Managing lifestyle change to reduce coronary risk: a synthesis of qualitative research on peoples’ experiences

Background Coronary heart disease is an incurable condition. The only approach known to slow its progression is healthy lifestyle change and concordance with cardio-protective medicines. Few people fully succeed in these daily activities so potential health improvements are not fully realised. Little is known about peoples’ experiences of managing lifestyle change. The aim of this study was to synthesise qualitative research to explain how participants make lifestyle change after a cardiac event and explore this within the wider illness experience. Methods A qualitative synthesis was conducted drawing upon the principles of meta-ethnography. Qualitative studies were identified through a systematic search of 7 databases using explicit criteria. Key concepts were identified and translated across studies. Findings were discussed and diagrammed during a series of audiotaped meetings. Results The final synthesis is grounded in findings from 27 studies, with over 500 participants (56% male) across 8 countries. All participants experienced a change in their self-identity from what was ‘familiar’ to ‘unfamiliar’. The transition process involved ‘finding new limits and a life worth living’ , ‘finding support for self’ and ‘finding a new normal’. Analyses of these concepts led to the generation of a third order construct, namely an ongoing process of ‘reassessing past, present and future lives’ as participants considered their changed identity. Participants experienced a strong urge to get back to ‘normal’. Support from family and friends could enable or constrain life change and lifestyle changes. Lifestyle change was but one small part of a wider ‘life’ change that occurred. Conclusions The final synthesis presents an interpretation, not evident in the primary studies, of a person-centred model to explain how lifestyle change is situated within ‘wider’ life changes. The magnitude of individual responses to a changed health status varied. Participants experienced distress as their notion of self identity shifted and emotions that reflected the various stages of the grief process were evident in participants’ accounts. The process of self-managing lifestyle took place through experiential learning; the level of engagement with lifestyle change reflected an individual’s unique view of the balance needed to manage ‘realistic change’ whilst leading to a life that was perceived as ‘worth living’. Findings highlight the importance of providing person centred care that aligns with both psychological and physical dimensions of recovery which are inextricably linked

International Veterinary Epilepsy Task Force consensus proposal: Medical treatment of canine epilepsy in Europe

In Europe, the number of antiepileptic drugs (AEDs) licensed for dogs has grown considerably over the last years. Nevertheless, the same questions remain, which include, 1) when to start treatment, 2) which drug is best used initially, 3) which adjunctive AED can be advised if treatment with the initial drug is unsatisfactory, and 4) when treatment changes should be considered. In this consensus proposal, an overview is given on the aim of AED treatment, when to start long-term treatment in canine epilepsy and which veterinary AEDs are currently in use for dogs. The consensus proposal for drug treatment protocols, 1) is based on current published evidence-based literature, 2) considers the current legal framework of the cascade regulation for the prescription of veterinary drugs in Europe, and 3) reflects the authors’ experience. With this paper it is aimed to provide a consensus for the management of canine idiopathic epilepsy. Furthermore, for the management of structural epilepsy AEDs are inevitable in addition to treating the underlying cause, if possible

Obstetric and perinatal factors as predictors of child behaviour at 5 years

Objective To identify whether obstetric and perinatal factors are independent predictors of child behaviour at 5 years. Methodology The Mater University Study of Pregnancy (MUSP) is a prospective cohort study of 8556 mothers enrolled in early pregnancy. The relationship of obstetric and perinatal factors, maternal lifestyle, age and gender of the child, and social disadvantage were examined as predictors of child behaviour in 5005 children completing a modified child behaviour checklist at 5 years. This checklist contained three independent groups of behaviour: externalizng, internalizing and SAT (social, attentional and thought problems). Results In the initial analysis a limited number of associations were present. After adjusting for measures of social disadvantage, only number of antenatal admissions was associated with child behaviour in all three scales, while maternal cigarette smoking in pregnancy and male gender were associated with externalising and SAT behaviours. Conclusions Most common epidemiologic obstetric and perinatal risk factors were not independent predictors of behaviour problems in children at 5 years

The Extracellular Matrix Component Psl Provides Fast-Acting Antibiotic Defense in Pseudomonas aeruginosa Biofilms

