Downward myocardial creep during stress PET imaging is inversely associated with mortality.

PURPOSE: The myocardial creep is a phenomenon in which the heart moves from its original position during stress-dynamic PET myocardial perfusion imaging (MPI) that can confound myocardial blood flow measurements. Therefore, myocardial motion correction is important to obtain reliable myocardial flow quantification. However, the clinical importance of the magnitude of myocardial creep has not been explored. We aimed to explore the prognostic value of myocardial creep quantified by an automated motion correction algorithm beyond traditional PET-MPI imaging variables. METHODS: Consecutive patients undergoing regadenoson rest-stress [82Rb]Cl PET-MPI were included. A newly developed 3D motion correction algorithm quantified myocardial creep, the maximum motion at stress during the first pass (60 s), in each direction. All-cause mortality (ACM) served as the primary endpoint. RESULTS: A total of 4,276 patients (median age 71 years; 60% male) were analyzed, and 1,007 ACM events were documented during a 5-year median follow-up. Processing time for automatic motion correction was < 12 s per patient. Myocardial creep in the superior to inferior (downward) direction was greater than the other directions (median, 4.2 mm vs. 1.3-1.7 mm). Annual mortality rates adjusted for age and sex were reduced with a larger downward creep, with a 4.2-fold ratio between the first (0 mm motion) and 10th decile (11 mm motion) (mortality, 7.9% vs. 1.9%/year). Downward creep was associated with lower ACM after full adjustment for clinical and imaging parameters (adjusted hazard ratio, 0.93; 95%CI, 0.91-0.95; p < 0.001). Adding downward creep to the standard PET-MPI imaging model significantly improved ACM prediction (area under the receiver operating characteristics curve, 0.790 vs. 0.775; p < 0.001), but other directions did not (p > 0.5). CONCLUSIONS: Downward myocardial creep during regadenoson stress carries additional information for the prediction of ACM beyond conventional flow and perfusion PET-MPI. This novel imaging biomarker is quantified automatically and rapidly from stress dynamic PET-MPI.

How and why do financial incentives contribute to helping people stop smoking? A realist review.

BACKGROUND: Tobacco smoking remains a key cause of preventable illness and death globally. In response, many countries provide extensive services to help people to stop smoking by offering a variety of effective behavioural and pharmacological therapies. However, many people who wish to stop smoking do not have access to or use stop smoking supports, and new modes of support, including the use of financial incentives, are needed to address this issue. A realist review of published international literature was undertaken to understand how, why, for whom, and in which circumstances financial incentives contribute to success in stopping smoking for general population groups and among pregnant women. METHODS: Systematic searches were undertaken from inception to February 2022 of five academic databases: MEDLINE (ovid), Embase.com, CIHAHL, Scopus and PsycINFO. Study selection was inclusive of all study designs. Twenty-two studies were included. Using Pawson and Tilley's iterative realist review approach, data collected were screened, selected, coded, analysed, and synthesised into a set of explanatory theoretical findings. RESULTS: Data were synthesised into six Context-Mechanism-Outcome Configurations and one overarching programme theory after iterative rounds of analysis, team discussion, and expert panel feedback. Our programme theory shows that financial incentives are particularly useful to help people stop smoking if they have a financial need, are pregnant or recently post-partum, have a high threshold for behaviour change, and/or respond well to external rewards. The incentives work through a number of mechanisms including the role their direct monetary value can play in a person's life and through a process of reinforcement where they can help build confidence and self-esteem. CONCLUSION: This is the first realist review to synthesise how, why, and for whom financial incentives work among those attempting to stop smoking, adding to the existing evidence demonstrating their efficacy. The findings will support the implementation of current knowledge into effective programmes which can enhance the impact of stop smoking care. PROSPERO REGISTRATION NUMBER: CRD42022298941.

Mitigating bias in deep learning for diagnosis of coronary artery disease from myocardial perfusion SPECT images.

