ORCID Profile
0000-0003-1270-7209
Current Organisations
Prince of Wales Hospital
,
Westmead Hospital
,
Liverpool Hospital
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Publisher: Elsevier BV
Date: 02-2018
Publisher: American Chemical Society (ACS)
Date: 10-07-2009
DOI: 10.1021/JP9029437
Abstract: A high-level quantum chemistry investigation has been carried out for the abstraction by chlorine atom of hydrogen from methane and five monosubstituted methanes, chosen to reflect the chemical functionalities contained in amino acids and peptides. A modified W1' procedure is used to calculate benchmark barriers and reaction energies for the six reactions. The reactions demonstrate a broad range of barrier heights and reaction energies, which can be rationalized using curve-crossing and molecular orbital theory models. In addition, the performance of a range of computationally less demanding electronic structure methods is assessed for calculating the energy profiles for the six reactions. It is found that the G3X(MP2)-RAD procedure compares best with the W1' benchmark, demonstrating a mean absolute deviation (MAD) from W1' of 2.1 kJ mol(-1). The more economical RMP2/G3XLarge and UB2-PLYP/G3XLarge methods are also shown to perform well, with MADs from W1' of 2.9 and 3.0 kJ mol(-1), respectively.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2017
Publisher: Royal Society of Chemistry (RSC)
Date: 1997
DOI: 10.1039/A607437E
Publisher: Elsevier BV
Date: 2020
Publisher: Frontiers Media SA
Date: 15-10-2021
Abstract: Aims: There has been a paradigm shift in diagnosis of cardiac transthyretin amyloidosis (ATTR) with non-invasive techniques including technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid ( 99m Tc-DPD) bone scintigraphy. We evaluated structural and functional biventricular alterations by transthoracic echocardiography (TTE) and determined the correlation with 99m Tc-DPD tracer uptake in ATTR. Materials and Methods: ATTR patients (wild-type, hereditary or asymptomatic transthyretin [ TTR ] variant carriers) with 99m Tc-DPD and TTE were selected 99m Tc-DPD uptake was analyzed quantitatively. TTE assessment of left ventricle (LV) and right ventricle (RV) parameters was performed. Results: Forty ATTR patients (wild-type n = 17 hereditary ATTR and TTR variant carriers n = 23 median age 68.8 ± 22 years) were included. TTE parameters displaying good correlation with 99m Tc-DPD tracer uptake included LV average wall thickness ( r = 0.837), LV indexed mass (LVMI r = 0.802), RV wall thickness ( r = 0.610), average e' ( r = −0.830), E/e' ratio ( r = 0.786), LV global longitudinal strain (GLS r = 0.714) and RV GLS ( r = 0.632 p & 0.001 for all). Hereditary ATTR and TTR variant carriers without cardiac tracer uptake had normal echocardiographic parameters. Receiver operating characteristic curves demonstrated strong diagnostic accuracies for structural (LV wall thickness, LVMI and RV wall thickness area under the curve (AUC) of 0.96 for all) and functional (LV and RV GLS AUC of 0.86 and 0.88, respectively) parameters. Conclusion: Good correlations between TTE biventricular structural and functional parameters were demonstrated with quantitative 99m Tc-DPD uptake. Echocardiography may potentially assume a significant role in longitudinal follow-up for monitoring disease progression and for evaluating treatment response.
Publisher: Elsevier BV
Date: 02-2020
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.15_13198
Publisher: Elsevier BV
Date: 07-1995
DOI: 10.1016/0020-7519(94)00216-B
Abstract: Infection with Ostertagia circumcincta is a major constraint on sheep production in temperate areas of the world. A potential control strategy is the use of genetically resistant sheep. Therefore we examined the association between MHC-DRB1 alleles and faecal egg counts following natural, predominately O. circumcincta infection in a flock of Scottish Blackface sheep. Nineteen DRB1 alleles were identified by a combination of variation in the length of simple repetitive sequences within the intron between exons 2 and 3 and hybridisation of selected oligonucleotides to polymorphisms within exon 2. Faecal s les were taken from 200 lambs from one to six months of age at intervals of 4 weeks. Genetic effects were strongest at 6 months of age. Least-squares analysis indicated that substitution of the most common allele (I) by allele G2 would result in a 58-fold reduction in faecal egg counts in 6-month-old lambs and a 22-fold reduction in 5-month-old lambs. These results suggest that the major histocompatibility complex plays an important role in the development of resistance to O. circumcincta.
