AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples...AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative" for HER2;those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colourin situ hybridisations(HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66 years(range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was;upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases;seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21(84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3 or more(13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases(68%) with HER2 over expression received palliative therapy,in comparison to thirty five out of seventy five(46.7%) in tumours not expressing HER2.No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not;median overall survival for HER2 positive tumours was 15 mo(95%CI,11-19 mo) compared to 13 mo(95%CI,9-17 mo) for HER2 negative ones.Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression(P = 0.576).Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis(P = 0.034 and P = 0.009 respectively).None of the patients included in this study received Trastuzumab.CONCLUSION:Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression.Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.展开更多
Background:Kiwi(Apteryx spp.)are flightless ratites from New Zealand whose numbers and distributions have declined following human arrival.Some of the kiwi species are known to hybridise but the extent of hybridizatio...Background:Kiwi(Apteryx spp.)are flightless ratites from New Zealand whose numbers and distributions have declined following human arrival.Some of the kiwi species are known to hybridise but the extent of hybridization is unknown.Methods:We reviewed hybridisation in kiwi(Apteryx spp.)and present new genetic data examining the extent of hybridisation between Rowi(A.rowi)and Little Spotted Kiwi(A.owenii)at Okarito,the location of the only remaining natural population of the threatened Rowi.We also genetically examined the syntype specimens of A.haastii Potts,1872,collected from near Okarito in the 1870s,which have unusual morphologies.Results:We found evidence of recurrent hybridisation between Rowi and Little Spotted Kiwi over the last 150 years,including one F1 hybrid found in the last 15 years,despite Little Spotted Kiwi’s likely extinction on the mainland in the 1970s.However,we found little evidence of introgression of Little Spotted Kiwi alleles into the extant Rowi popula-tion.The syntype specimens of A.haastii were also found to be hybrids between Little Spotted Kiwi and Rowi.Conclusions:Our genetic analyses indicate that,although we detected multiple instances of hybridisation between Rowi and Little Spotted Kiwi,it does not appear to be an ongoing threat to Rowi.Because the syntype specimens of A.haastii are hybrids and therefore not representative of the prevailing usage of the name for the Great Spotted Kiwi(A.haastii),we resurrect the nomen oblitum A.maxima Sclater and Hochstetter,1861 for the large spotted kiwi species.展开更多
Background:Modern ecosystems contain many invasive species as a result of the activity of acclimatisation societies that operated in the second half of the nineteenth century,and these species provide good opportuniti...Background:Modern ecosystems contain many invasive species as a result of the activity of acclimatisation societies that operated in the second half of the nineteenth century,and these species provide good opportunities for studying invasion biology.However,to gain insight into the ecological and genetic mechanisms that determine the rate of colonization and adaptation to new environments,we need a good understanding of the history of the introduced species,and a knowledge of the source population,timing,and number of individuals introduced is particularly important.However,any inaccuracies in the history of an introduction will affect subsequent assumptions and conclusions.Methods:Focusing on a single well-known species,the House Sparrow(Passer domesticus),we have documented the introduction into Australia using primary sources(e.g.acclimatisation records and newspaper articles).Results:Our revised history differs in a number of significant ways from previous accounts.Our evidence indicates that the House Sparrow was not solely introduced from source populations in England but also from Germany and most strikingly also from India—with the latter birds belonging to a different race.We also clarify the distinction between the number released and the number of founders,due to pre-release captive breeding programs,as well as identifying inaccuracies in a couple of well-cited sources with respect to the range expansion of the introduced populations.Conclusions:Our work suggests that caution is required for those studying introductions using the key sources of historical information and ideally should review original sources of information to verify the accuracy of published accounts.展开更多