PURPOSE: Artificial intelligence (AI) has high diagnostic accuracy for coronary artery disease (CAD) from myocardial perfusion imaging (MPI). However, when trained using high-risk populations (such as patients with correlating invasive testing), the disease probability can be overestimated due to selection bias. We evaluated different strategies for training AI models to improve the calibration (accurate estimate of disease probability), using external testing. METHODS: Deep learning was trained using 828 patients from 3 sites, with MPI and invasive angiography within 6 months. Perfusion was assessed using upright (U-TPD) and supine total perfusion deficit (S-TPD). AI training without data augmentation (model 1) was compared to training with augmentation (increased sampling) of patients without obstructive CAD (model 2), and patients without CAD and TPD < 2% (model 3). All models were tested in an external population of patients with invasive angiography within 6 months (n = 332) or low likelihood of CAD (n = 179). RESULTS: Model 3 achieved the best calibration (Brier score 0.104 vs 0.121, p < 0.01). Improvement in calibration was particularly evident in women (Brier score 0.084 vs 0.124, p < 0.01). In external testing (n = 511), the area under the receiver operating characteristic curve (AUC) was higher for model 3 (0.930), compared to U-TPD (AUC 0.897) and S-TPD (AUC 0.900, p < 0.01 for both). CONCLUSION: Training AI models with augmentation of low-risk patients can improve calibration of AI models developed to identify patients with CAD, allowing more accurate assignment of disease probability. This is particularly important in lower-risk populations and in women, where overestimation of disease probability could significantly influence down-stream patient management.

Is the public ready for a tobacco-free Ireland? A national survey of public knowledge and attitudes to tobacco endgame in Ireland.

AIM: Ireland will not meet the tobacco endgame goal set in its 2013 Tobacco-Free Ireland (TFI) policy of reducing smoking prevalence to less than 5% by 2025. Public opinion on tobacco endgame, a key lever to realise this goal, is uncharted in Ireland. This study aimed to measure public knowledge and attitudes to tobacco endgame. METHODS: A telephone-administered cross-sectional survey of 1000 randomly dialled members of the general public was conducted in 2022. Prevalence of awareness, perceived achievability and support for the TFI goal and tobacco endgame measures was calculated and compared across tobacco product use status. Logistic regression identified factors independently associated with goal support. FINDINGS: Although TFI goal awareness was low (34.0%), support was high (74.6%), although most (60.2%) believed it achievable beyond 2025. Product-focused measures were popular while support for supply-focused measures was mixed: for example, 86.1% supported nicotine content reduction while 40.3% supported user licencing. Phasing out tobacco sales was highly supported (82.8%); for most, this was contingent on support for currently addicted users. TFI goal support was independently associated with female sex (adjusted odds ratio (aOR) 1.47, 95% CI 1.05 to 2.07), higher education (aOR 1.80, 95% CI 1.21 to 2.66) and non-tobacco product use (aOR 2.67, 95% CI 1.66 to 4.30). CONCLUSIONS: Despite low awareness, tobacco endgame support is strong in Ireland. Public appetite for radically reducing tobacco product appeal and availability combined with public views on endgame achievability subject to extended timelines should be used to re-invigorate tobacco endgame discussion and planning in countries at risk of failing to meet declared targets.

Taming Tris(bipyridine)ruthenium(II) and Its Reactions in Water by Capture/Release with Shape-Switchable Symmetry-Matched Cyclophanes.

Electron/proton transfers in water proceeding from ground/excited states are the elementary reactions of chemistry. These reactions of an iconic class of molecules─polypyridineRu(II)─are now controlled by capturing or releasing three of them with hosts that are shape-switchable. Reversible erection or collapse of the host walls allows such switchability. Some reaction rates are suppressed by factors of up to 120 by inclusive binding of the metal complexes. This puts nanometric coordination chemistry in a box that can be open or shut as necessary. Such second-sphere complexation can allow considerable control to be exerted on photocatalysis, electrocatalysis, and luminescent sensing involving polypyridineRu(II) compounds. The capturing states of hosts are symmetry-matched to guests for selective binding and display submicromolar affinities. A perching complex, which is an intermediate state between capturing and releasing states, is also demonstrated.

Improved myocardial blood flow estimation with residual activity correction and motion correction in 18F-flurpiridaz PET myocardial perfusion imaging.

