Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the cas...Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the case of a 65-year-old man presenting with rectorrhagia and anal pain, initially diagnosed as hemorrhoidal disease. Subsequent proctological examination revealed an ulcerating-bourging tumor, confirmed histologically as an anorectal melanoma. After a normal extension workup, an abdominoperineal amputation was performed. Anorectal melanoma is a pathology with a poor prognosis, requiring early diagnosis to improve chances of survival.展开更多
Against the backdrop of increasingly prominent global energy shortages and environmental issues,the development of efficient energy conversion and storage technologies has become crucial.Zero-dimensional(0D)metal oxid...Against the backdrop of increasingly prominent global energy shortages and environmental issues,the development of efficient energy conversion and storage technologies has become crucial.Zero-dimensional(0D)metal oxide composites exhibit significant application value in the field of energy chemistry due to their unique properties,such as quantum size effect and high specific surface area.From a broad perspective,this paper reviews the main synthesis methods of these composites,including sol-gel method,hydrothermal/solvothermal method,precipitation method,and template method,while analyzing the characteristics of each method.It further discusses their applications in photocatalytic hydrogen production,fuel cells,lithium-ion batteries,and supercapacitors.Additionally,the current challenges,such as material dispersibility and interface bonding,are pointed out,and future development directions are prospected,aiming to provide references for related research.展开更多
Charcot-Marie-Tooth disease(CMT) is a heterogeneous group of inherited peripheral neuro pathies;it is characterized by muscle weakness and wasting,as well as sensory dysfunction,that typically begins during adolescenc...Charcot-Marie-Tooth disease(CMT) is a heterogeneous group of inherited peripheral neuro pathies;it is characterized by muscle weakness and wasting,as well as sensory dysfunction,that typically begins during adolescence and ultimately leads to lifelong disability.Occurring in~1 in 2500individuals,CMT is the most common hereditary neuromuscular condition and results from mutations in> 100 different genes.CMT is grouped into type1(CMT1),where demyelination and loss of nerve conduction velocity occur,type 2(CMT2),where motor and sensory axons degenerate without loss of myelination/nerve conduction velocity,and intermediate CMT,where both demyelination and axon loss present alongside intermediate nerve condu ction velocities.展开更多
The first liver transplantation(LT)in humans was performed by Thomas Starzl on March 1,1963[1,2](Fig.1).During the period 1963-1983,this challenging procedure was performed in four centers only,one in the USA and thre...The first liver transplantation(LT)in humans was performed by Thomas Starzl on March 1,1963[1,2](Fig.1).During the period 1963-1983,this challenging procedure was performed in four centers only,one in the USA and three in Western Europe:Denver,Cambridge,Hannover and Groningen.Their collected experience including only 540 cases(meaning 27(!)cases yearly)was the basis of the 1983 National Institutes of Health(NIH)development consensus conference leading to the conclusion that LT could become“a promising alternative to the current therapy in the management of the late phase of several forms of serious liver disease…candidates are those who exhausted alternative medical and surgical treatments…and are approaching the terminal phase of their illness”.Patients presenting liver tumors and inherited,liver based,metabolic diseases could also be considered for LT[3].This conference put forward ten absolute and five relative contraindications restricting thereby the access to LT to a minority of very well selected liver diseased patients.展开更多
Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging ther...Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging therapeutic opportunity of Janus kinase inhibitor(JAKi)in the role of systemic inflammation in AMD pathogenesis(2).This study offers a real-world examination of the relationship between JAKi and AMD,comparing the incidence of AMD in patients treated with JAKi and those receiving other immunotherapies for existing autoimmune diseases.展开更多
Epilepsy affects over 50 million people worldwide.Drug-resistant epilepsy(DRE)accounts for up to a third of these cases,and neuro-inflammation is thought to play a role in such cases.Despite being a long-debated issue...Epilepsy affects over 50 million people worldwide.Drug-resistant epilepsy(DRE)accounts for up to a third of these cases,and neuro-inflammation is thought to play a role in such cases.Despite being a long-debated issue in the field of DRE,the mechanisms underlying neuroinflammation have yet to be fully elucidated.The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics.Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes,such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis.The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems.We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application.We hope to provide an insightful overview to advance the quest for better DRE treatments.展开更多
BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but da...BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but data from cohort studies are scarce.AIM To investigate the association between insulin and pathological LFT,liver disease,and cirrhosis in a populationbased retrospective cohort study.METHODS Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used.LFT were obtained at two time points 8 years to 24 years after baseline.Liver disease diagnoses were obtained from nationwide registries.The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.RESULTS Total follow-up was 54054 person-years for women and 27556 person-years for men.Insulin levels were positively correlated with elevated LFT during follow-up,whereas physical activity and coffee consumption were negatively correlated.Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease,adjusted hazard ratio(aHR)of 4.3(95%CI:1.6-14.6)and cirrhosis(aHR=4.8,95%CI:1.6-14.6).CONCLUSION This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease.The results support the concept of metabolic dysfunction associated liver disease.展开更多
Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained...Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.展开更多
The exponential growth of food demand due to the increasing global population has the potential to seriously threaten the quality and quantity of food supplies due to climate change.This study explores the utilisation...The exponential growth of food demand due to the increasing global population has the potential to seriously threaten the quality and quantity of food supplies due to climate change.This study explores the utilisation of green urban spaces for achieving food self-sufficiency by investigating the extent to which sustainable urban farms could be used to reduce the consumption of imported produce in the UK.It also examines urban farming stakeholders'perspective on how food self-sufficiency can help realise the SDGs especially SDG 2(Zero hunger)and SDG 13(Climate action).The study adopts a mixed method approach through a survey with 115 respondents and semi-structured interviews conducted with 12 respondents from 4 different urban farming stakeholder groups.The findings of this study presented a strong correlation between stakeholders who had concerns about where their food came from and the carbon footprint of imported produce.The research shows that,urban farms will no doubt play a vital role in the future of food security in our cities/communities and that the SDGs could be realised through sustainable urban farms implemented within the relevant planning regulations/policies.展开更多
Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH ...Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.展开更多
The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic ...The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.展开更多
Spatter during laser powder bed fusion(LPBF)can induce surface defects,impacting the fatigue performance of the fabricated components.Here,we reveal and explain the links between vapour depression shape and spatter dy...Spatter during laser powder bed fusion(LPBF)can induce surface defects,impacting the fatigue performance of the fabricated components.Here,we reveal and explain the links between vapour depression shape and spatter dynamics during LPBF of an Al-Fe-Zr aluminium alloy using high-speed synchrotron x-ray imaging.We quantify the number,trajectory angle,velocity,and kinetic energy of the spatter as a function of vapour depression zone/keyhole morphology under industry-relevant processing conditions.The depression zone/keyhole morphology was found to influence the spatter ejection angle in keyhole versus conduction melting modes:(i)the vapour-pressure driven plume in conduction mode with a quasi-semi-circular depression zone leads to backward spatter whereas;and(ii)the keyhole rear wall redirects the gas/vapour flow to cause vertical spatter ejection and rear rim droplet spatter.Increasing the opening of the keyhole or vapour depression zone can reduce entrainment of solid spatter.We discover a spatter-induced cavity mechanism in which small spatter particles are accelerated towards the powder bed after laser-spatter interaction,inducing powder denudation and cavities on the printed surface.By quantifying these laser-spatter interactions,we suggest a printing strategy for minimising defects and improving the surface quality of LPBF parts.展开更多
文摘Anorectal melanoma is a rare tumor representing less than 1% of anorectal cancers and around 0.3% of malignant melanomas. Its prognosis is particularly poor due to the early occurrence of metastases. We report the case of a 65-year-old man presenting with rectorrhagia and anal pain, initially diagnosed as hemorrhoidal disease. Subsequent proctological examination revealed an ulcerating-bourging tumor, confirmed histologically as an anorectal melanoma. After a normal extension workup, an abdominoperineal amputation was performed. Anorectal melanoma is a pathology with a poor prognosis, requiring early diagnosis to improve chances of survival.
