Developing a new understanding of enabling health and wellbeing in Europe: harmonising health and social care delivery and informatics support to ensure holistic care

Europe faces significant challenges to its health and care services due to demographic change, being at the beginning of a large and continuing rise in the number and proportion of older citizens, while advances in healthcare mean that an increasing number of these and other adults will have enduring chronic health conditions. But for all citizens with actual or potential health problems, the maintenance of optimal health depends not just on healthcare services, but on support for nutrition, hygiene, mobility and shopping, socialisation, warm dry housing and other aspects of daily living, as without these health will be compromised and deteriorate. This demand surge is happening at a time when Information and Communication Technologies (ICT) are increasingly being used in other service sectors to enable consumer customisation and better resource management. An objective for all health systems, and for patients, is to minimise hospital stays and maximise care at home, but hitherto the practical need to observe the patient's state of health has extended hospital stays. Similarly there is a drive to minimise for quality of life and economic reasons admission to long-term institutional care and instead extend support to enable living at home. Traditionally any support needed by an individual has normally been provided by family members, often assisted by the local community, while social services have been the fall back provider when the family cannot support, either by direct provision or by mobilising specific services such as delivered hot meals. Housing agencies and other bodies have also had an important role. However, other demographic changes are significantly reducing the capacity of families to provide daily ongoing support. This means that health services are increasingly providing long-term monitoring and support to those living with chronic disease and frailty, while social services are increasingly needed to provide ongoing support. Many individual citizens are necessarily in receipt of both health and social care support, yet in all but a very few European countries these services are provided quite independently one from another, with minimal day to day liaison. A number of drivers for change are now necessitating significant change, and the social sciences have a key role to play in enabling successful progress. At a macro level, across Europe the combination of the economic downturn and the demographic-led increase in demand means that health and social care services are under ever increasing pressures, while constant growth of services is not affordable nor will the labour market support ever continuing expansion. This paper presents the case for systematic research activity in the social sciences, at European and national levels, to further the interlinked citizen- focused objectives of:close integration at delivery level of health care and social care support of individual's health, personalisation of care delivery including reasonable accommodation of individual choice, ensuring effective use of ICT applications based on user acceptability, bringing processes of consent, delegation, representation, coordination and privacy into the electronic era, ensuring respect for and teamwork with formal carers and the informal care team, ensuring equity in an electronic era regardless of digital literacy, assets and connectivity, examining stable and sustainable models of trusted infrastructure provision, establishing governance, authentication, management, and sustainability principles

Do Differing Enrichment Methodologies Affect the Belowground Productivity of Spartina Alterniflora?

Mariana E. Penny and Stephanie W. Plaisance are students in Environmental Science at Louisiana Tech University. Nathan Hammond is a student in Biological Sciences at Louisiana Tech University. Jennifer M. Hill is an Assistant Professor in Biological Sciences at Louisiana Tech University