PURPOSE: We sought to evaluate the diagnostic performance for coronary artery disease (CAD) of myocardial blood flow (MBF) quantification with 18F-flurpiridaz PET using motion correction (MC) and residual activity correction (RAC). METHODS: In total, 231 patients undergoing same-day pharmacologic rest and stress 18F-flurpiridaz PET from Phase III Flurpiridaz trial (NCT01347710) were studied. Frame-by-frame MC was performed and RAC was accomplished by subtracting the rest residual counts from the dynamic stress polar maps. MBF and myocardial flow reserve (MFR) were derived with a two-compartment early kinetic model for the entire left ventricle (global), each coronary territory, and 17-segment. Global and minimal values of three territorial (minimal vessel) and segmental estimation (minimal segment) of stress MBF and MFR were evaluated in the prediction of CAD. MBF and MFR were evaluated with and without MC and RAC (1: no MC/no RAC, 2: no MC/RAC, 3: MC/RAC). RESULTS: The area-under the receiver operating characteristics curve (AUC [95% confidence interval]) of stress MBF with MC/RAC was higher for minimal segment (0.89 [0.85-0.94]) than for minimal vessel (0.86 [0.81-0.92], p = 0.03) or global estimation (0.81 [0.75-0.87], p < 0.0001). The AUC of MFR with MC/RAC was higher for minimal segment (0.87 [0.81-0.93]) than for minimal vessel (0.83 [0.76-0.90], p = 0.014) or global estimation (0.77 [0.69-0.84], p < 0.0001). The AUCs of minimal segment stress MBF and MFR with MC/RAC were higher compared to those with no MC/RAC (p < 0.001 for both) or no MC/no RAC (p < 0.0001 for both). CONCLUSIONS: Minimal segment MBF or MFR estimation with MC and RAC improves the diagnostic performance for obstructive CAD compared to global assessment.

Association between electronic cigarette use and tobacco cigarette smoking initiation in adolescents: a systematic review and meta-analysis.

BACKGROUND: This systematic review of prospective longitudinal primary studies sought to determine whether electronic cigarette (e-cigarette) use by teenagers who had never smoked conventional tobacco cigarettes (tobacco cigarettes) at baseline was associated with subsequently commencing tobacco cigarette smoking. METHODS: The review followed the principles of a systematic review and meta-analysis. A key word search identified peer-reviewed articles published between 1 January 2005 and 2 October 2019 from seven bibliographic databases and one search engine. Using pre-prepared inclusion/exclusion criteria two researchers independently screened abstracts, and subsequently, full text papers. Selected articles were quality assessed in duplicate. Data on study participants characteristics, exposure and outcome measures were recorded in an adapted Cochrane Data Extraction Form. Feasibility assessment was done to detect clinical heterogeneity and choose an approach to meta-analysis. Analysis comprised pairwise random effects meta-analyses, and sensitivity and subgroup analyses. RESULTS: From the 6619 studies identified, 14 one-off primary studies in 21 articles were suitable for inclusion. The participants ages ranged from 13 to 19 years and comprised teenagers based in Europe and North America. Nine of the 14 one-off studies, with follow-up periods between 4 and 24 months, met the criteria for inclusion in a meta-analysis of the association between ever use of e-cigarettes and subsequent initiation of tobacco cigarette use. Based on primary study adjusted odds ratios, our meta-analysis calculated a 4.06 (95% confidence interval (CI): 3.00-5.48, I2 68%, 9 primary studies) times higher odds of commencing tobacco cigarette smoking for teenagers who had ever used e-cigarettes at baseline, though the odds ratio were marginally lower (to 3.71 times odds, 95%CI: 2.83-4. 86, I2 35%, 4 primary studies) when only the four high-quality studies were analysed. CONCLUSION: The systematic review found that e-cigarette use was associated with commencement of tobacco cigarette smoking among teenagers in Europe and North America, identifying an important health-related harm. Given the availability and usage of e-cigarettes, this study provides added support for urgent response by policymakers to stop their use by teenagers to decrease direct harms in this susceptible population group, as well as to conserve achievements in diminishing tobacco cigarette initiation.

Short-Term Air Pollution as a Risk for Stroke Admission: A Time-Series Analysis.

