The Aversion to Tampering with Nature (ATN) Scale: Individual Differences in (Dis)comfort with Altering the Natural World

People differ in their comfort with tampering with the natural world. Although some see altering nature as a sign of human progress, others see it as dangerous or hubristic. Across four studies, we investigate discomfort with tampering with the natural world. To do so, we develop the Aversion to Tampering with Nature (ATN) Scale, a short scale that is the first to directly measure this discomfort. We identify six activities that people believe tamper with nature (geoengineering, genetically modified organisms, pesticides, cloning, gene therapy, and nanoparticles) and show that ATN scores are associated with opposition to these activities. Furthermore, the ATN Scale predicts actual behavior: donations to an antiâ tampering cause. We demonstrate that ATN is related to previously identified constructs including trust in technology, naturalness bias, purity values, disgust sensitivity, aversion to playing God, and environmental beliefs and values. By illuminating who is concerned about tampering with nature and what predicts these beliefs, the ATN Scale provides opportunities to better understand public opposition to technological innovations, consumer preferences for â naturalâ products, and strategies for science communication.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154364/1/risa13414_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154364/2/risa13414.pd

Regulation of S1PR2 by the EBV oncogene LMP1 in aggressive ABC subtype diffuse large B cell lymphoma.

The Epstein-Barr virus (EBV) is found almost exclusively in the activated B cell (ABC) subtype of diffuse large B cell lymphoma (DLBCL), yet its contribution to this tumour remains poorly understood. We have focussed on the EBV-encoded latent membrane protein-1 (LMP1), a constitutively activated CD40 homologue expressed in almost all EBV-positive DLBCL and which can disrupt germinal centre (GC) formation and drive lymphomagenesis in mice. Comparison of the transcriptional changes that follow LMP1 expression with those that follow transient CD40 signalling in human GC B cells enabled us to define pathogenic targets of LMP1 aberrantly expressed in ABC-DLBCL. These included the down-regulation of S1PR2, a sphingosine-1-phosphate (S1P) receptor that is transcriptionally down-regulated in ABC-DLBCL, and when genetically ablated leads to DLBCL in mice. Consistent with this we found that LMP1-expressing primary ABC-DLBCL were significantly more likely to lack S1PR2 expression than were LMP1-negative tumours. Furthermore, we showed that the down-regulation of S1PR2 by LMP1 drives a signalling loop leading to constitutive activation of the phosphatidylinositol-3-kinase (PI3-K) pathway. Finally, core LMP1-PI3-K targets were enriched for lymphoma-related transcription factors and genes associated with shorter overall survival in patients with ABC-DLBCL. Our data identify a novel function for LMP1 in aggressive DLBCL

Right Heart Pulmonary Circulation Unit Response to Exercise in Patients with Controlled Systemic Arterial Hypertension: Insights from the RIGHT Heart International NETwork (RIGHT-NET)

Background. Systemic arterial hypertension (HTN) is the main risk factor for the development of heart failure with preserved ejection fraction (HFpEF). The aim of the study was was to assess the trends in PASP, E/E’ and TAPSE during exercise Doppler echocardiography (EDE) in hypertensive (HTN) patients vs. healthy subjects stratified by age. Methods. EDE was performed in 155 hypertensive patients and in 145 healthy subjects (mean age 62 ± 12.0 vs. 54 ± 14.9 years respectively, p < 0.0001). EDE was undertaken on a semi-recumbent cycle ergometer with load increasing by 25 watts every 2 min. Left ventricular (LV) and right ventricular (RV) dimensions, function and hemodynamics were evaluated. Results. Echo-Doppler parameters of LV and RV function were lower, both at rest and at peak exercise in hypertensives, while pulmonary hemodynamics were higher as compared to healthy subjects. The entire cohort was then divided into tertiles of age: at rest, no significant differences were recorded for each age group between hypertensives and normotensives except for E/E’ that was higher in hypertensives. At peak exercise, hypertensives had higher pulmonary artery systolic pressure (PASP) and E/E’ but lower tricuspid annular plane systolic excursion (TAPSE) as age increased, compared to normotensives. Differences in E/E’ and TAPSE between the 2 groups at peak exercise were explained by the interaction between HTN and age even after adjustment for baseline values (p < 0.001 for E/E’, p = 0.011 for TAPSE). At peak exercise, the oldest group of hypertensive patients had a mean E/E’ of 13.0, suggesting a significant increase in LV diastolic pressure combined with increased PASP. Conclusion. Age and HTN have a synergic negative effect on E/E’ and TAPSE at peak exercise in hypertensive subjects

Leaflet Area as a Determinant of Tricuspid Regurgitation Severity in Patients With Pulmonary Hypertension

Background: Tricuspid regurgitation (TR) is a risk factor for mortality in pulmonary hypertension (PH). TR severity varies among patients with comparable degrees of PH and right ventricular (RV) remodeling. The contribution of leaflet adaptation to the pathophysiology of TR has yet to be examined. We hypothesized that tricuspid leaflet area (TLA) is increased in PH, and that its size relative to RV remodeling determines TR severity. Methods and Results: A prospective cohort of 255 patients with PH from pre- and post-capillary etiologies was assembled from two centers. Patients underwent a 3-D echocardiogram focused on the tricuspid apparatus. TLA was measured with the Omni custom software package. Compared with normal controls, PH patients had a twofold increase in RV volumes, 62% increase in annulus area, and 49% increase in TLA. Those with severe TR demonstrated inadequate increase in TLA relative to the closure area, such that the ratio of TLA-to-closure area <1.78 was highly predictive of severe TR (odds ratio 68.7; 95% CI 16.2, 292.7). The median vena contracta width was 8.5 mm in the group with small TLA and large closure area as opposed to 4.8 mm in the group with large TLA and large closure area. Conclusions: TLA plays a significant role in determining which patients with PH develop severe functional TR. The ratio of TLA-to-closure area, reflecting the balance between leaflet adaptation vs. annular dilation and tethering forces, is an indicator of TR severity that may identify which patients stand to benefit from leaflet augmentation during tricuspid valve repair

3D Echo systematically underestimates right ventricular volumes compared to cardiovascular magnetic resonance in adult congenital heart disease patients with moderate or severe RV dilatation

<p>Abstract</p> <p>Background</p> <p>Three dimensional echo is a relatively new technique which may offer a rapid alternative for the examination of the right heart. However its role in patients with non-standard ventricular size or anatomy is unclear. This study compared volumetric measurements of the right ventricle in 25 patients with adult congenital heart disease using both cardiovascular magnetic resonance (CMR) and three dimensional echocardiography.</p> <p>Methods</p> <p>Patients were grouped by diagnosis into those expected to have normal or near-normal RV size (patients with repaired coarctation of the aorta) and patients expected to have moderate or worse RV enlargement (patients with repaired tetralogy of Fallot or transposition of the great arteries). Right ventricular end diastolic volume, end systolic volume and ejection fraction were compared using both methods with CMR regarded as the reference standard</p> <p>Results</p> <p>Bland-Altman analysis of the 25 patients demonstrated that for both RV EDV and RV ESV, there was a significant and systematic under-estimation of volume by 3D echo compared to CMR. This bias led to a mean underestimation of RV EDV by -34% (95%CI: -91% to + 23%). The degree of underestimation was more marked for RV ESV with a bias of -42% (95%CI: -117% to + 32%). There was also a tendency to overestimate RV EF by 3D echo with a bias of approximately 13% (95% CI -52% to +27%).</p> <p>Conclusions</p> <p>Statistically significant and clinically meaningful differences in volumetric measurements were observed between the two techniques. Three dimensional echocardiography does not appear ready for routine clinical use in RV assessment in congenital heart disease patients with more than mild RV dilatation at the current time.</p

Quantification of the relative contribution of the different right ventricular wall motion components to right ventricular ejection fraction

Abstract Three major mechanisms contribute to right ventricular (RV) pump function: (i) shortening of the longitudinal axis with traction of the tricuspid annulus towards the apex; (ii) inward movement of the RV free wall; (iii) bulging of the interventricular septum into the RV and stretching the free wall over the septum. The relative contribution of the aforementioned mechanisms to RV pump function may change in different pathological conditions. Our aim was to develop a custom method to separately assess the extent of longitudinal, radial and anteroposterior displacement of the RV walls and to quantify their relative contribution to global RV ejection fraction using 3D data sets obtained by echocardiography. Accordingly, we decomposed the movement of the exported RV beutel wall in a vertex based manner. The volumes of the beutels accounting for the RV wall motion in only one direction (either longitudinal, radial, or anteroposterior) were calculated at each time frame using the signed tetrahedron method. Then, the relative contribution of the RV wall motion along the three different directions to global RV ejection fraction was calculated either as the ratio of the given direction’s ejection fraction to global ejection fraction and as the frame-by-frame RV volume change (∆V/∆t) along the three motion directions. The ReVISION (Right VentrIcular Separate wall motIon quantificatiON) method may contribute to a better understanding of the pathophysiology of RV mechanical adaptations to different loading conditions and diseases

Real-time three-dimensional transthoracic echocardiography in daily practice: initial experience

<p>Abstract</p> <p>Aim of the work</p> <p>To evaluate the feasibility and possible additional value of transthoracic real-time three-dimensional echocardiography (RT3D-TTE) for the assessment of cardiac structures as compared to 2D-TTE.</p> <p>Methods</p> <p>320 patients (mean age 45 ± 8.4 years, 75% males) underwent 2D-TTE and RT3D-TTE using 3DQ-Q lab software for offline analysis. Volume quantification and functional assessment was performed in 90 patients for left ventricle and in 20 patients for right ventricle. Assessment of native (112 patients) and prosthetic (30 patients) valves morphology and functions was performed. RT3D-TTE was performed for evaluation of septal defects in 30 patients and intracardiac masses in 52 patients.</p> <p>Results</p> <p>RT3D-TTE assessment of left ventricle was feasible and reproducible in 86% of patients while for right ventricle, it was (55%). RT3D-TTE could define the surface anatomy of mitral valve optimally (100%), while for aortic and tricuspid was (88% and 81% respectively). Valve area could be planimetered in 100% for the mitral and in 80% for the aortic. RT3D-TTE provided a comprehensive anatomical and functional evaluation of prosthetic valves. RT3D-TTE enface visualization of septal defects allowed optimal assessment of shape, size, area and number of defects and evaluated the outcome post device closure. RT3D-TTE allowed looking inside the intracardiac masses through multiple sectioning, valuable anatomical delineation and volume calculation.</p> <p>Conclusion</p> <p>Our initial experience showed that the use of RT3D-TTE in the assessment of cardiac patients is feasible and allowed detailed anatomical and functional assessment of many cardiac disorders.</p

One session of remote ischemic preconditioning does not improve vascular function in acute normobaric and chronic hypobaric hypoxia

Application of repeated short duration bouts of ischemia to the limbs, termed remote ischemic preconditioning (RIPC), is a novel technique that may have protective effects on vascular function during hypoxic exposures. In separate parallel-design studies, at sea-level (SL; n=16), and after 8-12 days at high-altitude (HA; n=12; White Mountain, 3800m), participants underwent either a sham protocol or one session of 4x5 minutes of dual-thigh cuff occlusion with 5-minutes recovery. Brachial artery flow-mediated dilation (FMD; ultrasound), pulmonary artery systolic pressure (PASP; echocardiography), and internal carotid artery flow (ICA; ultrasound) were measured at SL in normoxia and isocapnic hypoxia [end-tidal PO (PETO ) maintained to 50mmHg], and during normal breathing at HA. The hypoxic ventilatory response (HVR) was measured at each location. All measures at SL and HA were obtained at baseline (BL), 1 hour, 24 hours, and 48 hours post-RIPC or sham. At SL, RIPC produced no changes in FMD, PASP, ICA flow, end-tidal gases or HVR in normoxia or hypoxia. At HA, although HVR increased 24 hours post RIPC compared to BL (2.05{plus minus}1.4 vs. 3.21{plus minus}1.2 L•min-1•%SaO2-1, p<0.01), there were no significant differences in FMD, PASP, ICA flow, resting end-tidal gases. Accordingly, a single session of RIPC is insufficient to evoke changes in peripheral, pulmonary, and cerebral vascular function in healthy adults. Although chemosensitivity may increase following RIPC at HA, this did not confer any vascular changes. The utility of a single RIPC session seems unremarkable during acute and chronic hypoxia

H2FPEF score predicts atherosclerosis presence in patients with systemic connective tissue disease

Background: Cardiovascular diseases are common cause of morbidity and mortality in patients with systemic connective tissue diseases (SCTD) due to accelerated atherosclerosis which couldn't be explained by traditional risk factors (CVDRF). Hypothesis: We hypothesized that recently developed score predicting probability of heart failure with preserved ejection fraction (H2FPEF), as well as a measure of right ventricular-pulmonary vasculature coupling [tricuspid annular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio], are predictive of atherosclerosis in SCTD. Methods: 203 patients (178 females) diagnosed with SCTD underwent standard and stress-echocardiography (SE) with TAPSE/PASP and left ventricular (LV) diastolic filling pressure (E/e') measurements, carotid ultrasound and computed tomographic coronary angiography. Patients who were SE positive for ischemia underwent coronary angiography (34/203). The H2FPEF score was calculated according to age, body mass index, presence of atrial fibrillation, ≥2 antihypertensives, E/e' and PASP. Results: Mean LV ejection fraction was 66.3 ± 7.1%. Atherosclerosis was present in 150/203 patients according to: 1) intima-media thickness>0.9 mm; and 2) Agatstone score > 300 or Syntax score ≥ 1. On binary logistic regression analysis, including CVDRF prevalence, echocardiographic parameters and H2FPEF score, only H2FPEF score remained significant for the prediction of atherosclerosis presence (χ2 = 19.3, HR 2.6, CI 1.5-4.3, p < 0.001), and resting TAPSE/PASP for the prediction of a SE positive for ischemia (χ2 = 10.4, HR 0.01, CI = 0.01-0.22, p = 0.004). On ROC analysis, the optimal threshold value for identifying patients with atherosclerosis was a H2FPEF score ≥2 (Sn 60.4%, Sp 69.4%, area 0.67, SE = 0.05, p < 0.001). Conclusions: H2FPEF score and resting TAPSE/PASP demonstrated clinical value for an atherosclerosis diagnosis in patients diagnosed with SCTD

Speckle Tracking Echocardiography for the Assessment of the Athlete's Heart: Is It Ready for Daily Practice?

PURPOSE OF REVIEW: To describe the use of speckle tracking echocardiography (STE) in the biventricular assessment of athletes' heart (AH). Can STE aid differential diagnosis during pre-participation cardiac screening (PCS) of athletes? RECENT FINDINGS: Data from recent patient, population and athlete studies suggest potential discriminatory value of STE, alongside standard echocardiographic measurements, in the early detection of clinically relevant systolic dysfunction. STE can also contribute to subsequent prognosis and risk stratification. Despite some heterogeneity in STE data in athletes, left ventricular global longitudinal strain (GLS) and right ventricular longitudinal strain (RV ɛ) indices can add to differential diagnostic protocols in PCS. STE should be used in addition to standard echocardiographic tools and be conducted by an experienced operator with significant knowledge of the AH. Other indices, including left ventricular circumferential strain and twist, may provide insight, but further research in clinical and athletic populations is warranted. This review also raises the potential role for STE measures performed during exercise as well as in serial follow-up as a method to improve diagnostic yield