Characterising the application of the “progressive overload” principle of exercise training within cardiac rehabilitation: A United Kingdom-based community programme

Background: Recent concerns have cast doubt over the effectiveness of cardiac rehabilitation [CR] programmes for improving cardiorespiratory fitness [CRF] in patients with a history of cardiac disease in the United Kingdom [UK]. We aimed to characterise the weekly progression of exercise training dose over an 8-week Phase III CR programme as we felt this may be partly responsible for the lack of improvement in CRF reported in previous studies. Design: Observational study. Methods: We evaluated a community-based Phase III CR programme in the UK. During each training session, patients wore an Apple Watch and the weekly progression of exercise training dose/load was quantified. The analysis was based on 332 individual training sessions. Exercise intensity [% heart rate reserve] during the cardiovascular [CV] exercise training component [%HRR-CV], CV training duration; estimated changes in cardiorespiratory fitness [change in estimated metabolic equivalents (METs)]; session rating of perceived exertion [sRPE], sRPE training load [sRPE-TL], and exercise training impulse [TRIMP] were evaluated. Results: Thirty cardiac patients [83% male; age [SD] 67.0 [10.0] years; body mass index [SD] 28.3 [4.6] kg∙m-2] were recruited to an 8-week programme [16 sessions in total]. Bayesian repeated-measures ANOVA indicated anecdotal evidence for the alternative hypothesis for changes in %HRR-CV (BF10 = 0.61), sRPE (BF10 = 1.1), and change in estimated METs (BF10 = 1.2) during CR. Conversely, Bayesian repeated-measures ANOVA showed extreme evidence for changes in CV training duration (BF10 = 2.438e+26), TRIMP (BF10 = 71436), and sRPE-TL (BF10 = 779570). Conclusion: The key exercise training principle of progressive overload was only partially applied. Increases observed in exercise dose were due to increases in the duration of CV training, rather than combined with increases in exercise intensity [%HRR-CV and sRPE]. Accordingly, allied health professionals must ensure that exercise intensity is more consistently progressed to optimise the exercise stimulus and improvements in CRF and patient outcomes

A Unified Framework for the Infection Dynamics of Zoonotic Spillover and Spread.

A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission. We developed a transparent, theoretical framework, based on a generalization of Poisson processes with memory of past human infections, that unifies these stages. Once we have quantified pathogen dynamics in the reservoir, with some knowledge of the mechanism of contact, the approach provides a tool to estimate the likelihood of spillover events. Comparisons with independent agent-based models demonstrates the ability of the framework to correctly estimate the relative contributions of human-to-human vs animal transmission. As an illustrative example, we applied our model to Lassa fever, a rodent-borne, viral haemorrhagic disease common in West Africa, for which data on human outbreaks were available. The approach developed here is general and applicable to a range of zoonoses. This kind of methodology is of crucial importance for the scientific, medical and public health communities working at the interface between animal and human diseases to assess the risk associated with the disease and to plan intervention and appropriate control measures. The Lassa case study revealed important knowledge gaps, and opportunities, arising from limited knowledge of the temporal patterns in reporting, abundance of and infection prevalence in, the host reservoir.Natural Environment Research Council (project no.: NEJ001570-1), Department for International Development, Economic and Social Research Council, National Institute for Health Research, Science and Technology Directorate, Department of Homeland Security, Fogarty International Center USA, European Union FP7 (project ANTIGONE (contract number 278976)), Royal Society (Wolfson Research Merit Award), Alborada Trust, US National Institute of Health (P20GM103501, BAANIAID-DAIT-NIHQI2008031, HHSN272201000022C, HHSN272200900049C, 1U19AI109762, 1R01AI104621, 2R44AI088843), USAID/NIH PEER Health grant.This is the final version of the article. It first appeared from the Public Library of Science via http://dx.doi.org/10.1371/journal.pntd.000495

Characterisation of the muon beams for the Muon Ionisation Cooling Experiment

A novel single-particle technique to measure emittance has been developed and used to characterise seventeen different muon beams for the Muon Ionisation Cooling Experiment (MICE). The muon beams, whose mean momenta vary from 171 to 281 MeV/c, have emittances of approximately 1.2–2.3 π mm-rad horizontally and 0.6–1.0 π mm-rad vertically, a horizontal dispersion of 90–190 mm and momentum spreads of about 25 MeV/c. There is reasonable agreement between the measured parameters of the beams and the results of simulations. The beams are found to meet the requirements of MICE

Hybridization in parasites: consequences for adaptive evolution, pathogenesis and public health in a changing world

[No abstract available

Lessons learned from shallow subglacial bedrock drilling campaigns in Antarctica

We review successes and challenges from five recent subglacial bedrock drilling campaigns intended to find evidence for Antarctic Ice Sheet retreat during warm periods in the geologic past. Insights into times when the polar ice sheets were smaller than present serve as guiding information for modeling efforts that aim to predict the rate and magnitude of future sea level rise that would accompany major retreat of the Antarctic Ice Sheet. One method to provide direct evidence for the timing of deglaciations and minimum extent of prior ice sheets is to extract subglacial bedrock cores for cosmogenic nuclide analysis from beneath the modern ice sheet surface. Here we summarize the lessons learned from five field seasons tasked with obtaining bedrock cores from shallow depths (<120 m beneath ice surface) across West Antarctica since 2016. We focus our findings on drilling efforts and technology and geophysical surveys with ground-penetrating radar. Shallow subglacial drilling provides a high risk, high reward means to test for past instabilities of the Antarctic Ice Sheet, and we highlight key challenges and solutions to increase the likelihood of success for future subglacial drilling efforts in polar regions

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Co-Regulation of NF-κB and Inflammasome-Mediated Inflammatory Responses by Myxoma Virus Pyrin Domain-Containing Protein M013

NF-κB and inflammasomes both play central roles in orchestrating anti-pathogen responses by rapidly inducing a variety of early-response cytokines and chemokines following infection. Myxoma virus (MYXV), a pathogenic poxvirus of rabbits, encodes a member of the cellular pyrin domain (PYD) superfamily, called M013. The viral M013 protein was previously shown to bind host ASC-1 protein and inhibit the cellular inflammasome complex that regulates the activation and secretion of caspase 1-regulated cytokines such as IL-1β and IL-18. Here, we report that human THP-1 monocytic cells infected with a MYXV construct deleted for the M013L gene (vMyxM013-KO), in stark contrast to the parental MYXV, rapidly induce high levels of secreted pro-inflammatory cytokines like TNF, IL-6, and MCP-1, all of which are regulated by NF-κB. The induction of these NF-κB regulated cytokines following infection with vMyxM013-KO was also confirmed in vivo using THP-1 derived xenografts in NOD-SCID mice. vMyxM013-KO virus infection specifically induced the rapid phosphorylation of IKK and degradation of IκBα, which was followed by nuclear translocation of NF-κB/p65. Even in the absence of virus infection, transiently expressed M013 protein alone inhibited cellular NF-κB-mediated reporter gene expression and nuclear translocation of NF-κB/p65. Using protein/protein interaction analysis, we show that M013 protein also binds directly with cellular NF-κB1, suggesting a direct physical and functional linkage between NF-κB1 and ASC-1. We further demonstrate that inhibition of the inflammasome with a caspase-1 inhibitor did not prevent the induction of NF-κB regulated cytokines following infection with vMyxM013-KO virus, but did block the activation of IL-1β. Thus, the poxviral M013 inhibitor exerts a dual immuno-subversive role in the simultaneous co-regulation of both the cellular inflammasome complex and NF-κB-mediated pro-inflammatory responses

Influence of Comorbidities on Therapeutic Progression of Diabetes Treatment in Australian Veterans: A Cohort Study

BACKGROUND: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84–0.91], P<0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. CONCLUSIONS / SIGNIFICANCE: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities.Agnes I. Vitry, Elizabeth E. Roughead, Adrian K. Preiss, Philip Ryan, Emmae N. Ramsay, Andrew L. Gilbert, Gillian E. Caughey, Sepehr Shakib, Adrian Esterman, Ying Zhang and Robyn A. McDermot