文摘Against the backdrop of increasingly prominent global energy shortages and environmental issues,the development of efficient energy conversion and storage technologies has become crucial.Zero-dimensional(0D)metal oxide composites exhibit significant application value in the field of energy chemistry due to their unique properties,such as quantum size effect and high specific surface area.From a broad perspective,this paper reviews the main synthesis methods of these composites,including sol-gel method,hydrothermal/solvothermal method,precipitation method,and template method,while analyzing the characteristics of each method.It further discusses their applications in photocatalytic hydrogen production,fuel cells,lithium-ion batteries,and supercapacitors.Additionally,the current challenges,such as material dispersibility and interface bonding,are pointed out,and future development directions are prospected,aiming to provide references for related research.
基金funding from the Medical Research Council (MR/S006990/1, MR/Y010949/1)the Rosetrees Trust (M806)the UCL Neurogenetic Therapies Programme funded by The Sigrid Rausing Trust and the UCL Therapeutic Acceleration Support scheme supported by funding from MRC IAA 2021 UCL MR/X502984/1 (to JNS)。
文摘Charcot-Marie-Tooth disease(CMT) is a heterogeneous group of inherited peripheral neuro pathies;it is characterized by muscle weakness and wasting,as well as sensory dysfunction,that typically begins during adolescence and ultimately leads to lifelong disability.Occurring in~1 in 2500individuals,CMT is the most common hereditary neuromuscular condition and results from mutations in> 100 different genes.CMT is grouped into type1(CMT1),where demyelination and loss of nerve conduction velocity occur,type 2(CMT2),where motor and sensory axons degenerate without loss of myelination/nerve conduction velocity,and intermediate CMT,where both demyelination and axon loss present alongside intermediate nerve condu ction velocities.
文摘The first liver transplantation(LT)in humans was performed by Thomas Starzl on March 1,1963[1,2](Fig.1).During the period 1963-1983,this challenging procedure was performed in four centers only,one in the USA and three in Western Europe:Denver,Cambridge,Hannover and Groningen.Their collected experience including only 540 cases(meaning 27(!)cases yearly)was the basis of the 1983 National Institutes of Health(NIH)development consensus conference leading to the conclusion that LT could become“a promising alternative to the current therapy in the management of the late phase of several forms of serious liver disease…candidates are those who exhausted alternative medical and surgical treatments…and are approaching the terminal phase of their illness”.Patients presenting liver tumors and inherited,liver based,metabolic diseases could also be considered for LT[3].This conference put forward ten absolute and five relative contraindications restricting thereby the access to LT to a minority of very well selected liver diseased patients.
基金supported by Health Education England/National Institute for Health Research(NIHR)(Clinical Lectureship CL-2020-18-009 for C.H.).
文摘Introduction Late age-related macular degeneration(AMD)is one of the leading causes of blindness globally(1).In their recent study published in JAMA Ophthalmology,Hallak et al.explore the potential of an emerging therapeutic opportunity of Janus kinase inhibitor(JAKi)in the role of systemic inflammation in AMD pathogenesis(2).This study offers a real-world examination of the relationship between JAKi and AMD,comparing the incidence of AMD in patients treated with JAKi and those receiving other immunotherapies for existing autoimmune diseases.
基金supported by the National Natural Science Foundation of China(82030037)the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders(11000023T000002036286).
文摘Epilepsy affects over 50 million people worldwide.Drug-resistant epilepsy(DRE)accounts for up to a third of these cases,and neuro-inflammation is thought to play a role in such cases.Despite being a long-debated issue in the field of DRE,the mechanisms underlying neuroinflammation have yet to be fully elucidated.The pro-inflammatory microenvironment within the brain tissue of people with DRE has been probed using single-cell multimodal transcriptomics.Evidence suggests that inflammatory cells and pro-inflammatory cytokines in the nervous system can lead to extensive biochemical changes,such as connexin hemichannel excitability and disruption of neurotransmitter homeostasis.The presence of inflammation may give rise to neuronal network abnormalities that suppress endogenous antiepileptic systems.We focus on the role of neuroinflammation and brain network anomalies in DRE from multiple perspectives to identify critical points for clinical application.We hope to provide an insightful overview to advance the quest for better DRE treatments.