Based on dynamometer test cycles or plain motorway operation, heavy truck hybridisation must be considered as uneconomic if only the kinetic vehicle energy can be recuperated. In mountainous regions, micro hybridizati...Based on dynamometer test cycles or plain motorway operation, heavy truck hybridisation must be considered as uneconomic if only the kinetic vehicle energy can be recuperated. In mountainous regions, micro hybridization by a 48V-belt generator or mild parallel hybridisation by a large high voltage electric drive can result in considerable fuel consumption savings as well as additional benefits for heavy load utility vehicles. Additional electric power and battery size are still critical design parameters as well as critical cost factors considering the limited space and depreciation time as well as the need for maximum payload. Based on vehicle model simulations, this contribution quantifies fuel consumption savings, recuperation energy harvesting and battery requirements for different truck sizes with test cycles based on realistic route topography. The main route topography parameter for the recuperation benefit is the effective incline that integrates all downhill sections that overcompensates the vehicle resistance by tire friction and air resistance. The simulation parameter studies lead to an analytical benefit estimation, based on load cycle parameters like effective velocity, effective incline as well as the vehicle parameters mass, drag coefficient and cross sectional area. Thus, the return on investment can be assessed by an analytic rule of thumb, based on tracked cycles of existing vehicles.展开更多
Hybridisation was traditionally considered rare on coral reefs. However, a rapid increase in hybrid studies over the last 20 years has revealed that hybridisation on coral reefs is common and widespread. In this revie...Hybridisation was traditionally considered rare on coral reefs. However, a rapid increase in hybrid studies over the last 20 years has revealed that hybridisation on coral reefs is common and widespread. In this review, we summarise the growing body of evidence arising from studies on stony corals and reef fishes to verify the occurrence of hybridisatiori, and we examine the influence hybridisation has had on the enormous level of biodiversity present on coral reefs. We discuss the challenges of dis- tinguishing hybridisation from alternative hypotheses (e.g. incomplete lineage sorting). This review also explores the evolutio- nary consequences of hybridisation, which range from increasing genetic diversity and the production of novel lineages that may outperform the parent species, to reverse speciation and extinction by genetic swamping. Instances of hybridisation can be natural or occur as a result of human impacts (e.g. habitat degradation) and distinguishing between these two very different causal me- chanisms is important for management. Currently, the legislative status of hybrids is unclear and hybrids are rarely protected in conservation programs. Failing to adequately manage hybridisation and hybrid lineages may lead to potential losses of evolutio- nary novelty, declines in phylogenetic diversity or species extinctions. To conserve existing coral reef biodiversity, and the processes that generate biodiversity, conservation policies must be re-defined and instances of hybridisation must be assessed and managed on a case-by-case basis [Current Zoology 61 (1): 132 145, 2015].展开更多
Advances in technology and optimisation are helping to improve decision making in the oil and gas industry.However,most of the traditional metaheuristic algorithms applied in well placement optimisation problems suffe...Advances in technology and optimisation are helping to improve decision making in the oil and gas industry.However,most of the traditional metaheuristic algorithms applied in well placement optimisation problems suffer from extensive parameter experimentations and local optimum trapping issues.This couples with the complex and heterogeneous nature of hydrocarbon reservoirs and increased decision variables poses severe simulation process demands.This study considered a functional composition integration approach to formulate a robust hybrid metaheuristic algorithm called HGWO-PSO.The HGWO-PSO leverages on the strengths of Grey Wolf Optimiser(GWO)and Particle Swarm Optimisation(PSO)and the Clerc's parameter setting considerations.A rigorous approach which enforces regulatory agreed minimum well spacing was incorporated in the optimisation process.Reservoir models ranging from unimodal to multimodal spatial systems were used as examples to test the explorative and exploitative capabilities of the algorithms.In this paper we show the performance curve and statistical analysis of HGWO-PSO as a well placement algorithm and compares its performance with that of standalone PSO,and GWO and the traditional Genetic Algorithm(GA).Results revealed that the HGWO-PSO demonstrated comparative performances in terms of exploration and exploitation obtaining the best optimal solutions which give highest contractor's NPVs in majority of cases considered.Again,the means and standard deviations for HGWO-PSO among the various runs showed consistent and efficient performance.The Wilcoxon signed rank test conducted gave very low p-values suggesting uniqueness of HGWO-PSO from the other metaheuristic variants.Additionally,the computational speed of HGWO-PSO was relatively better as compared to the individual GWO and PSO in most the test cases.The simulation results for all test cases confirm that implementation of HGWO-PSO can cause considerable improvement in locations of wells even in heterogeneous reservoirs.展开更多
