Publications by authors named "Ben Costello"

22 Publications

  • Page 1 of 1

Catheter Ablation Versus Medication in Atrial Fibrillation and Systolic Dysfunction: Late Outcomes of CAMERA-MRI Study.

JACC Clin Electrophysiol 2020 Dec 28;6(13):1721-1731. Epub 2020 Oct 28.

Department of Cardiology, The Baker Heart Research Institute, Melbourne, Australia; Department of Cardiology, The Alfred Hospital, Melbourne, Australia; Department of Cardiology, University of Melbourne, Melbourne, Australia. Electronic address:

Objectives: This study sought to determine the long-term outcomes of restoring sinus rhythm with catheter ablation (CA).

Background: The CAMERA-MRI (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Heart Failure-An MRI-Guided Multicenter Randomized Controlled Trial) study demonstrated that restoration of sinus rhythm with CA significantly improved left ventricular ejection fraction (LVEF) compared with medical rate control (MRC) at 6 months in persistent atrial fibrillation and otherwise unexplained systolic heart failure. However, the long-term outcomes have not been reported.

Methods: Patients enrolled in the CAMERA-MRI study were followed for 4 years with echocardiogram and cardiac magnetic resonance. CA involved pulmonary vein isolation and posterior left atrial wall isolation in 94%. Patients crossed over to CA after 6-month study duration. Arrhythmia burden was determined with implanted cardiac monitors or cardiac devices.

Results: Sixty-six patients (age 62 ± 10 years, atrial fibrillation duration of 22 ± 16 months, and LVEF 33 ± 9%) were randomized 1:1 to CA versus MRC. Eighteen of 33 patients crossed over from MRC group to CA group. At 4.0 ± 0.9 years, atrial fibrillation recurred in 27 patients (57%) in the CA group with a mean burden of 10.6 ± 21.2% after 1.4 ± 0.6 procedures. There was an absolute increase in LVEF with CA of 16.4 ± 13.3% compared with 8.6 ± 7.6% in MRC (p = 0.001). In the CA group, the absence of ventricular late gadolinium enhancement was associated with a greater improvement in absolute LVEF (19 ± 13% vs. 10 ± 11% in the late gadolinium enhancement-positive group; p = 0.04) and LVEF normalization in 19 patients (58%) versus 4 patients (18%) in the late gadolinium enhancement-positive group (p = 0.008) at 4.0 ± 0.9 years follow-up.

Conclusions: CA is superior to MRC in improving LVEF in the long term in patients with atrial fibrillation and systolic heart failure. The greatest recovery in systolic function was demonstrated in the absence of ventricular fibrosis on cardiac magnetic resonance.
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http://dx.doi.org/10.1016/j.jacep.2020.08.019DOI Listing
December 2020

Can post-mortem coronary artery calcium scores aid diagnosis in young sudden death?

Forensic Sci Med Pathol 2021 Mar 14;17(1):27-35. Epub 2020 Nov 14.

Victorian Institute of Forensic Medicine, 65 Kavanagh St, Southbank, VIC, 3006, Australia.

This study sought to explore the feasibility and utility of post-mortem coronary artery calcium (CAC) scoring in identifying patients with ischemic heart disease as cause of sudden death. 100 deceased patients aged 18-50 years underwent post-mortem examination in the setting of sudden death. At post-mortem, fifty cases were determined to have ischemic heart disease, and fifty had death attributed to trauma or unascertained causes. The CAC score was calculated in a blinded manner from post-mortem CTs performed on all cases. CAC scores were assessable in 97 non-decomposed cases (feasibility 97%). The median CAC score was 88 Agatston units [IQR 0-286] in patients deceased from ischemic heart disease vs 0 [IQR 0-0] in patients deceased from other causes (p < 0.0001). Presence of any coronary calcification differed significantly between ischemic heart disease and non-ischemic groups (adjusted odds ratio 10.7, 95% CI 3.2-35.5). All cases with a CAC score > 100 (n = 22) had ischemic heart disease as the cause of death. Fifteen cases had a CAC score of zero but severe coronary disease at post-mortem examination. Post-mortem CAC scoring is highly feasible. An elevated CAC score in cases 18-50 years old with sudden death predicts ischemic heart disease at post-mortem examination. However, a CAC score of zero does not exclude significant coronary artery disease. Post-mortem CAC score may be considered as a further assessment tool to help predict likely cause of death when there is an objection to or unavailability of post-mortem examination.
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http://dx.doi.org/10.1007/s12024-020-00335-zDOI Listing
March 2021

Towards the Identification of Antibiotic-Resistant Bacteria Causing Urinary Tract Infections Using Volatile Organic Compounds Analysis-A Pilot Study.

