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Breath Biopsy^(®) to Identify Exhaled Volatile Organic compounds Biomarkers for Liver cirrhosis Detection

Journal of clinical and Translational Hepatology 2023年第3期11卷 638-648页

作者： Giuseppe Ferrandino Giovanna De Palo Antonio Murgia Owen Birch Ahmed Tawfike Rob Smith Irene Debiram-Beecham Olga Gandelman Graham Kibble Anne Marie Lydon Alice Groves Agnieszka Smolinska Max Allsworth Billy Boyle Marc P.van der Schee Michael Allison rebecca c.fitzgerald Matthew Hoare Victoria K.Snowdon Owlstone Medical CambridgeUK Department of Oncology University of CambridgeHutchison/MRC Research CentreCambridgeUK Department of Pharmacology and Toxicology School for Nutrition and Translational Research in Metabo-lism(NUTRIM)Maastricht University Medical Centerthe Netherlands Department of Medicine University of CambridgeAddenbrooke’s HospitalCambridgeUK Addenbrookes Hepatology and Liver Transplantation Unit Addenbrookes Hospi-talCambridgeUK MRc cancer Unit Hutchison/MRC Research CentreUniversity of CambridgeCambridgeUK cRUK cambridge Institute CambridgeUK

Background and Aims:The prevalence of chronic liver dis-ease in adults exceeds 30%in some countries and there is significant interest in developing tests and treatments to help control disease progression and reduce healthcare *** is a rich sampling matrix that offers non-invasive so-lutions suitable for early-stage detection and disease *** previously investigated targeted analysis of a single biomarker,here we investigated a multiparametric approach to breath testing that would provide more robust and reliable results for clinical ***:To identify can-didate biomarkers we compared 46 breath samples from cir-rhosis patients and 42 from *** and analysis used Breath Biopsy OMNI™,maximizing signal and contrast to background to provide high confidence biomarker detec-tion based upon gas chromatography mass spectrometry(Gc-MS).Blank samples were also analyzed to provide de-tailed information on background volatile organic compounds(VOcs)***:A set of 29 breath VOcs differed significantly between cirrhosis and controls.A classification model based on these VOcs had an area under the curve(AUc)of 0.95±0.04 in cross-validated test *** seven best performing VOcs were sufficient to maximize classifica-tion performance.A subset of 11 VOcs was correlated with blood metrics of liver function(bilirubin,albumin,prothrom-bin time)and separated patients by cirrhosis severity using principal component ***:A set of seven VOcs consisting of previously reported and novel candidates show promise as a panel for liver disease detection and mon-itoring,showing correlation to disease severity and serum biomarkers at late stage.

关键词： Breath Biopsy Non-invasive Biomarker cirrhosis Liver function test.

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Timely completion of multiple life-saving interventions for traumatic haemorrhagic shock: a retrospective cohort study

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Burns & Trauma 2019年第1期7卷 204-212页

作者： Biswadev Mitra Jordan Bade-Boon Mark c.fitzgerald Ben Beck Peter A.cameron National Trauma Research Institute The Alfred Hospital89 Commercial RoadMelbourneVIC 3004Australia Emergency&Trauma centre The Alfred HospitalMelbourneAustralia School of Public Health and Preventive Medicine Monash University MelbourneAustralia Trauma Service The Alfred HospitalMelbourneAustralia Faculty of Medicine Laval University Quebec City QuebecCanada