Publisher: Royal Society of Chemistry (RSC)
Date: 1998
DOI: 10.1039/A801172I
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.HLC.2022.01.006
Abstract: Cardiac transthyretin amyloidosis (ATTR) patients have high rates of atrial arrhythmias. We evaluated echocardiographic structural and functional left atrial (LA) parameters and correlated these with technetium-99m 3,3-diphosphono-1,2-propanodicarboxylic acid ( ATTR patients (wild-type, hereditary and asymptomatic transthyretin [TTR] variant carriers) who had undergone Forty (40) ATTR patients (wild-type n=17 hereditary ATTR and TTR variant carriers n=23 median age 68.8±22 years) were included. TTE parameters including indexed LA minimum (LAV Left atrial structural and functional parameters demonstrated good correlations with quantitative
Publisher: Elsevier BV
Date: 02-2020
Publisher: AIP Publishing
Date: 14-09-2004
DOI: 10.1063/1.1782191
Abstract: An ab initio investigation of the potential energy surfaces and vibrational energies and wave functions of the anion, neutral, and cation Cu(H2O) complexes is presented. The equilibrium geometries and harmonic frequencies of the three charge states of Cu(H2O) are calculated at the MP2 level of theory. CCSD(T) calculations predict a vertical electron detachment energy for the anion complex of 1.65 eV and a vertical ionization potential for the neutral complex of 6.27 eV. Potential energy surfaces are calculated for the three charge states of the copper-water complexes. These potential energy surfaces are used in variational calculations of the vibrational wave functions and energies and from these, the dissociation energies D0 of the anion, neutral, and cation charge states of Cu(H2O) are predicted to be 0.39, 0.16, and 1.74 eV, respectively. In addition, the vertical excitation energies, that correspond to the 4 2P←4 2S transition of the copper atom, and ionization potentials of the neutral Cu(H2O) are calculated over a range of Cu(H2O) configurations. In hydrogen-bonded, Cu-HOH configurations, the vertical excitation and ionization energies are blueshifted with respect to the corresponding values for atomic copper, and in Cu-OH2 configurations where the copper atom is located near the oxygen end of water, both quantities are redshifted.
Publisher: American Chemical Society (ACS)
Date: 08-1998
DOI: 10.1021/JP982272I
Publisher: AIP Publishing
Date: 14-09-2004
DOI: 10.1063/1.1782176
Abstract: The short-time nuclear dynamics of Cu(H2O) is investigated using femtosecond photodetachment-photoionization spectroscopy and time-dependent quantum wave packet calculations. The Cu(H2O) dynamics is initiated in the electronic ground state of the complex by electron photodetachment from the Cu−(H2O) complex, where hydrogen atoms are oriented toward Cu. Several time-resolved resonant multiphoton ionization schemes are used to probe the ensuing reorientation and dissociation. Immediately following photodetachment, the neutral complex is far from its minimum energy geometry and possesses an internal energy comparable to the Cu-H2O dissociation energy and undergoes both large- litude H2O motion and dissociation. Dissociation is observed to occur on three distinct time scales: 0.6, 8, and 100 ps. These results are compared to the results of time-dependent J=0 wave packet calculations, propagating the initial anion vibrational wave functions on the ground-state potential of the neutral complex. An excellent agreement is obtained between the experimental results and the ionization signals derived from the calculated probability litudes. Related experiments and calculations are carried out on the Cu(D2O) complex, with results very similar to those of Cu(H2O).
Publisher: American Chemical Society (ACS)
Date: 26-09-2011
DOI: 10.1021/JA205962B
Abstract: Quantum chemistry computations have been used to investigate hydrogen-atom abstraction by chlorine atom from protonated and N-acetylated amino acids. The results are consistent with the decreased reactivity at the backbone α-carbon and adjacent side-chain positions that is observed experimentally. The in idual effects of NH(3)(+), COOH, and NHAc substituents have been examined and reveal important insights. The NH(3)(+) group in isolation is found to be deactivating at the α-position, while the acetamido group is activating. For the COOH group, polar effects lead to a contrathermodynamic deactivation of the thermodynamically most favorable α-abstraction. In the N-acetylamino acid, the α-position is deactivated by the combined inductive effect of the substituents and the presence of an early transition structure, again overriding the greater thermodynamic stability of the α-centered radical product. Deactivation of the α-, β-, and γ-positions results in a peculiar stability for amino acids and peptides and their derivatives with respect to radical degradation.
