190 research outputs found
FRAX-vs. T-score-based intervention thresholds for osteoporosis
No full textSummary:Many current guidelines for the assessment of osteoporosis, including those in Kuwait, initiate fracture risk assessment in men and women using BMD T-score thresholds. We compared the Kuwaiti guidelines with FRAX-based age-dependent intervention thresholds equivalent to that in women with a prior fragility fracture. FRAX-based intervention thresholds identified women at higher fracture probability than fixed T-score thresholds, particularly in the elderly.Purpose:A FRAX® model been recently calibrated for Kuwait, but guidance is needed on how to utilise fracture probabilities in the assessment and treatment of patients.Methods:We compared age-specific fracture probabilities, equivalent to women with no clinical risk factors and a prior fragility fracture (without BMD), with the age-specific fracture probabilities associated with femoral neck T-scores of −2.5 and −1.5 SD, in line with current guidelines in Kuwait. Upper and lower assessment thresholds for BMD testing were additionally explored using FRAX.Results:When a BMD T-score of −2.5 SD was used as an intervention threshold, FRAX probabilities of a major osteoporotic fracture in women aged 50 years were approximately twofold higher than those in women of the same age but with an average BMD. The increase in risk associated with the BMD threshold decreased progressively with age such that, at the age of 83 years or more, a T-score of −2.5 SD was associated with a lower probability of fracture than that of the age-matched general population with no clinical risk factors. The same phenomenon was observed from the age of 66 years at a T-score of −1.5 SD. A FRAX-based intervention threshold, defined as the 10-year probability of a major osteoporotic fracture in a woman of average BMI with a previous fracture, rose with age from 4.3% at the age of 50 years to 23%, at the age of 90 years, and identified women at increased risk at all ages. Qualitatively comparable findings were observed in the case of hip fracture probability and in men.Conclusion:Intervention thresholds based on BMD alone do not optimally target women at higher fracture risk than those on age-matched individuals without clinical risk factors, particularly in the elderly. In contrast, intervention thresholds based on fracture probabilities equivalent to a ‘fracture threshold’ consistently target women at higher fracture risk, irrespective of age
Quantum Computing Impact Now and the Future
No full textAbstract: The potential for quantum computing to disrupt a variety of industries by solving challenging computational problems more effectively than traditional computers has recently come to light. Quantum computers use qubits rather than conventional bits, utilizing the laws of quantum mechanics to enable exponential parallelism and the processing of massive amounts of data at once. This paper addresses the prospective applications of quantum computing and the potential effects it may have on many sectors, such as the Chemical, Aerospace And Defense, Life Sciences, Financial, Natural Gas, Cybersecurity, and Logistics Industries.
Keywords: quantum computing, potentials, industries, chemicals, aerospace and defense, life sciences, finance, natural gas, cybersecurity, and logistics.
