The effects of exercise training interventions on the health profile of inactive premenopausal women

A physically inactive lifestyle is associated with increased morbidity of non-communicable diseases, with such diseases representing the leading cause of death worldwide. It is well documented that regular participation in physical activity is associated with an improvement in a number of established health markers. However, it has been reported that 34-39 % of UK women aged 25-54 y fail to meet the minimum physical activity recommendations and many conventional exercise training interventions and initiatives are failing to meaningfully increase physical activity levels and adherence in previously inactive premenopausal women. A common barrier preventing premenopausal women from initiating and maintaining increased habitual physical activity is a ‘lack of time’. Physical activity initiation and maintenance can also be affected by the exercise environment with some individuals preferring to exercise alone while others prefer to exercise within a supervised or group environment. Increasing evidence suggests that high-intensity interval training (HIIT) performed independently, under supervision or within a group environment can provide a time-efficient alternative for improving several health markers in different populations. However, limited research has examined the effects of HIIT on health markers in inactive women and the effects of different methods of HIIT on overall health status. Therefore, the purpose of this thesis was to identify how alternative and smaller volumes of higher-intensity exercise influence enjoyment, adherence rates and health markers in previously inactive premenopausal women following 12-16 wks of training. Chapter 4 examined the effects of 16 wks of short duration small-sided football training and whole-body vibration (WBV) training on body composition, aerobic fitness and muscle oxidative capacity of previously inactive premenopausal women. Results from this study demonstrated that short duration small-sided football elicited superior health benefits, which included a reduction in body fat percentage and submaximal exercise heart rate (HR) as well as a decrease in PCr depletion for a given work rate during one-legged knee-extension exercise, compared to WBV training. Chapter 5 demonstrated that 15 wks of high-intensity swim training was an effective and time-efficient alternative exercise modality for the improvement of insulin sensitivity, glucose control and plasma soluble intracellular and vascular cell adhesion molecules compared to prolonged continuous swim training for previously inactive premenopausal women. Chapter 6 revealed that 12 wks of self-paced high-intensity interval and prolonged continuous cycling training both increased cardiorespiratory fitness and cognitive function and reduced resting HR in previously inactive premenopausal women. On the other hand, reductions in resting blood pressure (BP), submaximal HR and body mass and increases in mental well-being were training-type-specific. Finally, Chapter 7 identified that a novel 12 wk home-based DVD-directed exercise programme for previously inactive premenopausal women, encompassing movements commonly found within football training, was beneficial for the improvement of high-density lipoprotein cholesterol concentration and mental well-being when carried out at a moderate- to high-intensity. The exercise training interventions were well tolerated and adhered to by participants and resulted in improvements to some established health markers. However, the improved health profile of premenopausal women after the various training interventions was not uniform, with several training specific adaptations being manifest. Collectively, the combined training studies (n=175 participants) provide some support for shorter-duration, higher-intensity physical exercise training, including football, swimming, cycling and home-based DVD-directed exercise training, but not whole-body vibration training, to improve key health markers in previously inactive premenopausal women. The findings presented in this thesis demonstrate that several HIIT exercise modalities appear to be effective and feasible alternatives to prolonged continuous exercise training for improving health markers in previously inactive premenopausal women.FIFA-Medical Assessments and Research Centre (F-Marc

Blended Learning: Overview and Recommendations for Successful Implementation

Purpose – The purpose of this paper is to identify key themes within the blended learning literature and to develop a series of practical recommendations to facilitate the successful adaptation and implementation of a ‘‘blended approach to learning delivery’’. Design/methodology/approach – The literature was reviewed and informed a series of recommendations for organisations considering adopting or implementing blended approaches to teaching and training. Findings – Several key themes centering on the importance of evaluation, skills training, pedagogy, human factors, technology and implementation were identified. The emerging themes informed a series of practical recommendations to assist organisations considering blended learning approaches. Findings highlight the current limitations in the evidence base. Practical implications – The identified key themes and practical recommendations provide a useful assist to organisations considering adopting and implementing blended approaches to teaching and training. Originality/value – The paper highlights key areas for development in the blended learning literature and at the organisational level