Publisher: Royal Society of Chemistry (RSC)
Date: 1999
DOI: 10.1039/A805319G
Publisher: Wiley
Date: 12-07-2021
DOI: 10.1111/AJD.13659
Publisher: Elsevier BV
Date: 11-1997
Publisher: Informa UK Limited
Date: 23-07-2022
DOI: 10.1080/13506129.2022.2091985
Abstract: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. HELIOS-A enrolled 164 patients (vutrisiran, Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile. NCT03759379.
Publisher: Wiley
Date: 12-2022
DOI: 10.1111/IMJ.15974
Abstract: Amyloidosis is a collection of diseases caused by the misfolding of proteins that aggregate into insoluble amyloid fibrils and deposit in tissues. While these fibrils may aggregate to form insignificant localised deposits, they can also accumulate in multiple organs to the extent that amyloidosis can be an immediately life‐threatening disease, requiring urgent treatment. Recent advances in diagnostic techniques and therapies are dramatically changing the disease landscape and patient prognosis. Delays in diagnosis and treatment remain the greatest challenge, necessitating physician awareness of the common clinical presentations that suggest amyloidosis. The most common types are transthyretin (ATTR) amyloidosis followed by immunoglobulin light‐chain (AL) amyloidosis. While systemic AL amyloidosis was previously considered a death sentence with no effective therapies, significant improvement in patient survival has occurred over the past 2 decades, driven by greater understanding of the disease process, risk‐adapted adoption of myeloma therapies such as proteosome inhibitors (bortezomib) and monoclonal antibodies (daratumumab) and improved supportive care. ATTR amyloidosis is an underdiagnosed cause of heart failure. Technetium scintigraphy has made noninvasive diagnosis much easier, and ATTR is now recognised as the most common type of amyloidosis because of the increased identification of age‐related ATTR. There are emerging ATTR treatments that slow disease progression, decrease patient hospitalisations and improve patient quality of life and survival. This review aims to update physicians on recent developments in amyloidosis diagnosis and management and to provide a diagnostic and treatment framework to improve the management of patients with all forms of amyloidosis.
Publisher: Wiley
Date: 11-2018
DOI: 10.1111/IMJ.10_14079
Publisher: Royal Society of Chemistry (RSC)
Date: 1999
DOI: 10.1039/A808853E
Publisher: Oxford University Press (OUP)
Date: 2020
Abstract: An infiltrative cardiomyopathy is a common manifestation of AL-amyloidosis, with cardiac involvement associated with a poor prognosis. Wild-type transthyretin amyloidosis (wt-TTR), is a distinct clinical entity occurring predominantly in men & 65 yrs, that has gained interest recently due to novel treatment options. Regional strain analysis has been shown to discriminate both forms of cardiac amyloidosis from other causes of concentric left ventricular hypertrophy, with a characteristic pattern of ‘apical sparing’. Due to the significant difference in both the course of the disease and treatment options between groups, a non-invasive echocardiographic method of determining subtype would be valuable. Aim/Method: We sought to compare traditional and novel echocardiographic parameters in a cohort of AL ( n = 80) and wild type (wt-TTR) amyloid ( n = 32) patients. All amyloid patients underwent comprehensive transthoracic echocardiography, including both conventional parameters and LV longitudinal strain. Further novel parameters were computed including the ratio of global longitudinal strain (GLS) to LV ejection fraction (LVEF), as well as GLS to indexed LV mass. wt-TTR patients had significantly greater LV mass (176 ± 59g/m2vs118 ± 37g/m2, p & 0.001), and worse diastolic dysfunction as expressed as E/E’ (21.5 ± 11vs17 ± 8, p = 0.04). LVEF was significantly lower in wt-TTR patients however remained in the normal range in both groups (53 ± 6%vs57 ± 6%, p = 0.001), whilst GLS was significantly reduced compared to AL-amyloid patients (11.5 ± 3.4%vs16.2 ± 4.6%, p & 0.001). LVEF:GLS was significantly higher in wt-TTR patients (4.93 ± 1.4vs3.87 ± 1.3, p = 0.001) reflecting a more profound reduction in strain with a relatively preserved ejection fraction. Similarly, the ratio of GLS to LV mass was significantly lower in wt-TTR amyloidosis (0.078 ± 0.05vs0.155 ± 0.07, p & 0.001), reflecting a more significant reduction in strain for a given wall thickness in wt-TTR patients. GLS:LV mass was the strongest discriminator between subtypes (AUC 0.82), with a cutoff of 0.09 giving a sensitivity and specificity of 71% and 80% respectively, for detecting wt-TTR. In this cohort, patients with wt-TTR had significantly greater increase in LV wall thickness and diastolic dysfunction, which may in part reflect their increased age (77vs62). However, GLS was also significantly reduced compared to AL-amyloid, even when accounting for LV ejection fraction and LV mass, suggesting these composite parameters may have value in determining the subtype of cardiac amyloidosis.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Frontiers Media SA