Title: Quantum Computing Impact Now and the Future
Author: Abdullah Saad Alessa
International Journal of Computer Science and Information Technology Research
ISSN 2348-1196 (print), ISSN 2348-120X (online)
Vol. 11, Issue 3, July 2023 - September 2023
Page No: 125-127
Research Publish Journals
Website: www.researchpublish.com
Published Date: 26-August-2023
DOI: https://doi.org/10.5281/zenodo.8285375
Paper Download Link (Source)
https://www.researchpublish.com/papers/quantum-computing-impact-now-and-the-futureInternational Journal of Computer Science and Information Technology Research, ISSN 2348-1196 (print), ISSN 2348-120X (online), Research Publish Journals, Website: www.researchpublish.co
An "All Hands" Call to the Social Science Community: Establishing a Community Framework for Complexity Modeling Using Agent Based Models and Cyberinfrastructure
No full textTo date, many communities of practice (COP) in the social sciences have been struggling with how to deal with rapidly growing bodies of information. Many CoPs across broad disciplines have turned to community frameworks for complexity modeling (CFCMs) but this strategy has been slow to be discussed let alone adopted by the social sciences communities of practice (SS-CoPs). In this paper we urge the SS-CoPs that it is timely to develop and establish a CBCF for the social sciences for two major reasons: the rapid acquisition of data and the emergence of critical cybertools which can facilitate agent-based, spatially-explicit models. The goal of this paper is not to prescribe how a CFCM might be set up but to suggest of what components it might consist and what its advantages would be. Agent based models serve the establishment of a CFCM because they allow robust and diverse inputs and are amenable to output-driven modifications. In other words, as phenomena are resolved by a SS-CoP it is possible to adjust and refine ABMs (and their predictive ability) as a recursive and collective process. Existing and emerging cybertools such as computer networks, digital data collections and advances in programming languages mean the SS-CoP must now carefully consider committing the human organization to enabling a cyberinfrastructure tool. The combination of technologies with human interfaces can allow scenarios to be incorporated through 'if' 'then' rules and provide a powerful basis for addressing the dynamics of coupled and complex social ecological systems (cSESs). The need for social scientists to be more engaged participants in the growing challenges of characterizing chaotic, self-organizing social systems and predicting emergent patterns makes the application of ABMs timely. The enabling of a SS-CoP CFCM human-cyberinfrastructure represents an unprecedented opportunity to synthesize, compare and evaluate diverse sociological phenomena as a cohesive and recursive community-driven process.Community-Based Complex Models, Mathematics, Social Sciences
Aging- and obesity-associated metabolic reprogramming suppresses CD8+ T cell responses
No full textAging and obesity are growing global health issues and are associated with increased susceptibility towards infectious diseases, increased cancer risk and decreased vaccination efficacy. CD8+ T cells are the main effectors of cell-mediated adaptive immunity and form antigen-specific memory after pathogen clearance. However, upon antigen persistence during cancer or chronic infections, T cells become dysfunctional, a state termed T cell exhaustion. In CD8+ T cells, the transcription factor T cell factor 1 (TCF1, encoded by Tcf7) is a stemness marker and high expression is associated with CD8+ T cell longevity and superior functionality. The aim of this study was to identify synergistic effects of aging and obesity on the CD8+ T cell phenotype and function as well as on the plasma metabolite profile to ultimately find a causal relation.
A diet-induced obesity mouse model of young and aged mice was used to study the effect of aging and obesity on the CD8+ T cell phenotype as well as on the plasma metabolite profile. Flow cytometric analysis of naïve CD8+ T cells revealed a terminally differentiated, exhausted CD8+ T cell phenotype with reduced TCF1 expression in aged obese compared to young lean mice. Mass spectrometric analysis of plasma samples identified the tryptophan metabolite 3-Indolepropionic acid (3-IPA) to be synergistically decreased by aging and obesity. Treatment of primary murine and human CD8+ T cells with 3-IPA in therapeutic concentrations, increased TCF1 expression as well as other stemness markers and reversed T cell exhaustion in vitro. Using the lymphocytic choriomeningitis virus (LCMV) infection model, 3-IPA pre-treatment of antigen-specific CD8+ T cells rescued aging- and obesity-impaired anti-viral CD8+ T cell effector and memory functions.
To elucidate the molecular mechanism how 3-IPA increases CD8+ T cell stemness, a pull-down experiment was performed and γ-catenin was identified as a 3-IPA-binding protein. Further investigations revealed decelerated degradation of γ-catenin and its close homologue β-catenin upon 3-IPA treatment in activated CD8+ T cells. Moreover, 3-IPA treatment increased Tcf7 promoter activity in a luciferase assay, while the role of β- and γ-catenin in this context remains elusive.
In summary, aging and obesity synergistically decreased stemness, recall capacity and anti-viral effector functions of CD8+ T cells, thus making them a detrimental combination. Treatment of CD8+ T cells with 3-IPA restored those defects, suggesting a therapeutic potential of 3-IPA to overcome aging- and obesity-mediated CD8+ T cell dysfunctionality
Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study
No full textBACKGROUND AND PURPOSES:
This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.
