An oesophageal pulse oximetry system utilising a fibre-optic probe

A dual-wavelength fibre-optic pulse oximetry system is described for the purposes of estimating oxygen saturation (SpO2) from the oesophagus. A probe containing miniature right-angled glass prisms was used to record photoplethysmographic (PPG) signals from the oesophageal wall. Signals were recorded successfully in 19 of 20 patients, demonstrating that PPG signals could be reliably obtained from an internal vascularised tissue site such as the oesophageal epithelium. The value of the mean oxygen saturation recorded from the oesophagus was 94.0 ± 4.0%. These results demonstrate that SpO2 may be estimated in the oesophagus using a fibre-optic probe

Coronary CT angiography features of ruptured and high-risk atherosclerotic plaques: Correlation with intra-vascular ultrasound

BACKGROUND: Features of ruptured and high-risk plaque have been described on coronary computed tomography angiography (coronary CTA), but not systematically assessed against intravascular ultrasound (IVUS). We examined the ability of coronary CTA to identify IVUS defined ruptured plaque and Virtual Histology Intravascular Ultrasound (VH-IVUS) defined thin-cap fibroatheroma (TCFA). METHODS: Sixty-three patients (32 with acute coronary syndrome and 31 with stable angina) underwent coronary CTA, IVUS and VH-IVUS. Plaque rupture on CTA was defined as intra-plaque contrast and its frequency compared with IVUS-defined plaque rupture. We then examined the relationship of conventional coronary CTA high-risk features (low attenuation plaque, positive remodeling, spotty calcification and the Napkin-Ring sign) in VH-IVUS-defined TCFA. We compared these with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using x-ray attenuation cut-offs derived from the relationship of plaque to luminal contrast attenuation. RESULTS: Of the 71 plaques interrogated with IVUS, 39 were ruptured. Coronary CTA correctly detected 13-ruptured plaques with 3 false positives giving high specificity (91%) but low sensitivity (33%). None of the conventional coronary CTA high-risk features were significantly more frequent in the higher-risk (VH-IVUS defined thin-cap) compared with thick-cap fibroatheroma. However, the new index (necrotic core/fibrous plaque ratio) was higher in thin-cap (mean 0.90) vs. thick-cap fibroatheroma (mean 0.59), p < 0.05. CONCLUSIONS: Compared with intravascular ultrasound, coronary CTA identifies ruptured plaque with good specificity but poor sensitivity. We have identified a novel high-risk feature on coronary CTA (necrotic core/fibrous plaque ratio that is associated with VH-IVUS defined-TCFA.Supported by a British Heart Foundation grant FS/10/025/2819

Petition of Cato West, and others, on behalf of themselves and the other inhabitants of the Mississippi Territory. : With the documents accompanying the same. 13th January, 1800. Referred to Mr. Claiborne, Mr. Griswold, Mr. Henderson, Mr. Nott, and Mr. Bartlett. : (Published by order of the House of Representatives)

https://egrove.olemiss.edu/msterrdocs/1000/thumbnail.jp

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm &#946;-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

A survey of UK medical schools' arrangements for early patient contact

Background: Many U.K. medical schools have patient contact in the first two years of the undergraduate course. Aim: To compare the purposes and organization of early patient contact in UK medical schools and to relate these arrangements to the schools' curricular objectives. Methods: A telephone survey of lead educators in UK medicals schools. Categories of contact were plotted against phases of the course to discern patterns of organisation. Results: The quantity of contact varies considerably (four to 65 days). There is a pattern, with learning objectives around the social context of health and illness preceding skills based work and integrated clinical knowledge for practice coming later. Schools fall into three categories: close adherence to the preclinical/clinical split, with limited early contact acting as an introduction to social aspects of health; provision of substantial patient contact to maximize the integration of knowledge and skills; and transitional, with limited clinical goals. General practice provides between one third and one half of early patient contact. Conclusions: Arrangements meet the objectives set by each school and reflect differing educational philosophies. Change is toward more early contact. There appears to be no national guidance which supports a minimum quantity of patient contact or specific educational purpose in the early years of U.K. basic medical training

Understanding and Overcoming the Challenges Related to Cardiovascular Trials Involving Patients with Kidney Disease.

Cardiovascular disease is a prevalent and prognostically important comorbidity among patients with kidney disease, and individuals with kidney disease make up a sizeable proportion (30%-60%) of patients with cardiovascular disease. However, several systematic reviews of cardiovascular trials have observed that patients with kidney disease, particularly those with advanced kidney disease, are often excluded from trial participation. Thus, currently available trial data for cardiovascular interventions in patients with kidney disease may be insufficient to make recommendations on the optimal approach for many therapies. The Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and the US Food and Drug Administration, convened a multidisciplinary, international work group and hosted a stakeholder workshop intended to understand and develop strategies for overcoming the challenges with involving patients with kidney disease in cardiovascular clinical trials, with a particular focus on those with advanced disease. These efforts considered perspectives from stakeholders, including academia, industry, contract research organizations, regulatory agencies, patients, and care partners. This article outlines the key challenges and potential solutions discussed during the workshop centered on the following areas for improvement: building the business case, re-examining study design and implementation, and changing the clinical trial culture in nephrology. Regulatory and financial incentives could serve to mitigate financial concerns with involving patients with kidney disease in cardiovascular trials. Concerns that their inclusion could affect efficacy or safety results could be addressed through thoughtful approaches to study design and risk mitigation strategies. Finally, there is a need for closer collaboration between nephrologists and cardiologists and systemic change within the nephrology community such that participation of patients with kidney disease in clinical trials is prioritized. Ultimately, greater participation of patients with kidney disease in cardiovascular trials will help build the evidence base to guide optimal management of cardiovascular disease for this population

Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy

Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal-catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples oft he enantioisotopomer

Multiscale correlative tomography: an investigation of creep cavitation in 316 stainless steel

Creep cavitation in an ex-service nuclear steam header Type 316 stainless steel sample is investigated through a multiscale tomography workflow spanning eight orders of magnitude, combining X-ray computed tomography (CT), plasma focused ion beam (FIB) scanning electron microscope (SEM) imaging and scanning transmission electron microscope (STEM) tomography. Guided by microscale X-ray CT, nanoscale X-ray CT is used to investigate the size and morphology of cavities at a triple point of grain boundaries. In order to understand the factors affecting the extent of cavitation, the orientation and crystallographic misorientation of each boundary is characterised using electron backscatter diffraction (EBSD). Additionally, in order to better understand boundary phase growth, the chemistry of a single boundary and its associated secondary phase precipitates is probed through STEM energy dispersive X-ray (EDX) tomography. The difference in cavitation of the three grain boundaries investigated suggests that the orientation of grain boundaries with respect to the direction of principal stress is important in the promotion of cavity formation

Meeting Report on ICRR2019, the 16th International Congress on Radiation Research

This is an Accepted Manuscript of an article published by Taylor & Francis in International Journal of Radiation Biology on 13 Nov 2019, available online: https://www.tandfonline.com/doi/full/10.1080/09553002.2020.1688886. Uploaded in accordance with the publisher's self-archiving policy.NIHR Manchester Biomedical Research Centr