Date: 03-07-2023
DOI: 10.3389/FCVM.2023.1183485
Abstract: Differentiating phenotypes of cardiac “hypertrophy” characterised by increased wall thickness on echocardiography is essential for management and prognostication. Transthoracic echocardiography is the most commonly used screening test for this purpose. We sought to identify echocardiographic markers that distinguish infiltrative and storage disorders that present with increased left ventricular (LV) wall thickness, namely, cardiac amyloidosis (CA) and Anderson–Fabry disease (AFD), from hypertensive heart disease (HHT). Patients were retrospectively recruited from Westmead Hospital, Sydney, and Princess Alexandra Hospital, Brisbane. LV structural, systolic, and diastolic function parameters, as well as global (LVGLS) and segmental longitudinal strains, were assessed. Previously reported echocardiographic parameters including relative apical sparing ratio (RAS), LV ejection fraction-to-strain ratio (EFSR), mass-to-strain ratio (MSR) and amyloidosis index (AMYLI) score (relative wall thickness × E / e ′) were evaluated. A total of 209 patients {120 CA [58 transthyretin amyloidosis (ATTR) and 62 light-chain (AL) amyloidosis], 31 AFD and 58 HHT patients mean age 64.1 ± 13.7 years, 75% male} comprised the study cohort. Echocardiographic measurements differed across the three groups, The LV mass index was higher in both CA {median 126.6 [interquartile range (IQR) 106.4–157.9 g/m 2 ]} and AFD [median 134 (IQR 108.8–152.2 g/m 2 )] vs. HHT [median 92.7 (IQR 79.6–102.3 g/m 2 ), p & 0.05]. LVGLS was lowest in CA [median 12.29 (IQR 10.33–15.56%)] followed by AFD [median 16.92 (IQR 14.14–18.78%)] then HHT [median 18.56 (IQR 17.51–19.97%), p & 0.05]. Diastolic function measurements including average e ′ and E / e ′ were most impaired in CA and least impaired in AFD. Indexed left atrial volume was highest in CA. EFSR and MSR differentiated secondary (CA + AFD) from HHT [receiver operating curve–area under the curve (ROC-AUC) of 0.80 and 0.91, respectively]. RAS and AMYLI score differentiated CA from AFD (ROC-AUC of 0.79 and 0.80, respectively). A linear discriminant analysis with stepwise variable selection using linear combinations of LV mass index, average e ′, LVGLS and basal strain correctly classified 79% of all cases. Simple echocardiographic parameters differentiate between different “hypertrophic” cardiac phenotypes. These have potential utility as a screening tool to guide further confirmatory testing.
Publisher: Elsevier BV
Date: 03-2020
Publisher: Royal Society of Chemistry (RSC)
Date: 2004
DOI: 10.1039/B316330J
Abstract: Ultrafast pump-probe studies of I2- recombination in size-selected I2- (CO2)n cluster ions demonstrate long time coherent motions in size-selected clusters and the resulting non-statistical energy flow in the cluster. For I2- photodissociated to produce either I- + I or I- + I*, we identify a solvent-driven energy transfer process without a condensed phase counterpart. The mechanism involved is a Marcus-like solvent-driven curve crossing, with the driving force arising from asymmetric solvation, not just from solvent orientation. By substituting another halogen for one I atom, we "break" the I2- symmetry, and thus obtain direct information on the electron transfer process. New experiments on IBr- (CO2)n photodissociation products confirm the behavior suspected in the I2- studies. Time-resolved experiments on IBr- and theoretical modeling of the dynamics provide quantitative information on the multiple curve crossings encountered in the recombination process. In related investigations, femtosecond negative ion-neutral-positive ion charge reversal apparatus is employed to investigate transient neutral species evolving along a reaction coordinate. We report studies of the rearrangement dynamics of Cu(OH2) produced by photodetachment of the corresponding anion. Following a controlled delay period, a second ultrafast tunable laser pulse initiates resonant multiphoton photoionization of the time-evolving Cu...OH2 complex. The time-resolved Cu+ and Cu+(OH2) signals provide information both on the prompt dissociation of the complex and on energy redistribution between internal rotational and radial modes of the evolving complex. Calculations of the time evolution of the anion geometric configuration on the neutral potential energy surface yield deeper insight into the nature of the rearrangement process and the energy flow within the complex.
Publisher: Elsevier BV
Date: 2020
Publisher: SAGE Publications
Date: 1998
DOI: 10.1255/EJMS.197
Publisher: Royal Society of Chemistry (RSC)
Date: 1998
DOI: 10.1039/A800364E
Publisher: Elsevier BV
Date: 09-2023
Publisher: Elsevier BV
Date: 2021
Publisher: Massachusetts Medical Society
Date: 26-10-2023
Publisher: Elsevier BV
Date: 04-1999
Publisher: Wiley
Date: 19-12-2022
DOI: 10.1002/SKI2.200
Abstract: We present a series of five cases who presented to our institution with treatment‐refractory mucosal ulceration, all of whom were subsequently diagnosed with paraneoplastic pemphigus (PNP). This case series highlights the diagnostic and treatment considerations for PNP – in particular, the steroid‐dependent, recalcitrant, polymorphic manifestations the combination of histopathological and clinical findings that may overlap with clinically similar diseases, for ex le, pemphigus vulgaris and lichen planus the importance of immunopathological findings for its diagnosis, and the need for surveillance and management of life‐threatening bronchiolitis obliterans.
Publisher: Elsevier BV
Date: 2020
Publisher: AIP Publishing
Date: 18-01-2005
DOI: 10.1063/1.1836759
Abstract: The ultrafast relaxation dynamics of Cu(H2O)2 is investigated using femtosecond photodetachment-photoionization spectroscopy. In addition, stationary points on the Cu(H2O)2 anion, neutral, and cation potential energy surfaces are characterized by ab initio electronic structure calculations. Electron photodetachment from Cu−(H2O)2 initiates the dynamics on the ground-state potential energy surface of neutral Cu(H2O)2. The resulting Cu(H2O)2 complexes experience large- litude H2O reorientation and dissociation. The time evolution of the Cu(H2O)2 fragmentation products is monitored by time-resolved resonant multiphoton ionization. The parent ion, Cu+(H2O)2, is not detected above background levels. The rise to a maximum of the Cu+ signal from Cu−(H2O)2, and the decay of the Cu+(H2O) signal from Cu−(H2O)2 have similar τ≈10 ps time dependences to the corresponding signals from Cu−(H2O), but display clear differences at very short and long times. The experimental observations can be understood in terms of the following picture. Prompt dissociation of H2O from nascent Cu(H2O)2 gives rise to a vibrationally excited Cu(H2O) complex, which dissociates to Cu+H2O due to coupling of H2O internal rotation to the dissociation coordinate. This prompt dissociation removes all intra-H2O vibrational excitation from the intermediate Cu(H2O) fragment, which quenches the long time vibrational predissociation to Cu+H2O previously observed in analogous experiments on Cu−(H2O).
Publisher: Royal Society of Chemistry (RSC)
Date: 1997
DOI: 10.1039/A701965C
Publisher: Informa UK Limited
Date: 21-02-2022
DOI: 10.1080/13506129.2022.2026914
Abstract: Cardiac involvement in AL amyloidosis portends a poor prognosis. 2D-speckle tracking echocardiography (2D-STE) strain can identify subclinical cardiac involvement. This study performed multilayer and multiplanar 2D-STE myocardial strain analysis. We compared 75 AL amyloidosis patients to 49 hypertensive patients and 49 healthy controls. Longitudinal strain was obtained from epicardial, mid-myocardial and endocardial layers segmental strain was measured from mid-myocardial basal, mid and apical segments. Global longitudinal strain was reduced in epicardial (-14.3 ± -4.0% vs. -17.4 ± 2.2% vs. -17.5 ± -2.0%, Strain demonstrated myocardial involvement in all layers in AL amyloidosis, with reduced basal segmental longitudinal strain a likely marker of early disease.
No related grants have been discovered for Mark Taylor.