Saint Joseph University

Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including high energy physics, astrophysics and space science, medical physics and radiation protection. Over the past several years, major changes have been made to the toolkit in order to accommodate the needs of these user communities, and to efficiently exploit the growth of computing power made available by advances in technology. The adaptation of Geant4 to multithreading, advances in physics, detector modeling and visualization, extensions to the toolkit, including biasing and reverse Monte Carlo, and tools for physics and release validation are discussed here.

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics - from epidemiology, awareness, care and treatment to public health policies and leadership - that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD.

Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (approximately 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counseling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.

The frequencies of low-activity alleles of glucose-6-phosphate dehydrogenase in humans are highly correlated with the prevalence of malaria. These "deficiency" alleles are thought to provide reduced risk from infection by the Plasmodium parasite and are maintained at high frequency despite the hemopathologies that they cause. Haplotype analysis of "A-" and "Med" mutations at this locus indicates that they have evolved independently and have increased in frequency at a rate that is too rapid to be explained by random genetic drift. Statistical modeling indicates that the A- allele arose within the past 3840 to 11,760 years and the Med allele arose within the past 1600 to 6640 years. These results support the hypothesis that malaria has had a major impact on humans only since the introduction of agriculture within the past 10,000 years and provide a striking example of the signature of selection on the human genome.

BACKGROUND: Patients with homozygous familial hypercholesterolemia have markedly elevated cholesterol levels, which respond poorly to drug therapy, and a very high risk of premature cardiovascular disease. Inhibition of the microsomal triglyceride transfer protein may be effective in reducing cholesterol levels in these patients. METHODS: We conducted a dose-escalation study to examine the safety, tolerability, and effects on lipid levels of BMS-201038, an inhibitor of the microsomal triglyceride transfer protein, in six patients with homozygous familial hypercholesterolemia. All lipid-lowering therapies were suspended 4 weeks before treatment. The patients received BMS-201038 at four different doses (0.03, 0.1, 0.3, and 1.0 mg per kilogram of body weight per day), each for 4 weeks, and returned for a final visit after a 4-week drug washout period. Analysis of lipid levels, safety laboratory analyses, and magnetic resonance imaging of the liver for fat content were performed throughout the study. RESULTS: All patients tolerated titration to the highest dose, 1.0 mg per kilogram per day. Treatment at this dose decreased low-density lipoprotein (LDL) cholesterol levels by 50.9% and apolipoprotein B levels by 55.6% from baseline (P<0.001 for both comparisons). Kinetic studies showed a marked reduction in the production of apolipoprotein B. The most serious adverse events were elevation of liver aminotransferase levels and accumulation of hepatic fat, which at the highest dose ranged from less than 10% to more than 40%. CONCLUSIONS: Inhibition of the microsomal triglyceride transfer protein by BMS-201038 resulted in the reduction of LDL cholesterol levels in patients with homozygous familial hypercholesterolemia, owing to reduced production of apolipoprotein B. However, the therapy was associated with elevated liver aminotransferase levels and hepatic fat accumulation.

Specific staining of the extracellular matrix components is especially helpful in studying tissue remodeling, particularly in the case of connective tissue pathologies. As developed by Junqueira and colleagues in 1979, specific staining by Picrosirius red is one of the most important stains to study collagen networks in different tissues. Under polarized light, collagen bundles appear green, red or yellow, and are easily differentiated from the black background, thus allowing for quantitative morphometric analysis. As Junqueira and colleagues point out, many studies use color staining to differentiate collagen bundles and to specify collagen types, yet other studies report that polarized colors only reflect fiber thickness and packing. Using a simple histological example, our study illustrates the inability of Picrosirius red staining to differentiate collagen types, since the absorbed amount of polarized light by this dye strictly depends on the orientation of the collagen bundles.