Antibiotics (Basel) 2020 Nov 11;9(11). Epub 2020 Nov 11.

Department of Applied Sciences, Faculty of Health and Applied Sciences, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK.

Antibiotic resistance is an unprecedented threat to modern medicine. The analysis of volatile organic compounds (VOCs) from bacteria potentially offers a rapid way to determine antibiotic susceptibility in bacteria. This study aimed to find the optimal conditions to obtain the maximum number of VOCs detected which next allowed the assessment of differences in VOC profiles between susceptible and resistant isolates of causing urinary tract infections. The analysis of VOCs in the headspace above the bacterial cultures allowed the distinguishing of resistant and susceptible bacteria based on the abundance of six VOCs with 85.7% overall accuracy. The results of this preliminary study are promising, and with development could lead to a practical, faster diagnostic method for use in routine microbiology.
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http://dx.doi.org/10.3390/antibiotics9110797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697827PMC
November 2020

The Australia and New Zealand Cardio-Oncology Registry: evaluation of chemotherapy-related cardiotoxicity in a national cohort of paediatric cancer patients.

Intern Med J 2021 Feb;51(2):229-234

Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, Australia.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.
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http://dx.doi.org/10.1111/imj.14719DOI Listing
February 2021

Impact of sex, socio-economic status, and remoteness on therapy and survival in heart failure.

ESC Heart Fail 2019 10 16;6(5):944-952. Epub 2019 Oct 16.

Department of Cardiology, The Alfred Hospital, Melbourne, Victoria, Australia.

Aims: This study aims to determine if traditional markers of disadvantage [female sex, low socio-economic status (SES), and remoteness] are associated with lower prescription of evidence-based therapy and higher mortality among patients with moderate-severe heart failure with reduced ejection fraction.

Methods And Results: We recruited 452 consecutive class II-III heart failure with reduced ejection fraction patients. Baseline clinical data were recorded prospectively. The primary outcome was the association of female sex on overall survival. Secondary outcomes included association between evidence-based therapy delivery and sex and association of SES and remoteness on heart failure therapy and survival. The Australian Bureau of Statistics generated all indices. Median follow-up was 37.9 months. One hundred and nine patients (24.3%) were women. There was no difference in overall survival based on sex (hazard ratio = 1.19, 95% confidence interval: 0.74-1.92, 0.48). There was no difference in prescription of beta-blockers [χ (1) = 0.91, 0.66], angiotensin-converting enzyme inhibitors [χ (1) = 0.001, 0.97], nor aldosterone antagonists [χ (1) = 2.71, 0.10]. There was no difference in rates of primary prevention implantable cardioverter-defibrillator implantation in men compared with women [χ (1) = 0.35, 0.56]. Neither higher SES nor inner city residence conferred an overall survival benefit.

Conclusions: In this Australian cohort of heart failure patients, delivery of care and likelihood of death are comparable between the sexes, SES groups, and rural vs. city residents.
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http://dx.doi.org/10.1002/ehf2.12481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816230PMC
October 2019

The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia.

Blood Adv 2019 04;3(7):1084-1091

Department of Clinical Haematology, Austin Hospital, Melbourne, Australia.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age ( = .022) and dyslipidemia ( = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued ( = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.
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http://dx.doi.org/10.1182/bloodadvances.2018028035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457217PMC
April 2019

Regression of Diffuse Ventricular Fibrosis Following Restoration of Sinus Rhythm With Catheter Ablation in Patients With Atrial Fibrillation and Systolic Dysfunction: A Substudy of the CAMERA MRI Trial.

JACC Clin Electrophysiol 2018 08 27;4(8):999-1007. Epub 2018 Jun 27.

Department of Cardiology, Alfred Hospital, Victoria, Australia; Baker IDI Heart and Diabetes Institute, Victoria, Australia; Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Victoria, Australia. Electronic address:

Objectives: This study sought to determine if diffuse ventricular fibrosis improves in patients with atrial fibrillation (AF)-mediated cardiomyopathy following the restoration of sinus rhythm.

