Surveillance of Creutzfeldt-Jakob Disease in the United Kingdom, 1990-2006

Prion diseases are rare, invariably fatal, neurodegenerative diseases, occurring in sporadic, genetic and iatrogenic forms in animals and humans, for which there is no aeceptahlc diagnostic test in life and no effective treatment. In humans the commonest prion disease is Creutzfeldt-Jakob Disease (CJD). Systematic prospective public health surveillance (PHS) of CJD was initiated in the UK in 1990 in response to the detection of a novel prion disease in cattle, bovine spongiform encephalopathy (BSE). The aim of PHS was to detect any change in the elinico-pathological phenotypc of CJD that could be attributable to human exposure to BSE. In this thesis I present a series of studies that evaluate various aspects of the PHS of CJD in the UK, 1990 - 2006. From 1990 to 2006, 2154 suspect CJD cases were referred to the National CJD Surveillance Unit (NCJDSU); 57% had a clinical or neuropathological diagnosis of CJD. Sporadic CJD (sCJD) accounted for the majority of cases. Age adjusted sCJD incidence increased over time in association with an increasing use of CSF 14-3-3 protein for case classification. Genetic prion disease accounted for 9.4% of all cases; 54 iatrogenic CJD cases mediated by recognised routes of transmission were identified. Variant CJD (vCJD), a novel human prion disease, was characterised by the NCJDSU in 1996; by 2006 there had been 165 incident cases in the UK. The primary vCJD epidemic peaked in the UK in 2000 (27 incident cases) and has been in decline since. Secondary transmission of vCJD through the transfusion of labile blood components has been identified, occurring during an asymptomatic phase of illness. The prevalence of asymptomatic vCJD infection in the population is not known. In characterising vCJD and contributing to establishing an aetiological link with BSE, the NCJDSU met a primary aim of PHS. In an evaluation the NCJDSU was found to be flexible, acceptable, sensitive, timely and representative. Falling post mortem rates and an increasing reliance on clinical diagnostic criteria, with evidence of sub-optimal and differential use of investigations to support a diagnosis of sCJD and vCJD are of concern, as is the rising positive predictive value of the system in the face of falling referral rates. NCJDSU operational criteria for the assessment of EEGs for case classification in sCJD were prospectively validated. The sensitivity of EEG was low and specificity high; EEG remains a valuable non-invasive investigation in sCJD if used in conjunction with other diagnostic tools. With the establishment of systematic prospective PHS the reliance on death certificates to ascertain suspect cases has diminished. The sensitivity and specificity of a death certificate diagnosis of prion disease in the UK are high. Death certificate data provide valid estimates of prion disease mortality in the UK. Uncertainty around the epidemiology and pathogenesis of vCJD and the emergence of novel atypical prion diseases in animals which pose an as yet unknown threat to human health, provide the imperative to continue systematic prospective PHS of prion disease in humans in the UK for the foreseeable future. The NCJDSU is well placed to achieve this

The level of provision of specialist palliative care services in Scotland: an international benchmarking study

Objectives: Comparative benchmarking of specialist palliative care (SPC) services across jurisdictions can be used to assess the adequacy of provision. Published in 2016, the Scottish Atlas of Palliative Care unlocks the possibility of benchmarking Scotland’s provision against other European Union (EU) countries. Our objectives were to describe the provision of SPC services in Scotland and compare this with other EU countries, assessing coverage against European norms. Methods: We conducted a secondary analysis of data collected as part for the Scottish Atlas by structured telephone (n=33) or online (n=3) survey with informants from 14 territorial health boards and 15 hospices who provided information about SPC services in their locality. National-level Scottish data were compared with data from other EU countries allowing ranking for each service type and service coverage as calculated against European Association for Palliative Care norms. Results: Scotland had a total of 23 SPC inpatient units containing 349 beds, 27 SPC hospital support teams and 38 SPC home care teams. Relative to other EU countries, Scotland ranked seventh for provision of SPC inpatient units and hospital support teams, and fifth for home care teams. Coverage for these services was 85%, 100% and 72%, respectively. Conclusion: Scotland is positioned among the top 10 EU countries for the level of provision of SPC services. National policy in Scotland has focused on the delivery of palliative care at home or in a homely setting. These data support a focus on developing services in community settings to meet Scotland’s policy ambitions