Background:Early control of haemorrhage and optimisation of physiology are guiding principles of resuscitation after *** outcomes have been previously associated with single,timely *** aim of this study was to assess the association between multiple timely life-saving interventions(LSIs)and outcomes of traumatic haemorrhagic shock ***:A retrospective cohort study was undertaken of injured patients with haemorrhagic shock who presented to Alfered Emergency&Trauma centre between July 01,2010 and July 31,*** studied included chest decompression,control of external haemorrhage,pelvic binder application,transfusion of red cells and coagulation products and surgical control of bleeding through angio-embolisation or operative *** primary exposure variable was timely initiation of≥50%of the indicated *** association between the primary exposure variable and outcome of death at hospital discharge was adjusted for potential confounders using multivariable logistic regression *** association between total pre-hospital times and pre-hospital care times(time from ambulance at scene to trauma centre),in-hospital mortality and timely initiation of≥50%of the indicated interventions were ***:Of the 168 patients,54(32.1%)patients had≥50%of indicated LSI completed within the specified time *** delivery of LSI was independently associated with improved survival to hospital discharge(adjusted odds ratio(OR)for in-hospital death 0.17;95%confidence interval(cI)0.03–0.83;p=0.028).This association was independent of patient age,pre-hospital care time,injury severity score,initial serum lactate levels and *** patients with pre-hospital time of≥2 h,2(3.6%)received timely ***-hospital care times of≥2 h were associated with delayed LSIs and with in-hospital death(unadjusted OR 4.3;95%cI 1.4–13.0).conclusions:Timely completion of LSI when indicated was completed in a small

关键词： Wounds Bundle of care Haemorrhage shock Resuscitation Emergency department Blood products Timely life-saving interventions Trauma Injuries

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Biomarkers in Barrett's esophagus and esophageal adenocarcinoma:Predictors of progression and prognosis

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World Journal of Gastroenterology 2010年第45期16卷 5669-5681页

作者： chin-Ann J Ong Pierre Lao-Sirieix rebecca c.fitzgerald MRc cancer cell Unit Hutchison-MRC Research CentreCambridgeCB20XZUnited Kingdom

Barrett’s esophagus is a well-known premalignant lesion of the lower esophagus that is characterized by intestinal metaplasia of the squamous epithelium. It is clinically important due to the increased risk (0.5% per annum) of progression to esophageal adenocarcinoma (EA), which has a poor outcome unless diagnosed early. The current clinical management of Barrett’s esophagus is hampered by the lack of accurate predictors of progression. In addition, when patients develop EA, the current staging modalities are limited in stratifying patients into different prognostic groups in order to guide the optimal therapy for an individual patient. Biomarkers have the potential to improve radically the clinical management of patients with Barrett’s esophagus and EA but have not yet entered mainstream clinical practice. This is in contrast to other cancers like breast and prostate for which biomarkers are utilized routinely to inform clinical decisions. This review aims to highlight the most promising predictive and prognostic biomarkers in Barrett’s esophagus and EA and to discuss what is required to move the field forward towards clinical application.

关键词： Barrett’s esophagus Esophageal adenocar cinoma Esophageal dysplasia Prognosis

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Reconciling concepts, theory, and empirical patterns surrounding cascade reinforcement

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current Zoology 2016年第2期62卷 131-134页

作者： rebecca c. FULLER Department of Animal Biology University of Illinois Urbana IL 61801 USA

IntroductionReinforcement is a critically important process in speciation. It has been credited with often completing speciation, and it is unique in that natural selection directly favors the evolution of reproductive isolating barriers. Reinforcement occurs when selection favors increased prezygotic isolation between two lineages in order to avoid maladaptive hybridization in areas of sympatry （Noor 1999; Servedio and Noor 2003; coyne and Orr 2004）.

关键词：调和加固梯级

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Male-driven reproductive and agonistic character displacement in darters and its implications for speciation in allopatry

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current Zoology 2018年第1期64卷 101-113页

作者： Rachel L. MORAN rebecca c. FULLER School of Integrative Biology University of Illinois Champaign IL 61820 USA