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients

Background Prolonging kidney transplant survival is an important clinical priority. Induction immunosuppression with antibody therapy is recommended at transplantation and non‐depleting interleukin‐2 receptor monoclonal antibodies (IL2Ra) are considered first line. It is suggested that recipients at high risk of rejection should receive lymphocyte‐depleting antibodies but the relative benefits and harms of the available agents are uncertain. Objectives We aimed to: evaluate the relative and absolute effects of different antibody preparations (except IL2Ra) when used as induction therapy in kidney transplant recipients; determine how the benefits and adverse events vary for each antibody preparation; determine how the benefits and harms vary for different formulations of antibody preparation; and determine whether the benefits and harms vary in specific subgroups of recipients (e.g. children and sensitised recipients). Search methods We searched the Cochrane Kidney and Transplant's Specialised Register to 29 August 2016 through contact with the Information Specialist using search terms relevant to this review. Selection criteria Randomised controlled trials (RCTs) comparing monoclonal or polyclonal antibodies with placebo, no treatment, or other antibody therapy in adults and children who had received a kidney transplant. Data collection and analysis Two authors independently extracted data and assessed risk of bias. Dichotomous outcomes are reported as relative risk (RR) and continuous outcomes as mean difference (MD) together with their 95% confidence intervals (CI). Main results We included 99 studies (269 records; 8956 participants; 33 with contemporary agents). Methodology was incompletely reported in most studies leading to lower confidence in the treatment estimates. Antithymocyte globulin (ATG) prevented acute graft rejection (17 studies: RR 0.63, 95% CI 0.51 to 0.78). The benefits of ATG on graft rejection were similar when used with (12 studies: RR 0.61, 0.49 to 0.76) or without (5 studies: RR 0.65, 0.43 to 0.98) calcineurin inhibitor (CNI) treatment. ATG (with CNI therapy) had uncertain effects on death (3 to 6 months, 3 studies: RR 0.41, 0.13 to 1.22; 1 to 2 years, 5 studies: RR 0.75, 0.27 to 2.06; 5 years, 2 studies: RR 0.94, 0.11 to 7.81) and graft loss (3 to 6 months, 4 studies: RR 0.60, 0.34 to 1.05; 1 to 2 years, 3 studies: RR 0.65, 0.36 to 1.19). The effect of ATG on death‐censored graft loss was uncertain at 1 to 2 years and 5 years. In non‐CNI studies, ATG had uncertain effects on death but reduced death‐censored graft loss (6 studies: RR 0.55, 0.38 to 0.78). When CNI and older non‐CNI studies were combined, a benefit was seen with ATG at 1 to 2 years for both all‐cause graft loss (7 studies: RR 0.71, 0.53 to 0.95) and death‐censored graft loss (8 studies: RR 0.55, 0.39 to 0.77) but not sustained longer term. ATG increased cytomegalovirus (CMV) infection (6 studies: RR 1.55, 1.24 to 1.95), leucopenia (4 studies: RR 3.86, 2.79 to 5.34) and thrombocytopenia (4 studies: RR 2.41, 1.61 to 3.61) but had uncertain effects on delayed graft function, malignancy, post‐transplant lymphoproliferative disorder (PTLD), and new onset diabetes after transplantation (NODAT). Alemtuzumab was compared to ATG in six studies (446 patients) with early steroid withdrawal (ESW) or steroid minimisation. Alemtuzumab plus steroid minimisation reduced acute rejection compared to ATG at one year (4 studies: RR 0.57, 0.35 to 0.93). In the two studies with ESW only in the alemtuzumab arm, the effect of alemtuzumab on acute rejection at 1 year was uncertain compared to ATG (RR 1.27, 0.50 to 3.19). Alemtuzumab had uncertain effects on death (1 year, 2 studies: RR 0.39, 0.06 to 2.42; 2 to 3 years, 3 studies: RR 0.67, 95% CI 0.15 to 2.95), graft loss (1 year, 2 studies: RR 0.39, 0.13 to 1.30; 2 to 3 years, 3 studies: RR 0.98, 95% CI 0.47 to 2.06), and death‐censored graft loss (1 year, 2 studies: RR 0.38, 0.08 to 1.81; 2 to 3 years, 3 studies: RR 2.45, 95% CI 0.67 to 8.97) compared to ATG. Creatinine clearance was lower with alemtuzumab plus ESW at 6 months (2 studies: MD ‐13.35 mL/min, ‐23.91 to ‐2.80) and 2 years (2 studies: MD ‐12.86 mL/min, ‐23.73 to ‐2.00) compared to ATG plus triple maintenance. Across all 6 studies, the effect of alemtuzumab versus ATG was uncertain on all‐cause infection, CMV infection, BK virus infection, malignancy, and PTLD. The effect of alemtuzumab with steroid minimisation on NODAT was uncertain, compared to ATG with steroid maintenance. Alemtuzumab plus ESW compared with triple maintenance without induction therapy had uncertain effects on death and all‐cause graft loss at 1 year, acute rejection at 6 months and 1 year. CMV infection was increased (2 studies: RR 2.28, 1.18 to 4.40). Treatment effects were uncertain for NODAT, thrombocytopenia, and malignancy or PTLD. Rituximab had uncertain effects on death, graft loss, acute rejection and all other adverse outcomes compared to placebo. Authors' conclusions ATG reduces acute rejection but has uncertain effects on death, graft survival, malignancy and NODAT, and increases CMV infection, thrombocytopenia and leucopenia. Given a 45% acute rejection risk without ATG induction, seven patients would need treatment to prevent one having rejection, while incurring an additional patient experiencing CMV disease for every 12 treated. Excluding non‐CNI studies, the risk of rejection was 37% without induction with six patients needing treatment to prevent one having rejection. In the context of steroid minimisation, alemtuzumab prevents acute rejection at 1 year compared to ATG. Eleven patients would require treatment with alemtuzumab to prevent 1 having rejection, assuming a 21% rejection risk with ATG. Triple maintenance without induction therapy compared to alemtuzumab combined with ESW had similar rates of acute rejection but adverse effects including NODAT were poorly documented. Alemtuzumab plus steroid withdrawal would cause one additional patient experiencing CMV disease for every six patients treated compared to no induction and triple maintenance, in the absence of any clinical benefit. Overall, ATG and alemtuzumab decrease acute rejection at a cost of increased CMV disease while patient‐centred outcomes (reduced death or lower toxicity) do not appear to be improved

