The paired cranial crests of Sinosaurus （Theropoda） have been hypothesized as too weak to resist mechanical loads during combat. Finite element analysis （FEA） is used to test this hypothesis, first with geometry o...The paired cranial crests of Sinosaurus （Theropoda） have been hypothesized as too weak to resist mechanical loads during combat. Finite element analysis （FEA） is used to test this hypothesis, first with geometry obtained through direct laser scanning of a well-preserved fossil of the crest, and then with two conceptual FE models of both crests analyzing the structure-deformation effects of fenestration. In the original fossil model, under direct loading on the dorsal faces of the crest, we found that the areas surrounding cavities on the crest experience shear stress that implies a high chance of material failure - the fracture of bone. In the conceptual model, a series of computational studies were conducted with varying loading directions. One simulation found that the shear stress and strain in the material around the cavity presented more deformation compared with the conceptual model without the cavities, and under this morphologically realistic scenario the loading conditions would result in local bone fractures. These model-based computational results indicate that the crest could not resist high loads, because it could not effectively decentralize the loading stress. Future investigations need to focus on more comprehensive computational experiments with more conditions, e.g. dynamical loading conditions, and direct palaeontological evidence.展开更多
The guanine radical cation(G?+)is formed by one-electron oxidation from its parent guanine(G).G?+is rapidly deprotonated in the aqueous phase resulting in the formation of the neutral guanine radical[G(-H)?].The loss ...The guanine radical cation(G?+)is formed by one-electron oxidation from its parent guanine(G).G?+is rapidly deprotonated in the aqueous phase resulting in the formation of the neutral guanine radical[G(-H)?].The loss of proton occurs at the N1 nitrogen,which is involved in the classical Watson-Crick base pairing with cytosine(C).Employing the density functional theory(DFT),it has been observed that a new shifted base pairing configuration is formed between G(-H)?and C constituting only two hydrogen bonds after deprotonation occurs.Using the DFT method,G(-H)?was paired with thymine(T),adenine(A)and G revealing substantial binding energies comparable to those of classical G-C and A-T base pairs.Hence,G(-H)?does not display any particular specificity for C compared to the other bases.Taking into account the long lifetime of the G(-H)?radical in the DNA helix(5 s)and the rapid duplication rate of DNA during mitosis/meiosis(5-500 bases per s),G(-H)?can pair promiscuously leading to errors in the duplication process.This scenario constitutes a new mechanism which explains how one-electron oxidation of the DNA double helix can lead to mutations.展开更多
It was found that the discovery of 5.8%(84/1437) of all drugs on the market involved serendipity. Of these drugs, 31(2.2%) were discovered following an incident in the laboratory and 53(3.7%) were discovered in a clin...It was found that the discovery of 5.8%(84/1437) of all drugs on the market involved serendipity. Of these drugs, 31(2.2%) were discovered following an incident in the laboratory and 53(3.7%) were discovered in a clinical setting. In addition, 263(18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1%(347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2%(31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind.展开更多
Background Heart failure is a significant problem leading to repeated hospitalizations. Telemonitoring and hemodynamic monitoring have demonstrated success in reducing hospitalization rates, but not all studies report...Background Heart failure is a significant problem leading to repeated hospitalizations. Telemonitoring and hemodynamic monitoring have demonstrated success in reducing hospitalization rates, but not all studies reported significant effects. The aim of this systematic review and meta-analysis is to examine the effectiveness of telemonitoring and wireless hemodynamic monitoring devices in reducing hospitalizations in heart failure. Methods ＆ Results PubMed and Cochrane Library were searched up to 1st May 2017 for articles that investigated the effects of telemonitoring or hemodynamic monitoring on hospitalization rates in heart failure. In 31,501 patients （mean age： 68 ± 12 years; 61% male; follow-up 11 ± 8 months）, telemonitoring reduced hospitalization rates with a HR of 0.73 （95% CI： 0.65-0.83; P 〈 0.0001） with significant heterogeneity （I2 = 94%）. These effects were observed in the short-term （≤ 6 months： HR = 0.77, 95% CI： 0.65-0.89; P 〈 0.01） and long-term （≥ 12 months： HR = 0.73, 95% CI： 0.62-0.87; P 〈 0.0001）. In 4831 patients （mean age 66 ± 18 years; 66% male; follow-up 13 ± 4 months）, wireless hemodynamic monitoring also reduced hospitalization rates with a HR of 0.60 （95% CI： 0.53-0.69; P 〈 0.001） with significant heterogeneity （I2 = 64%）.This reduction was observed both in the short-term （HR = 0.55, 95% CI： 0.45-0.68; P 〈 0.001; I2 = 72%） and long-term （HR = 0.64, 95% CI： 0.57-0.72; P 〈 0.001; I2 = 55%）. Conclusions Telemonitoring and hemodynamic monitoring reduce hospitalization in both short- and long-term in heart failure patients展开更多
