal reflex. We first carry out non-dimensionalization to reduce the model to a non-dimensional system of only 3 composite parameters: non-dimensional beam power density, non-dimensional beam radius, and non-dimensional exposure time. If the beam power is kept on and steady, withdrawal reflex occurs eventually;the shortest exposure time for inducing withdrawal reflex corresponds to the smallest energy consumption at the given power density and beam radius. In the 2D space of power density and beam radius, the overall minimum energy occurs at the corner of very large power density and very small beam radius, which also produces a very large value of maximum skin temperature and a long time to withdrawal reflex. To reduce the burn injury risk, we introduce a cap on the maximum skin temperature. At each given total beam power, we carry out optimizations with respect to the beam radius, constrained by the prescribed temperature cap. The energy consumption varies negatively with the prescribed temperature cap: a lower temperature cap can be accommodated only with a higher energy consumption via the venue of a larger beam radius. The energy consumption is relatively flat with respect to the total beam power and attains a minimum at a moderately large total beam power. The time to withdrawal reflex is approximately inversely proportional to the total beam power. Our analysis demonstrates that a moderately large total beam power is a good compromise to achieve both low energy consumption and short time to withdrawal reflex.
基金supported by the National Natural Science Foundation of China (Grant 81420108022)Jiangsu Province Program of Innovative and Entrepreneurial Talents (2011 – 2014)
文摘The incidence of sepsis is increasing over time, along with an increased risk of dying from the condition. Sepsis care costs billions annually in the United States. Death from sepsis is understood to be a complex process, driven by a lack of normal immune homeostatic functions and excessive production of proinflammatory cytokines, which leads to multi-organ failure. The Toll-like receptor(TLR) family, one of whose members was initially discovered in Drosophila, performs an important role in the recognition of microbial pathogens. These pattern recognition receptors(PRRs), upon sensing invading microorganisms, activate intracellular signal transduction pathways. NOD signaling is also involved in the recognition of bacteria and acts synergistically with the TLR family in initiating an efficient immune response for the eradication of invading microbial pathogens. TLRs and NOD1/NOD2 respond to different pathogenassociated molecular patterns(PAMPs). Modulation of both TLR and NOD signaling is an area of research that has prompted much excitement and debate as a therapeutic strategy in the management of sepsis. Molecules targeting TLR and NOD signaling pathways exist but regrettably thus far none have proven efficacy from clinical trials.
文摘Background:Huntington's disease is a progressive neurodegenerative disorder.Brain atrophy,as measured by volumetric magnetic resonance imaging(MRI),is a downstream consequence of neurodegeneration,but microstructural changes within brain tissue are expected to precede this volumetric decline.The tissue microstructure can be assayed non-invasively using diffusion MRI,which also allows a tractographic analysis of brain connectivity.Methods:We here used ex vivo diffusion MRI(11.7 T)to measure microstructural changes in different brain regions of end-stage(14 weeks of age)wild type and R6/2 mice(male and female)modeling Huntington's disease.To probe the microstructure of different brain regions,reduce partial volume effects and measure connectivity between different regions,a 100μm isotropic voxel resolution was acquired.Results:Although fractional anisotropy did not reveal any difference between wild-type controls and R6/2 mice,mean,axial,and radial diffusivity were increased in female R6/2 mice and decreased in male R6/2 mice.Whole brain streamlines were only reduced in male R6/2 mice,but streamline density was increased.Region-to-region tractography indicated reductions in connectivity between the cortex,hippocampus,and thalamus with the striatum,as well as within the basal ganglia(striatum—globus pallidus—subthalamic nucleus—substantia nigra—thalamus).Conclusions:Biological sex and left/right hemisphere affected tractographic results,potentially reflecting different stages of disease progression.This proof-of-principle study indicates that diffusion MRI and tractography potentially provide novel biomarkers that connect volumetric changes across different brain regions.In a translation setting,these measurements constitute a novel tool to assess the therapeutic impact of interventions such as neuroprotective agents in transgenic models,as well as patients with Huntington's disease.
