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

Submaximal fitness and mortality risk reduction in coronary heart disease: a retrospective cohort study of community-based exercise rehabilitation.

To examine the association between submaximal cardiorespiratory fitness (sCRF) and all-cause mortality in a cardiac rehabilitation (CR) cohort.Retrospective cohort study of participants entering CR between 26 May 1993 and 16 October 2006, followed up to 1 November 2013 (median 14 years, range 1.2-19.4 years).A community-based CR exercise programme in Leeds, West Yorkshire, UK.A cohort of 534 men (76%) and 136 women with a clinical diagnosis of coronary heart disease (CHD), aged 22-82 years, attending CR were evaluated for the association between baseline sCRF and all-cause mortality. 416 participants with an exercise test following CR (median 14 weeks) were examined for changes in sCRF and all-cause mortality.All-cause mortality and change in sCRF expressed in estimated metabolic equivalents (METs).Baseline sCRF was a strong predictor of all-cause mortality; compared to the lowest sCRF group (<5 METs for women and <6 METs for men), mortality risk was 41% lower in those with moderate sCRF (HR 0.59; 95% CI 0.42 to 0.83) and 60% lower (HR 0.40; 95% CI 0.25 to 0.64) in those with higher sCRF levels (≥7 METs women and ≥8 METs for men). Although improvement in sCRF at 14 weeks was not associated with a significant mortality risk reduction (HR 0.91; 95% CI 0.79 to 1.06) for the whole cohort, in those with the lowest sCRF (and highest all-cause mortality) at baseline, each 1-MET improvement was associated with a 27% age-adjusted reduction in mortality risk (HR 0.73; 95% CI 0.57 to 0.94).Higher baseline sCRF is associated with a reduced risk of all-cause mortality over 14 years in adults with CHD. Improving fitness through exercise-based CR is associated with significant risk reduction for the least fit

Branding for the rest of us

Abstract Small and medium enterprises (SMEs) create 71% of private sector jobs yet only 40% of them project growth (Ratte, 2015). Believing that a properly constructed brand undergirds SME profitability and sustainability, I asked: What makes strong brands? How might we make these elements accessible to non-experts? I examined these questions through a literature survey spanning 30 years of brand planning models, interviews with contemporary experts, and interviews with current SME executives. I developed the Brand Actualization Tool (BAT) to make brand development accessible and thereby to enhance SMEs’ opportunities for growth and sustainability. BAT consists of five stages: Motivate – define the organization’s authentic brand vision; Embed – operationalize purpose across the organization; Engage – connect the brand and offering to customers; Evaluate – measure success with analytics; adjust activities; and Impact – project activities’ impact into the future. Next steps include validating the positive impact I found that BAT has by increasing the number of SMEs using it and studying their results. Key words: brand, branding, marketing, SME branding, brand models, brand planning tool, customer purchase behavior, purpose, visio

High allelic diversity in the methyltransferase gene of a phase variable type III restriction-modification system has implications for the fitness of Haemophilus influenzae

Phase variable restriction-modification (R-M) systems are widespread in Eubacteria. Haemophilus influenzae encodes a phase variable homolog of Type III R-M systems. Sequence analysis of this system in 22 non-typeable H.influenzae isolates revealed a hypervariable region in the central portion of the mod gene whereas the res gene was conserved. Maximum likelihood (ML) analysis indicated that most sites outside this hypervariable region experienced strong negative selection but evidence of positive selection for a few sites in adjacent regions. A phylogenetic analysis of 61 Type III mod genes revealed clustering of these H.influenzae mod alleles with mod genes from pathogenic Neisseriae and, based on sequence analysis, horizontal transfer of the mod–res complex between these species. Neisserial mod alleles also contained a hypervariable region and all mod alleles exhibited variability in the repeat tract. We propose that this hypervariable region encodes the target recognition domain (TRD) of the Mod protein and that variability results in alterations to the recognition sequence of this R-M system. We argue that the high allelic diversity and phase variable nature of this R-M system have arisen due to selective pressures exerted by diversity in bacteriophage populations but also have implications for other fitness attributes of these bacterial species

Atmospheric extinction coefficients in the Ic\mathrm{I_c} band for several major international observatories: Results from the BiSON telescopes, 1984 to 2016

Over 30 years of solar data have been acquired by the Birmingham Solar Oscillations Network (BiSON), an international network of telescopes used to study oscillations of the Sun. Five of the six BiSON telescopes are located at major observatories. The observational sites are, in order of increasing longitude: Mount Wilson (Hale) Observatory (MWO), California, USA; Las Campanas Observatory (LCO), Chile; Observatorio del Teide, Iza\~{n}a, Tenerife, Canary Islands; the South African Astronomical Observatory (SAAO), Sutherland, South Africa; Carnarvon, Western Australia; and the Paul Wild Observatory, Narrabri, New South Wales, Australia. The BiSON data may be used to measure atmospheric extinction coefficients in the $\mathrm{I_c}$ band (approximately 700-900 nm), and presented here are the derived atmospheric extinction coefficients from each site over the years 1984 to 2016.Comment: 15 pages, 10 figures, 4 tables. Accepted by Astronomical Journal: 2017 July 2

The Macrophage Scavenger Receptor A Is Host-Protective in Experimental Meningococcal Septicaemia

