Right Ventricular Functional Abnormalities in Arrhythmogenic Cardiomyopathy: Association With Life-Threatening Ventricular Arrhythmias

OBJECTIVES: This study aimed to perform an external validation of the value of right ventricular (RV) deformation patterns and RV mechanical dispersion in patients with arrhythmogenic cardiomyopathy (AC). Secondly, this study assessed the association of these parameters with life-threatening ventricular arrhythmia (VA). BACKGROUND: Subtle RV dysfunction assessed by echocardiographic deformation imaging is valuable in AC diagnosis and risk prediction. Two different methods have emerged, the RV deformation pattern recognition and RV mechanical dispersion, but these have neither been externally validated nor compared. METHODS: We analyzed AC probands and mutation-positive family members, matched from 2 large European referral centers. We performed speckle tracking echocardiography, whereby we classified the subtricuspid deformation patterns from normal to abnormal and assessed RV mechanical dispersion from 6 segments. We defined VA as sustained ventricular tachycardia, appropriate implantable cardioverter-defibrillator therapy, or aborted cardiac arrest. RESULTS: We included 160 subjects, 80 from each center (43% proband, 55% women, age 41 ± 17 years). VA had occurred in 47 (29%) subjects. In both cohorts, patients with a history of VA showed abnormal deformation patterns (96% and 100%) and had greater RV mechanical dispersion (53 ± 30 ms vs. 30 ± 21 ms; p < 0.001 for the total cohort). Both parameters were independently associated to VA (adjusted odds ratio: 2.71 [95% confidence interval: 1.47 to 5.00] per class step-up, and 1.26 [95% confidence interval: 1.07 to 1.49]/10 ms, respectively). The association with VA significantly improved when adding RV mechanical dispersion to pattern recognition (net reclassification improvement 0.42; p = 0.02 and integrated diagnostic improvement 0.06; p = 0.01). CONCLUSIONS: We externally validated 2 RV dysfunction parameters in AC. Adding RV mechanical dispersion to RV deformation patterns significantly improved the association with life-threatening VA, indicating incremental value

Monitoring of Myocardial Involvement in Early Arrhythmogenic Right Ventricular Cardiomyopathy Across the Age Spectrum

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by fibrofatty replacement of primarily the right ventricular myocardium, a substrate for life-threatening ventricular arrhythmias (VAs). Repeated cardiac imaging of at-risk relatives is important for early disease detection. However, it is not known whether screening should be age-tailored. OBJECTIVES: The goal of this study was to assess the need for age-tailoring of follow-up protocols in early ARVC by evaluating myocardial disease progression in different age groups. METHODS: We divided patients with early-stage ARVC and genotype-positive relatives without overt structural disease and VA at first evaluation into 3 groups: age 50 years without overt ARVC phenotype at first evaluation. Unlike recommended by current guidelines, our study suggests that follow-up of ARVC patients and relatives should not stop at older age

Integrating Exercise Into Personalized Ventricular Arrhythmia Risk Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy

BACKGROUND: Exercise is associated with sustained ventricular arrhythmias (VA) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) but is not included in the ARVC risk calculator (arvcrisk.com). The objective of this study is to quantify the influence of exercise at diagnosis on incident VA risk and evaluate whether the risk calculator needs adjustment for exercise. METHODS: We interviewed ARVC patients without sustained VA at diagnosis about their exercise history. The relationship between exercise dose 3 years preceding diagnosis (average METh/wk) and incident VA during follow-up was analyzed with time-to-event analysis. The incremental prognostic value of exercise to the risk calculator was evaluated by Cox models. RESULTS: We included 176 patients (male, 43.2%; age, 37.6±16.1 years) from 3 ARVC centers, of whom 53 (30.1%) developed sustained VA during 5.4 (2.7-9.7) years of follow-up. Exercise at diagnosis showed a dose-dependent nonlinear relationship with VA, with no significant risk increase 18, >24, and >36 METh/wk), was significantly associated with VA (hazard ratios, 2.53-2.91) but was also correlated with risk factors currently in the risk calculator model. Thus, adding athlete status to the model did not change the C index of 0.77 (0.71-0.84) and showed no significant improvement (Akaike information criterion change, <2). CONCLUSIONS: Exercise at diagnosis was dose dependently associated with risk of sustained VA in ARVC patients but only above 15 to 30 METh/wk. Exercise does not appear to have incremental prognostic value over the risk calculator. The ARVC risk calculator can be used accurately in athletic patients without modification

Equivalence classes of the second order ODEs with the constant Cartan invariant

Second order ordinary differential equations that possesses the constant invariant are investigated. Four basic types of these equations were found. For every type the complete list of nonequivalent equations is issued. As the exampes the equivalence problem for the Painleve II equation, Painleve III equation with three zero parameters, Emden equations and for some other equations is solved

Knowledge about complementary, alternative and integrative medicine (CAM) among registered health care providers in Swedish surgical care: a national survey among university hospitals

