East Midlands Research into Ageing Network (EMRAN) Discussion Paper Series

Academic geriatric medicine in Leicester . There has never been a better time to consider joining us. We have recently appointed a Professor in Geriatric Medicine, alongside Tom Robinson in stroke and Victoria Haunton, who has just joined as a Senior Lecturer in Geriatric Medicine. We have fantastic opportunities to support students in their academic pursuits through a well-established intercalated BSc programme, and routes on through such as ACF posts, and a successful track-record in delivering higher degrees leading to ACL post. We collaborate strongly with Health Sciences, including academic primary care. See below for more detail on our existing academic set-up. Leicester Academy for the Study of Ageing We are also collaborating on a grander scale, through a joint academic venture focusing on ageing, the ‘Leicester Academy for the Study of Ageing’ (LASA), which involves the local health service providers (acute and community), De Montfort University; University of Leicester; Leicester City Council; Leicestershire County Council and Leicester Age UK. Professors Jayne Brown and Simon Conroy jointly Chair LASA and have recently been joined by two further Chairs, Professors Kay de Vries and Bertha Ochieng. Karen Harrison Dening has also recently been appointed an Honorary Chair. LASA aims to improve outcomes for older people and those that care for them that takes a person-centred, whole system perspective. Our research will take a global perspective, but will seek to maximise benefits for the people of Leicester, Leicestershire and Rutland, including building capacity. We are undertaking applied, translational, interdisciplinary research, focused on older people, which will deliver research outcomes that address domains from: physical/medical; functional ability, cognitive/psychological; social or environmental factors. LASA also seeks to support commissioners and providers alike for advice on how to improve care for older people, whether by research, education or service delivery. Examples of recent research projects include: ‘Local History Café’ project specifically undertaking an evaluation on loneliness and social isolation; ‘Better Visits’ project focused on improving visiting for family members of people with dementia resident in care homes; and a study on health issues for older LGBT people in Leicester. Clinical Geriatric Medicine in Leicester We have developed a service which recognises the complexity of managing frail older people at the interface (acute care, emergency care and links with community services). There are presently 17 consultant geriatricians supported by existing multidisciplinary teams, including the largest complement of Advance Nurse Practitioners in the country. Together we deliver Comprehensive Geriatric Assessment to frail older people with urgent care needs in acute and community settings. The acute and emergency frailty units – Leicester Royal Infirmary This development aims at delivering Comprehensive Geriatric Assessment to frail older people in the acute setting. Patients are screened for frailty in the Emergency Department and then undergo a multidisciplinary assessment including a consultant geriatrician, before being triaged to the most appropriate setting. This might include admission to in-patient care in the acute or community setting, intermediate care (residential or home based), or occasionally other specialist care (e.g. cardiorespiratory). Our new emergency department is the county’s first frail friendly build and includes fantastic facilities aimed at promoting early recovering and reducing the risk of hospital associated harms. There is also a daily liaison service jointly run with the psychogeriatricians (FOPAL); we have been examining geriatric outreach to oncology and surgery as part of an NIHR funded study. We are home to the Acute Frailty Network, and those interested in service developments at the national scale would be welcome to get involved. Orthogeriatrics There are now dedicated hip fracture wards and joint care with anaesthetists, orthopaedic surgeons and geriatricians. There are also consultants in metabolic bone disease that run clinics. Community work Community work will consist of reviewing patients in clinic who have been triaged to return to the community setting following an acute assessment described above. Additionally, primary care colleagues refer to outpatients for sub-acute reviews. You will work closely with local GPs with support from consultants to deliver post-acute, subacute, intermediate and rehabilitation care services. Stroke Medicine 24/7 thrombolysis and TIA services. The latter is considered one of the best in the UK and along with the high standard of vascular surgery locally means one of the best performances regarding carotid intervention

Endoscopic dilatation/incision of primary obstructive megaureter. A systematic review. On behalf of the EAU paediatric urology guidelines panel

