The incidence and risk factors for new onset atrial fibrillation in the PROSPER study

Aims Atrial fibrillation/flutter (AF) is the most common arrhythmia in older people. It associates with reduced exercise capacity, increased risk of stroke, and mortality. We aimed to determine retrospectively whether pravastatin reduces the incidence of AF and whether any electrocardiographic measures or clinical conditions might be risk factors for its development. Methods and results The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, double-blind controlled trial that recruited 5804 individuals aged 70-82 years with a history of, or risk factors for, vascular disease. A total of 2891 were allocated to pravastatin and 2913 to placebo; mean follow-up was 3.2 years. Electrocardiograms (ECGs), which were recorded at baseline, annually thereafter, and at run-out, were processed by computer and reviewed manually. In all, 264 of 2912 (9.1%) of the placebo group and 283 of 2888 (9.8%) of the pravastatin-treated group developed AF [hazard ratio 1.08 (0.92,1.28), P = 0.35)]. Multivariate analysis showed that PR and QTc intervals, age, left ventricular hypertrophy, and ST-T abnormalities were related to development of AF after adjustment for many variables including alcohol consumption, which itself was univariately predictive of developing AF. Previous myocardial infarction on the ECG was not a risk factor. A history of vascular disease was strongly linked with developing AF but not diabetes and hypertension. Conclusion Pravastatin does not reduce the incidence of AF in older people at risk of vascular disease, at least in the short-medium term. Risk factors for AF include older age, prolongation of PR or QTc intervals, left ventricular hypertrophy, and ST-T abnormalities on the EC

Confounding-adjustment methods for the causal difference in medians

Background With continuous outcomes, the average causal effect is typically defined using a contrast of expected potential outcomes. However, in the presence of skewed outcome data, the expectation (population mean) may no longer be meaningful. In practice the typical approach is to continue defining the estimand this way or transform the outcome to obtain a more symmetric distribution, although neither approach may be entirely satisfactory. Alternatively the causal effect can be redefined as a contrast of median potential outcomes, yet discussion of confounding-adjustment methods to estimate the causal difference in medians is limited. In this study we described and compared confounding-adjustment methods to address this gap. Methods The methods considered were multivariable quantile regression, an inverse probability weighted (IPW) estimator, weighted quantile regression (another form of IPW) and two little-known implementations of g-computation for this problem. Methods were evaluated within a simulation study under varying degrees of skewness in the outcome and applied to an empirical study using data from the Longitudinal Study of Australian Children. Results Simulation results indicated the IPW estimator, weighted quantile regression and g-computation implementations minimised bias across all settings when the relevant models were correctly specified, with g-computation additionally minimising the variance. Multivariable quantile regression, which relies on a constant-effect assumption, consistently yielded biased results. Application to the empirical study illustrated the practical value of these methods. Conclusion The presented methods provide appealing avenues for estimating the causal difference in medians.Peer reviewe

On variational principles for coherent vortex structures

Different approaches are discussed of variational principles characterizing coherent vortex structures in two-dimensional flows. Turbulent flows seem to form ordered structures in the large scales of the motion and the self-organization principle predicts asymptotic states realizing an extremal value of the energy or a minimum of enstrophy. On the other hand the small scales take care of the increase of entropy, and asymptotic results can be obtained by applying the theory of equilibrium statistical mechanics

Building bridges: a critical analysis of university and industry collaboration to improve diverse access to elite professions

This article explores how both universities and industry can work together to improve access to graduate opportunities for disadvantaged students. Focusing on an initiative which involved students from a post-1992 university experiencing London's legal sector, this article analyses the factors which contribute to students' perceptions of their increased self-efficacy as a result of participating in the event. Utilising a focus group methodology, the article critically examines the barriers that can be imposed by students' socio-economic backgrounds which may prevent such initiatives from having a meaningful impact on diverse recruitment and fair access to higher professional occupations. Focusing in on 2 particular strands of the Triple Helix Model, this article also makes some recommendations as to how more effective bridges can be built between universities and industry to improve access for all to the elite professions