BACKGROUND AND AIMS: Internet addiction (IA) could be a major concern in university medical students aiming to develop into health professionals. The implications of this addiction as well as its association with sleep, mood disorders and self-esteem can hinder their studies, impact their long-term career goals and have wide and detrimental consequences for society as a whole. The objectives of this study were to: 1) Assess potential IA in university medical students, as well as factors associated with it; 2) Assess the relationships between potential IA, insomnia, depression, anxiety, stress and self-esteem. METHODS: Our study was a cross-sectional questionnaire-based survey conducted among 600 students of three faculties: medicine, dentistry and pharmacy at Saint-Joseph University. Four validated and reliable questionnaires were used: the Young Internet Addiction Test, the Insomnia Severity Index, the Depression Anxiety Stress Scales (DASS 21), and the Rosenberg Self Esteem Scale (RSES). RESULTS: The average YIAT score was 30 ± 18.474; Potential IA prevalence rate was 16.8% (95% confidence interval: 13.81-19.79%) and it was significantly different between males and females (p-value = 0.003), with a higher prevalence in males (23.6% versus 13.9%). Significant correlations were found between potential IA and insomnia, stress, anxiety, depression and self-esteem (p-value < 0.001); ISI and DASS sub-scores were higher and self-esteem lower in students with potential IA. CONCLUSIONS: Identifying students with potential IA is important because this addiction often coexists with other psychological problems. Therefore, interventions should include not only IA management but also associated psychosocial stressors such as insomnia, anxiety, depression, stress, and self-esteem.

Ochratoxin A (OTA) is a mycotoxin produced by several species of Aspergillus and Penicillium fungi that structurally consists of a para-chlorophenolic group containing a dihydroisocoumarin moiety that is amide-linked to L-phenylalanine. OTA is detected worldwide in various food and feed sources. Studies show that this molecule can have several toxicological effects such as nephrotoxic, hepatotoxic, neurotoxic, teratogenic and immunotoxic. A role in the etiology of Balkan endemic nephropathy and its association to urinary tract tumors has been also proved. In this review, we will explore the general aspect of OTA: physico-chemical properties, toxicological profile, OTA producing fungi, contaminated food, regulation, legislation and analytical methods. Due to lack of sufficient information related to the molecular background, this paper will discuss in detail the recent advances in molecular biology of OTA biosynthesis, based on information and on new data about identification and characterization of ochratoxin biosynthetic genes in both Penicillium and Aspergillus species. This review will also cover the development of the molecular methods for the detection and quantification of OTA producing fungi in various foodstuffs.

The Internet of Things (IoT) is the ability to provide everyday devices with a way of identification and another way for communication with each other. The spectrum of IoT application domains is very large including smart homes, smart cities, wearables, e-health, etc. Consequently, tens and even hundreds of billions of devices will be connected. Such devices will have smart capabilities to collect, analyze and even make decisions without any human interaction. Security is a supreme requirement in such circumstances, and in particular authentication is of high interest given the damage that could happen from a malicious unauthenticated device in an IoT system. This paper gives a near complete and up-to-date view of the IoT authentication field. It provides a summary of a large range of authentication protocols proposed in the literature. Using a multi-criteria classification previously introduced in our work, it compares and evaluates the proposed authentication protocols, showing their strengths and weaknesses, which constitutes a fundamental first step for researchers and developers addressing this domain.

This Special Report presents a description of Geant4-DNA user applications dedicated to the simulation of track structures (TS) in liquid water and associated physical quantities (e.g., range, stopping power, mean free path…). These example applications are included in the Geant4 Monte Carlo toolkit and are available in open access. Each application is described and comparisons to recent international recommendations are shown (e.g., ICRU, MIRD), when available. The influence of physics models available in Geant4-DNA for the simulation of electron interactions in liquid water is discussed. Thanks to these applications, the authors show that the most recent sets of physics models available in Geant4-DNA (the so-called "option4" and "option 6" sets) enable more accurate simulation of stopping powers, dose point kernels, and W-values in liquid water, than the default set of models ("option 2") initially provided in Geant4-DNA. They also serve as reference applications for Geant4-DNA users interested in TS simulations.

