77 research outputs found
Cryptocurrency Rollercoaster: Volatility Patterns and Market Dynamics in Positive and Negative Events
Dissertation presented as the partial requirement for obtaining a Master's degree in Statistics and Information Management, specialization in Risk Analysis and ManagementCryptocurrencies have gained considerable attention in financial research in recent years. This investigation focused on analysing the volatility dynamics and the impact of both positive and negative events across cryptocurrency markets, high-market and low-market. Employing the bivariate BEKK-MGARCH model, the research aims to identify how cross-market volatility shocks and volatility transmissions range between these markets. The analysis of individual cryptocurrency markets reveals a price volatility dependency on their historical shocks and volatility. Based on the findings, most of the cryptocurrency pairs exhibit uni-directional transmission, either in terms of shock impact or volatility effects. Notably, there is a stronger indication of volatility transmission from high-market to low-market cryptocurrencies, as opposed to the reverse direction. This implies that the performance of high-market cryptocurrencies exerts influence, either positively or negatively, on low-market. The study also highlights the existence of time-varying conditional correlations, mostly demonstrating a positive relationship. Moreover, the research integrates positive and negative events into the assessment, observing that within the event study conducted on price returns of cryptocurrencies over an eleven-day event window (-5,+5), negative events significantly have more impact on cryptocurrencies. These findings hold valuable implications for investors, particularly highlighting the importance of considering negative cryptocurrency-related events and taking into account the influence of the main digital currencies in the whole cryptocurrency market, serving as a precautionary measure to mitigate potential financial losses
Novel Endoscopic Techniques in Celiac Disease
Celiac disease (CD) is a systemic, immuneâmediated illness that primarily affects the small bowel. A few decades ago, in the era of Watson and Crosby capsules, we used to sample the small bowel without even looking at it. Nowadays, with the continuous developing field of digestive endoscopy, we can even see the duodenal villi up closely, allowing for an optical, realâtime diagnosis of villous atrophy. Advanced endoscopic techniques such as magnification, chromoendoscopy (dyeâbased and digital), water immersion, confocal endomicroscopy, endocytoscopy, and optical coherence tomography (OCT) have been evaluated in CD with good results: good agreement with histology, allowing for targeted biopsies and a reduction in the number of biopsies needed for diagnosis. Moreover, with the growing use of openâaccess endoscopy in many parts of the world, endoscopy is now contributing to increasing the diagnostic rate of CD, by recognition of endoscopic markers in patients without clinical suspicion of this disease. This is however an observerâdependent method; to overcome the endoscopists subjectiveness in assessing villous atrophy, in the last years, many papers have looked at means of computerized analysis of endoscopic images. Currently available data show that these automated, quantitative methods hold very promising for the future
Apheresis in Inflammatory Bowel Disease: Current Evidence
Inflammatory bowel diseases (IBD) have become a major focus for gastroenterologists worldwide, with the increasing incidence and complexity of cases, which pose therapeutic challenges. Currently available approaches fail in controlling the disease activity in a significant proportion of patients and some of the therapies are associated with significant adverse events. Although new molecules are on the horizon and treatment strategies have been optimized, novel therapeutic tools are much needed in IBD for patients who fail to attain control of the disease. Apheresis is now a common non-pharmacological therapeutic modality used in several pathologies, IBD also. In the current review, we summarize currently available evidence with respect to selective apheresis in IBD
Hematologic manifestations in celiac disease : a practical review
Celiac disease (CD) is a systemic autoimmune disease driven by gluten-ingestion in genetically predisposed individuals. Although it primarily affects the small bowel, CD can also involve other organs and manifest as an extraintestinal disease. Among the extraintestinal features of CD, hematologic ones are rather frequent and consist of anemia, thrombocytosis (thrombocytopenia also, but rare), thrombotic or hemorrhagic events, IgA deficiency, hyposplenism, and lymphoma. These hematologic alterations can be the sole manifestation of the disease and should prompt for CD testing in a suggestive clinical scenario. Recognition of these atypical, extraintestinal presentations, including hematologic ones, could represent a great opportunity to increase the diagnostic rate of CD, which is currently one of the most underdiagnosed chronic digestive disorders worldwide. In this review, we summarize recent evidence regarding the hematological manifestations of CD, with focus on practical recommendations for clinicians
Fingertip rapid point-of-care test in adult case-finding in coeliac disease
Background
Coeliac disease (CD), due to its protean clinical manifestation, is still very under diagnosed in adults and delays in diagnosis may take years and even decades. Simple tools to find cases in primary care may help to identify patients for further diagnostic tests. We have evaluated the usefulness of an on site rapid fingertip whole blood point-of-care test (POCT) for such a purpose.