Crop height measurement is widely used to analyze and estimate the overall crop condition and the amount of biomass production.Not only is manual measurement on a large scale time-consuming but also it is not practica...Crop height measurement is widely used to analyze and estimate the overall crop condition and the amount of biomass production.Not only is manual measurement on a large scale time-consuming but also it is not practical.Besides,advanced equipment is available but they require technical skills and are not reasonable for smallholders.This article investigates the feasibility of a simple and low-cost measurement system that can monitor crops height of paddy rice and wheat using laser technology.After designing and fabricating,this system was tested and evaluated in both laboratory and farm sections.In the laboratory,paddy rice height was measured,and in the field section,the height detection system measured wheat height.The results showed that the coefficient of determination(R3)between manual measurement and height detection system measurement for paddy rice was 0.96 and for wheat was 0.85.Besides,there was no significant difference between the two datasets at the level of 5%.Hence,this system can be a useful and accurate tool to monitor crops height in different growing steps.展开更多
Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed asse...Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.展开更多
Invasive techniques are becoming increasingly important in the presurgical evaluation of epilepsy.Adopting the electrophysiological source imaging(ESI)of interictal scalp electroencephalography(EEG)to localize the epi...Invasive techniques are becoming increasingly important in the presurgical evaluation of epilepsy.Adopting the electrophysiological source imaging(ESI)of interictal scalp electroencephalography(EEG)to localize the epileptogenic zone remains a challenge.The accuracy of the preoperative localization of the epileptogenic zone is key to curing epilepsy.The T1 MRI and the boundary element method were used to build the realistic head model.To solve the inverse problem,the distributed inverse solution and equivalent current dipole(ECD)methods were employed to locate the epileptogenic zone.Furthermore,a combination of inverse solution algorithms and Granger causality connectivity measures was evaluated.The ECD method exhibited excellent focalization in lateralization and localization,achieving a coincidence rate of 99.02%(p<0.05)with the stereo electroencephalogram.The combination of ECD and the directed transfer function led to excellent matching between the information flow obtained from intracranial and scalp EEG recordings.The ECD inverse solution method showed the highest performance and could extract the discharge information at the cortex level from noninvasive low-density EEG data.Thus,the accurate preoperative localization of the epileptogenic zone could reduce the number of intracranial electrode implantations required.展开更多
Prediction of the progression of an infectious disease outbreak is important for planning and coordinating a response.Differential equations are often used to model an epidemic outbreak's behaviour but are challen...Prediction of the progression of an infectious disease outbreak is important for planning and coordinating a response.Differential equations are often used to model an epidemic outbreak's behaviour but are challenging to parameterise.Furthermore,these models can suffer from misspecification,which biases predictions and parameter estimates.Stochastic models can help with misspecification but are even more expensive to simulate and perform inference with.Here,we develop an explicitly likelihood-based variation of the generalised profiling method as a tool for prediction and inference under model mis-specification.Our approach allows us to carry out identifiability analysis and uncertainty quantification using profile likelihood-based methods without the need for marginalisation.We provide justification for this approach by introducing a new interpretation of the model approximation component as a stochastic constraint.This preserves the rationale for using profiling rather than integration to remove nuisance parameters while also providing a link back to stochastic models.We applied an initial version of this method during an outbreak of measles in Samoa in 2019e2020 and found that it achieved relatively fast,accurate predictions.Here we present the most recent version of our method and its application to this measles outbreak,along with additional validation.展开更多
文摘The paired cranial crests of Sinosaurus （Theropoda） have been hypothesized as too weak to resist mechanical loads during combat. Finite element analysis （FEA） is used to test this hypothesis, first with geometry obtained through direct laser scanning of a well-preserved fossil of the crest, and then with two conceptual FE models of both crests analyzing the structure-deformation effects of fenestration. In the original fossil model, under direct loading on the dorsal faces of the crest, we found that the areas surrounding cavities on the crest experience shear stress that implies a high chance of material failure - the fracture of bone. In the conceptual model, a series of computational studies were conducted with varying loading directions. One simulation found that the shear stress and strain in the material around the cavity presented more deformation compared with the conceptual model without the cavities, and under this morphologically realistic scenario the loading conditions would result in local bone fractures. These model-based computational results indicate that the crest could not resist high loads, because it could not effectively decentralize the loading stress. Future investigations need to focus on more comprehensive computational experiments with more conditions, e.g. dynamical loading conditions, and direct palaeontological evidence.