文摘BACKGROUND Insulin resistance is a cardiometabolic risk factor characterized by elevated insulin levels.It is associated with fatty liver disease and elevated liver function tests(LFT)in cross-sectional studies,but data from cohort studies are scarce.AIM To investigate the association between insulin and pathological LFT,liver disease,and cirrhosis in a populationbased retrospective cohort study.METHODS Anthropometric and cardiometabolic factors of 857 men and 1228 women from prospective cohort studies were used.LFT were obtained at two time points 8 years to 24 years after baseline.Liver disease diagnoses were obtained from nationwide registries.The association between insulin levels and the development of elevated LFT or liver disease and cirrhosis was analyzed.RESULTS Total follow-up was 54054 person-years for women and 27556 person-years for men.Insulin levels were positively correlated with elevated LFT during follow-up,whereas physical activity and coffee consumption were negatively correlated.Individuals with both insulin levels in the upper tertile and alcohol consumption above MASLD thresholds had an increased risk for both liver disease,adjusted hazard ratio(aHR)of 4.3(95%CI:1.6-14.6)and cirrhosis(aHR=4.8,95%CI:1.6-14.6).CONCLUSION This population-based study provides evidence that high insulin levels are a risk factor for development of elevated liver enzymes and clinically manifest liver disease.The results support the concept of metabolic dysfunction associated liver disease.
基金funded by the following grants and contracts:Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38020400 to S.W.)the National Natural Science Foundation of China(32325013 to S.W.,32271186 to J.T.,31900408 to M.Z.)+5 种基金the CAS Project for Young Scientists in Basic Research(YSBR-077 to S.W.)Shanghai Science and Technology Commission Excellent Academic Leaders Program(22XD1424700 to S.W.)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-066 to L.J.and J.W.)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01 to L.J.and S.W.)the National Science and Technology Basic Research Project(2015FY111700 to L.J.)the 111 Project(B13016 to L.J.).
文摘Facial morphology,a complex trait influenced by genetics,holds great significance in evolutionary research.However,due to limited fossil evidence,the facial characteristics of Neanderthals and Denisovans have remained largely unknown.In this study,we conduct a large-scale multi-ethnic meta-analysis of the genome-wide association study(GWAS),including 9674 East Asians and 10,115 Europeans,quantitatively assessing 78 facial traits using 3D facial images.We identify 71 genomic loci associated with facial features,including 21 novel loci.We develop a facial polygenic score(FPS)that enables the prediction of facial features based on genetic information.Interestingly,the distribution of FPSs among populations from diverse continental groups exhibits relevant correlations with observed facial features.Furthermore,we apply the FPS to predict the facial traits of seven Neanderthals and one Denisovan using ancient DNA and align predictions with the fossil records.Our results suggest that Neanderthals and Denisovans likely share similar facial features,such as a wider but shorter nose and a wider endocanthion distance.The decreased mouth width is characterized specifically in Denisovans.The integration of genomic data and facial trait analysis provides valuable insights into the evolutionary history and adaptive changes in human facial morphology.
文摘The exponential growth of food demand due to the increasing global population has the potential to seriously threaten the quality and quantity of food supplies due to climate change.This study explores the utilisation of green urban spaces for achieving food self-sufficiency by investigating the extent to which sustainable urban farms could be used to reduce the consumption of imported produce in the UK.It also examines urban farming stakeholders'perspective on how food self-sufficiency can help realise the SDGs especially SDG 2(Zero hunger)and SDG 13(Climate action).The study adopts a mixed method approach through a survey with 115 respondents and semi-structured interviews conducted with 12 respondents from 4 different urban farming stakeholder groups.The findings of this study presented a strong correlation between stakeholders who had concerns about where their food came from and the carbon footprint of imported produce.The research shows that,urban farms will no doubt play a vital role in the future of food security in our cities/communities and that the SDGs could be realised through sustainable urban farms implemented within the relevant planning regulations/policies.