<p>Abstract</p> <p>Background</p> <p>Previous studies show an increased interest and usage of complementary and alternative medicine (CAM) in the general population and among health care workers both internationally and nationally. CAM usage is also reported to be common among surgical patients. Earlier international studies have reported that a large amount of surgical patients use it prior to and after surgery. Recent publications indicate a weak knowledge about CAM among health care workers. However the current situation in Sweden is unknown. The aim of this study was therefore to explore perceived knowledge about CAM among registered healthcare professions in surgical departments at Swedish university hospitals.</p> <p>Method</p> <p>A questionnaire was distributed to 1757 registered physicians, nurses and physiotherapists in surgical wards at the seven university hospitals in Sweden from spring 2010 to spring 2011. The questionnaire included classification of 21 therapies into conventional, complementary, alternative and integrative, and whether patients were recommended these therapies. Questions concerning knowledge, research, and patient communication about CAM were also included.</p> <p>Result</p> <p>A total of 737 (42.0%) questionnaires were returned. Therapies classified as complementary; were massage, manual therapies, yoga and acupuncture. Alternative therapies; were herbal medicine, dietary supplements, homeopathy and healing. Classification to integrative therapy was low, and unfamiliar therapies were Bowen therapy, iridology and Rosen method. Therapies recommended by > 40% off the participants were massage and acupuncture. Knowledge and research about CAM was valued as minor or none at all by 95.7% respectively 99.2%. Importance of possessing knowledge about it was valued as important by 80.9%. It was believed by 61.2% that more research funding should be addressed to CAM research, 72.8% were interested in reading CAM-research results, and 27.8% would consider taking part in such research. Half of the participants (55.8%) were positive to learning such therapy. Communication about CAM between patients and the health care professions was found to be rare.</p> <p>Conclusion</p> <p>There is a lack of knowledge about CAM and research about it among registered health care professions in Swedish surgical care. However, in contrast to previous studies the results revealed that the majority perceived it as important to gain knowledge in this field.</p

The association between weekly hours of physical activity and mental health: A three-year follow-up study of 15–16-year-old students in the city of Oslo, Norway

<p>Abstract</p> <p>Background</p> <p>Mental health problems are a worldwide public health burden. The literature concerning the mental health benefits from physical activity among adults has grown. Adolescents are less studied, and especially longitudinal studies are lacking. This paper investigates the associations between weekly hours of physical activity at age 15–16 and mental health three years later.</p> <p>Methods</p> <p>Longitudinal self-reported health survey. The baseline study consisted of participants from the youth section of the Oslo Health Study, carried out in schools in 2000–2001 (<it>n </it>= 3811). The follow-up in 2003–2004 was conducted partly at school and partly through mail. A total of 2489 (1112 boys and 1377 girls) participated in the follow-up. Mental health was measured by the Strengths and Difficulties Questionnaire with an impact supplement. Physical activity was measured by a question on weekly hours of physical activity outside of school, defined as exertion 'to an extent that made you sweat and/or out of breath'. Adjustments were made for well-documented confounders and mental health at baseline.</p> <p>Results</p> <p>In boys, the number of hours spent on physical activity per week at age 15–16 was negatively associated with emotional symptoms [B (95%CI) = -0.09 (-0.15, -0.03)] and peer problems [B (95%CI) = -0.08 (-0.14, -0.03)] at age 18–19 after adjustments. In girls, there were no significant differences in SDQ subscales at age 18–19 according to weekly hours of physical activity at age 15–16 after adjustments. Boys and girls with five to seven hours of physical activity per week at age 15–16 had the lowest mean scores for total difficulties and the lowest percentage with high impact score at age 18–19, but the differences were not statistically significant after adjustments.</p> <p>Conclusion</p> <p>Weekly hours of physical activity at age 15–16 years was weakly associated with mental health at three-year follow-up in boys. Results encourage a search for further knowledge about physical activity as a possible protective factor in relation to mental health problems in adolescence.</p

Autotrophic and heterotrophic acquisition of carbon and nitrogen by a mixotrophic chrysophyte established through stable isotope analysis

Collectively, phagotrophic algae (mixotrophs) form a functional continuum of nutritional modes between autotrophy and heterotrophy, but the specific physiological benefits of mixotrophic nutrition differ among taxa. Ochromonas spp. are ubiquitous chrysophytes that exhibit high nutritional flexibility, although most species generally fall towards the heterotrophic end of the mixotrophy spectrum. We assessed the sources of carbon and nitrogen in Ochromonas sp. strain BG-1 growing mixotrophically via short-term stable isotope probing. An axenic culture was grown in the presence of either heat-killed bacteria enriched with ^(15)N and ^(13)C, or unlabeled heat-killed bacteria and labeled inorganic substrates (^(13)C-bicarbonate and ^(15)N-ammonium). The alga exhibited high growth rates (up to 2 divisions per day) only until heat-killed bacteria were depleted. NanoSIMS and bulk IRMS isotope analyses revealed that Ochromonas obtained 84–99% of its carbon and 88–95% of its nitrogen from consumed bacteria. The chrysophyte assimilated inorganic ^(13)C-carbon and ^(15)N-nitrogen when bacterial abundances were very low, but autotrophic (photosynthetic) activity was insufficient to support net population growth of the alga. Our use of nanoSIMS represents its first application towards the study of a mixotrophic alga, enabling a better understanding and quantitative assessment of carbon and nutrient acquisition by this species

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. METHODS: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. RESULTS: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. CONCLUSIONS: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy

Aims Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. Methods and results Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44–9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73–0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92–0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). Conclusion Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICD

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration