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

Role of Right Ventricular Global Longitudinal Strain in Predicting Early and Long-Term Mortality in Cardiac Resynchronization Therapy Patients.

BACKGROUND: Right ventricular (RV) dysfunction has been associated with poor prognosis in chronic heart failure (HF). However, less data is available about the role of RV dysfunction in patients with cardiac resynchronization therapy (CRT). We aimed to investigate if RV dysfunction would predict outcome in CRT. DESIGN: We enrolled prospectively ninety-three consecutive HF patients in this single center observational study. All patients underwent clinical evaluation and echocardiography before CRT and 6 months after implantation. We assessed RV geometry and function by using speckle tracking imaging and calculated strain parameters. We performed multivariable Cox regression models to test mortality at 6 months and at 24 months. RESULTS: RV dysfunction, characterized by decreased RVGLS (RV global longitudinal strain) [10.2 (7.0-12.8) vs. 19.5 (15.0-23.9) %, p<0.0001] and RVFWS (RV free wall strain) [15.6 (10.0-19.3) vs. 17.4 (10.5-22.2) %, p = 0.04], improved 6 months after CRT implantation. Increasing baseline RVGLS and RVFWS predicted survival independent of other parameters at 6 months [hazard ratio (HR) = 0.37 (0.15-0.90), p = 0.02 and HR = 0.42 (0.19-0.89), p = 0.02; per 1 standard deviation increase, respectively]. RVGLS proved to be a significant independent predictor of mortality at 24 months [HR = 0.53 (0.32-0.86), p = 0.01], and RVFWS showed a strong tendency [HR = 0.64 (0.40-1.00), p = 0.05]. The 24-month survival was significantly impaired in patients with RVGLS below 10.04% before CRT implantation [area under the curve = 0.72 (0.60-0.84), p = 0.002, log-rank p = 0.0008; HR = 5.23 (1.76-15.48), p = 0.003]. CONCLUSIONS: Our findings indicate that baseline RV dysfunction is associated with poor short-term and long-term prognosis after CRT implantation

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

Chemoreceptor responsiveness at sea level does not predict the pulmonary pressure response to high altitude

The hypoxic ventilatory response (HVR) at sea level (SL) is moderately predictive of the change in pulmonary artery systolic pressure (PASP) to acute normobaric hypoxia. However, because of progressive changes in the chemoreflex control of breathing and acid-base balance at high altitude (HA), HVR at SL may not predict PASP at HA. We hypothesized that resting peripheral oxyhemoglobin saturation (SpO2) at HA would correlate better than HVR at SL to PASP at HA. In 20 participants at SL, we measured normobaric, isocapnic HVR (L/min·-%SpO2 -1) and resting PASP using echocardiography. Both resting SpO2 and PASP measures were repeated on day 2 (n=10), days 4-8 (n=12), and 2-3 weeks (n=8) after arrival at 5050m. These data were also collected at 5050m on life-long HA residents (Sherpa; n=21). Compared to SL, SpO2 decreased from 98.6 to 80.5% (P<0.001), while PASP increased from 21.7 to 34.0mmHg (P<0.001) after 2-3 weeks at 5050m. Isocapnic HVR at SL was not related to SpO2 or PASP at any time point at 5050m (all P>0.05). Sherpa had lower PASP (P<0.01) than lowlanders on days 4-8 despite similar SpO2. Upon correction for hematocrit, Sherpa PASP was not different from lowlanders at SL, but lower than lowlanders at all HA time points. At 5050m, whilst SpO2 was not related to PASP in lowlanders at any point (all R2=0.50), there was a weak relationship in the Sherpa (R2=0.16; P=0.07). We conclude that neither HVR at SL nor resting SpO2 at HA correlates with elevations in PASP at HA