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Atrial fibrillation (AF) is a significant risk factor for stroke. Based on the higher stroke associated with AF in the South Asian population, we constructed a one-year stroke prediction model using machine learning (ML) methods in KERALA-AF South Asian cohort. External validation was performed in the prospective APHRS-AF registry. We studied 2101 patients and 83 were to patients with stroke in KERALA-AF registry. The random forest showed the best predictive performance in the internal validation with receiver operator characteristic curve (AUC) and G-mean of 0.821 and 0.427, respectively. In the external validation, the light gradient boosting machine showed the best predictive performance with AUC and G-mean of 0.670 and 0.083, respectively. We report the first demonstration of ML's applicability in an Indian prospective cohort, although the more modest prediction on external validation in a separate multinational Asian registry suggests the need for ethnic-specific ML models., Competing Interests: Declaration of competing interest G.Y.H.L. reports: Consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, Anthos. No fees are received personally. G.Y.H.L. is a National Institute for Health and Care Research (NIHR) Senior Investigator and co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 899871. Other authors report no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This retrospective, single site observational study aimed to delineate five abnormal embryonic developmental phenotypes, assessing their prevalence, development potential and suitability for inclusion in embryo selection models for IVF. In total, 15,819 embryos from 4559 treatment cycles cultured in EmbryoScope® incubators between January 2014 and January 2016 were included. Time-lapse images were assessed retrospectively for five abnormal embryo phenotypes: direct cleavage, reverse cleavage, absent cleavage, chaotic cleavage and cell lysis. The prevalence of each abnormal phenotype was assessed. Final embryo disposition, embryo quality and implantation rate were determined and compared with a control embryo cohort. The collective prevalence for the five abnormal phenotypes was 11.4%; chaotic cleavage and direct cleavage together constituted 9.7%. Implantation rates were 17.4%, 0%, 25%, 2.1% and 0% for direct, reverse, absent, chaotic cleavage and cell lysis, respectively. The overall implantation rate for all abnormal embryos with known implantation status was significantly lower compared with the control population (6.9% versus 38.7%, P < 0.0001). The proportion of good quality embryos in each category of abnormal cleavage remained below 25%. Embryos exhibiting an abnormal phenotype may have reduced developmental capability, manifested in both embryo quality and implantation potential, when compared with embryos of normal phenotype., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Introduction: Pain treatment is best performed when a patient-centric, safety-based philosophy is used to determine an algorithmic process to guide care. Since 2007, the International Neuromodulation Society has organized a group of experts to evaluate evidence and create a Polyanalgesic Consensus Conference (PACC) to guide practice., Methods: The current PACC update was designed to address the deficiencies and innovations emerging since the previous PACC publication of 2012. An extensive literature search identified publications between January 15, 2007 and November 22, 2015 and authors contributed additional relevant sources. After reviewing the literature, the panel convened to determine evidence levels and degrees of recommendations for intrathecal therapy. This meeting served as the basis for consensus development, which was ranked as strong, moderate or weak. Algorithms were developed for intrathecal medication choices to treat nociceptive and neuropathic pain for patients with cancer, terminal illness, and noncancer pain, with either localized or diffuse pain., Results: The PACC has developed an algorithmic process for several aspects of intrathecal drug delivery to promote safe and efficacious evidence-based care. Consensus opinion, based on expertise, was used to fill gaps in evidence. Thirty-one consensus points emerged from the panel considerations., Conclusion: New algorithms and guidance have been established to improve care with the use of intrathecal drug delivery., (© 2017 International Neuromodulation Society.)

Posttranslational modification of proteins by the addition of ubiquitin and related modifiers has an essential role in cellular processes such as protein degradation and subcellular localization. This impacts on the study of cell and developmental biology in diseases such as cancer, and on the study of protein folding and stability in Alzheimer's disease and other diseases of protein aggregation and misfolding. Recently, there have been many additions to the ubiquitylation literature that have challenged, revised, and expanded our understanding and future directions of this process. Here we present a comprehensive overview of the classical textbook description of protein ubiquitylation and then review the recent literature that has challenged and revised the canonical models of protein ubiquitylation. We discuss the roles of noncanonical ubiquitylation at sites other than lysine residues, unconventional ubiquitylation of mixed and branched polyubiquitin chains, and highlight the role of other structural and posttranslational modifications in ubiquitylation that have been identified in the recent literature. By highlighting the assumptions that have been challenged and revised in the field of protein ubiquitylation, we hope to stimulate further study and questions about this ubiquitous protein modification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The International Neuromodulation Society (INS) has determined that there is a need for guidance regarding safety and risk reduction for implantable neurostimulation devices. The INS convened an international committee of experts in the field to explore the evidence and clinical experience regarding safety, risks, and steps to risk reduction to improve outcomes., Methods: The Neuromodulation Appropriateness Consensus Committee (NACC) reviewed the world literature in English by searching MEDLINE, PubMed, and Google Scholar to evaluate the evidence for ways to reduce risks of neurostimulation therapies. This evidence, obtained from the relevant literature, and clinical experience obtained from the convened consensus panel were used to make final recommendations on improving safety and reducing risks., Results: The NACC determined that the ability to reduce risk associated with the use of neurostimulation devices is a valuable goal and possible with best practice. The NACC has recommended several practice modifications that will lead to improved care. The NACC also sets out the minimum training standards necessary to become an implanting physician., Conclusions: The NACC has identified the possibility of improving patient care and safety through practice modification. We recommend that all implanting physicians review this guidance and consider adapting their practice accordingly., (© 2014 International Neuromodulation Society.)

Introduction: The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications., Methods: The NACC used literature reviews, expert opinion, clinical experience, and individual research. Authors consulted the Practice Parameters for the Use of Spinal Cord Stimulation in the Treatment of Neuropathic Pain (2006), systematic reviews (1984 to 2013), and prospective and randomized controlled trials (2005 to 2013) identified through PubMed, EMBASE, and Google Scholar., Results: Neurostimulation is relatively safe because of its minimally invasive and reversible characteristics. Comparison with medical management is difficult, as patients considered for neurostimulation have failed conservative management. Unlike alternative therapies, neurostimulation is not associated with medication-related side effects and has enduring effect. Device-related complications are not uncommon; however, the incidence is becoming less frequent as technology progresses and surgical skills improve. Randomized controlled studies support the efficacy of spinal cord stimulation in treating failed back surgery syndrome and complex regional pain syndrome. Similar studies of neurostimulation for peripheral neuropathic pain, postamputation pain, postherpetic neuralgia, and other causes of nerve injury are needed. International guidelines recommend spinal cord stimulation to treat refractory angina; other indications, such as congestive heart failure, are being investigated., Conclusions: Appropriate neurostimulation is safe and effective in some chronic pain conditions. Technological refinements and clinical evidence will continue to expand its use. The NACC seeks to facilitate the efficacy and safety of neurostimulation., (© 2014 International Neuromodulation Society.)

Introduction: Trialing for intrathecal pump placement is an essential part of the decision-making process in placing a permanent device. In both the United States and the international community, the proper method for trialing is ill defined., Methods: The Polyanalgesic Consensus Conference (PACC) is a group of well-published experienced practitioners who meet to update the state of care for intrathecal therapies on the basis of current knowledge in the literature and clinical experience. Anexhaustive search is performed to create a base of information that the panel considers when making recommendations for best clinical practices. This literature, coupled with clinical experience, is the basis for recommendations and for identification of gaps in the base of knowledge regarding trialing for intrathecal pump placement., Results: The panel has made recommendations for the proper methods of trialing for long-term intrathecal drug delivery., Conclusion: The use of intrathecal drug delivery is an important part of the treatment algorithm for moderate to severe chronic pain. It has become common practice to perform a temporary neuroaxial infusion before permanent device implantation. On the basis of current knowledge, the PACC has developed recommendations to improve care. The need to update these recommendations will be very important as new literature is published., (© 2012 International Neuromodulation Society.)

Background: Suspected cardiac chest pain accounts for over 25% of medical admissions but, as only a minority have acute coronary syndromes, there is a tremendous potential to reduce unnecessary admissions. We evaluated five markers of plaque rupture or instability as indicators that would allow safe early exclusion of acute myocardial infarction (AMI) at the time of presentation., Methods: Blood was drawn at the time of presentation from patients presenting to the Emergency Department with suspected cardiac chest pain and tested for cTnT and 5 novel biomarkers (pregnancy-associated plasma protein A (PAPP-A), thrombospondin, CD40 ligand, E-selectin and P-selectin). The primary outcome was a diagnosis of AMI. The secondary outcome was the occurrence of death, AMI or urgent revascularization (adverse cardiac events, ACE) within 30 days., Results: 713 patients were included. Median time from symptom onset to venepuncture was 210 min. Only P-selectin and PAPP-A had value for diagnosis of AMI, with C-statistics of 0.68 (95% CI 0.63-0.73) and 0.57 (0.51-0.63) respectively. On multivariate analysis, P-selectin, cTnT and ECG ischemia independently predicted ACE. A model combining all three had 97.6% sensitivity, 52.8% specificity and 99.0% negative predictive value (NPV) for AMI. Use of this model could obviate the need for hospital admission in 44.2% of patients, 2.5% of whom would be expected to develop ACE., Conclusions: P-selectin has early diagnostic value for AMI and prognostic value independent of cTnT and ECG findings. The combination of P-selectin, cTnT and ECG has high NPV. Further research into this promising biomarker is warranted., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objectives: Choline has been identified as a promising marker of coronary inflammation, plaque destabilisation and ischaemia. We sought to evaluate plasma choline levels for rapid confirmation or exclusion of acute myocardial infarction (AMI) in the Emergency Department (ED) and for predicting major adverse cardiac events (MACE)., Methods: We prospectively recruited 361 patients who presented to the ED with suspected cardiac chest pain within the previous 24 h. Blood was drawn at the time of presentation for plasma choline levels. All patients underwent troponin T testing > or = 12 h after symptom onset and were followed up for the occurrence of MACE within 6 months. Whole blood choline (WBCho) levels were also measured in a convenience sample of 39 patients., Results: Plasma choline levels did not help to predict a diagnosis of AMI (odds ratio (OR) 1.00 (95% confidence intervals (CI) 0.91-1.10, p = 0.98). For a diagnosis of AMI the area under the receiver operating characteristic (ROC) curve was 0.48. Plasma choline was not predictive of the combined endpoint of MACE (OR 1.03, 95% CI 0.95-1.12, p = 0.45) but predicted AMI within 6 months (OR 1.31, 95% CI 1.09-1.56, p = 0.003). WBCho levels were significantly different to plasma levels and were predictive of MACE., Conclusions: Plasma choline, measured at the time of ED presentation, is not a diagnostic marker of AMI but predicts AMI within 6 months. While plasma choline failed to predict MACE, WBCho was predictive and warrants further evaluation.