Methods
As CD is known to run within families, we tested 148 healthy relatives of 70 Romanian index cases with biopsy-proven CD (87% of all first-degree family members, median age 36 years) for the presence of circulating autoantibodies. In addition to performing the POCT (which measures blood erythrocyte self-TG2-autoantibody complexes) on site, blood was drawn for later evaluations of serum IgA-class endomysial antibodies (EMA). EMA-positive sera were further tested for transglutaminase 2 antibodies (TG2-IgA). All serological parameters were analyzed blindly in a centralized laboratory that had no knowledge of the on site POCT result. Endoscopic small intestinal biopsies was recommended for all POCT- or EMA-test positive subjects.
Results
In on site testing the POCT was positive in 12/148 first-degree relatives (8%) and all these subjects were also serum EMA-positive. A positive EMA test was found only in one other subject. All remaining 135 healthy first-degree relatives were negative for both POCT and EMA. Four subjects positive for both POCT and EMA were negative for TG2-IgA. Ten out of thirteen of the antibody-positive subjects agreed to undergo endoscopy. The POCT was found to be positive in 8/9 first-degree relatives having coeliac-type mucosal lesions of grade Marsh 2 (nâ=â3) or Marsh 3 (nâ=â6). The three POCT-positive subjects not agreeing to undergo endoscopy were also both EMA- and TG2-IgA-positive.
Conclusion
The fingertip whole blood rapid POCT might fulfill the unmet need for a simple and cheap case-finding biomarker for early detection and presumptive diagnosis of CD. Confirmatory studies are warranted in adult case-finding in specialized outpatient clinics and in primary care.BioMed Central open acces
Genetic correction of PSA values using sequence variants associated with PSA levels
To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMeasuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 Ă 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.info:eu-repo/grantAgreement/EC/FP7/202059/
218071
Urological Research Foundation
P50 CA90386-05S2
Robert H. Lurie Comprehensive Cancer Center
p30 CA60553
Health Technology Assessment Programme
96/20/06
96/20/99
Department of Health, England
Cancer Research UK
C522/A8649
Medical Research Council of England
G0500966
ID 75466
National Cancer Research Institute (NCRI), UK
Southwest National Health Service Research and Development
NCRI
National Institute for Health Resear
Identification of Lynch syndrome risk variants in the Romanian population.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadTwo familial forms of colorectal cancer (CRC), Lynch syndrome (LS) and familial adenomatous polyposis (FAP), are caused by rare mutations in DNA mismatch repair genes (MLH1, MSH2, MSH6, PMS2) and the genes APC and MUTYH, respectively. No information is available on the presence of high-risk CRC mutations in the Romanian population. We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes. The frequencies of all candidate variants were assessed in a cohort of 688 CRC cases and 4567 controls. Immunohistochemical (IHC) staining for MLH1, MSH2, MSH6, and PMS2 was performed on tumour tissue. We identified 11 candidate variants in 11 cases; six variants in MLH1, one in MSH6, one in PMS2, and three in APC. Combining information on the predicted impact of the variants on the proteins, IHC results and previous reports, we found three novel pathogenic variants (MLH1:p.Lys84ThrfsTer4, MLH1:p.Ala586CysfsTer7, PMS2:p.Arg211ThrfsTer38), and two novel variants that are unlikely to be pathogenic. Also, we confirmed three previously published pathogenic LS variants and suggest to reclassify a previously reported variant of uncertain significance to pathogenic (MLH1:c.1559-1G>C).European Union
EE
Geographic variation of mutagenic exposures in kidney cancer genomes
International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden1. In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence2. Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics
- âŠ