Bacteria within biofilms secrete and surround themselves with an extracellular matrix, which serves as a first line of defense against antibiotic attack. Polysaccharides constitute major elements of the biofilm matrix and are implied in surface adhesion and biofilm organization, but their contributions to the resistance properties of biofilms remain largely elusive. Using a combination of static and continuous-flow biofilm experiments we show that Psl, one major polysaccharide in the Pseudomonas aeruginosa biofilm matrix, provides a generic first line of defense toward antibiotics with diverse biochemical properties during the initial stages of biofilm development. Furthermore, we show with mixed-strain experiments that antibiotic-sensitive “non-producing” cells lacking Psl can gain tolerance by integrating into Psl-containing biofilms. However, non-producers dilute the protective capacity of the matrix and hence, excessive incorporation can result in the collapse of resistance of the entire community. Our data also reveal that Psl mediated protection is extendible to E. coli and S. aureus in co-culture biofilms. Together, our study shows that Psl represents a critical first bottleneck to the antibiotic attack of a biofilm community early in biofilm development.National Institutes of Health (U.S.). National Institute of Environmental Health Sciences (Training Grant in Toxicology 5 T32 ES7020-37

Strategies to reduce medication errors with reference to older adults

Background  In Australia, around 59% of the general population uses prescription medication with this number increasing to about 86% in those aged 65 and over and 83% of the population over 85 using two or more medications simultaneously. A recent report suggests that between 2% and 3% of all hospital admissions in Australia may be medication related with older Australians at higher risk because of higher levels of medicine intake and increased likelihood of being admitted to hospital. The most common medication errors encountered in hospitals in Australia are prescription/medication ordering errors, dispensing, administration and medication recording errors. Contributing factors to these errors have largely not been reported in the hospital environment. In the community, inappropriate drugs, prescribing errors, administration errors, and inappropriate dose errors are most common. Objectives  To present the best available evidence for strategies to prevent or reduce the incidence of medication errors associated with the prescribing, dispensing and administration of medicines in the older persons in the acute, subacute and residential care settings, with specific attention to persons aged 65 years and over. Search strategy  Bibliographic databases PubMed, Embase, Current contents, The Cochrane Library and others were searched from 1986 to present along with existing health technology websites. The reference lists of included studies and reviews were searched for any additional literature. Selection criteria  Systematic reviews, randomised controlled trials and other research methods such as non-randomised controlled trials, longitudinal studies, cohort or case-control studies, or descriptive studies that evaluate strategies to identify and manage medication incidents. Those people who are involved in the prescribing, dispensing or administering of medication to the older persons (aged 65 years and older) in the acute, subacute or residential care settings were included. Where these studies were limited, evidence available on the general patient population was used. Data collection and analysis  Study design and quality were tabulated and relative risks, odds ratios, mean differences and associated 95% confidence intervals were calculated from individual comparative studies containing count data where possible. All other data were presented in a narrative summary. Results  Strategies that have some evidence for reducing medication incidents are: •  computerised physician ordering entry systems combined with clinical decision support systems; •  individual medication supply systems when compared with other dispensing systems such as ward stock approaches; •  use of clinical pharmacists in the inpatient setting; •  checking of medication orders by two nurses before dispensing medication; •  a Medication Administration Review and Safety committee; and •  providing bedside glucose monitors and educating nurses on importance of timely insulin administration. In general, the evidence for the effectiveness of intervention strategies to reduce the incidence of medication errors is weak and high-quality controlled trials are needed in all areas of medication prescription and delivery

lincRNAs act in the circuitry controlling pluripotency and differentiation

Although thousands of large intergenic non-coding RNAs (lincRNAs) have been identified in mammals, few have been functionally characterized, leading to debate about their biological role. To address this, we performed loss-of-function studies on most lincRNAs expressed in mouse embryonic stem (ES) cells and characterized the effects on gene expression. Here we show that knockdown of lincRNAs has major consequences on gene expression patterns, comparable to knockdown of well-known ES cell regulators. Notably, lincRNAs primarily affect gene expression in trans. Knockdown of dozens of lincRNAs causes either exit from the pluripotent state or upregulation of lineage commitment programs. We integrate lincRNAs into the molecular circuitry of ES cells and show that lincRNA genes are regulated by key transcription factors and that lincRNA transcripts bind to multiple chromatin regulatory proteins to affect shared gene expression programs. Together, the results demonstrate that lincRNAs have key roles in the circuitry controlling ES cell state.Broad InstituteHarvard UniversityNational Human Genome Research Institute (U.S.)Merkin Family Foundation for Stem Cell Researc

