The role of real-time ultrasound in the assessment and management of preterm labour

In this thesis the use of real-time ultrasound in the assessment and management of preterm labour has been studied, with particular reference to the observation of fetal breathing movements, gross fetal body movements and the state of the uterine cervix. In addition, a longitudinal analysis of the trends in preterm labour in the John Radcliffe Hospital in Oxford between 1973 and 1981 has been performed. Finally, an attempt has been made to clarify the relationship between prostaglandin E2 and fetal breathing movements. The analysis of the trends in preterm labour in Oxford has shown that the incidence of preterm delivery remains unaltered. Of these patients, however, those eligible for tocolytic therapy (unexplained spontaneous preterm labour) form a small proportion. The incidence of extreme prematurity in this group is very low and the neonatal outcome is good. The presence or absence of Fetal Breathing Movements (FBM) by defined criteria is shown to be a highly sensitive index of whether the preterm labour is going to progress to delivery or not in singleton pregnancies with intact membranes. Its significance is lost when the membranes are ruptured and in multiple pregnancies. In pregnancies complicated by antepartum haemorrhage the presence or absence of Fetal Breathing Movements does not predict further haemorrhage leading to delivery. Fetal Breathing Movement status on admission bears no relationship to neonatal outcome and gives no indication of the presence of intrauterine infection. Silent chorioamnionitis has been highlighted as an important cause of "unexplained" preterm labour. Gross Fetal Body Movements (FM) are shown to give no early indication of impending preterm delivery. Evidence is presented to suggest that significant diminution in Fetal Movements is related to poor neonatal outcome. Ultrasonic measurement of the uterine cervix has been found to be technically feasible but of no benefit in the diagnosis of ongoing preterm labour. The relationship between prostaglandin E2 (PGE2) and the cessation of fetal breathing movement has been approached by elucidating the maternal absorption of PGE2 from a vaginal pessary. This then enabled me to sample fetal blood at the time of maximal maternal concentrations (the time we expect the fetal concentration to be greatest). This was performed by fetoscopy and demonstrated that a significant rise in fetal bicycleprostaglandin-E-metabolite (bicyclo-PGEM) occurs following maternal vaginal administration of PGE2. Using this information FBM has been assessed two and a half hours following the vaginal administration of PGE2. Although inconclusive, no reduction in FBM was demonstrated. as the bicyclo-PGE metabolite is used to assess PGE levels, this evidence decreases the probability that PGE mediates the reduction in FBM with the onset of labour

Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity

Inherited renal cell carcinoma (RCC) is associated with multiple familial cancer syndromes but most individuals with features of non-syndromic inherited RCC do not harbor variants in the most commonly tested renal cancer predisposition genes (CPGs). We investigated whether undiagnosed cases might harbor mutations in CPGs that are not routinely tested for by testing 118 individuals with features suggestive of inherited RCC (family history of RCC, two or more primary RCC aged <60 years, or early onset RCC ≤46 years) for the presence of pathogenic variants in a large panel of CPGs. All individuals had been prescreened for pathogenic variants in the major RCC genes. We detected pathogenic or likely pathogenic (P/LP) variants of potential clinical relevance in 16.1% (19/118) of individuals, including P/LP variants in BRIP1 (n = 4), CHEK2 (n = 3), MITF (n = 1), and BRCA1 (n = 1). Though the power to detect rare variants was limited by sample size the frequency of truncating variants in BRIP1, 4/118, was significantly higher than in controls (P = 5.92E-03). These findings suggest that the application of genetic testing for larger inherited cancer gene panels in patients with indicators of a potential inherited RCC can increase the diagnostic yield for P/LP variants. However, the clinical utility of such a diagnostic strategy requires validation and further evaluation and in particular, confirmation of rarer RCC genotype-phenotype associations is required.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Cancer Research UK H2020 European Research Council. Grant Number: OncoTreat National Institute for Health Researchpublished version, accepted version (12 month embargo), submitted versio

Manufactured caverns in carbonate rock

Disclosed is a process for manufacturing underground caverns suitable in one embodiment for storage of large volumes of gaseous or liquid materials. The method is an acid dissolution process that can be utilized to form caverns in carbonate rock formations. The caverns can be used to store large quantities of materials near transportation facilities or destination markets. The caverns can be used for storage of materials including fossil fuels, such as natural gas, refined products formed from fossil fuels, or waste materials, such as hazardous waste materials. The caverns can also be utilized for applications involving human access such as recreation or research. The method can also be utilized to form calcium chloride as a by-product of the cavern formation process

Policy and place: requirements of a successful place-based policy

How does one identify, articulate, and relate the forces and influences at work in different geographic places? A satisfactory answer to this fundamental question is required for the formulation of a place-based public policy. Since 1986 the authors of this paper have been concerned with this question, and have evaluated different approaches to answering it. In this paper, a framework for the formulation of a place-based policy is presented, followed by a description of the requirements of such a policy

Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity.

Inherited renal cell carcinoma (RCC) is associated with multiple familial cancer syndromes but most individuals with features of non-syndromic inherited RCC do not harbor variants in the most commonly tested renal cancer predisposition genes (CPGs). We investigated whether undiagnosed cases might harbor mutations in CPGs that are not routinely tested for by testing 118 individuals with features suggestive of inherited RCC (family history of RCC, two or more primary RCC aged <60 years, or early onset RCC ≤46 years) for the presence of pathogenic variants in a large panel of CPGs. All individuals had been prescreened for pathogenic variants in the major RCC genes. We detected pathogenic or likely pathogenic (P/LP) variants of potential clinical relevance in 16.1% (19/118) of individuals, including P/LP variants in BRIP1 (n = 4), CHEK2 (n = 3), MITF (n = 1), and BRCA1 (n = 1). Though the power to detect rare variants was limited by sample size the frequency of truncating variants in BRIP1, 4/118, was significantly higher than in controls (P = 5.92E-03). These findings suggest that the application of genetic testing for larger inherited cancer gene panels in patients with indicators of a potential inherited RCC can increase the diagnostic yield for P/LP variants. However, the clinical utility of such a diagnostic strategy requires validation and further evaluation and in particular, confirmation of rarer RCC genotype-phenotype associations is required

Fracture Dissolution of Carbonate Rock: An Innovative Process for Gas Storage

The goal of the project is to develop and assess the feasibility and economic viability of an innovative concept that may lead to commercialization of new gas-storage capacity near major markets. The investigation involves a new approach to developing underground gas storage in carbonate rock, which is present near major markets in many areas of the United States. Because of the lack of conventional gas storage and the projected growth in demand for storage capacity, many of these areas are likely to experience shortfalls in gas deliverability. Since depleted gas reservoirs and salt formations are nearly non-existent in many areas, alternatives to conventional methods of gas storage are required. The need for improved methods of gas storage, particularly for ways to meet peak demand, is increasing. Gas-market conditions are driving the need for higher deliverability and more flexibility in injection/withdrawal cycling. In order to meet these needs, the project involves an innovative approach to developing underground storage capacity by creating caverns in carbonate rock formations by acid dissolution. The basic concept of the acid-dissolution method is to drill to depth, fracture the carbonate rock layer as needed, and then create a cavern using an aqueous acid to dissolve the carbonate rock. Assessing feasibility of the acid-dissolution method included a regional geologic investigation. Data were compiled and analyzed from carbonate formations in six states: Indiana, Ohio, Kentucky, West Virginia, Pennsylvania, and New York. To analyze the requirements for creating storage volume, the following aspects of the dissolution process were examined: weight and volume of rock to be dissolved; gas storage pressure, temperature, and volume at depth; rock solubility; and acid costs. Hydrochloric acid was determined to be the best acid to use because of low cost, high acid solubility, fast reaction rates with carbonate rock, and highly soluble products (calcium chloride) that allow for the easy removal of calcium waste from the well. Physical and chemical analysis of core samples taken from prospective geologic formations for the acid dissolution process confirmed that many of the limestone samples readily dissolved in concentrated hydrochloric acid. Further, some samples contained oily residues that may help to seal the walls of the final cavern structure. These results suggest that there exist carbonate rock formations well suited for the dissolution technology and that the presence of inert impurities had no noticeable effect on the dissolution rate for the carbonate rock. A sensitivity analysis was performed for characteristics of hydraulic fractures induced in carbonate formations to enhance the dissolution process. Multiple fracture simulations were conducted using modeling software that has a fully 3-D fracture geometry package. The simulations, which predict the distribution of fracture geometry and fracture conductivity, show that the stress difference between adjacent beds is the physical property of the formations that has the greatest influence on fracture characteristics by restricting vertical growth. The results indicate that by modifying the fracturing fluid, proppant type, or pumping rate, a fracture can be created with characteristics within a predictable range, which contributes to predicting the geometry of storage caverns created by acid dissolution of carbonate formations. A series of three-dimensional simulations of cavern formation were used to investigate three different configurations of the acid-dissolution process: (a) injection into an open borehole with production from that same borehole and no fracture; (b) injection into an open borehole with production from that same borehole, with an open fracture; and (c) injection into an open borehole connected by a fracture to an adjacent borehole from which the fluids are produced. The two-well configuration maximizes the overall mass transfer from the rock to the fluid, but it results in a complex cavern shape. Numerical simulations were performed to evaluate the ability of storage caverns produced by the acid-dissolution method to store natural gas. In addition, analyses were conducted to evaluate cavern stability during gas injection and withdrawal from storage caverns created in carbonate formations by the acid-dissolution method. The stability analyses were conducted using FLAC2D, a commercially available geotechnical analysis and design software. The analyses indicate that a tall cylindrical cavern with a domed roof and floor will be stable under the expected range of in situ and operational conditions. This result suggests that it should be feasible to avoid mechanical instabilities that could potentially diminish the effectiveness of the storage facility. The feasibility of using pressure transients measured at the ground surface was investigated as a means to evaluate (Abstract truncated

Daily Dietary Intake Patterns Improve after Visiting a Food Pantry among Food-Insecure Rural Midwestern Adults.

Emergency food pantries provide food at no cost to low-resource populations. The purpose of this study was to evaluate single-day dietary intake patterns before and after visiting a food pantry among food-secure and food-insecure pantry clients. This observational cohort study comprised a paired, before-and-after design with a pantry visit as the intervention. Participants (n = 455) completed a demographic and food security assessment, and two 24-h dietary recalls. Adult food security was measured using the U.S. Household Food Security Survey Module. Dietary intake patterns were assessed using Automated Self-Administered 24-h Recall data and classified by Healthy Eating Index (HEI-2010) scores, dietary variety, number of eating occasions, and energy intake. Paired t-tests and Wilcoxon signed-rank tests compared outcomes before and after a pantry visit. Mean dietary variety increased after the pantry visit among both food-secure (p = 0.02) and food-insecure (p \u3c 0.0001) pantry clients. Mean energy intake (p = 0.0003), number of eating occasions (p = 0.004), and HEI-2010 component scores for total fruit (p \u3c 0.001) and whole fruit (p \u3c 0.0003) increased among food-insecure pantry clients only. A pantry visit may improve dietary intake patterns, especially among food-insecure pantry clients

Genome-Wide Effects of Long-Term Divergent Selection

To understand the genetic mechanisms leading to phenotypic differentiation, it is important to identify genomic regions under selection. We scanned the genome of two chicken lines from a single trait selection experiment, where 50 generations of selection have resulted in a 9-fold difference in body weight. Analyses of nearly 60,000 SNP markers showed that the effects of selection on the genome are dramatic. The lines were fixed for alternative alleles in more than 50 regions as a result of selection. Another 10 regions displayed strong evidence for ongoing differentiation during the last 10 generations. Many more regions across the genome showed large differences in allele frequency between the lines, indicating that the phenotypic evolution in the lines in 50 generations is the result of an exploitation of standing genetic variation at 100s of loci across the genome