METHODS:
The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings.
RESULTS:
The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events.
CONCLUSIONS:
In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings
Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients with Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study
No full textBackground and Purposes - This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods - The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results - The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions - In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc
Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients with Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema: The ALESSA Score Study
No full textBackground and Purposes - This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods - The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results - The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions - In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings. © 2017 American Heart Association, Inc
The IRX1/HOXA connection : insights into a novel t(4;11)- specific cancer mechanism
No full textOne hallmark of MLL-r leukemia is the highly specific gene expression signature indicative for commonly deregulated target genes. An usual read-out for this transcriptional deregulation is the HOXA gene cluster, where upregulated HOXA genes are detected in MLL-r AML and ALL patients. In case of t(4;11) leukemia, this simple picture becomes challenged, because these patients separate into HOXAhi- and HOXAlo-patients. HOXAlo-patients showed a reduced HOXA gene transcription, but instead overexpressed the homeobox gene IRX1. This transcriptional pattern was associated with a higher relapse rate and worse outcome. Here, we demonstrate that IRX1 binds to the MLL-AF4 complex at target gene promotors and counteract its promotor activating function. In addition, IRX1 induces transcription of HOXB4 and EGR family members. HOXB4 is usually a downstream target of c-KIT, WNT and TPO signaling pathways and necessary for maintaining and expanding in hematopoietic stem cells. EGR proteins control a p21-dependent quiescence program for hematopoietic stem cells. Both IRX1-dependend actions may help t(4;11) leukemia cells to establish a stem cell compartment. We also demonstrate that HDACi administration is functionally interfering with IRX1 and MLL-AF4, a finding which could help to improve new treatment options for t(4;11) patients
Modern-Day Management of the Dysglycemic Continuum: An Expert Viewpoint from the Arabian Gulf
No full textThamer Alessa,1 Fatheya Al Awadi,2 Juma Al Kaabi,3 Ali Al Mamari,4 Ebaa Al Ozairi,5 Dalal Alromaihi,6 Tarik Elhadd,7 Abdallah A Gunaid,8 Mohamed Hassanein,9 Amin A Jayyousi,10 Raya Kalimat,11 Kerstin MG Brand12 1Division of Endocrinology, Jaber Al-Ahmad Hospital, Kuwait City, Kuwait; 2Endocrine Department, Dubai Hospital, Dubai Academic Health Corporation (DAHC), Dubai, United Arab Emirates; 3Department of Internal Medicine, College of Medicine and Health Sciences, The United Arab Emirates University, Al-Ain, United Arab Emirates; 4Department of Medicine, Sultan Qaboos University Hospital, Muscat, Oman; 5Clinical Research Unit, Dasman Diabetes Institute, Dasman, Kuwait; 6Internal Medicine Department, Royal College of Surgeons in Ireland-Medical University of Bahrain, Adliya, Kingdom of Bahrain; 7Endocrine Section, Department of Medicine, Hamad Medical Corporation, Doha, Qatar; 8Internal Medicine, Sana’a University Faculty of Medicine, Sanaa, Yemen; 9Department of Endocrinology and Diabetes, Dubai Hospital, Dubai Academic Health Corporation (DAHC), Dubai, United Arab Emirates; 10Department of Endocrinology, Hamad Medical Corporation, Doha, Qatar; 11Medical Affairs, Merck Serono Middle East FZ-LLC, Dubai, United Arab Emirates; 12Global Research & Development Medical – MU CM&E, Merck Healthcare KGaA, Darmstadt, GermanyCorrespondence: Thamer Alessa, Division of Endocrinology, Jaber Al-Ahmad hospital, South Surra, Ministries Area, Kuwait City, 13060, Kuwait, Email [email protected]: Prediabetes is the first stage of a continuum that extends through the diagnosis of clinical type 2 diabetes towards long-standing diabetes with multiple comorbidities. The diagnosis of prediabetes provides an opportunity to interrupt the diabetes continuum at