BACKGROUND: The harmful effects of outdoor air pollution on stroke incidence are becoming increasingly recognised. We examined the impact of different air pollutants (PM2.5, PM10, NO2, ozone, and SO2) on admission for all strokes in two Irish urban centres from 2013 to 2017. METHODS: Using an ecological time series design with Poisson regression models, we analysed daily hospitalisation for all strokes and is-chaemic stroke by residence in Dublin or Cork, with air pollution level monitoring data with a lag of 0-2 days from exposure. Splines of temperature, relative humidity, day of the week, and time were included as confounders. Analysis was also performed across all four seasons. Data are presented as relative risks (RRs) and 95% confidence intervals (95% CI) per interquartile range (IQR) increase in each pollutant. RESULTS: There was no significant association between all stroke admission and any individual air pollutant. On seasonal analysis, during winter in the larger urban centre (Dublin), we found an association between all stroke cases and an IQR increase in NO2 (RR 1.035, 95% CI: 1.003-1.069), PM10 (RR 1.032, 95% CI: 1.007-1.057), PM2.5 (RR 1.024, 95% CI: 1.011-1.039), and SO2 (RR 1.035, 95% CI: 1.001-1.071). There was no significant association found in the smaller urban area of Cork. On meta-analysis, there remained a significant association between NO2 (RR 1.013, 95% CI: 1.001-1.024) and PM2.5 (1.009, 95% CI 1.004-1.014) per IQR increase in each. DISCUSSION: Short-term air pollution in winter was found to be associated with hospitalisation for all strokes in a large urban centre in Ireland. As Ireland has relatively low air pollution internationally, this highlights the need to introduce policy changes to reduce air pollution in all countries.

Detection and quantitation of right ventricular reversible perfusion defects by stress SPECT myocardial perfusion imaging: A proof-of-principle study.

BACKGROUND: In patients with right dominant coronary circulation, the right ventricular (RV) myocardium and the inferior region of the left ventricular (LV) myocardium share a common source of blood flow. We hypothesized that stress/rest SPECT myocardial perfusion imaging (MPI) could detect reversible perfusion defects in the RV in some patients with LV inferior wall perfusion abnormalities. MATERIAL AND METHODS: We identified 2 groups of patients with LV inferior wall perfusion defects (with or without defects in other regions of LV myocardium) from our database. Patients in group 1 (n = 17) had reversible perfusion defects in the RV free wall by visual analysis, while patients in group 2 (n = 17) did not. The images were processed with filtered back projection and, separately, with iterative reconstruction. The images were then re-processed using an automated quantitative software that is specifically designed to include the RV in the region of interest. RESULTS: There were 76% men in group 1 and 94% in group 2 (P <0.05). The mean age was 65±20 in group 1 vs. 63±18 years in group 2 (P < 0.05). The stress type was exercise in 30% in group 1 and 35% in group 2, with the remaining patients studied with pharmacological stress testing (P = NS). The presence of RV reversible perfusion defects using filtered back projection was more evident in 13 patients (75%), while it was better seen with iterative reconstruction in 4 patients (25%). By automated analysis, the RV reversible perfusion defect size was 19 ± 14% of RV myocardium. CONCLUSION: This proof-of-principle study demonstrates that reversible RV perfusion defects suggestive of ischemia can be detected by SPECT myocardial perfusion imaging in some patients with LV inferior ischemia by visual analysis and can be quantitated by automated programs. Further studies on the diagnostic and prognostic relevance of assessing RV ischemia on SPECT MPI are needed.

Comparison of the health and well-being of smoking and non-smoking school-aged children in Ireland.

BACKGROUND: Although most young people are aware of the long-term consequences of smoking, it has been shown that young smokers expect to give up before any health damage occurs. Little is known in an Irish context about the association between smoking and young people's current health. This could be helpful to help reduce smoking initiation and encouraging quitting. The study aimed to determine the association between smoking and health and well-being indicators among Irish school-aged children. METHODS: The 2014 Irish Health Behaviour in School-aged Children study was analysed, which comprised a random stratified sample of 9,623 schoolchildren (aged 10-18). The prevalence of eight self-reported health complaints and two subjective well-being measures were compared across strata classified by self-reported smoking status using Pearson's chi square and independent t tests. Logistic regression and ordinal regression were used to control for age, gender, and social class. RESULTS: A significantly larger proportion of smokers (p < .001) reported fair to poor health (32% versus 11% for non-smokers), lower mean life satisfaction scores (6.2 compared with 7.5), and each of eight health complaints at least once a week (range = 25-50% compared with 15-21%). These patterns remained significant after adjusting for differences in age, gender, and social class profile (p < .001). CONCLUSIONS: The study demonstrates the potential of developing initiatives, which target smoking in adolescence as opposed to the longer term health effects of smoking which are well known. The findings can be utilized to counteract positive perceptions of smoking among schoolchildren. This, combined with providing supports to help children quit, may help achieve government targets to reduce smoking prevalence.

Factors influencing trainee doctor emigration in a high income country: a mixed methods study.