Aim:Murine tumour cell lines have been used in thousands of studies.Strikingly,it is rather the rule than exception for most of them that not much is known about their genetic characteristics.The squamous cell carcino...Aim:Murine tumour cell lines have been used in thousands of studies.Strikingly,it is rather the rule than exception for most of them that not much is known about their genetic characteristics.The squamous cell carcinoma(SCC)cell line KLN 205 is such an example.KLN 205 cells have not been studied yet for karyotype or acquired copy number variations(CNVs),but they have been used as models for(metastatic)lung cancer,lung-SCC,non-small cell lung cancer,tongue cancer and subcutaneous SCC.Here,it was characterised cytogenomically for the first time.Methods:The cell line KLN 205 was characterised comprehensively by molecular cytogenetics using multicolour banding as well as molecular karyotyping.Based on these results,a map of the imbalances and breakpoints determined in the murine genome was translated to the human genome.Results:Here,it could be shown that this>40-year-old cell line has a stable,approximately tetraploid karyotype comprising 77-82 chromosomes.However,there are few structural chromosomal aberrations:only six derivatives involving chromosomes 2,3,5,9,10 and/or 19 could be found.According to the literature,SCCs derived from different human tissues,as well as lung SCC and non-small cell lung cancer,display overall similar CNV patterns.Conclusion:Thus,according to the genetic profile found here,KLN 205 can be applied as a general model for human SCC;it is also suited as a model for lung cancer in general.Further molecular genetic characterisation of KLN 205 cell line may find more lung-and/or SCC-specific alterations.展开更多
文摘AIM:To determine the incidence of human epidermal growth factor receptor 2(HER2) over expression in oesophageal cancers.METHODS:A retrospective study,of one hundred consecutive cases of endoscopic histological samples of oesophageal cancers from a single British cancer network were included.Cancer cases were diagnosed between April 2007 and June 2010.HER2 over expression was assessed using immunohistochemistry,those that scored "0" and "+1" were considered "negative" for HER2;those that scored "+3" were considered "Positive".Cases that were scored "+2" on immunohistochemistry further went on to have HER2 gene analysis using the Ventana HER brightfield dual-colourin situ hybridisations(HER B DISH) assay and either came back to be positive or negative for HER2 over expression.Overall survival was measured from date of histological diagnosis until date of death.93% of the cases were followed up till five years or death,and all were followed up till two years.Cases of gastro-oesophageal junctional tumours were excluded.RESULTS:The median age of our sample was 66 years(range:38-91 years).Eighty one were male and 19 female.Ninety-one of the cases were adenocarcinoma of the oesophagus and the rest were cases of squamous cell carcinoma.The anatomical distribution of the tumours was;upper oesophagus 2,middle oesophagus 11,and 87 were in the lower oesophagus.Operative resection was completed in 15 cases;seven cases had attempted surgical resections,i.e.,open and close,33 patients received definitive chemo-radiation and 52 had palliative treatment.Twenty-five of the cancers showed evidence of HER2 over expression,all were adenocarcinomas.Of the 25 cases that showed evidence of HER2 over expression,21(84%) were located in the lower third of the oesophagus.On staging,24 out of the 25 HER2 positive cases were at stage 3 or more(13 at stage 3 and 11 at stage 4),For HER2 negative cases 37 were at stage 3 and 32 were staged as stage 4.Seventeen out of twenty five cases(68%) with HER2 over expression received palliative therapy,in comparison to thirty five out of seventy five(46.7%) in tumours not expressing HER2.No significant difference in overall survival was demonstrated between patients whose cancers showed evidence of HER2 over expression and those who did not;median overall survival for HER2 positive tumours was 15 mo(95%CI,11-19 mo) compared to 13 mo(95%CI,9-17 mo) for HER2 negative ones.Two years cumulative survival for cases with HER2 over expression was 33.7% compared to 31.6% in cases without HER2 over expression(P = 0.576).Only cancer's stage significantly affected overall survival on both univariant and multivariable analysis(P = 0.034 and P = 0.009 respectively).None of the patients included in this study received Trastuzumab.CONCLUSION:Twenty-seven point five percent of oesophageal adenocarcinomas showed evidence of HER2 over expression.Routine testing for human HER2 in oesophageal adenocarcinomas can have significant implication on treatments offered to patients that may potentially affect their prognosis.
基金KR was supported by the Allan Wilson Centre for Molecular Ecology and Evolution,the Bank of New Zealand Save the Kiwi Trust,and the New Zealand Department of Conservation.LS was funded by a Rutherford Discovery Fellowship from the Royal Society of New Zealand(contract number RDF-MNZ1201).