Background.  Expert panels of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics, based on the preclinical and clinical literature known up to those times, presentations of the expert panels, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and nonphysicians has convened in 2007 to update information known regarding IT therapies and to update information on new and novel opioid and nonopioid analgesic compounds that might show promise for IT use. Methods.  A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians to discuss new and novel analgesic agents for IT use. Results.  The panelists identified several agents that were worthy of future studies for the clinical and rational use of IT agents that are presented in this article. Conclusions.  A list of nonopioid IT analgesics, including gabapentin, adenosine, octreotide, the χ-conopeptide, Xen2174, the conopeptide, neurotensis 1 agonist, CGX-1160, the ω-conotoxin, AM-336, and physostigmine, were identified as worthy of future research by the panelists., (© 2008 International Neuromodulation Society.)

Background.  Expert panel of physicians and nonphysicians, all expert in intrathecal (IT) therapies, convened in the years 2000 and 2003 to make recommendations for the rational use of IT analgesics based on the preclinical and clinical literature known up to those times, presentations of the expert panel, discussions on current practice and standards, and the result of surveys of physicians using IT agents. An expert panel of physicians and convened in 2007 to review previous recommendations and to form recommendations for the rational use of IT agents as they pertain to new scientific and clinical information regarding the etiology, prevention and treatment for IT granuloma. Method.  A review of preclinical and clinical literature from 2000 to 2006 was undertaken and disseminated to an expert panel of physicians. Focused discussions concerning the rational use of IT agents and its relationship to the etiology of, prevention of, and treatment of IT granuloma were held. Results.  This report presents here new knowledge of the etiology of catheter tip granuloma and guidelines for its prevention and treatment., (© 2008 International Neuromodulation Society.)

Purpose: To assess nuchal translucency measurements that were performed as part of routine prenatal screening for Down syndrome., Methods: Collect ultrasound measurements of nuchal translucency and crown rump length provided by individual sonographers over a 6-month period to six North American prenatal screening laboratories, along with the laboratory's nuchal translucency interpretation in multiples of the median. For sonographers with 50 or more observations, compute three nuchal translucency quality measures (medians, standard deviations, and slopes), based on epidemiological monitoring., Results: Altogether, 23,462 nuchal translucency measurements were submitted by 850 sonographers. Among the 140 sonographers (16%) who submitted more than 50 observations, 76 (54%) were found to have all three quality measures in the target range. These 140 sonographers collectively accounted for 14,210 nuchal translucency measurements (61%). The most common single measure to be out of range was nuchal translucency multiples of the median, found for 29 of the 140 sonographers (21%)., Conclusion: Laboratories should routinely monitor the quality of nuchal translucency measurements that are received for incorporation into Down syndrome screening risk calculations and interpretations. When possible, instituting sonographer-specific medians and providing individualized feedback about performance and numbers of women tested offer the potential to yield more consistent and improved performance.

Background.  Expert panels of physicians and nonphysicians in the field of intrathecal therapies convened in 2000 and 2003 to make recommendations for the rational use of intrathecal analgesics based on the preclinical and clinical literature known up to those times. An expert panel of physicians convened in 2007 to update previous recommendations and to form guidelines for the rational use of intrathecal opioid and nonopioid agents. Methods.  A review of preclinical and clinical published relevant studies from 2000 to 2006 was undertaken and disseminated to a convened expert panel of physicians and nonphysicians. Focused discussions were held on the rational use of intrathecal agents and a survey asking questions regarding intrathecal therapies management was given to the panelists. Results.  The panelists, after review of the literature from 2000 to 2006 and discussion, created an updated algorithm for the rational use of intrathecal opioid and nonopioid agents in patients with nonmalignant and end-of-life pain. Of note is that the panelists felt that ziconotide, based on new and relevant literature and experience, should be updated to a line one intrathecal drug.

A follow-up of 3143 women from four screening centres, who were assessed after screening mammography, showed that 371 had breast cancer diagnosed at that assessment and 62 developed a breast cancer in the following 6 years. Of these, 32 were judged to be false-negatives at assessment, with 23 of the 32 at the site originally suspected. The results show that the assessment process is not infallible and that the scale of the problem only becomes clear when an exhaustive search is made for missed cancers.