文摘The guanine radical cation(G?+)is formed by one-electron oxidation from its parent guanine(G).G?+is rapidly deprotonated in the aqueous phase resulting in the formation of the neutral guanine radical[G(-H)?].The loss of proton occurs at the N1 nitrogen,which is involved in the classical Watson-Crick base pairing with cytosine(C).Employing the density functional theory(DFT),it has been observed that a new shifted base pairing configuration is formed between G(-H)?and C constituting only two hydrogen bonds after deprotonation occurs.Using the DFT method,G(-H)?was paired with thymine(T),adenine(A)and G revealing substantial binding energies comparable to those of classical G-C and A-T base pairs.Hence,G(-H)?does not display any particular specificity for C compared to the other bases.Taking into account the long lifetime of the G(-H)?radical in the DNA helix(5 s)and the rapid duplication rate of DNA during mitosis/meiosis(5-500 bases per s),G(-H)?can pair promiscuously leading to errors in the duplication process.This scenario constitutes a new mechanism which explains how one-electron oxidation of the DNA double helix can lead to mutations.
文摘It was found that the discovery of 5.8%(84/1437) of all drugs on the market involved serendipity. Of these drugs, 31(2.2%) were discovered following an incident in the laboratory and 53(3.7%) were discovered in a clinical setting. In addition, 263(18.3%) of the pharmaceuticals in clinical use today are chemical derivatives of the drugs discovered with the aid of serendipity. Therefore, in total, 24.1%(347/1437) of marketed drugs can be directly traced to serendipitous events confirming the importance of this elusive phenomenon. In the case of anticancer drugs, 35.2%(31/88) can be attributed to a serendipitous event, which is somewhat larger than for all drugs. The therapeutic field that has benefited the most from serendipity are central nervous system active drugs reflecting the difficulty in designing compounds to pass the blood-brain-barrier and the lack of laboratory-based assays for many of the diseases of the mind.