文摘Background:Kiwi(Apteryx spp.)are flightless ratites from New Zealand whose numbers and distributions have declined following human arrival.Some of the kiwi species are known to hybridise but the extent of hybridization is unknown.Methods:We reviewed hybridisation in kiwi(Apteryx spp.)and present new genetic data examining the extent of hybridisation between Rowi(A.rowi)and Little Spotted Kiwi(A.owenii)at Okarito,the location of the only remaining natural population of the threatened Rowi.We also genetically examined the syntype specimens of A.haastii Potts,1872,collected from near Okarito in the 1870s,which have unusual morphologies.Results:We found evidence of recurrent hybridisation between Rowi and Little Spotted Kiwi over the last 150 years,including one F1 hybrid found in the last 15 years,despite Little Spotted Kiwi’s likely extinction on the mainland in the 1970s.However,we found little evidence of introgression of Little Spotted Kiwi alleles into the extant Rowi popula-tion.The syntype specimens of A.haastii were also found to be hybrids between Little Spotted Kiwi and Rowi.Conclusions:Our genetic analyses indicate that,although we detected multiple instances of hybridisation between Rowi and Little Spotted Kiwi,it does not appear to be an ongoing threat to Rowi.Because the syntype specimens of A.haastii are hybrids and therefore not representative of the prevailing usage of the name for the Great Spotted Kiwi(A.haastii),we resurrect the nomen oblitum A.maxima Sclater and Hochstetter,1861 for the large spotted kiwi species.
基金SCA was supported by Macquarie University Research Excellence Scholarships(No.2013077)SCG was supported by an Australian Research Council Future Fellowship(FT130101253)
文摘Background:Modern ecosystems contain many invasive species as a result of the activity of acclimatisation societies that operated in the second half of the nineteenth century,and these species provide good opportunities for studying invasion biology.However,to gain insight into the ecological and genetic mechanisms that determine the rate of colonization and adaptation to new environments,we need a good understanding of the history of the introduced species,and a knowledge of the source population,timing,and number of individuals introduced is particularly important.However,any inaccuracies in the history of an introduction will affect subsequent assumptions and conclusions.Methods:Focusing on a single well-known species,the House Sparrow(Passer domesticus),we have documented the introduction into Australia using primary sources(e.g.acclimatisation records and newspaper articles).Results:Our revised history differs in a number of significant ways from previous accounts.Our evidence indicates that the House Sparrow was not solely introduced from source populations in England but also from Germany and most strikingly also from India—with the latter birds belonging to a different race.We also clarify the distinction between the number released and the number of founders,due to pre-release captive breeding programs,as well as identifying inaccuracies in a couple of well-cited sources with respect to the range expansion of the introduced populations.Conclusions:Our work suggests that caution is required for those studying introductions using the key sources of historical information and ideally should review original sources of information to verify the accuracy of published accounts.
文摘Based on dynamometer test cycles or plain motorway operation, heavy truck hybridisation must be considered as uneconomic if only the kinetic vehicle energy can be recuperated. In mountainous regions, micro hybridization by a 48V-belt generator or mild parallel hybridisation by a large high voltage electric drive can result in considerable fuel consumption savings as well as additional benefits for heavy load utility vehicles. Additional electric power and battery size are still critical design parameters as well as critical cost factors considering the limited space and depreciation time as well as the need for maximum payload. Based on vehicle model simulations, this contribution quantifies fuel consumption savings, recuperation energy harvesting and battery requirements for different truck sizes with test cycles based on realistic route topography. The main route topography parameter for the recuperation benefit is the effective incline that integrates all downhill sections that overcompensates the vehicle resistance by tire friction and air resistance. The simulation parameter studies lead to an analytical benefit estimation, based on load cycle parameters like effective velocity, effective incline as well as the vehicle parameters mass, drag coefficient and cross sectional area. Thus, the return on investment can be assessed by an analytic rule of thumb, based on tracked cycles of existing vehicles.