Background: AF coexists in 30% of heart failure (HF) patients and may be an underrecognized reversible cause of left ventricular systolic dysfunction. Myocardial fibrosis is the hallmark of adverse cardiac remodeling in HF, yet its reversibility is unclear.

Methods: Patients with persistent AF and an idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%) were randomized to catheter ablation (CA) or ongoing medical rate control as a pre-specified substudy of the CAMERA-MRI (Catheter Ablation versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction-an MRI-Guided Multi-centre Randomised Controlled Trial) trial. All patients had cardiac magnetic resonance imaging scans (including myocardial T1 time), serum B-type natriuretic peptide, 6-min walk tests, and Short Form-36 questionnaires performed at baseline and 6 months. Sixteen patients with no history of AF or left ventricular systolic dysfunction were enrolled as normal controls for T1 time.

Results: Thirty-six patients (18 in each treatment arm) were included in this substudy. Demographics, comorbidities, and myocardial T1 times were well matched at baseline. At 6 months, patients in the CA group had a significant reduction in myocardial T1 time from baseline compared with the medical rate control group (-124 ms; 95% confidence interval [CI]: -23 to -225 ms; p = 0.0176), although it remained higher than that of normal controls at 6 months (p = 0.0017). Improvements in myocardial T1 time with CA were associated with significant improvements in absolute LVEF (+12.5%; 95% CI: 5.9% to 19.0%; p = 0.0004), left ventricular end-systolic volume (p = 0.0019), and serum B-type natriuretic peptide (-216 ng/l; 95% CI: -23 to -225 ng/l; p = 0.0125).

Conclusions: The improvement in LVEF and reverse ventricular remodeling following successful CA of AF-mediated cardiomyopathy is accompanied by a regression of diffuse fibrosis. This suggests timely treatment of arrhythmia-mediated cardiomyopathy may minimize irreversible ventricular remodeling.
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http://dx.doi.org/10.1016/j.jacep.2018.04.013DOI Listing
August 2018

Medical Management of Rheumatic Heart Disease: A Systematic Review of the Evidence.

Cardiol Rev 2018 Jul/Aug;26(4):187-195

School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.

Rheumatic heart disease (RHD) is an important cause of heart disease globally. Its management can encompass medical and procedural (catheter and surgical) interventions. Literature pertaining to the medical management of RHD from PubMed 1990-2016 and via selected article reference lists was reviewed. Areas included symptom management, left ventricular dysfunction, rate control in mitral stenosis, atrial fibrillation, anticoagulation, infective endocarditis prophylaxis, and management in pregnancy. Diuretics, angiotensin blockade and beta-blockers for left ventricular dysfunction, and beta-blockers and If inhibitors for rate control in mitral stenosis reduced symptoms and improved left ventricular function, but did not alter disease progression. Rhythm control for atrial fibrillation was preferred, and where this was not possible, rate control with beta-blockers was recommended. Anticoagulation was indicated where there was a history of cardioembolism, atrial fibrillation, spontaneous left atrial contrast, and mechanical prosthetic valves. While warfarin remained the agent of choice for mechanical valve implantation, non-vitamin K antagonist oral anticoagulants may have a role in RHD-related AF, particularly with valvular regurgitation. Evidence for anticoagulation after bioprosthetic valve implantation or mitral valve repair was limited. RHD patients are at increased risk of endocarditis, but the evidence supporting antibiotic prophylaxis before procedures that may induce bacteremia is limited and recommendations vary. The management of RHD in pregnancy presents particular challenges, especially regarding decompensation of previously stable disease, the choice of anticoagulation, and the safety of medications in both pregnancy and breast feeding.
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http://dx.doi.org/10.1097/CRD.0000000000000185DOI Listing
October 2018

The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia.

Blood Adv 2017 May 15;1(13):802-811. Epub 2017 May 15.

Austin Hospital, Melbourne, Australia.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion ( < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced ( = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions ( = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.
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http://dx.doi.org/10.1182/bloodadvances.2016003889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727806PMC
May 2017

Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction: The CAMERA-MRI Study.

J Am Coll Cardiol 2017 Oct 27;70(16):1949-1961. Epub 2017 Aug 27.

The Baker Heart & Diabetes Institute, Clinical Electrophysiology Research, Melbourne, Australia; The Heart Centre, The Alfred Hospital, Melbourne, Australia; Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia. Electronic address:

Background: Atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) frequently co-exist despite adequate rate control. Existing randomized studies of AF and LVSD of varying etiologies have reported modest benefits with a rhythm control strategy.

