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The interplay between Epstein-Barr virus DNA and gut microbiota in the development of arthritis in a mouse model
Get PDFEpstein-Barr virus (EBV) DNA may influence the development of autoimmune diseases by increasing the production of proinflammatory cytokines. Such cytokines have been associated with inducing the dysbiosis of colonic microbiota, which, in turn, is a risk factor for autoimmune diseases such as rheumatoid arthritis (RA). Therefore, we investigated the role that EBV DNA may play in modulating the intestinal microbiota and consequent exacerbation of arthritis in a mouse model. Mice were treated with collagen (arthritis-inducing agent), EBV DNA and collagen, EBV DNA, or water. Fecal samples were collected from arthritic and control mice, and 16S rRNA sequencing was performed to determine the effect of EBV DNA on the composition of colonic microbiota. EBV DNA causes a change in the alpha diversity of the microbiota resulting in an increased Chao1 microbial richness and decreased Shannon diversity index in the RA mouse model. In addition, the abundance of particular genera/genus clusters was significantly altered among the various groups, with the EBV DNA-exacerbated arthritic group having the highest number of altered genera/genus cluster abundances. This group also had the highest number of cells co-expressing IL-17A, FOXP3, and IFNγ in the colons. Antimicrobial-cleared mice transplanted with fecal samples from EBV DNA-exacerbated arthritic mice showed a higher incidence and enhanced severity of RA compared to those transplanted with fecal samples from water or collagen-treated mice. IMPORTANCE Epstein-Barr virus (EBV) DNA alters the composition and diversity of the gut microbiota in a rheumatoid arthritis (RA) mouse model. These induced changes are associated with enhanced severity of symptoms. This better understanding of the various factors involved in the development of RA will possibly help in creating individualized treatments for RA patients including target mediators triggered by viral DNA. Given that a large swathe of the population harbors EBV, a significant proportion of subjects with arthritis may benefit from possible approaches that target EBV or mediators triggered by this virus. Copyright © 2023 Fadlallah et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license
Theoretical Guarantees of Contrastive Learning in a Novel Explainable AI Method and a Deep Fairness Evaluation Framework
Get PDFGiven the social implications of autonomous systems in high-stake areas, recent years have witnessed an outpouring of research on designing explainable and fair AI models. In this work, we consider the intersection of contrastive learning with explainable AI and fairness evaluation schemes. Current methods that provide contrastive explainability do not simultaneously satisfy model-agnosticism, immutability, semi-immutability, and attainability constraints. In the fairness framework, existing metrics rely on statistical and causal tools that do not cover all bias cases and do not leverage advances in contrastive learning.
To this end, we present CEnt, a Contrastive Entropy-based explanation method, to locally contrast the prediction of any classifier. CEnt generates contrastive examples and visual contrasts that achieve better proximity rates than existing methods without compromising latency, feasibility, and attainability.
We utilize contrastive sets to devise a novel individual fairness evaluation technique that respects attainability and plausibility by relying on a manifold-like distance metric. Inspired by counterfactual ExAI, we suggest three metrics to evaluate the faithfulness of our metric and we study its interconnection with attainability and plausibility. We demonstrate the effectiveness of our method at detecting bias cases missed by other metrics that do not always satisfy faithfulness requirements.
Furthermore, we extend our fairness metric to textual settings by developing a local method to detect bias cases in textual settings with little reliance on existing ontologies. Our evaluation method computes the statistical mutual information and the geometrical inter-dependency with the sensitive information embedding to evaluate the fairness of a classifier. Likewise, we extend contrastive faithfulness guarantees to natural language by relying on transformers' encodings.
Lastly, we devise a novel mitigation strategy that operates in the latent space by encouraging a classifier to have the same outcome when the latent representation is perturbed with a sensitive direction. Our strategy is effective at diluting, even removing, bias in classifiers without compromising performance.