文摘Hybridisation was traditionally considered rare on coral reefs. However, a rapid increase in hybrid studies over the last 20 years has revealed that hybridisation on coral reefs is common and widespread. In this review, we summarise the growing body of evidence arising from studies on stony corals and reef fishes to verify the occurrence of hybridisatiori, and we examine the influence hybridisation has had on the enormous level of biodiversity present on coral reefs. We discuss the challenges of dis- tinguishing hybridisation from alternative hypotheses (e.g. incomplete lineage sorting). This review also explores the evolutio- nary consequences of hybridisation, which range from increasing genetic diversity and the production of novel lineages that may outperform the parent species, to reverse speciation and extinction by genetic swamping. Instances of hybridisation can be natural or occur as a result of human impacts (e.g. habitat degradation) and distinguishing between these two very different causal me- chanisms is important for management. Currently, the legislative status of hybrids is unclear and hybrids are rarely protected in conservation programs. Failing to adequately manage hybridisation and hybrid lineages may lead to potential losses of evolutio- nary novelty, declines in phylogenetic diversity or species extinctions. To conserve existing coral reef biodiversity, and the processes that generate biodiversity, conservation policies must be re-defined and instances of hybridisation must be assessed and managed on a case-by-case basis [Current Zoology 61 (1): 132 145, 2015].
文摘Advances in technology and optimisation are helping to improve decision making in the oil and gas industry.However,most of the traditional metaheuristic algorithms applied in well placement optimisation problems suffer from extensive parameter experimentations and local optimum trapping issues.This couples with the complex and heterogeneous nature of hydrocarbon reservoirs and increased decision variables poses severe simulation process demands.This study considered a functional composition integration approach to formulate a robust hybrid metaheuristic algorithm called HGWO-PSO.The HGWO-PSO leverages on the strengths of Grey Wolf Optimiser(GWO)and Particle Swarm Optimisation(PSO)and the Clerc's parameter setting considerations.A rigorous approach which enforces regulatory agreed minimum well spacing was incorporated in the optimisation process.Reservoir models ranging from unimodal to multimodal spatial systems were used as examples to test the explorative and exploitative capabilities of the algorithms.In this paper we show the performance curve and statistical analysis of HGWO-PSO as a well placement algorithm and compares its performance with that of standalone PSO,and GWO and the traditional Genetic Algorithm(GA).Results revealed that the HGWO-PSO demonstrated comparative performances in terms of exploration and exploitation obtaining the best optimal solutions which give highest contractor's NPVs in majority of cases considered.Again,the means and standard deviations for HGWO-PSO among the various runs showed consistent and efficient performance.The Wilcoxon signed rank test conducted gave very low p-values suggesting uniqueness of HGWO-PSO from the other metaheuristic variants.Additionally,the computational speed of HGWO-PSO was relatively better as compared to the individual GWO and PSO in most the test cases.The simulation results for all test cases confirm that implementation of HGWO-PSO can cause considerable improvement in locations of wells even in heterogeneous reservoirs.
基金supported by grant#2013.032.1 of the Wilhelm Sander-Stiftung.
文摘Aim:Murine tumour cell lines have been used in thousands of studies.Strikingly,it is rather the rule than exception for most of them that not much is known about their genetic characteristics.The squamous cell carcinoma(SCC)cell line KLN 205 is such an example.KLN 205 cells have not been studied yet for karyotype or acquired copy number variations(CNVs),but they have been used as models for(metastatic)lung cancer,lung-SCC,non-small cell lung cancer,tongue cancer and subcutaneous SCC.Here,it was characterised cytogenomically for the first time.Methods:The cell line KLN 205 was characterised comprehensively by molecular cytogenetics using multicolour banding as well as molecular karyotyping.Based on these results,a map of the imbalances and breakpoints determined in the murine genome was translated to the human genome.Results:Here,it could be shown that this>40-year-old cell line has a stable,approximately tetraploid karyotype comprising 77-82 chromosomes.However,there are few structural chromosomal aberrations:only six derivatives involving chromosomes 2,3,5,9,10 and/or 19 could be found.According to the literature,SCCs derived from different human tissues,as well as lung SCC and non-small cell lung cancer,display overall similar CNV patterns.Conclusion:Thus,according to the genetic profile found here,KLN 205 can be applied as a general model for human SCC;it is also suited as a model for lung cancer in general.Further molecular genetic characterisation of KLN 205 cell line may find more lung-and/or SCC-specific alterations.