BACKGROUND: The Global Code of Practice on the International Recruitment of Health Personnel focuses particularly on migration of doctors from low- and middle-income countries. Less is understood about migration from high-income countries. Recession has impacted several European countries in recent years, and in some cases emigration has reached unprecedented levels. This study measures and explores the predictors of trainee doctor emigration from Ireland. METHODS: Using a partially mixed sequential dominant (quantitative) study design, a nationally representative sample of 893 trainee doctors was invited to complete an online survey. Of the 523 who responded (58.6% response rate), 423 were still in Ireland and responded to questions on factors influencing intention to practice medicine abroad and are the subjects of this study. Explanatory factors for intention to practice medicine in Ireland in the foreseeable future, the primary outcome, included demographic variables and experiences of working within the Irish health system. Associations were examined using univariable and multivariable logistic regression to estimate odds ratios for factors influencing the primary outcome. Qualitative interviews were conducted with 50 trainee doctors and analysed thematically, exploring issues associated with intention to practice medicine abroad. RESULTS: There were high levels of dissatisfaction among trainee doctors around working conditions, training and career progression opportunities in Ireland. However, most factors did not discriminate between intention to leave or stay. Factors that did predict intention to leave included dissatisfaction with one's work-life balance (odds ratio (OR) 2.51; 95% confidence interval (CI) 1.53-4.10; P < 0.001); feeling that the quality of training in Ireland was poor (OR 1.82; 95% CI 1.09-3.05; P = 0.002) and leaving for family or personal reasons (OR 1.85; 95% CI 1.08-3.17; P = 0.027). Qualitative findings illustrated the stress of doing postgraduate training with inadequate supervision, lack of ring-fenced training time and pressures on personal and family life. CONCLUSIONS: Large-scale dissatisfaction with working, training and career opportunities point to systemic factors that need to be addressed by health workforce planners if Ireland is to retain and benefit from a motivated medical workforce, given trainees' perceptions that there are better opportunities abroad.

Comparative proteomics implicates a role for multiple secretion systems in electrode-respiring Geobacter sulfurreducens biofilms.

Geobacter sulfurreducens is a dissimilatory metal-reducing bacterium capable of forming thick electron-conducting biofilms on solid electrodes. Here, we employ for the first time comparative proteomics to identify key physiological changes involved in G. sulfurreducens adaptation from fumarate-respiring planktonic cells to electron-conducting biofilms. Increased levels of proteins involved in outer membrane biogenesis, cell motility and secretion are expressed in biofilms. Of particular importance to the electron-conducting biofilms are proteins associated with secretion systems of Type I, II, V and Type IV pili. Furthermore, enzymes involved in lipopolysaccharide and peptidoglycan biosynthesis show increased levels of expression in electron-conducting biofilms compared to planktonic cells. These observations point to similarities in long-range electron transfer mechanisms between G. sulfurreducens and Shewanella oneidensis, while highlighting the wider significance of secretion systems beyond that of Type IV pili identified to date in the adaptation of G. sulfurreducens to electrode respiration.

"Same-Patient Processing" for multiple cardiac SPECT studies. 1. Improving LV segmentation accuracy.

OBJECTIVES: This paper describes a novel approach (same-patient processing, or SPP) aimed at improving left ventricular segmentation accuracy in patients with multiple SPECT studies, and evaluates its performance compared to conventional processing in a large population of 962 patients undergoing rest and stress electrocardiography-gated SPECT MPI, for a total of 5,772 image datasets (6 per patient). METHODS: Each dataset was independently processed using a standard algorithm, and a shape quality control score (SQC) was produced for every segmentation. Datasets with a SQC score higher than a specific threshold, suggesting algorithmic failure, were automatically reprocessed with the SPP-modified algorithm, which incorporates knowledge of the segmentation mask location in the other datasets belonging to the same patient. Experienced operators blinded as to whether datasets had been processed based on the standard or SPP approach assessed segmentation success/failure for each dataset. RESULTS: The SPP approach reduced segmentation failures from 219/5772 (3.8%) to 42/5772 (0.7%) overall, with particular improvements in attenuation corrected (AC) datasets with high extra-cardiac activity (from 100/962 (10.4%) to 12/962 (1.4%) for rest AC, and from 41/962 (4.3%) to 9/962 (0.9%) for stress AC). The number of patients who had at least one of their 6 datasets affected by segmentation failure decreased from 141/962 (14.7%) to 14/962 (1.7%) using the SPP approach. CONCLUSION: Whenever multiple image datasets for the same patient exist and need to be processed, it is possible to deal with the images as a group rather than individually. The same-patient processing approach can be implemented automatically, and may substantially reduce the need for manual reprocessing due to cardiac segmentation failure.