Our work motivates follow-on research in the fields of contrastive explainable AI, bias detection, and mitigation in deep networks. Generative models can be employed to improve the privacy guarantees of our techniques and enhance the quality and plausibility of the generated contrastive examples
A Quality improvement initiative to reduce central line-associated bloodstream infections in a neonatal intensive care unit in a low-and-middle-income country
Get PDFBackground Premature and sick neonates in the neonatal intensive care unit (NICU) are in need of central lines placing them at high risk of contracting a central line-associated bloodstream infection (CLABSI). CLABSI extends length of stay to 10-14 days post negative cultures and increases morbidity, use of multiple antibiotics, mortality and hospital cost. To reduce CLABSI rate at the American University of Beirut Medical Center NICU, the National Collaborative Perinatal Neonatal Network developed a quality improvement project to reduce CLABSI rate by 50% over a 1-year period and to sustain reduced CLABSI rate. Methods Central line insertion and maintenance bundles were implemented for all infants admitted to the NICU necessitating central lines placement. Bundles included hand washing, wearing protective material and sterile drapes during central lines insertion and maintenance. Results CLABSI rate decreased by 76% from 4.82 (6 infections; 1244 catheter days) to 1.09 (2 infection; 1830 catheter days) per 1000 CL days after 1 year. Following the bundles' success in reducing CLABSI rate, they were incorporated permanently to NICU standard procedure and bundle checklists were added to the medical sheets. CLABSI rate was maintained at 1.15 per 1000 CL days during the second year. It then decreased to 0.66 per 1000 CL days in the third year before reaching zero in the fourth year. In total, zero CLABSI rate was sustained for 23 consecutive months. Conclusion Reducing CLABSI rate is necessary to improving newborn quality of care and outcome. Our bundles were successful in drastically reducing and sustaining a low CLABSI rate. It was even successful in achieving a zero CLABSI unit for 2 years. © 2023 BMJ Publishing Group. All rights reserved
Fructose intake and its association with relative telomere length: an exploratory study among healthy Lebanese adults
Get PDFIntroduction: Shorter relative telomere length (RTL) has been associated with increased incidence of morbidity. Although still disputed, available evidence suggests that dietary factors, including sugar-sweetened beverages (SSB) may be linked with shorter RTL. It was argued that the link between SSB and RTL may be explained by the sugar content of these beverages, and specifically fructose given its impact on oxidative stress and the inflammatory response. However, none of the existing studies have examined the specific link between fructose intake and RTL. This exploratory study aimed at (1) assessing the intake of dietary fructose (total, added and natural) in Lebanese healthy adults and (2) examining dietary fructose as a predictor of short telomere length. Methods: Following a cross-sectional design (n = 282), anthropometric and biochemical data were collected. RTL was assessed by utilizing real-time polymerase chain reaction (RT-qPCR) to amplify both telomere and single-copy gene segments. Dietary intake was evaluated using a culture-specific food frequency questionnaire (FFQ). Intakes of added fructose, naturally-occurring fructose, and total fructose were estimated. Results: Mean intakes of added and natural fructose were of 39.03 ± 34.12 and 12.28 ± 8.59 g/day, respectively, representing 4.80 ± 3.56 and 1.78 ± 1.41% of total energy intake (EI). Mean total fructose intake was of 51.31 ± 35.55 g/day, contributing 6.58 ± 3.71% EI. Higher intakes of total and added fructose were significantly associated with shorter RTL 2nd RTL tertile as compared to the 3rd RTL tertile; relative risk ratio (RRR) = 3.10 [95% confidence interval (CI): 1.38, 6.94] and RRR = 2.33 (95% CI: 1.02, 5.36), respectively after adjustment for confounders identified using a directed acyclic graph (DAG). Conclusion: In conclusion, although we could not observe a dose-dependent relation between fructose intakes and RTL shortening and although the study is limited by its small sample size, the findings suggest that total and added dietary fructose intakes may be associated with shorter RTL. Larger studies, of longitudinal nature, are needed to further confirm the study findings. Copyright © 2023 Messerlian, Zgheib, Chokor, Nasrallah, Tamim and Nasreddine
Imaging findings of the injured in the massive Beirut blast
Get PDFPurpose: (1) Describe imaging utilization and findings within two weeks of the 2020 Beirut blast according to the mechanism of injury, (2) determine the appropriate imaging modality per organ/system, and (3) describe changes in the workflow of a radiology department to deal with massive crises. Materials and methods: Two hundred sixty patients presented to the largest emergency department in Beirut and underwent imaging within 2 weeks of the blast. In this retrospective study, patients were divided into early (1) and late (2) imaging groups. Patients’ demographic, outcome, type and time of imaging studies, body parts imaged, and mechanism and types of injuries were documented. Results: Two hundred five patients in group 1 underwent 502 and 55 patients in group 2 underwent 145 imaging studies. Tertiary blast injuries from direct impact and falling objects were the most common type of injuries followed by secondary (shrapnel) injuries. Both types of injuries affected mostly the head and neck and upper extremities. Plain radiographs were adequate for the extremities and CT for the head and neck. A regularly updated and practiced emergency plan is essential to mobilize staff and equipment and efficiently deliver radiology services during crises. Conclusion: Because the powerful Beirut blast occurred at the port located in the periphery of the city, most injuries seen on imaging were of the upper extremities and head and neck caused by the severe blast wind or penetrating shrapnel and resulted from people using their arms to protect their heads and bodies from direct impact and falling objects. © 2023, The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER)
Diet Quality Associated with Risk of Non-communicable Diseases and Nutrient Inadequacy among Female University Students using the Global Diet Quality Score
Get PDFBackground: Lebanon has been facing an increasing burden of non-communicable diseases (NCDs). Poor diet quality is a major driver of NCDs. The Global Diet Quality Score (GDQS) is a global measure of diet quality that is designed to be sensitive to diet-related outcomes associated with NCDs and nutrient inadequacy.