文摘Portal hypertension(PH)has traditionally been observed as a consequence of significant fibrosis and cirrhosis in advanced non-alcoholic fatty liver disease(NAFLD).However,recent studies have provided evidence that PH may develop in earlier stages of NAFLD,suggesting that there are additional pathogenetic mechanisms at work in addition to liver fibrosis.The early development of PH in NAFLD is associated with hepatocellular lipid accumulation and ballooning,leading to the compression of liver sinusoids.External compression and intraluminal obstacles cause mechanical forces such as strain,shear stress and elevated hydrostatic pressure that in turn activate mechanotransduction pathways,resulting in endothelial dysfunction and the development of fibrosis.The spatial distribution of histological and functional changes in the periportal and perisinusoidal areas of the liver lobule are considered responsible for the pre-sinusoidal component of PH in patients with NAFLD.Thus,current diagnostic methods such as hepatic venous pressure gradient(HVPG)measurement tend to underestimate portal pressure(PP)in NAFLD patients,who might decompensate below the HVPG threshold of 10 mmHg,which is traditionally considered the most relevant indicator of clinically significant portal hypertension(CSPH).This creates further challenges in finding a reliable diagnostic method to stratify the prognostic risk in this population of patients.In theory,the measurement of the portal pressure gradient guided by endoscopic ultrasound might overcome the limitations of HVPG measurement by avoiding the influence of the pre-sinusoidal component,but more investigations are needed to test its clinical utility for this indication.Liver and spleen stiffness measurement in combination with platelet count is currently the best-validated non-invasive approach for diagnosing CSPH and varices needing treatment.Lifestyle change remains the cornerstone of the treatment of PH in NAFLD,together with correcting the components of metabolic syndrome,using nonselective beta blockers,whereas emerging candidate drugs require more robust confirmation from clinical trials.
文摘The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts,above the hilar confluence of the hepatic ducts.The disease is more prevalent in Asia,mainly owing to socioeconomic and dietary factors,as well as the prevalence of biliary parasites.In the last century,owing to migration,its global incidence has increased.The main pathophysiological mechanisms involve cholangitis,bile infection and biliary strictures,creating a self-sustaining cycle that perpetuates the disease,frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of“recurrent pyogenic cholangitis”.Furthermore,long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma.Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment.The management of symptomatic patients and those with complications can be complex,and relies upon a multidisciplinary team of hepatologists,endoscopists,interventional radiologists and hepatobiliary surgeons,with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications.This comprehensive review provides insight on various aspects of hepatolithiasis,with a focus on epidemiology,new evidence on pathophysiology,most important clinical aspects,different classification systems and contemporary management.
基金support from the UKRI-EPSRC,Grants Numbered EP/W006774/1,EP/P006566/1,EP/W003333/1,and EP/V061798/1funded by the support from a Royal Academy of Engineering Chair in Emerging Technologies(CiET1819/10)+1 种基金CLAL is funded in part by EP/W037483/1 and IPG Photonics/Royal Academy of Engineering Senior Research Fellowship in SEARCH(ref:RCSRF2324-18-71)This research used resources of the European Synchrotron Radiation Facility(ESRF)in Beamline ID19(ME-1573).
文摘Spatter during laser powder bed fusion(LPBF)can induce surface defects,impacting the fatigue performance of the fabricated components.Here,we reveal and explain the links between vapour depression shape and spatter dynamics during LPBF of an Al-Fe-Zr aluminium alloy using high-speed synchrotron x-ray imaging.We quantify the number,trajectory angle,velocity,and kinetic energy of the spatter as a function of vapour depression zone/keyhole morphology under industry-relevant processing conditions.The depression zone/keyhole morphology was found to influence the spatter ejection angle in keyhole versus conduction melting modes:(i)the vapour-pressure driven plume in conduction mode with a quasi-semi-circular depression zone leads to backward spatter whereas;and(ii)the keyhole rear wall redirects the gas/vapour flow to cause vertical spatter ejection and rear rim droplet spatter.Increasing the opening of the keyhole or vapour depression zone can reduce entrainment of solid spatter.We discover a spatter-induced cavity mechanism in which small spatter particles are accelerated towards the powder bed after laser-spatter interaction,inducing powder denudation and cavities on the printed surface.By quantifying these laser-spatter interactions,we suggest a printing strategy for minimising defects and improving the surface quality of LPBF parts.
