Exercise dose and all-cause mortality within extended cardiac rehabilitation: a cohort study.

AIMS: To investigate the relationship between exercise participation, exercise 'dose' expressed as metabolic equivalent (MET) hours (h) per week, and prognosis in individuals attending an extended, community-based exercise rehabilitation programme. METHODS: Cohort study of 435 participants undertaking exercise-based cardiac rehabilitation (CR) in Leeds, West Yorkshire, UK between 1994 and 2006, followed up to 1 November 2013. MET intensity of supervised exercise was estimated utilising serial submaximal exercise test results and corresponding exercise prescriptions. Programme participation was routinely monitored. Cox regression analysis including time-varying and propensity score adjustment was applied to identify predictors of long-term, all-cause mortality across exercise dose and programme duration groups. RESULTS: There were 133 events (31%) during a median follow-up of 14 years (range, 1.2 to 18.9 years). The significant univariate association between exercise dose and all-cause mortality was attenuated following multivariable adjustment for other predictors, including duration in the programme. Longer-term adherence to supervised exercise training (>36 months) was associated with a 33% lower mortality risk (multivariate-adjusted HR: 0.67; 95% CI: 0.47 to 0.97; p=0.033) compared with all lesser durations of CR (3, 12, 36 months), even after adjustment for baseline fitness, comorbidities and survivor bias. CONCLUSION: Exercise dose (MET-h per week) appears less important than long-term adherence to supervised exercise for the reduction of long-term mortality risk. Extended, supervised CR programmes within the community may play a key role in promoting long-term exercise maintenance and other secondary prevention therapies for survival benefit

Putting the C Back into the ABCs: A Multi-Year, Multi-Region Investigation of Condom Use by Ugandan Youths 2003-2010

A major strategy for preventing transmission of HIV and other STIs is the consistent use of condoms during sexual intercourse. Condom use among youths is particularly important to reduce the number of new cases and the national prevalence. Condom use has been often promoted by the Uganda National AIDS Commission. Although a number of studies have established an association between condom use at one's sexual debut and future condom use, few studies have explored this association over time, and whether the results are generalizable across multiple locations. This multi time point, multi district study assesses the relationship between sexual debut and condom use and consistent use of condoms thereafter. Uganda has used Lot Quality Assurance Sampling surveys since 2003 to monitor district level HIV programs and improve access to HIV health services. This study includes 4518 sexually active youths interviewed at five time points (2003-2010) in up to 23 districts located across Uganda. Using logistic regression, we measured the association of condom use at first sexual intercourse on recent condom usage, controlling for several factors including: age, sex, education, marital status, age at first intercourse, geographical location, and survey year. The odds of condom use at last intercourse, using a condom at last intercourse with a non-regular partner, and consistently using a condom are, respectively, 9.63 (95%WaldCI = 8.03-11.56), 3.48 (95%WaldCI = 2.27-5.33), and 11.12 (95%WaldCI = 8.95-13.81) times more likely for those individuals using condoms during their sexual debut. These values did not decrease by more than 20% when controlling for potential confounders. The results suggest that HIV prevention programs should encourage condom use among youth during sexual debut. Success with this outcome may have a lasting influence on preventing HIV and other STIs later in life

Characterisation and expression of microRNAs in developing wings of the neotropical butterfly Heliconius melpomene.

BACKGROUND: Heliconius butterflies are an excellent system for studies of adaptive convergent and divergent phenotypic traits. Wing colour patterns are used as signals to both predators and potential mates and are inherited in a Mendelian manner. The underlying genetic mechanisms of pattern formation have been studied for many years and shed light on broad issues, such as the repeatability of evolution. In Heliconius melpomene, the yellow hindwing bar is controlled by the HmYb locus. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that have key roles in many biological processes, including development. miRNAs could act as regulators of genes involved in wing development, patterning and pigmentation. For this reason we characterised miRNAs in developing butterfly wings and examined differences in their expression between colour pattern races. RESULTS: We sequenced small RNA libraries from two colour pattern races and detected 142 Heliconius miRNAs with homology to others found in miRBase. Several highly abundant miRNAs were differentially represented in the libraries between colour pattern races. These candidates were tested further using Northern blots, showing that differences in expression were primarily due to developmental stage rather than colour pattern. Assembly of sequenced reads to the HmYb region identified hme-miR-193 and hme-miR-2788; located 2380 bp apart in an intergenic region. These two miRNAs are expressed in wings and show an upregulation between 24 and 72 hours post-pupation, indicating a potential role in butterfly wing development. A search for miRNAs in all available H. melpomene BAC sequences (~2.5 Mb) did not reveal any other miRNAs and no novel miRNAs were predicted. CONCLUSIONS: Here we describe the first butterfly miRNAs and characterise their expression in developing wings. Some show differences in expression across developing pupal stages and may have important functions in butterfly wing development. Two miRNAs were located in the HmYb region and were expressed in developing pupal wings. Future work will examine the expression of these miRNAs in different colour pattern races and identify miRNA targets among wing patterning genes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Mutator Dynamics on a Smooth Evolutionary Landscape

We investigate a model of evolutionary dynamics on a smooth landscape which features a ``mutator'' allele whose effect is to increase the mutation rate. We show that the expected proportion of mutators far from equilibrium, when the fitness is steadily increasing in time, is governed solely by the transition rates into and out of the mutator state. This results is a much faster rate of fitness increase than would be the case without the mutator allele. Near the fitness equilibrium, however, the mutators are severely suppressed, due to the detrimental effects of a large mutation rate near the fitness maximum. We discuss the results of a recent experiment on natural selection of E. coli in the light of our model.Comment: 4 pages, 3 figure

Vitamin D deficiency promotes large rupture-prone abdominal aortic aneurysms and cholecalciferol supplementation limits progression of aneurysms in a mouse model

Vitamin D deficiency has been associated with human abdominal aortic aneurysm (AAA); however, its role in AAA pathogenesis is unclear. The aim of the present study was to inves-tigate the effect of vitamin D deficiency on AAA development and examine if administering cholecalciferol (CCF) could limit growth of established AAA within the angiotensin-II (AngII) infused apolipoprotein E-deficient mouse model. Mice were rendered vitamin D deficiency through dietary restriction and during AngII infusion developed larger AAAs as assessed by ultrasound and ex vivo morphometry that ruptured more commonly (48% vs. 19%; P=0.028) than controls. Vitamin D deficiency was associated with increased aortic expression of osteopontin and matrix metalloproteinase-2 and -9 than controls. CCF administration to mice with established aortic aneurysms limited AAA growth as assessed by ultrasound (P<0.001) and ex vivo morphometry (P=0.036) and reduced rupture rate (8% vs. 46%; P=0.031). This effect was associated with up-regulation of circulating and aortic sclerostin. Incubation of human aortic smooth muscle cells with 1,25-dihyroxyvitamin D3 (the active metabolite of vitamin D) for 48 h induced up-regulation of sclerostin (P<0.001) and changed the expression of a range of other genes important in extracellular matrix remodeling. The present study suggests that vitamin D deficiency promotes development of large rupture-prone aortic aneurysms in an experimental model. CCF administration limited both growth and rupture of established aneurysms. These effects of vitamin D appeared to be mediated via changes in genes involved in extracellular matrix remodeling, particularly sclerostin

Fixing the BMS Frame of Numerical Relativity Waveforms with BMS Charges

The Bondi-van der Burg-Metzner-Sachs (BMS) group, which uniquely describes the symmetries of asymptotic infinity and therefore of the gravitational waves that propagate there, has become increasingly important for accurate modeling of waveforms. In particular, waveform models, such as post-Newtonian (PN) expressions, numerical relativity (NR), and black hole perturbation theory, produce results that are in different BMS frames. Consequently, to build a model for the waveforms produced during the merging of compact objects, which ideally would be a hybridization of PN, NR, and black hole perturbation theory, one needs a fast and robust method for fixing the BMS freedoms. In this work, we present the first means of fixing the entire BMS freedom of NR waveforms to match the frame of either PN waveforms or black hole perturbation theory. We achieve this by finding the BMS transformations that change certain charges in a prescribed way -- e.g., finding the center-of-mass transformation that maps the center-of-mass charge to a mean of zero. We find that this new method is 20 times faster, and more correct when mapping to the superrest frame, than previous methods that relied on optimization algorithms. Furthermore, in the course of developing this charge-based frame fixing method, we compute the PN expression for the Moreschi supermomentum to 3PN order without spins and 2PN order with spins. This Moreschi supermomentum is effectively equivalent to the energy flux or the null memory contribution at future null infinity $\mathscr{I}^{+}$. From this PN calculation, we also compute oscillatory ($m\not=0$ modes) and spin-dependent memory terms that have not been identified previously or have been missing from strain expressions in the post-Newtonian literature. <br

