From the bottom to the top: Assessing the potential subsurface migration of fracking-related fluids along natural geological pathways

Over the last century humans have increasingly gone from just extracting fluids from the subsurface to also injecting them, for example hydraulic fracturing (fracking) for shale gas. Concurrently, there has been increased environmental interest in how injected fluids might interact with natural groundwater systems. One potential environmental impact of fracking is the contamination of shallow groundwater from the upward migration of injected and formation fluids along natural geological pathways. High-permeability fault and fracture zones have generally been regarded as the highest-risk pathway. Therefore, the first aim of this thesis was to determine a horizontal respect distance between fluid injection locations and known faults. Using published microseismic data a horizontal respect distance of ~900 m was proposed. The second aim of this thesis was to consider complex geological structure in numerical models to investigate hydrogeological factors which might increase the vulnerability of shallow groundwater resources to the potential upward migration of fracking-related fluids. Using 2D and 3D numerical models four hydrogeological factors increased the vulnerability of a shallow aquifer to upward fluid migration from an underlying shale reservoir: increased stimulated fracture extent; greater amounts of overpressure; the presence of low-permeability faults; and the absence of deep high-permeability formations. Low-permeability faults acted to compartmentalise groundwater, thereby discouraging regional horizontal flow whilst encouraging upward flow through strata. The integration of groundwater quality and seismic reflection data provided a novel method for identifying compartmentalisation, but compartmentalisation could not be identified from surface water quality data in the studied basin. However, analysis of surface water quality data could demonstrate regional-scale groundwater-surface water interactions. Importantly, this thesis highlights the need to understand and model interactions between deep groundwater, shallow groundwater, and surface waters by integrating data from a variety of industry and environmental regulatory sources

Patterns and frequency of anxiety in women undergoing gynaecological surgery

Patterns and frequency of anxiety in women undergoing gynaecological surgery Aims. Within a gynaecological surgical setting to identify the patterns and frequency of anxiety pre- and postoperatively; to identify any correlation between raised anxiety levels and postoperative pain; to identify events, from the patients’ perspective, that may increase or decrease anxiety in the pre- and postoperative periods. Background. It is well documented that surgery is associated with increased anxiety, which has an adverse impact on patient outcomes. Few studies have been conducted to obtain the patient’s perspective on the experience of anxiety and the events and situations that aggravate and ameliorate it. Method. The study used a mixed method approach. The sample consisted of women undergoing planned gynaecological surgery. Anxiety was assessed using the State Trait Anxiety Inventory. Trait anxiety was measured at the time of recruitment. State anxiety was then assessed at six time points during the pre- and postoperative periods. Postoperative pain was also measured using a 10 cm visual analogue scale. Taped semi-structured telephone interviews were conducted approximately a week after discharge. Results. State anxiety rose steadily from the night before surgery to the point of leaving the ward to go to theatre. Anxiety then increased sharply prior to the anaesthetic decreasing sharply afterwards. Patients with higher levels of trait anxiety were more likely to experience higher levels of anxiety throughout their admission. Elevated levels of pre- and postoperative anxiety were associated with increased levels of postoperative pain. Telephone interviews revealed a range of events/situations that patients recalled distressing them and many were related to inadequate information. Conclusion. This study found higher rates of anxiety than previously reported and anxiety levels appeared raised before admission to hospital. This has important clinical and research implications.Relevance to clinical practice. Patients with high levels of anxiety may be identified preoperatively and interventions designed to reduce anxiety could be targeted to this vulnerable group. Patient experiences can inform the delivery of services to meet their health needs better

MHC Class I Bound to an Immunodominant Theileria parva Epitope Demonstrates Unconventional Presentation to T Cell Receptors

