Measuring venous oxygenation using the photoplethysmograph waveform

OBJECTIVE: We investigate the hypothesis that the photoplethysmograph (PPG) waveform can be analyzed to infer regional venous oxygen saturation. METHODS: Fundamental to the successful isolation of the venous saturation is the identification of PPG characteristics that are unique to the peripheral venous system. Two such characteristics have been identified. First, the peripheral venous waveform tends to reflect atrial contraction. Second, ventilation tends to move venous blood preferentially due to the low pressure and high compliance of the venous system. Red (660 nm) and IR (940 nm) PPG waveforms were collected from 10 cardiac surgery patients using an esophageal PPG probe. These waveforms were analyzed using algorithms written in Mathematica. Four time-domain saturation algorithms (ArtSat, VenSat, ArtInstSat, VenInstSat) and four frequency-domain saturation algorithms (RespDC, RespAC, Cardiac, and Harmonic) were applied to the data set. RESULTS: Three of the algorithms for calculating venous saturation (VenSat, VenInstSat, and RespDC) demonstrate significant difference from ArtSat (the conventional time-domain algorithm for measuring arterial saturation) using the Wilcoxon signed-rank test with Bonferroni correction (p < 0.0071). CONCLUSIONS: This work introduces new algorithms for PPG analysis. Three algorithms (VenSat, VenInstSat, and RespDC) succeed in detecting lower saturation blood. The next step is to confirm the accuracy of the measurement by comparing them to a gold standard (i.e., venous blood gas)

Using support vector machines on photoplethysmographic signals to discriminate between hypovolemia and euvolemia

Identifying trauma patients at risk of imminent hemorrhagic shock is a challenging task in intraoperative and battlefield settings given the variability of traditional vital signs, such as heart rate and blood pressure, and their inability to detect blood loss at an early stage. To this end, we acquired N = 58 photoplethysmographic (PPG) recordings from both trauma patients with suspected hemorrhage admitted to the hospital, and healthy volunteers subjected to blood withdrawal of 0.9 L. We propose four features to characterize each recording: goodness of fit (r2), the slope of the trend line, percentage change, and the absolute change between amplitude estimates in the heart rate frequency range at the first and last time points. Also, we propose a machine learning algorithm to distinguish between blood loss and no blood loss. The optimal overall accuracy of discriminating between hypovolemia and euvolemia was 88.38%, while sensitivity and specificity were 88.86% and 87.90%, respectively. In addition, the proposed features and algorithm performed well even when moderate blood volume was withdrawn. The results suggest that the proposed features and algorithm are suitable for the automatic discrimination between hypovolemia and euvolemia, and can be beneficial and applicable in both intraoperative/emergency and combat casualty care

Cytoplasmic chromatin triggers inflammation in senescence and cancer

Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders

Respiratory Physiology and the Impact of Different Modes of Ventilation on the Photoplethysmographic Waveform

The photoplethysmographic waveform sits at the core of the most used, and arguably the most important, clinical monitor, the pulse oximeter. Interestingly, the pulse oximeter was discovered while examining an artifact during the development of a noninvasive cardiac output monitor. This article will explore the response of the pulse oximeter waveform to various modes of ventilation. Modern digital signal processing is allowing for a re-examination of this ubiquitous signal. The effect of ventilation on the photoplethysmographic waveform has long been thought of as a source of artifact. The primary goal of this article is to improve the understanding of the underlying physiology responsible for the observed phenomena, thereby encouraging the utilization of this understanding to develop new methods of patient monitoring. The reader will be presented with a review of respiratory physiology followed by numerous examples of the impact of ventilation on the photoplethysmographic waveform

The Influence of Corporate Front-Group Stealth Campaigns

This research examined corporate front-group stealth campaigns. An experiment was conducted to examine the influence of front-group stealth campaigns on a variety of measures. It was anticipated that corporate front-group stealth campaigns, which feature names that mask the true interests of sponsors, positively affect public opinion, unless they are exposed as intentionally misleading, in which case they boomerang against sponsors. The experiment examined the potential of the inoculation strategy to preempt the influence of corporate front-group stealth campaigns. The pattern of results supported all of these expectations. Front-group stealth campaigns proved to be effective, at least in the short term. Front-group stealth campaigns eroded public attitudes toward the issue in question and boosted perceptions of the front group, but not the corporate sponsor. However, when front-group stealth campaigns were subsequently exposed, positive effects dissipated and perceptions of corporate sponsors boomeranged. Results revealed that inoculation can protect against the influence of front-group stealth campaigns.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

The Concise Guide to PHARMACOLOGY 2023/24:Introduction and Other Protein Targets

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4