Rational design of sulfonamide inhibitor specific for human carbonic anhydrase I isozyme

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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

Causes and consequences of tipping points in river delta social-ecological systems

The sustainability of social-ecological systems within river deltas globally is in question as rapid development and environmental change trigger "negative” or “positive” tipping points depending on actors’ perspectives, e.g., regime shift from abundant sediment deposition to sediment shortage, agricultural sustainability to agricultural collapse or shift from rural to urban land. Using a systematic review of the literature, we show how cascading effects across anthropogenic, ecological, and geophysical processes have triggered numerous tipping points in the governance, hydrological and land use management of the world’s river deltas. Crossing tipping points had both positive and negative effects that generally enhanced economic development to the detriment of the environment. Assessment of deltas that featured prominently in the review revealed how outcomes of tipping points can inform the long-term trajectory of deltas towards sustainability or collapse. Management of key drivers at the delta scale can trigger positive tipping points to place social-ecological systems on a pathway towards sustainable development

The nature of the compact HII region Sh 2-89 and its stellar content

We present an analysis of the structure and properties of the compact HII region Sh 2-89, and certain of the young stellar objects (YSOs) within this regime, using mid-infrared (MIR) mapping derived from the Spitzer Space Telescope (SST) and visual slit spectroscopy of the inner regions of the source. We show that the region has a bipolar structure, and contains a variety of Class I and II YSOs. Much of the MIR emission appears to be dominated by PAH emission bands, which cause strong increases in flux in the 5.8 and 8.0 microns photometric channels, whilst the variation of H_alpha, [NII] at 6583 A, [SII] at 6716+6731 A, and MIR emission profiles confirms the presence of complex ionisation fronts, and ionisation stratification.Comment: 12 pages, 6 figures, Accepted for publication in MNRAS. 33 pages in arXi

Enzymology of the branched-chain amino acid oxidation disorders: the valine pathway

Valine is one of the three branched-chain amino acids which undergoes oxidation within mitochondria. In this paper, we describe the current state of knowledge with respect to the enzymology of the valine oxidation pathway and the different disorders affecting oxidation

Response of a CMS HGCAL silicon-pad electromagnetic calorimeter prototype to 20-300 GeV positrons

The Compact Muon Solenoid Collaboration is designing a new high-granularity endcap calorimeter, HGCAL, to be installed later this decade. As part of this development work, a prototype system was built, with an electromagnetic section consisting of 14 double-sided structures, providing 28 sampling layers. Each sampling layer has an hexagonal module, where a multipad large-area silicon sensor is glued between an electronics circuit board and a metal baseplate. The sensor pads of approximately 1 cm$^2$ are wire-bonded to the circuit board and are readout by custom integrated circuits. The prototype was extensively tested with beams at CERN's Super Proton Synchrotron in 2018. Based on the data collected with beams of positrons, with energies ranging from 20 to 300 GeV, measurements of the energy resolution and linearity, the position and angular resolutions, and the shower shapes are presented and compared to a detailed Geant4 simulation