Prevalence of alcohol-related attendance at an inner-city emergency department and its impact: a dual prospective and retrospective cohort study

Background: Alcohol-related hospital attendances at Emergency Departments (ED) are a potentially avoidable burden on National Health Services (NHS) resources. Understanding the number and type of patients attending EDs with alcohol intoxication is important in estimating the workload and cost implications. We used best practice from previous studies to establish the prevalence of adult alcohol-related ED attendances and estimate the costs of clinical management and subsequent health service use. Methods: The setting was a large inner-city ED in northeast England, United Kingdom. Data were collected via (i) retrospective review of hospital records for all ED attendances for four pre-specified weeks in 2010/11 to identify alcohol-related cases along with 12 months follow-up of the care episode, and (ii) prospective 24/7 assessment via breath alcohol concentration testing of patients presenting to ED in the corresponding weeks in 2012/13. Results: The prevalence rates of alcohol-related attendances were 12% and 15% for the retrospective and prospective cohorts. Prospectively, the rates ranged widely from 4% to 60% during the week, rising to over 70% at weekends. Younger males attending in the early morning hours at weekends made up the largest proportion of alcohol-related attendances. The mean cost per attendance was £249 (SD £1,064); the mean total cost for those admitted was £851 (SD £2,549). The most common reasons for attending were trauma-related injuries, followed by psychiatric problems. Conclusions: Alcohol-related attendances are a major and avoidable burden on emergency care. However, targeted interventions at weekends and early morning hours could capture the majority of cases and help prevent future re-attendance

Toll-like receptor orchestrates a tumor suppressor response in non-small cell lung cancer

Targeting early-stage lung cancer is vital to improve survival. However, the mechanisms and components of the early tumor suppressor response in lung cancer are not well understood. In this report, we study the role of Toll-like receptor 2 (TLR2), a regulator of oncogene-induced senescence, which is a key tumor suppressor response in premalignancy. Using human lung cancer samples and genetically engineered mouse models, we show that TLR2 is active early in lung tumorigenesis, where it correlates with improved survival and clinical regression. Mechanistically, TLR2 impairs early lung cancer progression via activation of cell intrinsic cell cycle arrest pathways and the proinflammatory senescence-associated secretory phenotype (SASP). The SASP regulates non-cell autonomous anti-tumor responses, such as immune surveillance of premalignant cells, and we observe impaired myeloid cell recruitment to lung tumors after Tlr2 loss. Last, we show that administration of a TLR2 agonist reduces lung tumor growth, highlighting TLR2 as a possible therapeutic target.F.R.M. is funded by a Wellcome Trust clinical research fellowship through the Edinburgh Clinical Academic Track (ECAT) program (203913/Z/16/Z), a Wellcome Trust-ISSF3 award (IS3-R1.07 20/21), and a Wellcome Trust iTPA award (209710/Z/17/Z). J.C.A. core lab funding was received from Cancer Research UK (C47559/A16243, Training and Career Development Board – Career Development Fellowship), the University of Edinburgh (Chancellor’s Fellowship), and the Ministry of Science and Innovation of the Government of Spain (Proyecto PID2020-117860GB-100 financiado por MCIN/AEI/10.13039/501100011033). S.W. is supported by a Cancer Research UK senior fellowship (A29576). J.C. is supported by a Wellcome Trust clinical lectureship through the ECAT program (203913/Z/16/Z). M.M. is supported by a CRUK Edinburgh Centre Award (C157/A25140). S.V. and J.F.P. are funded by National Institute on Aging (NIA) grants (R01AG 68048-1 and UG3CA 268103-1)

Exploring conductivity in ex-situ doped Si thin films as thickness approaches 5nm