Macrophage Scavenger Receptor A (SR-A) is a major non-opsonic receptor for Neisseria meningitidis on mononuclear phagocytes in vitro, and the surface proteins NMB0278, NMB0667, and NMB1220 have been identified as ligands for SR-A. In this study we ascertain the in vivo role of SR-A in the recognition of N. meningitidis MC58 (serogroup B) in a murine model of meningococcal septicaemia. We infected wild-type and SR-A−/− animals intraperitoneally with N. meningitidis MC58 and monitored their health over a period of 50 hours. We also determined the levels of bacteraemia in the blood and spleen, and measured levels of the pro-inflammatory cytokine interleukin-6 (IL-6). The health of SR-A−/− animals deteriorated more rapidly, and they showed a 33% reduction in survival compared to wild-type animals. SR-A−/− animals consistently exhibited higher levels of bacteraemia and increased levels of IL-6, compared to wild-type animals. Subsequently, we constructed a bacterial mutant (MC58-278-1220) lacking two of the SR-A ligands, NMB0278 and NMB1220. Mutation of NMB0667 proved to be lethal. When mice were infected with the mutant bacteria MC58-278-1220, no significant differences could be observed in the health, survival, bacteraemia, and cytokine production between wild-type and SR-A−/− animals. Overall, mutant bacteria appeared to cause less severe symptoms of septicaemia, and a competitive index assay showed that higher levels of wild-type bacteria were recovered when animals were infected with a 1∶1 ratio of wild-type MC58 and mutant MC58-278-1220 bacteria. These data represent the first report of the protective role of SR-A, a macrophage-restricted, non-opsonic receptor, in meningococcal septicaemia in vivo, and the importance of the recognition of bacterial protein ligands, rather than lipopolysaccharide

Continuous infusion of an agonist of the tumor necrosis factor receptor 2 in the spinal cord improves recovery after traumatic contusive injury.

AimThe activation of the TNFR2 receptor is beneficial in several pathologies of the central nervous system, and this study examines whether it can ameliorate the recovery process following spinal cord injury.MethodsEHD2-sc-mTNFR2 , an agonist specific for TNFR2, was used to treat neurons exposed to high levels of glutamate in vitro. In vivo, it was infused directly to the spinal cord via osmotic pumps immediately after a contusion to the cord at the T9 level. Locomotion behavior was assessed for 6 weeks, and the tissue was analyzed (lesion size, RNA and protein expression, cell death) after injury. Somatosensory evoked potentials were also measured in response to hindlimb stimulation.ResultsThe activation of TNFR2 protected neurons from glutamate-mediated excitotoxicity through the activation of phosphoinositide-3 kinase gamma in vitro and improved the locomotion of animals following spinal cord injury. The extent of the injury was not affected by infusing EHD2-sc-mTNFR2 , but higher levels of neurofilament H and 2', 3'-cyclic-nucleotide 3'-phosphodiesterase were observed 6 weeks after the injury. Finally, the activation of TNFR2 after injury increased the neural response recorded in the cortex following hindlimb stimulation.ConclusionThe activation of TNFR2 in the spinal cord following contusive injury leads to enhanced locomotion and better cortical responses to hindlimb stimulation

Surfaces roughness effects on the transmission of Gaussian beams by anisotropic parallel plates

Influence of the plate surfaces roughness in precise ellipsometry experiments is studied. The realistic case of a Gaussian laser beam crossing a uniaxial platelet is considered. Expression for the transmittance is determined using the first order perturbation theory. In this frame, it is shown that interference takes place between the specular transmitted beam and the scattered field. This effect is due to the angular distribution of the Gaussian beam and is of first order in the roughness over wavelength ratio. As an application, a numerical simulation of the effects of quartz roughness surfaces at normal incidence is provided. The interference term is found to be strongly connected to the random nature of the surface roughness.Comment: 18 pages, Journal of Physics D: Applied Physics, volume 36, issue 21, pages 2697 - 270

Effects of quercetin on exercise performance, physical activity and blood supply in a novel model of sustained hind-limb ischaemia

Background: There are currently few effective drugs to treat the leg symptoms of peripheral arterial disease (PAD). Previous studies have suggested that the nutraceutical, quercetin, can improve exercise performance and reduce pain sensitivity in healthy mice and improve blood supply in a rodent model of acute hind-limb ischaemia. These models may not be relevant to people with PAD. The aim of this study was to examine the effect of quercetin on exercise performance, physical activity and blood supply in a novel mouse model of sustained hind-limb ischaemia. Methods: Hind-limb ischaemia was induced in 6-month-old male apolipoprotein E-deficient mice using a novel two-stage surgical procedure. Five days after induction of ischaemia, mice were allocated to commence dietary quercetin or a control diet for 4 weeks. The primary outcome was exercise performance evaluated using a treadmill test. Other outcomes included physical activity, estimated by an open field test, and hind-limb blood supply, assessed by laser Doppler monitoring. Results: A sustained reduction in relative limb blood supply (P < 0.001) was achieved consistently in all 48 mice before allocation to a control (n = 24) or quercetin (n = 24) diet. Quercetin did not improve exercise performance (P = 0.785), physical activity (P = 0.151) or relative limb blood supply (P = 0.954) over the 4-week assessment period. Conclusion: These data suggest that quercetin does not improve exercise performance, physical activity or limb blood supply in mice with sustained hind-limb ischaemia, and therefore is unlikely be an effective treatment for PAD