The RMS Survey: 6 cm continuum VLA observations towards candidate massive YSOs in the northern hemisphere

(Abridged) Context: The Red MSX Source (RMS) survey is an ongoing multi-wavelength observational programme designed to return a large, well-selected sample of massive young stellar objects (MYSOs). We have identified $\sim$2000 MYSO candidates located throughout the Galaxy by comparing the colours of MSX and 2MASS point sources to those of known MYSOs. Aims: To identify the populations of UCHII regions and PNe within the sample and examine their Galactic distribution. Method: We have conducted high resolution radio continuum observations at 6 cm towards 659 MYSO candidates in the northern hemisphere (10\degr< l < 250\degr) using the VLA. In addition to these targeted observations we present archival data towards a further 315 RMS sources extracted from a previous VLA survey of the inner Galaxy. Results: We find radio emission towards 272 ($\sim$27% of the observed sample). Using results from other parts of our multi-wavelength survey we separate these RMS-radio associations into two distinct types of objects, classifying 51 as PNe and a further 208 as either compact or UC HII regions. Using this well selected sample of HII regions we estimate their Galactic scale height to be 0.6\degr. Conclusions: Using radio continuum and archival data we have identified 79 PNe and 391 HII regions within the northern RMS catalogue. We estimate the total fraction of contamination by PNe in the RMS sample is of order 10%. The sample of HII regions is probably the best representation to date of the Galactic population of HII regions as a whole.Comment: Accepted for publication in Astronomy and Astrophysics. 15 pages, 9 figures and 5 tables. Full versions of Tables 3, 4 and 5 and Figs. 2, 4 and 7 will only be available via CDS or the RMS website at http:/www.ast.leeds.ac.uk/cgi-bin/RMS/RMS_VLA_IMAGES.cg

Prohibitin-1 maintains the angiogenic capacity of endothelial cells by regulating mitochondrial function and senescence

Prohibitin 1 (PHB1) is a highly conserved protein that is mainly localized to the inner mitochondrial membrane and has been implicated in regulating mitochondrial function in yeast. Because mitochondria are emerging as an important regulator of vascular homeostasis, we examined PHB1 function in endothelial cells. PHB1 is highly expressed in the vascular system and knockdown of PHB1 in endothelial cells increases mitochondrial production of reactive oxygen species via inhibition of complex I, which results in cellular senescence. As a direct consequence, both Akt and Rac1 are hyperactivated, leading to cytoskeletal rearrangements and decreased endothelial cell motility, e.g., migration and tube formation. This is also reflected in an in vivo angiogenesis assay, where silencing of PHB1 blocks the formation of functional blood vessels. Collectively, our results provide evidence that PHB1 is important for mitochondrial function and prevents reactive oxygen species–induced senescence and thereby maintains the angiogenic capacity of endothelial cells

Towards enduring autonomous robots via embodied energy.

Autonomous robots comprise actuation, energy, sensory and control systems built from materials and structures that are not necessarily designed and integrated for multifunctionality. Yet, animals and other organisms that robots strive to emulate contain highly sophisticated and interconnected systems at all organizational levels, which allow multiple functions to be performed simultaneously. Herein, we examine how system integration and multifunctionality in nature inspires a new paradigm for autonomous robots that we call Embodied Energy. Whereas most untethered robots use batteries to store energy and power their operation, recent advancements in energy-storage techniques enable chemical or electrical energy sources to be embodied directly within the structures and materials used to create robots, rather than requiring separate battery packs. This perspective highlights emerging examples of Embodied Energy in the context of developing autonomous robots

Structural basis for phosphorylation and lysine acetylation cross-talk in a kinase motif associated with myocardial ischemia and cardioprotection