Silicon (Si) has been scaled below 10 nm in multigate and silicon-on-insulator (SOI) device technologies, but clearly Si thickness cannot be reduced indefinitely, as we will run out of atoms eventually. As thickness approaches 5 nm, surfaces and interfaces will significantly impact the electrical behavior of Si, and surface physics cannot be discounted. Below that, bulk material properties will be altered considerably in the few-monolayer limit. One of the most basic defining properties of a semiconductor is its conductivity. To improve conductivity, while inducing a channel by appropriate biasing, it is necessary to define an accurate impurity doping strategy to reduce parasitic resistance. In this paper, we investigated the changing electrical conductivity of SOI films as a function of the Si thickness, in the range of 3–66 nm. SOI films were ex situ doped using three different approaches: liquid/vapor phase monolayer doping of phosphorus using allyldiphenylphosphine, gas-phase doping of arsenic using arsine (AsH3), and room-temperature beam-line ion implantation of phosphorus. The circular transfer length method and micro-four-point probe measurements were used to determine the resistivity of the Si films, mitigating the contribution from contact resistance. The resistivity of the Si films was observed to increase with decreasing Si film thickness below 20 nm, with a dramatic increase observed for a Si thickness at 4.5 nm. This may drastically impact the number of parallel conduction paths (i.e., nanowires) required in gate-all-around devices. Density functional theory modeling indicates that the surface of the Si film with a thickness of 4.5 nm is energetically more favorable for the dopant atom compared to the core of the film

Renal outcome in adults with renal insufficiency and irregular asymmetric kidneys

BACKGROUND: The commonest cause of end-stage renal failure (ESRF) in children and young adults is congenital malformation of the kidney and urinary tract. In this retrospective review, we examine whether progression to ESRF can be predicted and whether treatment with angiotensin converting enzyme inhibitors (ACEI) can delay or prevent this. METHODS: We reviewed 78 patients with asymmetric irregular kidneys as a consequence of either primary vesico-ureteric reflux or renal dysplasia (Group 1, n = 44), or abnormal bladder function (Group 2, n = 34). Patients (median age 24 years) had an estimated GFR (eGFR) < 60 ml/min/1.73 m(2 )with at least 5 years of follow up (median 143 months). 48 patients received ACEI. We explored potential prognostic factors that affect the time to ESRF using Cox-regression analyses. RESULTS: At start, mean (SE) creatinine was 189 (8) μmol/l, mean eGFR 41 (1) ml/min 1.73 m(2), mean proteinuria 144 (14) mg/mmol creatinine (1.7 g/24 hrs). Of 78 patients, 36 (46%) developed ESRF, but none of 19 with proteinuria less than 50 mg/mmol and only two of 18 patients with eGFR above 50 ml/min did so. Renal outcome between Groups 1 and 2 appeared similar with no evidence for a difference. A benefit in favour of treatment with ACEI was observed above an eGFR of 40 ml/min (p = 0.024). CONCLUSION: The similar outcome of the two groups supports the nephrological nature of progressive renal failure in young men born with abnormal bladders. There is a watershed GFR of 40–50 ml/min at which ACEI treatment can be successful at improving renal outcome

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Modernism, class and colonialism in Robert Noonan’s The Ragged Trousered Philanthropists

This essay explores Robert Noonan’s 1914 novel, The Ragged Trousered Philanthropists, as a work of Irish modernist fiction. Reading its fragmented narrative as a reflection of the author’s subaltern position as an Irish republican and socialist, it interprets Noonan’s work as the product of the anticolonial and class struggles in which he was involved. Its critique of capitalist and imperial hegemony and the assertions that suffering, injustice and violence are normal, natural or inevitable phenomena reflects the author’s frustration, anger and desperation. In this way the novel counters and decentres the bourgeois-imperial dynamic that was reflected in the textual stability of Victorian realism. The Ragged Trousered Philanthropists is an uneasy text that is at once ruptured and uncertain of its own aesthetic status and conveys, through its shifting, episodic plot, the precariousness of a working-class existence permanently poised “on the brink of destitution.” © 2018 Informa UK Limited, trading as Taylor & Francis Grou

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation