Improving outcomes for older people in the emergency department : a review of reviews

Background: There has been a recognised trend of increasing use of emergency and urgent care and emergency departments (EDs) by older people, which is marked by a substantial evidence base reporting interventions for this population and guidance from key organisations. Despite this, outcomes for this population remain suboptimal. A plethora of reviews in this area provides challenges for clinicians and commissioners in determining which interventions and models of care best meet people’s needs. The aim of this review was to identify effective ED interventions which have been reported for older people, and to provide a clear summary of the myriad reviews and numerous intervention types in this area. Methods: A review of reviews, reporting interventions for older people, either initiated or wholly delivered within the ED. Results: A total of 15 review articles describing 83 primary studies met our content and reporting standards criteria. The majority (n=13) were systematic reviews (four using meta-analysis.) Across the reviews, 26 different outcomes were reported with inconsistency. Follow-up duration varied within and across the reviews. Based on how authors had reported results, evidence clusters were developed: (1) staff-focused reviews, (2) discharge intervention reviews, (3) population-focused reviews and (4) intervention component reviews. Conclusions: The evidence base describing interventions is weak due to inconsistent reporting, differing emphasis placed on the key characteristics of primary studies (staff, location and outcome) by review authors and varying quality of reviews. No individual interventions have been found to be more promising, but interventions initiated in the ED and continued into other settings have tended to result in more favourable patient and health service outcomes. Despite many interventions reported within the reviews being holistic and patient focused, outcomes measured were largely service focused. PROSPERO registration number: PROSPERO CRD42018111461

The Use of mHealth to Deliver Tailored Messages Reduces Reported Energy and Fat Intake.

Evidence supports the role of feedback in reinforcing motivation for behavior change. Feedback that provides reinforcement has the potential to increase dietary self-monitoring and enhance attainment of recommended dietary intake. The aim of this study was to examine the impact of daily feedback (DFB) messages, delivered remotely, on changes in dietary intake. This was a secondary analysis of the Self- Monitoring And Recording using Technology (SMART) Trial, a single-center, 24-month randomized clinical trial of behavioral treatment for weight loss. Participants included 210 obese adults (mean body mass index, 34.0 kg/m2) who were randomized to either a paper diary (PD), personal digital assistant (PDA), or PDA plus daily tailored feedback messages (PDA + FB). To determine the role of daily tailored feedback in dietary intake, we compared the self-monitoring with DFB group (DFB group; n = 70) with the self-monitoring without DFB group (no-DFB group, n = 140). All participants received a standard behavioral intervention for weight loss. Self-reported changes in dietary intake were compared between the DFB and no-DFB groups and were measured at baseline and at 6, 12, 18, and 24 months. Linear mixed modeling was used to examine percentage changes in dietary intake from baseline. Compared with the no-DFB group, the DFB group achieved a larger reduction in energy (−22.8% vs −14.0%; P = .02) and saturated fat (−11.3% vs −0.5%; P = .03) intake and a trend toward a greater decrease in total fat intake (−10.4% vs −4.7%; P = .09). There were significant improvements over time in carbohydrate intake and total fat intake for both groups (P values < .05). Daily tailored feedback messages designed to target energy and fat intake and delivered remotely in real time using mobile devices may play an important role in the reduction of energy and fat intake

Structure of the poly-C9 component of the complement membrane attack complex

The membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major component of the MAC, a multi-protein complex that forms pores in the membrane of target pathogens. In contrast to homologous proteins such as perforin and the cholesterol-dependent cytolysins (CDCs), all of which require the membrane for oligomerisation, C9 assembles directly onto the nascent MAC from solution. However, the molecular mechanism of MAC assembly remains to be understood. Here we present the 8 Å cryo-EM structure of a soluble form of the poly-C9 component of the MAC. These data reveal a 22-fold symmetrical arrangement of C9 molecules that yield an 88-strand pore-forming β-barrel. The N-terminal thrombospondin-1 (TSP1) domain forms an unexpectedly extensive part of the oligomerisation interface, thus likely facilitating solution-based assembly. These TSP1 interactions may also explain how additional C9 subunits can be recruited to the growing MAC subsequent to membrane insertion

Emergency care for older people living with frailty: patient and carer perspectives

Background Little is known about how frailty impacts on older people’s experiences of emergency care, despite patient experience being essential to providing person-centred care. This qualitative study reports on the experiences of older people with frailty in the ED and their and their carers’ preferences for emergency care. Methods Older people (aged 75+ years) who were at least mildly frail and/or their carers, with current or recent experience of emergency care, were recruited from three EDs in England between January and June 2019. Data were collected via semi-structured in-depth interviews which explored participants’ views on their recent experience of emergency care and their priorities and preferred outcomes. Interviews were audio-recorded, transcribed verbatim and analysed following the principles of the Framework approach. Results Forty participants were interviewed: 24 patients and 16 carers who, between them, described ED attendances for 28 patients across the three sites. Often informed by previous negative experiences, there was a strong desire to avoid conveyance to EDs, and a sense of helplessness or acquiescence to attend. Although staff attitudes were on the whole seen as positive, the ED experience was dominated by negative experiences relating to very basic issues such as a lack of help with eating, drinking, toileting and discomfort from long waits on hard trolleys. Participants reported that communication and involvement in decision making could be improved, including involving next of kin, who were viewed as critical to supporting vulnerable older people during sometimes very protracted waits. Conclusion Frailty reflects a vulnerability and a need for support in basic activities of daily living, which EDs in this study, and perhaps more widely, are not set up to provide. Changes at the levels of clinical practice and service design are required to deliver even the most basic care for older people with frailty in the ED environment

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc

Understanding conflict among experts working on controversial species: A case study on the Australian dingo

Expert elicitation can be valuable for informing decision-makers on conservation and wildlife management issues. To date, studies eliciting expert opinions have primarily focused on identifying and building consensus on key issues. Nonetheless, there are drawbacks of a strict focus on consensus, and it is important to understand and emphasize dissent, too. This study adopts a dissensus-based Delphi to understand conflict among dingo experts. Twenty-eight experts participated in three rounds of investigation. We highlight disagreement on most of the issues explored. In particular, we find that disagreement is underpinned by what we call “conflict over values” and “conflict over evidence.” We also note the broader role played by distrust in influencing such conflicts. Understanding and recognizing the different elements shaping disagreement is critical for informing and improving decision-making and can also enable critique of dominant paradigms in current practices. We encourage greater reflexivity and open deliberation on these aspects and hope our study will inform similar investigations in other contexts.Valerio Donfrancesco, Benjamin L. Allen, Rob Appleby, Linda Behrendorff, Gabriel Conroy, Mathew S. Crowther, Christopher R. Dickman, Tim Doherty, Bronwyn A. Fancourt, Christopher E. Gordon, Stephen M. Jackson, Chris N. Johnson, Malcolm S. Kennedy, Loukas Koungoulos, Mike Letnic, Luke K.-P. Leung, Kieren J. Mitchell, Bradley Nesbitt, Thomas Newsome, Carlo Pacioni, Justine Phillip, Brad V. Purcell, Euan G. Ritchie, Bradley P. Smith, Danielle Stephens, Jack Tatler, Lily M. van Eeden, Kylie M. Cairn

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

The Physics of Star Cluster Formation and Evolution

© 2020 Springer-Verlag. The final publication is available at Springer via https://doi.org/10.1007/s11214-020-00689-4.Star clusters form in dense, hierarchically collapsing gas clouds. Bulk kinetic energy is transformed to turbulence with stars forming from cores fed by filaments. In the most compact regions, stellar feedback is least effective in removing the gas and stars may form very efficiently. These are also the regions where, in high-mass clusters, ejecta from some kind of high-mass stars are effectively captured during the formation phase of some of the low mass stars and effectively channeled into the latter to form multiple populations. Star formation epochs in star clusters are generally set by gas flows that determine the abundance of gas in the cluster. We argue that there is likely only one star formation epoch after which clusters remain essentially clear of gas by cluster winds. Collisional dynamics is important in this phase leading to core collapse, expansion and eventual dispersion of every cluster. We review recent developments in the field with a focus on theoretical work.Peer reviewe