Fixing the BMS Frame of Numerical Relativity Waveforms

Understanding the Bondi-Metzner-Sachs (BMS) frame of the gravitational waves produced by numerical relativity is crucial for ensuring that analyses on such waveforms are performed properly. It is also important that models are built from waveforms in the same BMS frame. Up until now, however, the BMS frame of numerical waveforms has not been thoroughly examined, largely because the necessary tools have not existed. In this paper, we show how to analyze and map to a suitable BMS frame for numerical waveforms calculated with the Spectral Einstein Code (SpEC). However, the methods and tools that we present are general and can be applied to any numerical waveforms. We present an extensive study of 13 binary black hole systems that broadly span parameter space. From these simulations, we extract the strain and also the Weyl scalars using both SpECTRE's Cauchy-characteristic extraction module and also the standard extrapolation procedure with a displacement memory correction applied during post-processing. First, we show that the current center-of-mass correction used to map these waveforms to the center-of-mass frame is not as effective as previously thought. Consequently, we also develop an improved correction that utilizes asymptotic Poincar\'e charges instead of a Newtonian center-of-mass trajectory. Next, we map our waveforms to the post-Newtonian (PN) BMS frame using a PN strain waveform. This helps us find the unique BMS transformation that minimizes the $L^{2}$ norm of the difference between the numerical and PN strain waveforms during the early inspiral phase. We find that once the waveforms are mapped to the PN BMS frame, they can be hybridized with a PN strain waveform much more effectively than if one used any of the previous alignment schemes, which only utilize the Poincar\'e transformations

Adding Gravitational Memory to Waveform Catalogs using BMS Balance Laws

Accurate models of gravitational waves from merging binary black holes are crucial for detectors to measure events and extract new science. One important feature that is currently missing from the Simulating eXtreme Spacetimes (SXS) Collaboration's catalog of waveforms for merging black holes, and other waveform catalogs, is the gravitational memory effect: a persistent, physical change to spacetime that is induced by the passage of transient radiation. We find, however, that by exploiting the Bondi-Metzner-Sachs (BMS) balance laws, which come from the extended BMS transformations, we can correct the strain waveforms in the SXS catalog to include the missing displacement memory. Our results show that these corrected waveforms satisfy the BMS balance laws to a much higher degree of accuracy. Furthermore, we find that these corrected strain waveforms coincide especially well with the waveforms obtained from Cauchy-characteristic extraction (CCE) that already exhibit memory effects. These corrected strain waveforms also evade the transient junk effects that are currently present in CCE waveforms. Lastly, we make our code for computing these contributions to the BMS balance laws and memory publicly available as a part of the python package $\texttt{sxs}$, thus enabling anyone to evaluate the expected memory effects and violation of the BMS balance laws

Small RNA Profile in Moso Bamboo Root and Leaf Obtained by High Definition Adapters

Moso bamboo (Phyllostachy heterocycla cv. pubescens L.) is an economically important fast-growing tree. In order to gain better understanding of gene expression regulation in this important species we used next generation sequencing to profile small RNAs in leaf and roots of young seedlings. Since standard kits to produce cDNA of small RNAs are biased for certain small RNAs, we used High Definition adapters that reduce ligation bias. We identified and experimentally validated five new microRNAs and a few other small non-coding RNAs that were not microRNAs. The biological implication of microRNA expression levels and targets of microRNAs are discussed