Introduction: Historically, ureteral reimplantation (UR) has been the gold standard for treatment of primary obstructive megaureter (POM) with declining renal function, worsening obstruction, or recurrent urinary tract infections. In infants, open surgery with reimplantation of a grossly dilated ureter into a small bladder, can be technically challenging with significant morbidity. Therefore, less invasive endoscopic management such as dilatation or incision of the ureter–vesical junction, has emerged as an alternative to reimplantation during the last decades. Objective: To systematically evaluate the effectivity, safety, and potential benefits of endoscopic treatment (dilatation with or without balloon or incision) of POM in comparison to UR. Study design: A systematic review was conducted. Randomized controlled trials (RCTs), nonrandomized comparative studies (NRSs), and single-arm case series including a minimum of 20 participants and a mean follow-up more than 12 months were eligible for inclusion. Results: Of 504 articles identified, 8 articles including 338 patients were eligible for inclusion (0 RCTs, 1 NRSs, and 7 case series). Age at time of surgery was minimum 15 days to a maximum of 192 months. Indications for endoscopic treatment (ET) included patients with loss of split renal function (&gt;10%) and worsening of hydroureteronephrosis. The studies analysed reported a success rate ranging from 35% to 97%. Success was defined as stabilization of differential renal function without further procedures. A post-operative complication rate of 23–60% was reported (mostly transient haematuria, urinary tract infections and stent migration or intolerance). In 14% of the cases salvage UR following initial ET, was performed due to relapse of symptomatic POM. Conclusion: Endoscopic treatment for persistent or progressive POM in children is a minimally invasive alternative to UR with a long-term modest success rate. Additionally, it can be performed within a wide age span, with equal success rate and complication rates.</p

General practitioner workforce planning: assessment of four policy directions

<p>Abstract</p> <p>Background</p> <p>Estimating the supply of GPs into the future is important in forecasting shortages. The lengthy training process for medicine means that adjusting supply to meet demand in a timely fashion is problematic. This study uses Ireland as a case study to determine the future demand and supply of GPs and to assess the potential impact of several possible interventions to address future shortages.</p> <p>Methods</p> <p>Demand was estimated by applying GP visit rates by age and sex to national population projections. Supply was modelled using a range of parameters derived from two national surveys of GPs. A stochastic modelling approach was adopted to determine the probable future supply of GPs. Four policy interventions were tested: increasing vocational training places; recruiting GPs from abroad; incentivising later retirement; increasing nurse substitution to enable practice nurses to deliver more services.</p> <p>Results</p> <p>Relative to most other European countries, Ireland has few GPs per capita. Ireland has an ageing population and demand is estimated to increase by 19% by 2021. Without intervention, the supply of GPs will be 5.7% less than required in 2021. Increasing training places will enable supply to meet demand but only after 2019. Recruiting GPs from overseas will enable supply to meet demand continuously if the number recruited is approximately 0.8 per cent of the current workforce per annum. Later retirement has only a short-term impact. Nurse substitution can enable supply to meet demand but only if large numbers of practice nurses are recruited and allowed to deliver a wide range of GP services.</p> <p>Conclusions</p> <p>A significant shortfall in GP supply is predicted for Ireland unless recruitment is increased. The shortfall will have numerous knock-on effects including price increases, longer waiting lists and an increased burden on hospitals. Increasing training places will not provide an adequate response to future shortages. Foreign recruitment has ethical considerations but may provide a rapid and effective response. Increased nurse substitution appears to offer the best long-term prospects of addressing GP shortages and presents the opportunity to reshape general practice to meet the demands of the future.</p

Failure to repair endogenous DNA damage in β-cells causes adult-onset diabetes in mice

Age is the greatest risk factor for the development of type 2 diabetes mellitus (T2DM). Age-related decline in organ function is attributed to the accumulation of stochastic damage, including damage to the nuclear genome. Islets of T2DM patients display increased levels of DNA damage. However, whether this is a cause or consequence of the disease has not been elucidated. Here, we asked if spontaneous, endogenous DNA damage in β-cells can drive β-cell dysfunction and diabetes, via deletion of Ercc1, a key DNA repair gene, in β-cells. Mice harboring Ercc1-deficient β-cells developed adult-onset diabetes as demonstrated by increased random and fasted blood glucose levels, impaired glucose tolerance, and reduced insulin secretion. The inability to repair endogenous DNA damage led to an increase in oxidative DNA damage and apoptosis in β-cells and a significant loss of β-cell mass. Using electron microscopy, we identified β-cells in clear distress that showed an increased cell size, enlarged nuclear size, reduced number of mature insulin granules, and decreased number of mitochondria. Some β-cells were more affected than others consistent with the stochastic nature of spontaneous DNA damage. Ercc1-deficiency in β-cells also resulted in loss of β-cell function as glucose-stimulated insulin secretion and mitochondrial function were impaired in islets isolated from mice harboring Ercc1-deficient β-cells. These data reveal that unrepaired endogenous DNA damage is sufficient to drive β-cell dysfunction and provide a mechanism by which age increases the risk of T2DM. </p

Culture and Hybridization Experiments on an Ulva Clade Including the Qingdao Strain Blooming in the Yellow Sea

In the summer of 2008, immediately prior to the Beijing Olympics, a massive green tide of the genus Ulva covered the Qingdao coast of the Yellow Sea in China. Based on molecular analyses using the nuclear encoded rDNA internal transcribed spacer (ITS) region, the Qingdao strains dominating the green tide were reported to be included in a single phylogenetic clade, currently regarded as a single species. On the other hand, our detailed phylogenetic analyses of the clade, using a higher resolution DNA marker, suggested that two genetically separate entities could be included within the clade. However, speciation within the Ulva clade has not yet been examined. We examined the occurrence of an intricate speciation within the clade, including the Qingdao strains, via combined studies of culture, hybridization and phylogenetic analysis. The two entities separated by our phylogenetic analyses of the clade were simply distinguished as U. linza and U. prolifera morphologically by the absence or presence of branches in cultured thalli. The inclusion of sexual strains and several asexual strains were found in each taxon. Hybridizations among the sexual strains also supported the separation by a partial gamete incompatibility. The sexually reproducing Qingdao strains crossed with U. prolifera without any reproductive boundary, but a complete reproductive isolation to U. linza occurred by gamete incompatibility. The results demonstrate that the U. prolifera group includes two types of sexual strains distinguishable by crossing affinity to U. linza. Species identification within the Ulva clade requires high resolution DNA markers and/or hybridization experiments and is not possible by reliance on the ITS markers alone

Environmental geotechnics: Challenges and opportunities in the post-Covid-19 world

The outbreak of the coronavirus disease 2019 (Covid-19) pandemic not only has created a health crisis across the world but is also expected to impact negatively the global economy and societies at a scale that is maybe larger than that of the 2008 financial crisis. Simultaneously, it has inevitably exerted many negative consequences on the geoenvironment on which human beings depend. The current paper articulates the role of environmental geotechnics in elucidating and mitigating the effects of the current pandemic. It is the belief of all authors that the Covid-19 pandemic presents not only significant challenges but also opportunities for the development of the environmental geotechnics field. This discipline should make full use of geoenvironmental researchers' and engineers' professional skills and expertise to look for development opportunities from this crisis, to highlight the irreplaceable position of the discipline in the global fight against pandemics and to contribute to the health and prosperity of communities, to serve humankind better. In order to reach this goal while taking into account the specificity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the uncertainty of its environmental effects, it is believed that more emphasis should be placed on the following research directions: pathogen-soil interactions; isolation and remediation technologies for pathogen-contaminated sites; new materials for pathogen-contaminated soil; recycling and safe disposal of medical wastes; quantification of uncertainty in geoenvironmental and epidemiological problems; emerging technologies and adaptation strategies in civil, geotechnical and geoenvironmental infrastructures; pandemic-induced environmental risk management; and modelling of pathogen transport and fate in geoenvironment, among others. Moreover, Covid-19 has made it clear to the environmental geotechnics community the importance of urgent international co-operation and of multidisciplinary research actions that must extend to a broad range of scientific fields, including medical and public health disciplines, in order to meet the complexities posed by the Covid-19 pandemic