Selection against hybridization can cause mating traits to diverge between species in sympatry via reproductive character displacement （RcD）. Additionally, selection against interspecific fighting can cause aggressive traits to diverge between sympatric species via agonistic character displacement （AcD）. By directly affecting conspecific recognition traits, RcD and AcD between species can also incidentally cause divergence in mating and fighting traits among populations within a species [termed cascade RcD （cRcD） and cascade AcD]. Here, we demonstrate patterns consistent with male-driven RcD and AcD in 2 groups of darters （orangethroat darter clade ceasia and rainbow darter Etheostoma caeruleum）. In both groups, males that occur in sympatry （between ceasia and E. caeruleum） have higher levels of preference for mating and fighting with conspecifics over heterospecifics than do males from allopatry. This is consistent with RcD and AcD. We also found patterns consistent with cRcD and cascade AcD among species of ceasia. ceasia males that are sympatric to E. caeruleum （but allopatric to one another） also have heightened preferences for mat- ing and fighting with conspecific versus heterospecific ceasia. In contrast, ceasia males that are allopatric to E. caeruleum readily mate and fight with heterospecific ceasia. We suggest that RcD and AcD between ceasia and E. caeruleum has incidentally led to divergence in mating and fighting traits among ceasia species. This study is unique in that male preferences evolve via both RcD （male preference for conspecific females） and AcD （male preference to fight conspecific males） which leads to subsequent divergence among allopatric lineages.

关键词： agonistic character displacement behavioral isolation cascade reinforcement reinforcement reproductive charac-ter displacement speciation.

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Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals

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cellular & Molecular Immunology 2017年第1期14卷 118-126页

作者： Jelena S Bezbradica rebecca c coll Kate Schroder Institute for Molecular Bioscience (IMB) IMB Centre for Inflammation and Disease Research and Australian Infectious Diseases Research Centre The University of Queensland Brisbane St Lucia Queensland 4072 Australia

Inflammation is the host response to microbial infection or sterile injury that aims to eliminate the insult, repair the tissue and restore homeostasis. Macrophages and the NLRP3 inflammasome are key sentinels for both types of insult. Although it is well established that the NLRP3 inflammasome is activated by microbial products and molecules released during sterile injury, it is unclear whether the responses elicited by these different types of signals are distinct. In this study, we used lipopolysaccharide and tumor necrosis factor as prototypical microbial and sterile signal 1 stimuli, respectively, to prime the NLRP3 inflammasome. We then used the bacterial toxin nigericin and a common product released from necrotic cells, ATP, as prototypical microbial and sterile signal 2 stimuli, respectively, to trigger the assembly of the NLRP3 inflammasome complex in mouse and human macrophages. We found that NLRP3 inflammasome responses were weakest when both signal 1 and signal 2 were sterile, but responses were faster and stronger when at least one of the two signals was microbial. Ultimately, the most rapid and potent responses were elicited when both signals were microbial. Together, these data suggest that microbial versus sterile signals are distinct, both kinetically and in magnitude, in their ability to generate inflammasome-dependent responses. This hierarchy of NLRP3 responses to sterile versus microbial stimuli likely reflects the urgent need for the immune system to respond rapidly to the presence of infection to halt pathogen dissemination.

关键词： inflammasome NLRP3 sterile inflammation TNF

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Efficient above-band-gap light emission in germanium

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chinese Optics Letters 2009年第4期7卷 271-273页

作者： Kenneth E.Lee Eugene A.fitzgerald Lionel c.Kimerling Jurgen Michel Department of Materials Science and Engineering Microphotonics CenterMassachusetts Institute of Technology

We report an above-band-gap radiative transition in the photoluminescence spectra of single crystalline Ge in the temperature range of 20-296 K. The temperature-independence of the peak position at -0.74 eV is remarkably different from the behavior of direct and indirect gap transitions in Ge. This transition is observed in n-type, p-type, and intrinsic single crystal Ge alike, and its intensity decreases with the increase of temperature with a small activation energy of 56 meV. Some aspects of the transition are analogous to III-V semiconductors with dilute nitrogen doping, which suggests that the origin could be related to an isoelectronic defect.

关键词： Activation energy Germanium Photoluminescence Semiconductor doping Single crystals

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A perspective on sensory drive

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current Zoology 2018年第4期64卷 465-470页

作者： rebecca c. FULLER John A. ENDLER Department of Animal Biology School of Integrative Biology University of Illinois at Urbana-Champaign Champaign IL 61820 USA centre for Integrative Ecology School of Life and Environmental Sciences Deakin University Waurn Ponds VIC 3216 Australia

In 1992, The American Naturalist published a special supplement entitled：＂Sensory Drive. Does Sensory Drive Biology Bias or constrain the Direction of Evolution？＂ organized by John Endler. The supplement contained a seminal paper on ＂sensory drive＂ by Endler （1992a） as well as several other well-cited papers on sensory exploitation （Ryan and Keddy-Hector 1992）.

关键词：开车博物学生物学报纸

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Asymmetric reinforcement in Lucania killifish:assessing reproductive isolation when both sexes choose

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current Zoology 2021年第2期67卷 215-224页

作者： Michelle E.ST.JOHN rebecca c.FULLER School of Integrative Biology University of liois Urbana-ChampaignChampaignIL 61820USA

Reinforcement can occur when maladaptive hybridization in sympatry favors the evolution of con-specific preferences and target traits that promote behav ioral isolation(BI).In many systems,enhanced BI is due to increased female preference for *** others,BI is driven by male preference,and in other systems both sexes exert *** of these patterns can be atributed to classic sex-specific costs and benefits of ***,sex differences in conspecific preference can emerge due to asymmetric postzygotic isolation(e.g.,hybrid offspring from female A × male B have lower fitness than hybrid offspring from female B × male A),which can lead to asymmetric BI(e.g.,female A and male B are less likely to mate than female B and male A).Understanding reinforcement requires understanding how conspecific preferences evolve in ***,estimating conspecific preferences can be difficult when both sexes are *** this study,we use Lucania killifish to test the hypothesis that patterns of reinforcement are driven by asymmetric postzygotic isolation between *** true,we predicted that sympatric female Lucania goodei and sympatric male *** should have lower levels of BI compared with their sympatric counterparts,as they produce hybrid offspring with the highest *** address the problem of measuring BI when both sexes are choosy,we inferred the contribution to BI of each partner using assays where one sex in the mating pair comes from an allopatric population with potentially low preference,whereas the other comes from a sympatric population with high *** one hybrid cross direction,we found that both female *** and male *** have high contributions to BI in *** the other hybrid cross direction,we found that only female *** contribute to *** male *** readily engaged in hybrid spawnings with allo-patric *** *** results indicate that both asymmetric postzygotic isolation

关键词： reinforcement behavioral isolatin female mate choice male mate choice asymmetric costs to hybridization

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Viral hepatitis in 2021:The challenges remaining and how we should tackle them

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World Journal of Gastroenterology 2022年第1期28卷 76-95页

作者： rebecca Dunn Aaron Wetten Stuart McPherson Mhairi c Donnelly Gastroenterology University Hospital of North TeesStockton on Tees TS198PEUnited Kingdom Liver Unit Freeman HospitalNewcastle NE77DNUnited Kingdom Translational and clinical Research Institute Newcastle UniversityNewcastle NE17RUUnited Kingdom

Viral hepatitis results in 1.4 million deaths *** World Health Organization(WHO)set an ambitious target to eliminate viral hepatitis by 2030,but significant challenges *** include inequalities in access to healthcare,reaching at risk populations and providing access to screening and effective *** around viral hepatitis persists and must be *** WHO goal of global elimination by 2030 is a worthy aim,but remains ambitious and the coronavirus 2019 pandemic undoubtedly has set back *** review article will focus on hepatitis A to E,highlighting problems that have been resolved in the field over the past decade,those that remain to be resolved and suggest directions for future problem solving and research.

关键词： Hepatitis A Hepatitis B Hepatitis c Hepatitis D Hepatitis E cOVID-19

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