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Exploring new physics frontiers through numerical relativity

The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology

Assessing control of postural stability in community-living older adults using performance-based limits of stability

<p>Abstract</p> <p>Background</p> <p>Balance disability measurements routinely used to identify fall risks in frail populations have limited value in the early detection of postural stability deficits in community-living older adults. The objectives of the study were to 1) measure performance-based limits of stability (LOS) in community-living older adults and compare them to theoretical LOS computed from data proposed by the Balance Master^®system, 2) explore the feasibility of a new measurement approach based on the assessment of postural stability during weight-shifting tasks at performance-based LOS, 3) quantify intra-session performance variability during multiple trials using the performance-based LOS paradigm.</p> <p>Methods</p> <p>Twenty-four healthy community-living older adults (10 men, 14 women) aged between 62 to 85 (mean age ± sd, 71.5 ± 6 yrs) participated in the study. Subjects' performance-based LOS were established by asking them to transfer their body weight as far as possible in three directions (forward, right and left) without changing their base of support. LOS were computed as the maximal excursion of the COP in each direction among three trials. Participants then performed two experimental tasks that consisted in controlling, with the assistance of visual feedback, their centre of pressure (COP) within two predefined targets set at 100% of their performance-based LOS. For each tasks 8 trials were performed. Ground reaction forces and torques during performance-based LOS evaluation and experimental tasks were recorded with a force plate. Sway area and medio-lateral mean COP displacement speed variables were extracted from force plate recordings.</p> <p>Results</p> <p>Significant differences between theoretical LOS computed from maximum leaning angles derived from anthropometric characteristics and performance-based LOS were observed. Results showed that a motor learning effect was present as the participants optimized their weight-shifting strategy through the first three trials of each task using the visual biofeedback provided on their COP. Reliable measures of control of postural stability at performance-based LOS can be obtained after two additional trials after the learning phase (0.69 > ICC > 1.0).</p> <p>Conclusion</p> <p>Establishing performance-based LOS instead of relying on estimations of theoretical LOS offers a more individualized and realistic insight on the true LOS of an individual. Performance-based LOS can be used as targets during weight-shifting postural tasks with real time visual feedback of the COP displacement to assess postural stability of community-living older adults. In order to obtain reliable results, a learning phase allowing subjects to learn how to control their COP displacement is needed.</p

Differential regulation of lineage commitment in human and mouse primed pluripotent stem cells by the nucleosome remodelling and deacetylation complex.

Differentiation of mammalian pluripotent cells involves large-scale changes in transcription and, among the molecules that orchestrate these changes, chromatin remodellers are essential to initiate, establish and maintain a new gene regulatory network. The Nucleosome Remodelling and Deacetylation (NuRD) complex is a highly conserved chromatin remodeller which fine-tunes gene expression in embryonic stem cells. While the function of NuRD in mouse pluripotent cells has been well defined, no study yet has defined NuRD function in human pluripotent cells. Here we find that while NuRD activity is required for lineage commitment from primed pluripotency in both human and mouse cells, the nature of this requirement is surprisingly different. While mouse embryonic stem cells (mESC) and epiblast stem cells (mEpiSC) require NuRD to maintain an appropriate differentiation trajectory as judged by gene expression profiling, human induced pluripotent stem cells (hiPSC) lacking NuRD fail to even initiate these trajectories. Further, while NuRD activity is dispensable for self-renewal of mESCs and mEpiSCs, hiPSCs require NuRD to maintain a stable self-renewing state. These studies reveal that failure to properly fine-tune gene expression and/or to reduce transcriptional noise through the action of a highly conserved chromatin remodeller can have different consequences in human and mouse pluripotent stem cells