T cell receptor (TCR) recognition of peptide-MHC class I (pMHC) complexes is a crucial event in the adaptive immune response to pathogens. Peptide epitopes often display a strong dominance hierarchy, resulting in focusing of the response on a limited number of the most dominant epitopes. Such T cell responses may be additionally restricted by particular MHC alleles in preference to others. We have studied this poorly understood phenomenon using Theileria parva, a protozoan parasite that causes an often fatal lymphoproliferative disease in cattle. Despite its antigenic complexity, CD8+ T cell responses induced by infection with the parasite show profound immunodominance, as exemplified by the Tp1214–224 epitope presented by the common and functionally important MHC class I allele N*01301. We present a high-resolution crystal structure of this pMHC complex, demonstrating that the peptide is presented in a distinctive raised conformation. Functional studies using CD8+ T cell clones show that this impacts significantly on TCR recognition. The unconventional structure is generated by a hydrophobic ridge within the MHC peptide binding groove, found in a set of cattle MHC alleles. Extremely rare in all other species, this feature is seen in a small group of mouse MHC class I molecules. The data generated in this analysis contribute to our understanding of the structural basis for T cell-dependent immune responses, providing insight into what determines a highly immunogenic p-MHC complex, and hence can be of value in prediction of antigenic epitopes and vaccine design

Real-time ultrasound (RTU) imaging methods for quality control of meats

In this chapter the use of real-time ultrasonography to predict in vivo carcass composition and meat traits will be reviewed. The chapter begins by discussing background and principles of ultrasound. Then aspects affecting the suitability of realtime ultrasonography and image analysis for predicting carcass composition and meat traits of meat producing species and fish will be presented. This chapter also provides an overview of the present and future trends in the application of real-time ultrasonography in the meat industry. © 2012 Woodhead Publishing Limited All rights reserved.info:eu-repo/semantics/publishedVersio

Resolution of inflammation: a new therapeutic frontier

Dysregulated inflammation is a central pathological process in diverse disease states. Traditionally, therapeutic approaches have sought to modulate the pro- or anti-inflammatory limbs of inflammation, with mixed success. However, insight into the pathways by which inflammation is resolved has highlighted novel opportunities to pharmacologically manipulate these processes — a strategy that might represent a complementary (and perhaps even superior) therapeutic approach. This Review discusses the state of the art in the biology of resolution of inflammation, highlighting the opportunities and challenges for translational research in this field

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus

Background: Multiple laboratory tests are used to diagnose and manage patients with diabetes mellitus. The quality of the scientific evidence supporting the use of these tests varies substantially. Approach: An expert committee compiled evidence-based recommendations for the use of laboratory testing for patients with diabetes. A new system was developed to grade the overall quality of the evidence and the strength of the recommendations. Draft guidelines were posted on the Internet and presented at the 2007 Arnold O. Beckman Conference. The document was modified in response to oral and written comments, and a revised draft was posted in 2010 and again modified in response to written comments. The National Academy of Clinical Biochemistry and the Evidence-Based Laboratory Medicine Committee of the American Association for Clinical Chemistry jointly reviewed the guidelines, which were accepted after revisions by the Professional Practice Committee and subsequently approved by the Executive Committee of the American Diabetes Association. Content: In addition to long-standing criteria based on measurement of plasma glucose, diabetes can be diagnosed by demonstrating increased blood hemoglobin A$_{1c}$ (HbA$_{1c}$) concentrations. Monitoring of glycemic control is performed by self-monitoring of plasma or blood glucose with meters and by laboratory analysis of HbA$_{1c}$. The potential roles of noninvasive glucose monitoring, genetic testing, and measurement of autoantibodies, urine albumin, insulin, proinsulin, C-peptide, and other analytes are addressed. Summary: The guidelines provide specific recommendations that are based on published data or derived from expert consensus. Several analytes have minimal clinical value at present, and their measurement is not recommended

Формирование эмоциональной культуры как компонента инновационной культуры студентов

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1 and Darwin was one of the first to recognise that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity, ROH), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3,4. Here we use ROH to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts and find statistically significant associations between summed runs of homozygosity (SROH) and four complex traits: height, forced expiratory lung volume in 1 second (FEV1), general cognitive ability (g) and educational attainment (nominal p<1 × 10−300, 2.1 × 10−6, 2.5 × 10−10, 1.8 × 10−10). In each case increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing convincing evidence for the first time that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5,6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein (LDL) cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Introduction: Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods: This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results: Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (&gt;80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions: Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700