"Same-patient processing" for multiple cardiac SPECT studies. 2. Improving quantification repeatability.

OBJECTIVES: This paper investigates the ability of grouped quantification (an expression of the same-patient processing approach, or SPP) to improve repeatability of measurements in patients with multiple SPECT studies, and evaluates its performance compared to standard quantification in a population of 100 patients undergoing rest, stress, gated rest, and gated stress SPECT MPI. All acquisitions were performed twice, back-to-back, for a total of 800 image datasets (8 per patient). METHODS: Each dataset was automatically processed (a) independently, using standard quantitative software, and (b) as a group, together with the other 7 datasets belonging to the same patient, using an SPP-modified version of the software that registered the images to one another using a downhill simplex algorithm for the search of optimal translation, rotation, and scaling parameters. RESULTS: Overall, grouped quantification resulted in significantly lower differences between repeated measurements of stress ungated volumes (1.40 ± 2.76 mL vs 3.33 ± 5.06 mL, P < .05), end-diastolic volumes (1.78 ± 2.78 vs 3.49 ± 5.35 mL, P < .05), end-systolic volumes (1.17 ± 1.96 vs 2.44 ± 3.35 mL, P < .05), and LVEFs (-0.45 ± 2.29% vs -1.16 ± 3.30%, P < .05). Additionally, grouped quantification produced better repeatability (lower repeatability coefficients) for stress and rest ungated volumes (5.4 vs 9.9 and 5.2 vs 13.1, respectively), stress TPD (2.6 vs 3.6), stress and rest end-diastolic volumes (5.5 vs 10.5 and 7.2 vs 14.7, respectively), stress and rest end-systolic volumes (3.8 vs 6.6 and 5.3 vs 10.3, respectively), stress and rest LVEFs (4.5 vs 6.5 and 4.7 vs 8.2, respectively), and rest total motion deficit (5.6 vs 9.6). CONCLUSION: It is possible to improve the repeatability of quantitative measurements of parameters of myocardial perfusion and function derived from SPECT MPI studies of a same patient by group processing of image datasets belonging to that patient. This application of the same-patient processing approach is an extension of the "paired processing" technique already described by our group, and can be performed in automated fashion through incorporation in the quantitative algorithm.

New Luminescent Polynuclear Metal Complexes with Anticancer Properties: Toward Structure-Activity Relationships.

A series of new heterodinuclear luminescent complexes with two different organic ligands have been synthesized and characterized. A luminescent Ru(II)(polypyridine) moiety and a metal-based anticancer fragment (AuCl, (p-cymene)RuCl2, (p-cymene)OsCl2, (Cp*)RhCl2, or Au-thioglucose) are the two general features of these complexes. All of the bimetallic compounds have been evaluated for their antiproliferative properties in vitro in human cancer cell lines. Only the complexes containing an Au(I) fragment exhibit antiproliferative activity in the range of cisplatin or higher. The photophysical and electrochemical properties of the bimetallic species have been investigated, and fluorescence microscopy experiments have been performed successfully. The most promising bimetallic cytotoxic complexes (i.e., with the Au-thioglucose scaffold) have shown to be easily taken up by cancer cells at 37 °C in the cytoplasm or in specific organelles. Interestingly, experiments repeated at 4 °C showed no uptake of the bimetallic species inside cells, which confirms involvement of active transport processes. To evaluate the role of glucose transporters in the cell uptake of the gold complexes, inhibition of the GluT-1 (glucose transporter isoform with high level of expression in cancer cells) was achieved, showing only scarce influence on the compounds' uptake. Finally, the observed absence of interactions with nucleic acid model structures suggests that the gold compounds may have different intracellular targets with respect to cisplatin.

Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones: Very strong correlation to pleurotin and thioredoxin reductase inhibition.

The thioredoxin (Trx)-thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR. The cytotoxicity data for benzo[1,2,4]triazin-7-ones showed very strong correlation (Pearson correlation coefficients ∼0.8) to pleurotin using National Cancer Institute COMPARE analysis. A new 3-CF3 substituted benzo[1,2,4]triazin-7-one gave submicromolar inhibition of TrxR, although the parent compound 1,3-diphenylbenzo[1,2,4]triazin-7-one was more cytotoxic against cancer cell lines. Benzo[1,2,4]triazin-7-ones exhibited different types of reversible inhibition of TrxR, and cyclic voltammetry showed characteristic quasi-reversible redox processes. Cell viability studies indicated strong dependence of cytotoxicity on substitution at the 6-position of the 1,3-diphenylbenzo[1,2,4]triazin-7-one ring.

Charge transport in films of Geobacter sulfurreducens on graphite electrodes as a function of film thickness.

Harnessing, and understanding the mechanisms of growth and activity of, biofilms of electroactive bacteria (EAB) on solid electrodes is of increasing interest, for application to microbial fuel and electrolysis cells. Microbial electrochemical cell technology can be used to generate electricity, or higher value chemicals, from organic waste. The capability of biofilms of electroactive bacteria to transfer electrons to solid anodes is a key feature of this emerging technology, yet the electron transfer mechanism is not fully characterized as yet. Acetate oxidation current generated from biofilms of an EAB, Geobacter sulfurreducens, on graphite electrodes as a function of time does not correlate with film thickness. Values of film thickness, and the number and local concentration of electrically connected redox sites within Geobacter sulfurreducens biofilms as well as a charge transport diffusion co-efficient for the biofilm can be estimated from non-turnover voltammetry. The thicker biofilms, of 50 ± 9 µm, display higher charge transport diffusion co-efficient than that in thinner films, as increased film porosity of these films improves ion transport, required to maintain electro-neutrality upon electrolysis.

Knowledge, attitudes and practices of Irish doctors regarding stop smoking care and electronic cigarettes.

BACKGROUND: Smoking continues to cause harm on a huge scale in Ireland. Doctors can help this harm through providing safe, effective and clinically sound stop smoking care, but the needs of Irish doctors in this area are largely uncharted. AIMS: We assessed the knowledge, attitudes and practices of Irish doctors regarding stop smoking care and electronic cigarettes. METHODS: An Internet-based cross-sectional survey was administered to members of the Royal College of Physicians in Ireland and the Irish College of General Practitioners. Descriptive statistics for key parameters were derived and factors associated with more consistent practice of brief intervention, a key component of stop smoking care, were analysed using chi-square testing. RESULTS: There were 250 responses (58.7% female, 53.0% aged under 45 years, 55.1% graduated in medicine before 2000 and 57.2% worked in general practice). Most (84.9%) reported often or always asking about patient's smoking behaviour, and most (86.1%) reported often or always advising patients to stop. However, providing or arranging effective stop smoking care was weak and less consistently practised, and while most (91.4%) saw it as a responsibility, few doctors (28.5%) agreed they were sufficiently trained in this area of clinical care. Confidence in the knowledge of e-cigarettes was poor. CONCLUSIONS: While there is a strong reservoir support and areas of good reported practice in stop smoking care among doctors in Ireland, the development of their knowledge and skills in arranging effective care should be supported if doctors are to fulfil their huge potential role in tackling the harm caused by smoking.

Specialist cancer hospital-based smoking cessation service provision in Ireland.

BACKGROUND: While much progress has been made in reducing tobacco use in many countries, both active and passive smoking remain challenges. The benefits of smoking cessation are universally recognized, and the hospital setting is an ideal setting where smokers can access smoking cessation services as hospital admission can be a cue to action. Consistent delivery of good quality smoking cessation care across health services is an important focus for reducing the harm of tobacco use, especially among continued smokers. AIMS: Our objective was to document the smoking cessation medication and support services provided by specialist adult cancer hospitals across Ireland, a country with a stated tobacco endgame goal. METHODS: A cross-sectional survey based on recent national clinical guidelines was used to determine smoking cessation care delivery across eight specialist adult cancer tertiary referral university hospitals and one specialist radiotherapy center. Survey responses were collected using Qualtrics, a secure online survey software tool. The data was grouped, anonymized, and analyzed in Microsoft Excel. RESULTS: All responding hospitals demonstrated either some level of smoking cessation information or a service available to patients. However, there is substantial variation in the type and level of smoking cessation information offered, making access to smoking cessation services inconsistent and inequitable. CONCLUSION: The recently launched National Clinical Guideline for smoking cessation provides the template for all hospitals to ensure health services are in a position to contribute to Ireland's tobacco endgame goal.