Objectives: This study aims to assess the diet quality of Lebanese female students at the American University of Beirut using the GDQS, determine the food groups that are driving a low GDQS score, explore drivers of consumption of these food groups, and assess changes in diet quality (GDQS) and food groups consumption that occurred over time.
Methods: This study was implemented in 2 phases. Phase 1 was a cross-sectional survey conducted among female students at the American University of Beirut (AUB). Three hundred Eighty-Four female students at AUB aged between 18-24 years were recruited. The sample size was determined using the World Health Organization (WHO) sample size calculator. Diet quality was assessed using the GDQS App, which is an electronic data collection tool developed by Intake to provide a standard, easy-to-use, low-cost, and time-relevant method for collecting data. A multi-component questionnaire which includes sociodemographic, lifestyle factors and drivers of consumption as well as self- reported anthropometric measurements was also collected from participants using face-to-face interviews.
Phase 2 was a secondary analysis of dietary intake data stemming from the national nutrition survey carried out in Lebanon between 2008 and 2009. Data pertinent to Lebanese female adults aged 18-24 years were analyzed to determine the diet quality (GDQS) and investigate the changes in diet quality and food groups consumption overtime.
The Statistical Package for the Social Sciences (SPSS; version 25) was used for all computations.
Results: In 2022, the mean total GDQS, GDQS+ and GDQS- scores of Lebanese AUB female students were 16.1±4.8, 7.0±3.7, and 9.1±2.9, respectively. Only 8.3% of the participants had a high GDQS score suggesting low risk of disease outcomes, whereas 48.4% had a moderate GDQS score suggesting moderate risk and 43.2% had a low GDQS score suggesting high risk for NCDs. Living at parental home, living in rural areas and high-intensity physical activity were associated with higher GDQS scores compared to living at student residence, living in urban areas and low and moderate-intensity physical activity. Low consumption of other fruits (fruits other than deep orange and citrus fruits), dark green leafy vegetables, legumes, deep orange tubers, nuts and seeds, whole grains, fish, and low-fat dairy and high consumption of processed meat, refined grains, sweets, sugar sweetened beverages, juice, white root tubers and purchased deep fried foods were shown as determinants of low GDQS score. Of the factors influencing consumption of the food groups taste was mostly reported as a predominant factor followed by past eating habits, availability, and cost. Compared to 2008/2009, the consumption of citrus fruits, dark green leafy vegetables and sugar sweetened beverages were lower in 2022 whereas the consumption of dairy, liquid oils, juice, cruciferous vegetables, poultry, white roots tubers and deep-fried foods were higher in 2022.
Conclusion: The study showed that in 2022, the majority of young Lebanese female AUB students have a low and moderate GDQS score suggesting high risk of NCDs. Low consumption of fruits, vegetables, legumes, deep orange tubers, nuts and seeds, whole grains, fish, low fat dairy and eggs and high consumption of processed meat, refined grains, sweets, sugar sweetened beverages, juice, white root tubers and purchased deep fried foods were major contributors to low GDQS score. This study also identified taste as most significant driver of consumption followed by past eating habits, availability and cost and showed that the diet quality among young Lebanese female adults has worsened over time. Interventions strategies to address such targeted poor dietary habits are needed to promote adherence of university students to healthy diets for mitigating the increase in NCDs in the country
Entrepreneurship and Peacebuilding: A Review and Synthesis
Get PDFEntrepreneurship is the dominant form of enterprise in conflict-affected settings, yet little is known about the role of entrepreneurship in peacebuilding. In response, this article undertakes a review of entrepreneurship in conflict-affected regions to integrate research from business and management with research from political science, international relations, and parallel domains. Three views of entrepreneurship emerge—the destructive view, economic view, and social cohesion view—showing how entrepreneurship can concurrently create conflict but also potentially generate peace. The article identifies new avenues for pro-peace entrepreneurship: namely, through personal transformation, social contributions, inclusive interactions, conflict trigger removal, intergroup policy persuasion, and acting as legal champions. This article also discusses several pathways forward for business-for-peace research alongside additional implications for the deployment of business-based support programs in conflict settings. © The Author(s) 2022
A comprehensive analysis of guided-wave propagation in 3D-printed PLA plates with different infill densities – Experimental study
Get PDFThanks to its many advantages, additive manufacturing (AM) is witnessing a gigantic shift from small applications to the production of complex industrial components, including safety–critical applications like aerospace and civil construction. This arises the need to develop accurate and robust technologies for evaluating and monitoring the structural integrity of AM components. The objective of this study is to comprehend how ultrasonic guided waves (GWs) propagate in 3D-printed poly(lactic acid) (PLA) plates of different infill densities. The experimental investigation involves five intact PLA plates printed with infill densities ranging from 20 to 100% at a step of 20%. A scanning laser Doppler vibrometer was used to visualize GW propagation by performing full-wavefield area-scans. Spatial-time, frequency-wavenumber, and wavenumber-wavenumber analyses were performed to scrutinize the available GW modes and their slowness profiles within the anisotropic structure. In addition, the tuning of the fundamental Lamb-wave (LW) modes at different excitation frequencies was examined, and the amplitude attenuation of the generally most pronounced mode (A0 mode) was investigated for different infill densities at an excitation of 50 kHz. A reference methodology is presented to experimentally identify more than five propagating modes in the frequency-wavenumber domain then obtain their phase-velocity dispersion curves. Significant variations are observed in the dispersion characteristics when lowering the infill density leading to the appearance of more modes at lower cutoff frequencies and drops in both the group and phase velocities in most of the cases. A complex behavior of the guided waves was observed in the dispersion curves of the 20%-infill plate, with possible mode interruptions/disturbance at an excitation frequency beyond 70 kHz. The appearance of shear-horizontal modes is noticed/strengthened at oblique propagation directions which may be attributed to mode conversion of the LW modes after obliquely interacting with the internal structure of the plates. Though high wave attenuation is a characteristic of the used polymer material, this attenuation is further increased at lower infill densities. The tuning behavior of the fundamental LW modes is also shown to be significantly affected by the infill density. The presented results can serve as reference propagation and dispersion characteristics for researchers working on similar materials and geometries. Such knowledge and understanding can be particularly useful for GW-based structural healthy monitoring of AM structures. © 2023 The Author
Pharmacotherapy of obesity: an update on the available medications and drugs under investigation
Get PDFObesity is an epidemic and a public health threat. Medical weight management remains one of the options for the treatment of excess weight and recent advances have revolutionized how we treat, and more importantly how we will be treating obesity in the near future. Metreleptin and Setmelanotide are currently indicated for rare obesity syndromes, and 5 other medications (orlistat, phentermine/topiramate, naltrexone/bupropion, liraglutide, semaglutide) are approved for non-syndromic obesity. Tirzepatide is about to be approved, and other drugs, with exciting novel mechanisms of action primarily based on incretins, are currently being investigated in different phases of clinical trials. The majority of these compounds act centrally, to reduce appetite and increase satiety, and secondarily, in the gastrointestinal tract to slow gastric emptying. All anti-obesity medications improve weight and metabolic parameters, with variable potency and effects depending on the specific drug. The currently available data do not support a reduction in hard cardiovascular outcomes, but it is almost certain that such data are forthcoming in the very near future. The choice of the anti-obesity medication needs to take into consideration the patient's clinical and biochemical profile, co-morbidities, and drug contra-indications, as well as expected degree of weight loss and improvements in cardio-renal and metabolic risk. It also remains to be seen whether precision medicine may offer personalized solutions to individuals with obesity, and whether it may represent the future of medical weight management along with the development of novel, very potent, anti-obesity medications currently in the pipeline. Funding: None. © 2023 The Author
An investment-based explanation of currency excess returns
Get PDFThis paper offers an investment-based explanation for currency excess returns using fundamental macroeconomic drivers emanating from physical investment across countries. To obtain valid factors for our proposed production model, we draw on an international investment-based asset-pricing model where representative firms in two countries choose structure and equipment capital to maximize profits. We empirically test the model for the factors constructed by sorting currencies based on differences in gross fixed capital formation, and investment in equipment and structures. Our findings show that the investment risk factors are priced in the cross-section of currency excess returns. The prices of risk associated with investment are negative and significant. This indicates that the currencies of countries with a higher sensitivity to investment risk earn lower excess returns. Furthermore, we show that this investment effect is not systematically related to the forward premium effect. © 2023 Elsevier Lt