Objectives: The goal of this study was to determine whether catheter ablation (CA) for AF could improve LVSD compared with medical rate control (MRC) where the etiology of the LVSD was unexplained, apart from the presence of AF.

Methods: This multicenter, randomized clinical trial enrolled patients with persistent AF and idiopathic cardiomyopathy (left ventricular ejection fraction [LVEF] ≤45%). After optimization of rate control, patients underwent cardiac magnetic resonance (CMR) to assess LVEF and late gadolinium enhancement, indicative of ventricular fibrosis, before randomization to either CA or ongoing MRC. CA included pulmonary vein isolation and posterior wall isolation. AF burden post-CA was assessed by using an implanted loop recorder, and adequacy of MRC was assessed by using serial Holter monitoring. The primary endpoint was change in LVEF on repeat CMR at 6 months.

Results: A total of 301 patients were screened; 68 patients were enrolled between November 2013 and October 2016 and randomized with 33 in each arm (accounting for 2 dropouts). The average AF burden post-CA was 1.6 ± 5.0% at 6 months. In the intention-to-treat analysis, absolute LVEF improved by 18 ± 13% in the CA group compared with 4.4 ± 13% in the MRC group (p < 0.0001) and normalized (LVEF ≥50%) in 58% versus 9% (p = 0.0002). In those undergoing CA, the absence of late gadolinium enhancement predicted greater improvements in absolute LVEF (10.7%; p = 0.0069) and normalization at 6 months (73% vs. 29%; p = 0.0093).

Conclusions: AF is an underappreciated reversible cause of LVSD in this population despite adequate rate control. The restoration of sinus rhythm with CA results in significant improvements in ventricular function, particularly in the absence of ventricular fibrosis on CMR. This outcome challenges the current treatment paradigm that rate control is the appropriate strategy in patients with AF and LVSD. (Catheter Ablation Versus Medical Rate Control in Atrial Fibrillation and Systolic Dysfunction [CAMERA-MRI]; ACTRN12613000880741).
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http://dx.doi.org/10.1016/j.jacc.2017.08.041DOI Listing
October 2017

Chemotherapy-related cardiotoxicity: are Australian practitioners missing the point?

Intern Med J 2017 Oct;47(10):1166-1172

Cardiac Development Laboratory, Murdoch Children's Research Institute, Melbourne, Victoria, Australia.

Background: It has long been established that cardiotoxicity occurs as a result of exposure to certain chemotherapeutics, particularly anthracyclines. Historically, clinicians equate cardiotoxicity with a poor prognosis, in a small percentage of patients and deem long-term surveillance as optional. Emerging evidence suggests that anthracycline cardiotoxicity (ACT) is a life-long risk with an incidence approaching 20%.

Aims: To elucidate the incidence of anthracycline cardiotoxicity within a current paediatric oncology survivor cohort.

Methods: Participants were identified through the Haematology-Oncology database at the Royal Children's Hospital, Melbourne. Patients were identified from a retrospective audit of outpatient attendances between January 2008 and December 2015. Patients with a cancer diagnosis exposed to anthracyclines were eligible for the study. Patient demographics and echocardiogram findings were recorded with patients subcategorised according to degree of ACT. More significant ACT defined as fractional shortening (FS) <24% and less significant if FS 24-28% or a decline in baseline ejection fraction of >10%.

Results: Two hundred and eighty-six of a total 481 identified patients were eligible for study inclusion. Twenty patients displayed significant ACT with FS <24%. Ten patients had a FS 24-28% and 25 patients with a decline in ejection fraction from baseline of >10%. Overall, 6.6% demonstrated significant cardiac complications, whilst 19.6 % demonstrated some degree of ACT and decline in myocardial function. When stratified for cumulative anthracycline dose, the incidence of severe cardiac dysfunction was 5.1% (<250 mg/m ) and 25% (>250 mg/m ) CONCLUSION: This study demonstrates, in keeping with modern literature, the higher incidence of anthracycline associated cardiac toxicity and a need for better surveillance and follow up.
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http://dx.doi.org/10.1111/imj.13481DOI Listing
October 2017

Detecting bladder cancer using volatile analyses: is this the future?

Bioanalysis 2014 May;6(9):1147-50

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http://dx.doi.org/10.4155/bio.14.44DOI Listing
May 2014

The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva.