OBJECTIVE: To estimate the minimum clinically important improvement (MCII) and patient acceptable symptom state (PASS) values for 4 generic outcomes in 5 rheumatic diseases and 7 countries. METHODS: We conducted a multinational (Australia, France, Italy, Lebanon, Morocco, Spain, and The Netherlands) 4-week cohort study involving 1,532 patients who were prescribed nonsteroidal antiinflammatory drugs for ankylosing spondylitis, chronic back pain, hand osteoarthritis, hip and/or knee osteoarthritis, or rheumatoid arthritis. The MCII and PASS values were estimated with the 75th percentile approach for 4 generic outcomes: pain, patient global assessment, functional disability, and physician global assessment, all normalized to a 0-100 score. RESULTS: For the whole sample, the estimated MCII values for absolute change at 4 weeks were -17 (95% confidence interval [95% CI] -18, -15) for pain; -15 (95% CI -16, -14) for patient global assessment; -12 (95% CI -13, -11) for functional disability assessment; and -14 (95% CI -15, -14) for physician global assessment. For the whole sample, the estimated PASS values were 42 (95% CI 40, 44) for pain; 43 (95% CI 41, 45) for patient global assessment; 43 (95% CI 41, 44) for functional disability assessment; and 39 (95% CI 37, 40) for physician global assessment. Estimates were consistent across diseases and countries (for subgroups ≥20 patients). CONCLUSION: This work allows for promoting the use of values of MCII (15 of 100 for absolute improvement, 20% for relative improvement) and PASS (40 of 100) in reporting the results of trials of any of the 5 involved rheumatic diseases with pain, patient global assessment, physical function, or physician global assessment used as outcome criteria.

Aims. The Euclid space telescope will measure the shapes and redshifts of galaxies to reconstruct the expansion history of the Universe and the growth of cosmic structures. The estimation of the expected performance of the experiment, in terms of predicted constraints on cosmological parameters, has so far relied on various individual methodologies and numerical implementations, which were developed for different observational probes and for the combination thereof. In this paper we present validated forecasts, which combine both theoretical and observational ingredients for different cosmological probes. This work is presented to provide the community with reliable numerical codes and methods for Euclid cosmological forecasts. Methods. We describe in detail the methods adopted for Fisher matrix forecasts, which were applied to galaxy clustering, weak lensing, and the combination thereof. We estimated the required accuracy for Euclid forecasts and outline a methodology for their development. We then compare and improve different numerical implementations, reaching uncertainties on the errors of cosmological parameters that are less than the required precision in all cases. Furthermore, we provide details on the validated implementations, some of which are made publicly available, in different programming languages, together with a reference training-set of input and output matrices for a set of specific models. These can be used by the reader to validate their own implementations if required. Results. We present new cosmological forecasts for Euclid . We find that results depend on the specific cosmological model and remaining freedom in each setting, for example flat or non-flat spatial cosmologies, or different cuts at non-linear scales. The numerical implementations are now reliable for these settings. We present the results for an optimistic and a pessimistic choice for these types of settings. We demonstrate that the impact of cross-correlations is particularly relevant for models beyond a cosmological constant and may allow us to increase the dark energy figure of merit by at least a factor of three.

Hypovitaminosis D is associated with poor dietary intake and inadequate sunshine exposure. It is common worldwide, particularly in European elderly people. Information about vitamin D status in young adult populations from the Middle East is scarce. Furthermore, the relationship between hypovitaminosis D and some lifestyle factors such as style of clothing and dwelling location is not well defined. We assessed vitamin D intake and measured serum calcium, phosphorus, albumin, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, and urinary-free deoxypyridinoline (DPD) in 316 Lebanese volunteers (99 men and 217 women) aged 30-50 years; 156 were recruited from rural areas and 160 from urban areas. Fifty-one women from each area were veiled. The average daily vitamin D intake was 100.3 +/- 67.9 IU and was found to be higher in men compared with women, in urban subjects compared with rural ones and in nonveiled women compared with veiled ones. The mean level of 25(OH)D was 9.71 +/- 7.07 ng/ml. Hypovitaminosis D [25(OH)D < 12 ng/ml] affected 72.8% of our population. It was more common in women than in men (83.9% vs. 48.5%). Severe hypovitaminosis D [25(OH)D < 5 ng/ml] was observed in 30.7% of our subjects and was more prevalent in women (41.5%), particularly in the veiled ones (61.8%). 25(OH)D levels were the lowest in veiled women, and in women living in rural areas. Rural men had the highest 25(OH)D levels despite their very low vitamin D intake. In a multivariate model, inadequate vitamin D intake, urban dwelling, veil wearing, and high parity in women were independent predictors of hypovitaminosis D. 25(OH)D was related inversely to PTH and free DPD whereas osteocalcin achieved only a weak positive correlation with 25(OH)D. In the absence of information regarding time spent outdoors, our results show that hypovitaminosis D is common among young Lebanese people and is related mostly to low vitamin D intake. This should emphasize the need for more vitamin D in our population.