An introductory view on archaeoastronomy

Archaeoastronomy is still a marginalised topic in academia and is described by the Sophia Centre, the only UK institution offering a broader MA containing this field, as ‘the study of the incorporation of celestial orientation, alignments or symbolism in human monuments and architecture’. By many it is associated with investigating prehistoric monuments such as Stonehenge and combining astronomy and archaeology. The following will show that archaeoastronomy is far more than just an interdisciplinary field linking archaeology and astronomy. It merges aspects of anthropology, ethno-astronomy and even educational research, and is possibly better described as cultural astronomy. In the past decades it has stepped away from its quite speculative beginnings that have led to its complete rejection by the archaeology community. Overcoming these challenges it embraced full heartedly solid scientific and statistical methodology and achieved more credibility. However, in recent times the humanistic influences of a cultural context motivate a new generation of archaeoastronomers that are modernising this subject; and humanists might find it better described as post-modern archaeoastronomy embracing the pluralism of today’s academic approach to landscape and ancient people

Development of a complex intervention to test the effectiveness of peer support in type 2 diabetes

BACKGROUND: Diabetes is a chronic illness which requires the individual to assume responsibility for their own care with the aim of maintaining glucose and blood pressure levels as close to normal as possible. Traditionally self management training for diabetes has been delivered in a didactic setting. In recent times alternatives to the traditional delivery of diabetes care have been investigated, for example, the concept of peer support which emphasises patient rather than professional domination. The aim of this paper is to describe the development of a complex intervention of peer support in type 2 diabetes for a randomised control trial in a primary care setting. METHODS: The Medical Research Council (MRC) framework for the development and evaluation of complex interventions for randomised control trials (RCT) was used as a theoretical guide to designing the intervention. The first three phases (Preclinical Phase, Phase 1, Phase 2) of this framework were examined in depth. The Preclinical Phase included a review of the literature relating to type 2 diabetes and peer support. In Phase 1 the theoretical background and qualitative data from 4 focus groups were combined to define the main components of the intervention. The preliminary intervention was conducted in Phase 2. This was a pilot study conducted in two general practices and amongst 24 patients and 4 peer supporters. Focus groups and semi structured interviews were conducted to collect additional qualitative data to inform the development of the intervention. RESULTS: The four components of the intervention were identified from the Preclinical Phase and Phase 1. They are: 1. Peer supporters; 2. Peer supporter training; 3. Retention and support for peer supporters; 4. Peer support meetings. The preliminary intervention was implemented in the Phase 2. Findings from this phase allowed further modeling of the intervention, to produce the definitive intervention. CONCLUSION: The MRC framework was instrumental in the development of a robust intervention of peer support of type 2 diabetes in primary care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42541690

Cyr61/CCN1 Displays High-Affinity Binding to the Somatomedin B 1–44 Domain of Vitronectin

OV) family of extracellular-associated (matricellular) proteins that present four distinct functional modules, namely insulin-like growth factor binding protein (IGFBP), von Willebrand factor type C (vWF), thrombospondin type 1 (TSP), and C-terminal growth factor cysteine knot (CT) domain. While heparin sulphate proteoglycans reportedly mediate the interaction of Cyr61 with the matrix and cell surface, the role of other extracellular associated proteins has not been revealed. at high concentrations attenuate Cyr61 binding to immobilized VTNC, while monomeric VTNC was ineffective. Therefore, immobilization of VTNC exposes cryptic epitopes that recognize Cyr61 with high affinity, as reported for a number of antibodies, β-endorphin, and other molecules. domain suggests that VTNC represent a point of anchorage for CCN family members to the matrix. Results are discussed in the context of the role of CCN and VTNC in matrix biology and angiogenesis