an early stage to ensure long-term optimization of clinical outcomes. All people with prediabetes should receive intervention to improve their lifestyles (quality of diet and level of physical activity), as this has been proven beyond doubt to reduce substantially the risk of conversion to diabetes. Additionally, a large base of clinical evidence supports the use of metformin in preventing or delaying the transition from prediabetes to clinical type 2 diabetes, for some people with prediabetes. For many years, guidelines for the management of type 2 diabetes focused on lowering blood glucose, with metformin prescribed first for those without contraindications. More recently, guidelines have shifted towards prevention of diabetes complications as the primary goal, with increased use of GLP-1 receptor agonists (or multi-agonist incretin peptides) or SGLT-2 inhibitors for patients with existing atherosclerotic cardiovascular disease, heart failure or chronic kidney disease. Access to these medications often remains challenging. Metformin remains a suitable option for initial pharmacologic intervention to manage glycemia for many people with prediabetes or type 2 diabetes along with other therapy to maintain control of blood glucose or to address specific comorbidities as the patient progresses along the diabetes continuum.Keywords: type 2 diabetes, prediabetes, diabetes continuum, metformin, antidiabetic therapy, diabetes complication
Le bilinguisme favorise-t-il l'apprentissage de la grammaire d'une nouvelle langue ?
No full textPeu d'études se sont focalisées sur l'apprentissage de la syntaxe chez des sujets bilingues. Pourtant, nombre d'études se sont intéressées aux avantages des bilingues dans d'autres domaines. Les études actuelles portant sur la syntaxe se concentrent le plus souvent sur l'apprentissage de régularités statistiques dans des langues artificielles. L'objectif de cette étude vise donc à étudier l'apprentissage de la grammaire d'une langue naturelle chez des enfants d'âge scolaire bilingues et monolingues. Les enfants sont issus des écoles publiques et privées genevoises. Les participants sont soumis à un échantillon réduit de norvégien. Ils apprennent dans un premier temps des substantifs, puis sont soumis à des phrases simples, des phrases relatives puis des questions relatives. Chaque étape est composée d'une phase d'entraînement, puis d'une phase de test. Seule la dernière étape, celle des questions relatives, est composée uniquement d'une phase de test. Les phrases relatives et les questions relatives impliquent un mouvement syntaxique. Nous considérons que les bilingues présentent un avantage dans l'extraction de la règle sous-jacente au mouvement syntaxique par rapport à leurs homologues monolingues. Cet avantage se traduit par de meilleures performances à la généralisation lexicale, c'est-à-dire à la généralisation de la règle du mouvement syntaxique à de nouveaux verbes rencontrés, puis à la généralisation syntaxique, c'est-à-dire à la phase de questions relatives, structure syntaxique encore non rencontrée dans l'input. Puis, nous considérons que l'avantage des bilingues pourrait être plus général et pas uniquement langagier. Afin d'étudier cette hypothèse, les participants sont amenés à extraire des règles visuelles sur les matrices de Raven. Enfin, la littérature actuelle considère d'autres facteurs pouvant influencer l'apprentissage de la grammaire d'une seconde langue. Nous ajoutons alors deux variables afin d'étudier leur potentiel effet sur la généralisation lexicale et syntaxique, la mémoire phonologique à court terme et les fonctions exécutives. Les résultats trouvés vont à l'encontre de nos hypothèses. Les bilingues ne montrent pas d'avantage dans l'extraction de règles langagières. Ils ne présentent pas d'avantage dans l'extraction de règles de façon plus générale. Enfin, l'ajout des variables de mémoire phonologique à court terme et les fonctions exécutives n'expliquent pas mieux les performances à la généralisation lexicale et syntaxique. Les résultats ne soutiennent pas nos hypothèses initialement considérées et nous ne répliquons pas les résultats de la littérature. L'absence de résultats concluants peut être expliqué en partie par le manque de contrôle de certaines variables et le choix des tâches qui n'est pas toujours adéquat
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