文摘Background Heart failure is a significant problem leading to repeated hospitalizations. Telemonitoring and hemodynamic monitoring have demonstrated success in reducing hospitalization rates, but not all studies reported significant effects. The aim of this systematic review and meta-analysis is to examine the effectiveness of telemonitoring and wireless hemodynamic monitoring devices in reducing hospitalizations in heart failure. Methods ＆ Results PubMed and Cochrane Library were searched up to 1st May 2017 for articles that investigated the effects of telemonitoring or hemodynamic monitoring on hospitalization rates in heart failure. In 31,501 patients （mean age： 68 ± 12 years; 61% male; follow-up 11 ± 8 months）, telemonitoring reduced hospitalization rates with a HR of 0.73 （95% CI： 0.65-0.83; P 〈 0.0001） with significant heterogeneity （I2 = 94%）. These effects were observed in the short-term （≤ 6 months： HR = 0.77, 95% CI： 0.65-0.89; P 〈 0.01） and long-term （≥ 12 months： HR = 0.73, 95% CI： 0.62-0.87; P 〈 0.0001）. In 4831 patients （mean age 66 ± 18 years; 66% male; follow-up 13 ± 4 months）, wireless hemodynamic monitoring also reduced hospitalization rates with a HR of 0.60 （95% CI： 0.53-0.69; P 〈 0.001） with significant heterogeneity （I2 = 64%）.This reduction was observed both in the short-term （HR = 0.55, 95% CI： 0.45-0.68; P 〈 0.001; I2 = 72%） and long-term （HR = 0.64, 95% CI： 0.57-0.72; P 〈 0.001; I2 = 55%）. Conclusions Telemonitoring and hemodynamic monitoring reduce hospitalization in both short- and long-term in heart failure patients
文摘Crop height measurement is widely used to analyze and estimate the overall crop condition and the amount of biomass production.Not only is manual measurement on a large scale time-consuming but also it is not practical.Besides,advanced equipment is available but they require technical skills and are not reasonable for smallholders.This article investigates the feasibility of a simple and low-cost measurement system that can monitor crops height of paddy rice and wheat using laser technology.After designing and fabricating,this system was tested and evaluated in both laboratory and farm sections.In the laboratory,paddy rice height was measured,and in the field section,the height detection system measured wheat height.The results showed that the coefficient of determination(R3)between manual measurement and height detection system measurement for paddy rice was 0.96 and for wheat was 0.85.Besides,there was no significant difference between the two datasets at the level of 5%.Hence,this system can be a useful and accurate tool to monitor crops height in different growing steps.
基金supported by a grant from the Health Research New Zealand(HRC)22/559(to AJG and LB)。
文摘Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental disability.Detailed assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and electroencephalography.At present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic encephalopathy.This review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent articles.This review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic accuracy.Many challenges limit the timing consistency,particularly the need for intensive care and clinical monitoring.Conversely,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after birth.This suggests that in the future it will be important to explore a wider range of times after hypoxic-ischemic encephalopathy to fully understand the optimal timing for predicting long-term outcomes.
基金Supported by the National Key R&D Program of China(2022YFC2402203)the Key R&D Program of Hebei(21372002D)。
文摘Invasive techniques are becoming increasingly important in the presurgical evaluation of epilepsy.Adopting the electrophysiological source imaging(ESI)of interictal scalp electroencephalography(EEG)to localize the epileptogenic zone remains a challenge.The accuracy of the preoperative localization of the epileptogenic zone is key to curing epilepsy.The T1 MRI and the boundary element method were used to build the realistic head model.To solve the inverse problem,the distributed inverse solution and equivalent current dipole(ECD)methods were employed to locate the epileptogenic zone.Furthermore,a combination of inverse solution algorithms and Granger causality connectivity measures was evaluated.The ECD method exhibited excellent focalization in lateralization and localization,achieving a coincidence rate of 99.02%(p<0.05)with the stereo electroencephalogram.The combination of ECD and the directed transfer function led to excellent matching between the information flow obtained from intracranial and scalp EEG recordings.The ECD inverse solution method showed the highest performance and could extract the discharge information at the cortex level from noninvasive low-density EEG data.Thus,the accurate preoperative localization of the epileptogenic zone could reduce the number of intracranial electrode implantations required.
文摘Prediction of the progression of an infectious disease outbreak is important for planning and coordinating a response.Differential equations are often used to model an epidemic outbreak's behaviour but are challenging to parameterise.Furthermore,these models can suffer from misspecification,which biases predictions and parameter estimates.Stochastic models can help with misspecification but are even more expensive to simulate and perform inference with.Here,we develop an explicitly likelihood-based variation of the generalised profiling method as a tool for prediction and inference under model mis-specification.Our approach allows us to carry out identifiability analysis and uncertainty quantification using profile likelihood-based methods without the need for marginalisation.We provide justification for this approach by introducing a new interpretation of the model approximation component as a stochastic constraint.This preserves the rationale for using profiling rather than integration to remove nuisance parameters while also providing a link back to stochastic models.We applied an initial version of this method during an outbreak of measles in Samoa in 2019e2020 and found that it achieved relatively fast,accurate predictions.Here we present the most recent version of our method and its application to this measles outbreak,along with additional validation.