Myocardial ischemia and cardioprotection by ischemic pre-conditioning induce signal networks aimed at survival or cell death if the ischemic period is prolonged. These pathways are mediated by protein post-translational modifications that are hypothesized to cross-talk with and regulate each other. Phosphopeptides and lysine-acetylated peptides were quantified in isolated rat hearts subjected to ischemia or ischemic pre-conditioning, with and without splitomicin inhibition of lysine deacetylation. We show lysine acetylation (acetyl-Lys)-dependent activation of AMP-activated protein kinase, AKT, and PKA kinases during ischemia. Phosphorylation and acetyl-Lys sites mapped onto tertiary structures were proximal in >50% of proteins investigated, yet they were mutually exclusive in 50 ischemic pre-conditioning- and/or ischemia-associated peptides containing the KXXS basophilic protein kinase consensus motif. Modifications in this motif were modeled in the C terminus of muscle-type creatine kinase. Acetyl-Lys increased proximal dephosphorylation by 10-fold. Structural analysis of modified muscle-type creatine kinase peptide variants by two-dimensional NMR revealed stabilization via a lysine-phosphate salt bridge, which was disrupted by acetyl-Lys resulting in backbone flexibility and increased phosphatase accessibility

Secondary analysis of teaching methods in introductory physics: A 50 k-student study

Citation: Von Korff, J., Archibeque, B., Gomez, K. A., Heckendorf, T., McKagan, S. B., Sayre, E. C., . . . Sorell, L. (2016). Secondary analysis of teaching methods in introductory physics: A 50 k-student study. American Journal of Physics, 84(12), 969-974. doi:10.1119/1.4964354Physics education researchers have developed many evidence-based instructional strategies to enhance conceptual learning of students in introductory physics courses. These strategies have historically been tested using assessments such as the Force Concept Inventory (FCI) and the Force and Motion Conceptual Evaluation (FMCE). We have performed a review and analysis of FCI and FMCE data published between 1995 and 2014. We confirm previous findings that interactive engagement teaching techniques are significantly more likely to produce high student learning gains than traditional lecture-based instruction. We also establish that interactive engagement instruction works in many settings, including those with students having a high and low level of prior knowledge, at liberal arts and research universities, and enrolled in both small and large classes. (C) 2016 Author(s)

Bleeding and thrombotic complications associated with anticoagulation prior to lung transplantation: A case series

Background: Scarce data is available on therapeutic anticoagulation (AC) in patients undergoing pulmonary transplantation. We describe our institutional experience with AC-induced coagulopathy in recipients at the time of transplantation and evaluate its impact on posttransplant outcomes. Methods: Records of adult patients on therapeutic AC at the time of lung transplantation from January 2014 to July 2021 were reviewed. Administration of preoperative pharmacologic reversal was assessed, with adequate reversal defined as international normalized ratio (INR) ≤1.5. We evaluated the incidence of major bleeding complications [delayed sternal closure, reoperation due to bleeding, chest tube output ≥1,500 cc, ≥4 units of packed red blood cells, ≥4 units of platelets, or ≥5 units of fresh frozen plasma (FFP)], major thrombotic complications [venous thromboembolism (VTE) or other major thrombosis on imaging], and inpatient mortality. Results: Of 602 lung transplant recipients, 10 patients taking preoperative warfarin were included in the study. While most patients received pharmacologic reversal preoperatively (n=9, 90%), successful reversal was rarely achieved (n=3, 30%). Inadequate INR reversal was associated with major bleeding events (n=6, 60%). Major thrombotic complications were more frequent (n=7, 70%) than bleeding events. Notably, all fatalities within the cohort (n=2, 20%) were associated with thrombotic, but not bleeding, complications. Conclusions: This is the first known report on the incidence and impact of AC-induced coagulopathy in patients undergoing lung transplantation. Major thrombotic events are frequent and associated with high mortality. Routine surveillance and treatment may be warranted