Implications of Elemental Abundances in Dwarf Spheroidal Galaxies

Unusual elemental abundance patterns observed for stars belonging to nearby dwarf spheroidal (dSph) galaxies are discussed. Analysis of the [alpha/H] vs. [Fe/H] diagrams where alpha represents Mg or average of alpha-elements reveals that Fe from Type Ia supernovae (SNe Ia) does not contribute to the stellar abundances in the dSph galaxies where the member stars exhibit low alpha/Fe ratios except for the most massive dSph galaxy, the Sagitarrius. The more massive dwarf (irregular) galaxy, the Large Magellanic Cloud, also have an SNe Ia signature in the stellar abundances. These findings suggest that the condition of whether SNe Ia contribute to chemical evolution in dwarf galaxies is likely to depend on the mass scale of galaxies. Unusual Mg abundances in some dSph stars are also found to be the origin of the large scatter in the [Mg/Fe] ratios and responsible for a seemingly decreasing [Mg/Fe] feature with increasing [Fe/H]. In addition, the lack of massive stars in the dSph galaxies does not satisfactorily account for the low-alpha signature. Considering the assemblage of deficient elements (O, Mg, Si, Ca, Ti, and Zn), all of which are synthesized in pre-SN massive stars and in SN explosions, the low-alpha signature appears to reflect the heavy-element yields of massive stars with smaller rotation compared to solar neighborhood stars.Comment: 7 pages, 4 figures, accepted by A&

Research Techniques Made Simple: Analysis of Autophagy in the Skin.

Autophagy is required for normal skin homeostasis and its disordered regulation is implicated in a range of cutaneous diseases. Several well-characterized biomarkers of autophagy are used experimentally to quantify autophagic activity or clinically to correlate autophagy with disease progression. This article discusses the advantages and limitations of different approaches for measuring autophagy as well as the techniques for modulating autophagy. These include analysis of endogenous LC3, a central autophagy regulatory protein, and measurement of LC3 flux using a dual-fluorescent reporter, which provides a quantitative readout of autophagy in cell culture systems in vitro and animal models in vivo. Degradation of SQSTM1/p62 during autophagy is proposed as an alternative biomarker allowing the analysis of autophagy both experimentally and clinically. However, the complex regulation of individual autophagy proteins and their involvement in multiple pathways means that several proteins must be analyzed together, preferably over a time course to accurately interpret changes in autophagic activity. Genetic modification of autophagy proteins can be used to better understand basic autophagic mechanisms contributing to health and disease, whereas small molecule inhibitors of autophagy regulatory proteins, lysosomal inhibitors, or activators of cytotoxic autophagy have been explored as potential treatments for skin disorders where autophagy is defective. [Abstract copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Beta Cephei stars in the ASAS-3 data. I. Long-term variations of periods and amplitudes

We analysed V-filter ASAS-3 photometry of 41 known Beta Cephei-type stars. The ASAS-3 photometry was combined with the archival data, if available, to determine long-term stability of periods and amplitudes of excited modes. We detected amplitude changes in three Beta Cephei stars, BW Cru, V836 Cen, and V348 Nor. Period changes were found in KK Vel and V836 Cen. Our analysis shows that intrinsic period changes are more common among multiperiodic stars, apparently because they are caused by some kind of mode interaction. In addition, we found new modes for seven stars, and for ten others we provide new solutions or remove ambiguities in the detected frequencies. One candidate hybrid Beta Cephei/SPB star, HD133823, is discovered.Comment: 22 pages, 11 figures, accepted for publication in A&