J Breath Res 2014 Sep 19;8(3):034001. Epub 2014 Jun 19.

Univ-Clinic for Anesthesia and Intensive Care, Innsbruck Medical University, Anichstr, 35, A-6020 Innsbruck, Austria. Breath Research Institute of the University of Innsbruck, Rathausplatz 4, A-6850 Dornbirn, Austria.

Breath analysis is a young field of research with its roots in antiquity. Antoine Lavoisier discovered carbon dioxide in exhaled breath during the period 1777-1783, Wilhelm (Vilém) Petters discovered acetone in breath in 1857 and Johannes Müller reported the first quantitative measurements of acetone in 1898. A recent review reported 1765 volatile compounds appearing in exhaled breath, skin emanations, urine, saliva, human breast milk, blood and feces. For a large number of compounds, real-time analysis of exhaled breath or skin emanations has been performed, e.g., during exertion of effort on a stationary bicycle or during sleep. Volatile compounds in exhaled breath, which record historical exposure, are called the 'exposome'. Changes in biogenic volatile organic compound concentrations can be used to mirror metabolic or (patho)physiological processes in the whole body or blood concentrations of drugs (e.g. propofol) in clinical settings-even during artificial ventilation or during surgery. Also compounds released by bacterial strains like Pseudomonas aeruginosa or Streptococcus pneumonia could be very interesting. Methyl methacrylate (CAS 80-62-6), for example, was observed in the headspace of Streptococcus pneumonia in concentrations up to 1420 ppb. Fecal volatiles have been implicated in differentiating certain infectious bowel diseases such as Clostridium difficile, Campylobacter, Salmonella and Cholera. They have also been used to differentiate other non-infectious conditions such as irritable bowel syndrome and inflammatory bowel disease. In addition, alterations in urine volatiles have been used to detect urinary tract infections, bladder, prostate and other cancers. Peroxidation of lipids and other biomolecules by reactive oxygen species produce volatile compounds like ethane and 1-pentane. Noninvasive detection and therapeutic monitoring of oxidative stress would be highly desirable in autoimmunological, neurological, inflammatory diseases and cancer, but also during surgery and in intensive care units. The investigation of cell cultures opens up new possibilities for elucidation of the biochemical background of volatile compounds. In future studies, combined investigations of a particular compound with regard to human matrices such as breath, urine, saliva and cell culture investigations will lead to novel scientific progress in the field.
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http://dx.doi.org/10.1088/1752-7155/8/3/034001DOI Listing
September 2014

An investigation of fecal volatile organic metabolites in irritable bowel syndrome.

PLoS One 2013 13;8(3):e58204. Epub 2013 Mar 13.

Department of Gastroenterology, University of Bristol/Bristol Royal Infirmary, Bristol, United Kingdom.

Diagnosing irritable bowel syndrome (IBS) can be a challenge; many clinicians resort to invasive investigations in order to rule out other diseases and reassure their patients. Volatile organic metabolites (VOMs) are emitted from feces; understanding changes in the patterns of these VOMs could aid our understanding of the etiology of the disease and the development of biomarkers, which can assist in the diagnosis of IBS. We report the first comprehensive study of the fecal VOMs patterns in patients with diarrhea-predominant IBS (IBS-D), active Crohn's disease (CD), ulcerative colitis (UC) and healthy controls. 30 patients with IBS-D, 62 with CD, 48 with UC and 109 healthy controls were studied. Diagnosis of IBS-D was made using the Manning criteria and all patients with CD and UC met endoscopic, histologic and/or radiologic criteria. Fecal VOMs were extracted by solid phase microextraction (SPME) and analyzed by gas chromatography-mass spectrometry (GC-MS). 240 VOMs were identified. Univariate analysis showed that esters of short chain fatty acids, cyclohexanecarboxylic acid and its ester derivatives were associated with IBS-D (p<0.05), while aldehydes were more abundant in IBD (p<0.05). A predictive model, developed by multivariate analysis, separated IBS-D from active CD, UC and healthy controls with a sensitivity of 94%, 96% and 90%; and a specificity of 82%, 80% and 80% respectively (p<0.05). The understanding of the derivation of these VOMs may cast light on the etiology of IBS-D and IBD. These data show that fecal VOMs analyses could contribute to the diagnosis of IBS-D, for which there is no laboratory test, as well as IBD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0058204PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596408PMC
September 2013

A digital health solution for using and managing medications: wirelessly observed therapy.