Temporal trends and risk factors for readmission for infections, gastrointestinal and immobility complications after an incident hospitalisation for stroke in Scotland between 1997 and 2005

Background: Improvements in stroke management have led to increases in the numbers of stroke survivors over the last decade and there has been a corresponding increase of hospital readmissions after an initial stroke hospitalisation. The aim of this study was to examine the one year risk of having a readmission due to infective, gastrointestinal or immobility (IGI) complications and to identify temporal trends and any risk factors.<p></p> Methods: Using a cohort of first hospitalised for stroke patients who were discharged alive, time to first event (readmission for IGI complications or death) within 1 year was analysed in a competing risks framework using cumulative incidence methods. Regression on the cumulative incidence function was used to model the risks of having an outcome using the covariates age, sex, socioeconomic status, comorbidity, discharge destination and length of hospital stay.<p></p> Results: There were a total of 51,182 patients discharged alive after an incident stroke hospitalisation in Scotland between 1997–2005, and 7,747 (15.1%) were readmitted for IGI complications within a year of the discharge. Comparing incident stroke hospitalisations in 2005 with 1997, the adjusted risk of IGI readmission did not increase (HR = 1.00 95% CI (0.90, 1.11). However, there was a higher risk of IGI readmission with increasing levels of deprivation (most deprived fifth vs. least deprived fifth HR = 1.16 (1.08, 1.26).<p></p> Conclusions: Approximately 15 in 100 patients discharged alive after an incident hospitalisation for stroke in Scotland between 1997 and 2005 went on to have an IGI readmission within one year. The proportion of readmissions did not change over the study period but those living in deprived areas had an increased risk

Tracing river chemistry in space and time : dissolved inorganic constituents of the Fraser River, Canada

Author Posting. © The Author(s), 2013. This is the author's version of the work. It is posted here by permission of Elsevier for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 124 (2014): 283-308, doi:10.1016/j.gca.2013.09.006.The Fraser River basin in southwestern Canada bears unique geologic and climatic features which make it an ideal setting for investigating the origins, transformations and delivery to the coast of dissolved riverine loads under relatively pristine conditions. We present results from sampling campaigns over three years which demonstrate the lithologic and hydrologic controls on fluxes and isotope compositions of major dissolved inorganic runoff constituents (dissolved nutrients, major and trace elements, 87Sr/86Sr, δD). A time series record near the Fraser mouth allows us to generate new estimates of discharge-weighted concentrations and fluxes, and an overall chemical weathering rate of 32 t km-2 y-1. The seasonal variations in dissolved inorganic species are driven by changes in hydrology, which vary in timing across the basin. The time series record of dissolved 87Sr/86Sr is of particular interest, as a consistent shift between higher (“more radiogenic”) values during spring and summer and less radiogenic values in fall and winter demonstrates the seasonal variability in source contributions throughout the basin. This seasonal shift is also quite large (0.709 – 0.714), with a discharge-weighted annual average of 0.7120 (2 s.d. = 0.0003). We present a mixing model which predicts the seasonal evolution of dissolved 87Sr/86Sr based on tributary compositions and water discharge. This model highlights the importance of chemical weathering fluxes from the old sedimentary bedrock of headwater drainage regions, despite their relatively small contribution to the total water flux.This work was supported by the WHOI Academic Programs Office and MIT PAOC Houghton Fund to BMV, a WHOI Arctic Research Initiative grant to ZAW, NSF-ETBC grant OCE-0851015 to BPE and TIE, and NSF grant EAR-1226818 to BPE

Seagrass restoration is possible: insights and lessons from Australia and New Zealand

Seagrasses are important marine ecosystems situated throughout the world's coastlines. They are facing declines around the world due to global and local threats such as rising ocean temperatures, coastal development and pollution from sewage outfalls and agriculture. Efforts have been made to reduce seagrass loss through reducing local and regional stressors, and through active restoration. Seagrass restoration is a rapidly maturing discipline, but improved restoration practices are needed to enhance the success of future programs. Major gaps in knowledge remain, however, prior research efforts have provided valuable insights into factors influencing the outcomes of restoration and there are now several examples of successful large-scale restoration programs. A variety of tools and techniques have recently been developed that will improve the efficiency, cost effectiveness, and scalability of restoration programs. This review describes several restoration successes in Australia and New Zealand, with a focus on emerging techniques for restoration, key considerations for future programs, and highlights the benefits of increased collaboration, Traditional Owner (First Nation) and stakeholder engagement. Combined, these lessons and emerging approaches show that seagrass restoration is possible, and efforts should be directed at upscaling seagrass restoration into the future. This is critical for the future conservation of this important ecosystem and the ecological and coastal communities they support

Seagrass restoration is possible:Insights and lessons from Australia and New Zealand

Seagrasses are important marine ecosystems situated throughout the world’s coastlines. They are facing declines around the world due to global and local threats such as rising ocean temperatures, coastal development and pollution from sewage outfalls and agriculture. Efforts have been made to reduce seagrass loss through reducing local and regional stressors, and through active restoration. Seagrass restoration is a rapidly maturing discipline, but improved restoration practices are needed to enhance the success of future programs. Major gaps in knowledge remain, however, prior research efforts have provided valuable insights into factors influencing the outcomes of restoration and there are now several examples of successful large-scale restoration programs. A variety of tools and techniques have recently been developed that will improve the efficiency, cost effectiveness, and scalability of restoration programs. This review describes several restoration successes in Australia and New Zealand, with a focus on emerging techniques for restoration, key considerations for future programs, and highlights the benefits of increased collaboration, Traditional Owner (First Nation) and stakeholder engagement. Combined, these lessons and emerging approaches show that seagrass restoration is possible, and efforts should be directed at upscaling seagrass restoration into the future. This is critical for the future conservation of this important ecosystem and the ecological and coastal communities they support

Temporal trends in hospitalisation for stroke recurrence following incident hospitalisation for stroke in Scotland

<p>Background: There are few studies that have investigated temporal trends in risk of recurrent stroke. The aim of this study was to examine temporal trends in hospitalisation for stroke recurrence following incident hospitalisation for stroke in Scotland during 1986 to 2001.</p> <p>Methods: Unadjusted survival analysis of time to first event, hospitalisation for recurrent stroke or death, was undertaken using the cumulative incidence method which takes into account competing risks. Regression on cumulative incidence functions was used to model the temporal trends of first recurrent stroke with adjustment for age, sex, socioeconomic status and comorbidity. Complete five year follow-up was obtained for all patients. Restricted cubic splines were used to determine the best fitting relationship between the survival events and study year.</p> <p>Results: There were 128,511 incident hospitalisations for stroke in Scotland between 1986 and 2001, 57,351 (45%) in men. A total of 13,835 (10.8%) patients had a recurrent hospitalisation for stroke within five years of their incident hospitalisation. Another 74,220 (57.8%) patients died within five years of their incident hospitalisation without first having a recurrent hospitalisation for stroke. Comparing incident stroke hospitalisations in 2001 with 1986, the adjusted risk of recurrent stroke hospitalisation decreased by 27%, HR = 0.73 95% CI (0.67 to 0.78), and the adjusted risk of death being the first event decreased by 28%, HR = 0.72 (0.70 to 0.75).</p> <p>Conclusions: Over the 15-year period approximately 1 in 10 patients with an incident hospitalisation for stroke in Scotland went on to have a hospitalisation for recurrent stroke within five years. Approximately 6 in 10 patients died within five years without first having a recurrent stroke hospitalisation. Using hospitalisation and death data from an entire country over a 20-year period we have been able to demonstrate not only an improvement in survival following an incident stroke, but also a reduction in the risk of a recurrent event.</p&gt

Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets

Background. Gliomas exhibit high glycolytic rates, and monocarboxylate transporters (MCTs) play a major role in the maintenance of the glycolytic metabolism through the proton-linked transmembrane transport of lactate. However, their role in gliomas is poorly studied. Thus, we aimed to characterize the expression of MCT1, MCT4, and their chaperone CD 147 and to assess the therapeutic impact of MCT inhibition in gliomas. Methods. MCTs and CD 147 expressions were characterized by immunohistochemistry in nonneoplastic brain and glioma samples. The effect of CHC (MCT inhibitor) and MCT1 silencing was assessed in in vitro and in vivo glioblastoma models. Results. MCT1, MCT4, and CD 147 were overexpressed in the plasma membrane of glioblastomas, compared with diffuse astrocytomas and nonneoplastic brain. CHC decreased glycolytic metabolism, migration, and invasion and induced cell death in U251 cells (more glycolytic) but only affected proliferation in SW1088 (more oxidative). The effectiveness of CHC in glioma cells appears to be dependent on MCT membrane expression. MCT1 downregulation showed similar effects on different glioma cells, supporting CHC as an MCT1 inhibitor. There was a synergistic effect when combining CHC with temozolomide treatment in U251 cells. In the CAM in vivo model, CHC decreased the size of tumors and the number of blood vessels formed. Conclusions. This is the most comprehensive study reporting the expression of MCTs and CD 147 in gliomas. The MCT1 inhibitor CHC exhibited anti-tumoral and anti-angiogenic activity in gliomas and, of importance, enhanced the effect of temozolomide. Thus, our results suggest that development of therapeutic approaches targeting MCT1 may be a promising strategy in glioblastoma treatment.Life and Health Sciences Research Institute, University of Minho, Portugal; Fundacao para a Ciencia e Tecnologia [SFRH/BI/33503/2008, SFRH/BPD/69479/2010, SFRH/BD/36463/2007]info:eu-repo/semantics/publishedVersio

The International Companion to Scottish Poetry

A range of leading international scholars provide the reader with a comprehensive and innovative investigation of the extraordinary richness and diversity of Scotland\u2019s poetry. Addressing Languages and Chronologies, Poetic Forms, and Topics and Themes, this International Companion covers the entire subject from from the early Middle Ages to the modern day, and explores the connections, influences and interrelations between English, Gaelic, Latin, Old Norse and Scots verse. CONTENTS Series Editors\u2019 Preface Introduction (Carla Sassi) Part 1: Languages and Chronologies Early Celtic Poetry (to 1500) (Thomas Owen Clancy) Scots poetry in the Fourteenth and Fifteenth Centuries (R. D. S. Jack) Poetry in Latin (Roger Green) Poetry in the Languages and Dialects of Northern Scotland (Roberta Frank, Brian Smith) The Sixteenth and Seventeenth Centuries (S\uecm Innes, Alessandra Petrina) The Eighteenth Century (Ronald Black, Gerard Carruthers) The Nineteenth Century (Ian Duncan, Sheila Kidd) The Poetry of Modernity (1870\u20131950) (Emma Dymock, Scott Lyall) Contemporary Poetry (1950\u2013) (Attila D\uf3sa, Michelle Macleod) Part 2: Poetic Forms The Form of Scottish Gaelic poetry (William Gillies) Scots Poetic Forms (Derrick McClure) The Ballad in Scots and English (Suzanne Gilbert) Part 3: Topics and Themes Nature, Landscape and Rural Life (Louisa Gairn) Nation and Home (Carla Sassi, Silke Stroh) Protest and Politics (Wilson McLeod, Alan Riach) Love and Erotic Poetry (Peter Mackay) Faith and Religion (Meg Bateman, James McGonigal) Scottish Poetry as World Poetry (Paul Barnaby) The Literary Environment (Robyn Marsack) Endnotes Further Reading Notes on Contributors Index

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK