The structural and diagenetic evolution of injected sandstones: examples from the Kimmeridgian of NE Scotland

Abstract: Injected sandstones occurring in the Kimmeridgian of NE Scotland along the bounding Great Glen and Helmsdale faults formed when basinal fluids moved upward along the fault zones, fluidizing Oxfordian sands encountered at shallow depth and injecting them into overlying Kimmeridgian strata. The orientation of dykes, in addition to coeval faults and fractures, was controlled by a stress state related to dextral strike-slip along the bounding fault zones. Diagenetic studies of cements allow the reconstruction of the fluid flow history. The origin of deformation bands in sandstone dykes and sills was related to the contraction of the host-rocks against dyke and sill walls following the initial stage of fluidized flow, and these deformation bands are the earliest diagenetic imprint. Early non-ferroan calcite precipitated in injection structures at temperatures between 70 and 100 8C, indicating that it precipitated from relatively hot basinal fluids that drove injection. Coeval calcite-filled fractures show similar temperatures, suggesting that relatively hot fluids were responsible for calcite precipitation in any permeable pathway created by dextral simple shear along the faults. During progressive burial, percolating sea water was responsible for completely cementing the still relatively porous injected sandstones with a second generation of ferroan calcite, which contains fluid inclusions with homogenization temperatures below 50 8C. During this phase, depositional host sandstones were also cemented

Exploring State Data Sources to Monitor Rural Emergency Medical Services Performance Improvement

In 1981, responsibility for overseeing emergency medical services (EMS) largely shifted to states and localities, contributing to the creation of a fragmented national picture of the state of EMS that is most evident in the resultant data collection and reporting issues that curb the availability of EMS data. These patchwork systems of care disproportionately affect rural areas, where myriad challenges – from a high reliance on a volunteer workforce to low call volumes and inadequate reimbursement – hinder performance. Previous studies by the Flex Monitoring Team (FMT) highlighted how little is known about the administrative, operational, and clinical capacity of rural EMS, which are key to investigate further before considering traditional EMS outcome measures. In this study, the FMT convened an expert panel comprised of representatives from a variety of stakeholders to highlight existing data challenges EMS face, identify data to support rural EMS performance measurement, as well as reassess the FMT’s 2017 rural-relevant EMS performance measures. Among the themes raised by the panel, experts suggested that improved engagement in oversight by state EMS agencies would increase accountability by local EMS; however, they cited a lack of staff capacity and expertise to analyze data in states, as well as disagreement between states on relevant measures. The FMT created EMS capacity measures to monitor and improve rural EMS capacity, along with the National Highway Traffic Safety Administration’s EMS Compass outcome measures to monitor performance. Potential opportunities identified by the panel to source standardized data for those measures include an assessment tool developed through the Joint Committee of Rural Emergency Care, or for the relevant data to be collected by state EMS agencies through their existing EMS service licensure process, many of which already collect some of the relevant data. Electronic patient care records, the typical source of data to calculate EMS clinical and non-clinical performance measures, can be collected and reported to states through the National EMS Information System (NEMSIS). Though not perfect, targeted efforts to improve the collection of local EMS data provides an opportunity for state EMS agencies and State Flex Programs (SFPs) to train local services in data collection, in addition to educating them on how to access and use their own data for performance improvement. This collaboration can also play a role in supporting improved health information exchange between EMS, hospitals, and other providers, which help improve the quality of pre-hospital care and assist in monitoring the quality and outcomes of care across the system of care. The importance of reliable, standardized, and timely data from local and state EMS is underscored by the recently launched Medicare Ground Ambulance Data Collection System, a Centers for Medicare and Medicaid Services study that will collect information to evaluate how ground ambulance costs relate to current payment policies. In turn, this will be used to formulate a report to Congress assessing the adequacy of Medicare ground ambulance payment rates and geographic variations in cost. As the data will be used to assess reimbursement rates across urban, rural, and super rural areas, accurate data collection and reporting is vital. The expert panel also reaffirmed the validity of FMT’s rural-relevant measures and raised questions about monitoring the measures longitudinally or developing measures to assess financial performance and sustainability. Additional work is needed to understand how to best use these measures to track rural EMS capacity over time, as well as identify the relevant financial measures

The Health Care Costs of Financial Exploitation in Maine

This study sought to determine the Medicare and Medicaid costs experienced by dual eligible older adults in Maine for whom Maine Adult Protective Services (APS) substantiated allegations of elder financial exploitation and to compare them to those of Maine’s general older population. The analysis is an important step forward in estimating the medical costs associated with elder abuse. Elder financial exploitation may result in significant public burden on Medicare and Medicaid, shouldered by taxpayers. Efforts to detect, investigate, prosecute, and mitigate this abuse will benefit not only the victims, but also the financial stewardship of these public programs

Long term geological record of a global deep subsurface microbial habitat in sand injection complexes

Peer reviewedPublisher PD

Nuclear receptors in vascular biology

Nuclear receptors sense a wide range of steroids and hormones (estrogens, progesterone, androgens, glucocorticoid, and mineralocorticoid), vitamins (A and D), lipid metabolites, carbohydrates, and xenobiotics. In response to these diverse but critically important mediators, nuclear receptors regulate the homeostatic control of lipids, carbohydrate, cholesterol, and xenobiotic drug metabolism, inflammation, cell differentiation and development, including vascular development. The nuclear receptor family is one of the most important groups of signaling molecules in the body and as such represent some of the most important established and emerging clinical and therapeutic targets. This review will highlight some of the recent trends in nuclear receptor biology related to vascular biology

Perivascular Fat and the Microcirculation: Relevance to Insulin Resistance, Diabetes, and Cardiovascular Disease

Type 2 diabetes and its major risk factor, obesity, are a growing burden for public health. The mechanisms that connect obesity and its related disorders, such as insulin resistance, type 2 diabetes, and hypertension, are still undefined. Microvascular dysfunction may be a pathophysiologic link between insulin resistance and hypertension in obesity. Many studies have shown that adipose tissue-derived substances (adipokines) interact with (micro)vascular function and influence insulin sensitivity. In the past, research focused on adipokines from perivascular adipose tissue (PVAT). In this review, we focus on the interactions between adipokines, predominantly from PVAT, and microvascular function in relation to the development of insulin resistance, diabetes, and cardiovascular disease

Therapeutic Surgical Management of Palpable Melanoma Groin Metastases: Superficial or Combined Superficial and Deep Groin Lymph Node Dissection

Item does not contain fulltextBACKGROUND: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. METHODS: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. RESULTS: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p = 0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. CONCLUSIONS: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan

The Nutritional Induction of COUP-TFII Gene Expression in Ventromedial Hypothalamic Neurons Is Mediated by the Melanocortin Pathway

BACKGROUND: The nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) is an important coordinator of glucose homeostasis. We report, for the first time, a unique differential regulation of its expression by the nutritional status in the mouse hypothalamus compared to peripheral tissues. METHODOLOGY/PRINCIPAL FINDINGS: Using hyperinsulinemic-euglycemic clamps and insulinopenic mice, we show that insulin upregulates its expression in the hypothalamus. Immunofluorescence studies demonstrate that COUP-TFII gene expression is restricted to a subpopulation of ventromedial hypothalamic neurons expressing the melanocortin receptor. In GT1-7 hypothalamic cells, the MC4-R agonist MTII leads to a dose dependant increase of COUP-TFII gene expression secondarily to a local increase in cAMP concentrations. Transfection experiments, using a COUP-TFII promoter containing a functional cAMP responsive element, suggest a direct transcriptional activation by cAMP. Finally, we show that the fed state or intracerebroventricular injections of MTII in mice induce an increased hypothalamic COUP-TFII expression associated with a decreased hepatic and pancreatic COUP-TFII expression. CONCLUSIONS/SIGNIFICANCE: These observations strongly suggest that hypothalamic COUP-TFII gene expression could be a central integrator of insulin and melanocortin signaling pathway within the ventromedial hypothalamus. COUP-TFII could play a crucial role in brain integration of circulating signal of hunger and satiety involved in energy balance regulation

Essential Role of Chromatin Remodeling Protein Bptf in Early Mouse Embryos and Embryonic Stem Cells

We have characterized the biological functions of the chromatin remodeling protein Bptf (Bromodomain PHD-finger Transcription Factor), the largest subunit of NURF (Nucleosome Remodeling Factor) in a mammal. Bptf mutants manifest growth defects at the post-implantation stage and are reabsorbed by E8.5. Histological analyses of lineage markers show that Bptf−/− embryos implant but fail to establish a functional distal visceral endoderm. Microarray analysis at early stages of differentiation has identified Bptf-dependent gene targets including homeobox transcriptions factors and genes essential for the development of ectoderm, mesoderm, and both definitive and visceral endoderm. Differentiation of Bptf−/− embryonic stem cell lines into embryoid bodies revealed its requirement for development of mesoderm, endoderm, and ectoderm tissue lineages, and uncovered many genes whose activation or repression are Bptf-dependent. We also provide functional and physical links between the Bptf-containing NURF complex and the Smad transcription factors. These results suggest that Bptf may co-regulate some gene targets of this pathway, which is essential for establishment of the visceral endoderm. We conclude that Bptf likely regulates genes and signaling pathways essential for the development of key tissues of the early mouse embryo

Somatic Mutation Profiles of MSI and MSS Colorectal Cancer Identified by Whole Exome Next Generation Sequencing and Bioinformatics Analysis

BACKGROUND: Colorectal cancer (CRC) is with approximately 1 million cases the third most common cancer worldwide. Extensive research is ongoing to decipher the underlying genetic patterns with the hope to improve early cancer diagnosis and treatment. In this direction, the recent progress in next generation sequencing technologies has revolutionized the field of cancer genomics. However, one caveat of these studies remains the large amount of genetic variations identified and their interpretation. METHODOLOGY/PRINCIPAL FINDINGS: Here we present the first work on whole exome NGS of primary colon cancers. We performed 454 whole exome pyrosequencing of tumor as well as adjacent not affected normal colonic tissue from microsatellite stable (MSS) and microsatellite instable (MSI) colon cancer patients and identified more than 50,000 small nucleotide variations for each tissue. According to predictions based on MSS and MSI pathomechanisms we identified eight times more somatic non-synonymous variations in MSI cancers than in MSS and we were able to reproduce the result in four additional CRCs. Our bioinformatics filtering approach narrowed down the rate of most significant mutations to 359 for MSI and 45 for MSS CRCs with predicted altered protein functions. In both CRCs, MSI and MSS, we found somatic mutations in the intracellular kinase domain of bone morphogenetic protein receptor 1A, BMPR1A, a gene where so far germline mutations are associated with juvenile polyposis syndrome, and show that the mutations functionally impair the protein function. CONCLUSIONS/SIGNIFICANCE: We conclude that with deep sequencing of tumor exomes one may be able to predict the microsatellite status of CRC and in addition identify potentially clinically relevant mutations