IEEE Pulse 2012 Sep-Oct;3(5):23-6

Proteus Digital Health Incorporated, Redwood City, California, USA.

Taking oral medication on a prescribed schedule can be a nuisance, especially for elderly individuals and busy people with lots of things on their minds. Nonetheless, taking medication as prescribed is important for maintaining health and well-being. In cases where medication use is part of a clinical trial, taking prescribed medication is important to the entire investigation and outcome of the study, including the determination of whether a drug is effective and safe.
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http://dx.doi.org/10.1109/MPUL.2012.2205777DOI Listing
February 2013

Time-dependent wave selection for information processing in excitable media.

Phys Rev E Stat Nonlin Soft Matter Phys 2012 Jun 26;85(6 Pt 2):066129. Epub 2012 Jun 26.

Faculty of Environment and Technology, University of the West of England, Bristol BS16 1QY, United Kingdom.

We demonstrate an improved technique for implementing logic circuits in light-sensitive chemical excitable media. The technique makes use of the constant-speed propagation of waves along defined channels in an excitable medium based on the Belousov-Zhabotinsky reaction, along with the mutual annihilation of colliding waves. What distinguishes this work from previous work in this area is that regions where channels meet at a junction can periodically alternate between permitting the propagation of waves and blocking them. These valvelike areas are used to select waves based on the length of time that it takes waves to propagate from one valve to another. In an experimental implementation, the channels that make up the circuit layout are projected by a digital projector connected to a computer. Excitable channels are projected as dark areas and unexcitable regions as light areas. Valves alternate between dark and light: Every valve has the same period and phase, with a 50% duty cycle. This scheme can be used to make logic gates based on combinations of or and and-not operations, with few geometrical constraints. Because there are few geometrical constraints, compact circuits can be implemented. Experimental results from an implementation of a four-bit input, two-bit output integer square root circuit are given.
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http://dx.doi.org/10.1103/PhysRevE.85.066129DOI Listing
June 2012

Physarum attraction: Why slime mold behaves as cats do?

Commun Integr Biol 2012 May;5(3):297-9

University of the West of England; Bristol, UK.

We discuss potential chemical substances responsible for attracting acellular slime mold Physarun polycephalum to valerian root. The contributes toward fundamental research into pheromones and chemo-attracts of primitive organisms such as slime molds. The results show that significant information could be gained about the action of compounds on higher organisms.
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http://dx.doi.org/10.4161/cib.19924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419120PMC
May 2012

Transient ST-segment elevation resembling acute myocardial infarction in a patient with a right secondary spontaneous pneumothorax.

Heart Lung Circ 2013 Feb 15;22(2):149-52. Epub 2012 Jul 15.

Department of Cardiology, Royal Hobart Hospital, Tasmania, Australia.

A rare cause of ST-segment elevation mimicking myocardial infarction has been reported in the setting of acute pneumothorax. We present a middle-aged woman with a right-sided secondary pneumothorax who developed severe chest pain associated with ST-segment elevation suggestive of acute myocardial infarction. Symptoms resolved immediately after advancement of the dislodged chest drain. A subsequent coronary angiogram was normal. This case highlights an uncommon electrocardiographic alteration and discusses possible pathophysiological mechanisms.
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http://dx.doi.org/10.1016/j.hlc.2012.06.006DOI Listing
February 2013

Computing with liquid crystal fingers: models of geometric and logical computation.

Phys Rev E Stat Nonlin Soft Matter Phys 2011 Dec 12;84(6 Pt 1):061702. Epub 2011 Dec 12.

Unconventional Computing Centre, University of the West of England, Bristol BS16 1QY, UK.

When a voltage is applied across a thin layer of cholesteric liquid crystal, fingers of cholesteric alignment can form and propagate in the layer. In computer simulation, based on experimental laboratory results, we demonstrate that these cholesteric fingers can solve selected problems of computational geometry, logic, and arithmetics. We show that branching fingers approximate a planar Voronoi diagram, and nonbranching fingers produce a convex subdivision of concave polygons. We also provide a detailed blueprint and simulation of a one-bit half-adder functioning on the principles of collision-based computing, where the implementation is via collision of liquid crystal fingers with obstacles and other fingers.
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http://dx.doi.org/10.1103/PhysRevE.84.061702DOI Listing
December 2011

Logical and arithmetic circuits in Belousov-Zhabotinsky encapsulated disks.

Phys Rev E Stat Nonlin Soft Matter Phys 2011 Nov 23;84(5 Pt 2):056110. Epub 2011 Nov 23.

Faculty of Environment and Technology, University of the West of England, Bristol, England.

Excitation waves on a subexcitable Belousov-Zhabotinsky (BZ) substrate can be manipulated by chemical variations in the substrate and by interactions with other waves. Symbolic assignment and interpretation of wave dynamics can be used to perform logical and arithmetic computations. We present chemical analogs of elementary logic and arithmetic circuits created entirely from interconnected arrangements of individual BZ encapsulated cell-like disk. Interdisk wave migration is confined in carefully positioned connecting pores. This connection limits wave expansion and unifies the input-output characteristic of the disks. Circuit designs derived from numeric simulations are optically encoded onto a homogeneous photosensitive BZ substrate.
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http://dx.doi.org/10.1103/PhysRevE.84.056110DOI Listing
November 2011

Analysis of faecal volatile organic compounds in preterm infants who develop necrotising enterocolitis: a pilot study.

J Pediatr Gastroenterol Nutr 2009 Nov;49(5):559-65

Clinical Science at South Bristol, Bristol Royal Infirmary, Marlborough St, Bristol, UK.

Objective: : To determine differences in the profiles of volatile organic compounds (VOCs) in faecal samples from preterm infants who develop necrotising enterocolitis (NEC) compared with non-NEC controls.

Materials And Methods: : Daily faecal samples from preterm infants were collected prospectively during an 8-month period from a level 3 regional neonatal intensive care unit. Six infants subsequently developed NEC and were matched with 7 non-NEC infants. Solid-phase microextraction and gas chromatography and mass spectrometry were used to extract and identify the VOCs from the headspace above the faecal samples taken before the onset of NEC and after the disease was diagnosed. Faecal samples at similar ages were also studied from the control infants.

Results: : Two hundred twenty-four different VOCs were extracted from 65 samples. Volatile organic compounds increased in number with age for non-NEC infants. In the days before and after the diagnosis of NEC a reduction in the number of VOCs extracted was observed. In addition, 4 specific esters present in controls-2-ethylhexyl acetic ester, decanoic acid ethyl ester, dodecanoic acid ethyl ester, and hexadecanoic acid ethyl ester-were consistently absent from all faecal samples in those infants who developed NEC in the 4 days before the onset of the disease.

Conclusion: : This pilot study shows that VOC extraction from faeces may be used to identify infants that are at risk of developing NEC.
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http://dx.doi.org/10.1097/MPG.0b013e3181a3bfbcDOI Listing
November 2009

An intronic variant of the TGFBR1 gene is associated with carcinomas of the kidney and bladder.

Int J Cancer 2004 Nov;112(3):420-5

Wood Hudson Cancer Research Laboratory, Newport, KY, USA.

TGF-beta signaling is frequently perturbed in many human cancers, including renal cell carcinomas (RCCs) and transitional cell carcinomas (TCCs) of the bladder. Genetic alterations of the TGF-beta type 1 receptor (TGFBR1) may contribute to these perturbations. We therefore examined variations in the TGFBR1 gene by PCR, SSCP and RFLP in carcinomas of the urinary system and in tissues from noncancer, age-matched controls. A G-->A variant 24 bp downstream of the exon/intron 7 boundary of the TGFBR1 gene (Int7G24A) was evident in patients with RCC (46.5%, n = 86) and bladder and upper urinary tract TCC (49.2%, n = 65) significantly more frequently than in age-matched controls (28.3%, n = 113, p < 0.002 by chi2 test). Moreover, 8 homozygous variant carriers were found in the cancer groups, whereas not a single homozygous variant carrier was found in the control group. The Int7G24A allele (both heterozygous G/A and homozygous A/A carriers) was associated with increased RCC incidence (OR = 2.20, 95% CI 1.22-3.96) and TCC incidence (OR = 2.45, 95% CI 1.89-3.16). One somatic mutation of serine to phenylalanine at codon 57 of the TGFBR1 gene was confirmed in an upper urinary tract TCC. In conclusion, the Int7G24A variant in the TGFBR1 gene is significantly more frequent in patients with RCC and TCC than normal age-matched controls, suggesting that it may represent a risk factor for the development of kidney and bladder carcinomas.
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http://dx.doi.org/10.1002/ijc.20419DOI Listing
November 2004