BACKGROUND: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke and other vascular events is not well known. In this follow-up to a report on 1-year outcomes from a registry of TIA clinics in 21 countries that enrolled 4789 patients with a TIA or minor ischemic stroke from 2009 through 2011, we examined the 5-year risk of stroke and vascular events. METHODS: We evaluated patients who had had a TIA or minor stroke within 7 days before enrollment in the registry. Among 61 sites that participated in the 1-year outcome study, we selected 42 sites that had follow-up data on more than 50% of their enrolled patients at 5 years. The primary outcome was a composite of stroke, acute coronary syndrome, or death from cardiovascular causes (whichever occurred first), with an emphasis on events that occurred in the second through fifth years. In calculating the cumulative incidence of the primary outcome and secondary outcomes (except death from any cause), we treated death as a competing risk. RESULTS: score for the risk of stroke (range, 0 to 7, with higher scores indicating greater risk) of 4 or more were each associated with an increased risk of subsequent stroke. CONCLUSIONS: In a follow-up to a 1-year study involving patients who had a TIA or minor stroke, the rate of cardiovascular events including stroke in a selected cohort was 6.4% in the first year and 6.4% in the second through fifth years. (Funded by AstraZeneca and others.).

Autosomal recessive mutations in proteasome subunit β 8 (PSMB8), which encodes the inducible proteasome subunit β5i, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes α7), PSMB4 (encodes β7), PSMB9 (encodes β1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production.

The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway.

We study the relationship between Bitcoin and commodities by assessing the ability of Bitcoin to act as a diversifier, hedge, or safe haven against daily movements in commodities in general, and energy commodities in particular. We focus on energy commodities because energy, in the form of electricity, is an essential input in the Bitcoin production. For the entire period, results show that Bitcoin is a strong hedge and a safe-haven against movements in both commodity indices. We further examine whether that ability is also present for non-energy commodities and our analysis show insignificant results when energy commodities are excluded from the general commodity index. We also account for the December 2013 Bitcoin price crash and our results reveal that Bitcoin hedge and safe-haven properties against commodities and energy commodities are only present in the pre-crash period, whereas in the post-crash period Bitcoin is no more than a diversifier. In addition to uncovering the time-varying role of Bitcoin, we highlight the dissimilarity in the dynamic correlations between the extreme downward and extreme upward movements.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

The crisis in Syria has resulted in vast numbers of refugees seeking asylum in Syria's neighbouring countries as well as in Europe. Refugees are at considerable risk of developing common mental disorders, including depression, anxiety, and posttraumatic stress disorder (PTSD). Most refugees do not have access to mental health services for these problems because of multiple barriers in national and refugee specific health systems, including limited availability of mental health professionals. To counter some of challenges arising from limited mental health system capacity the World Health Organization (WHO) has developed a range of scalable psychological interventions aimed at reducing psychological distress and improving functioning in people living in communities affected by adversity. These interventions, including Problem Management Plus (PM+) and its variants, are intended to be delivered through individual or group face-to-face or smartphone formats by lay, non-professional people who have not received specialized mental health training, We provide an evidence-based rationale for the use of the scalable PM+ oriented programmes being adapted for Syrian refugees and provide information on the newly launched STRENGTHS programme for adapting, testing and scaling up of PM+ in various modalities in both neighbouring and European countries hosting Syrian refugees.

Two decades following their description, the significance of Modic vertebral endplate and marrow changes remains a matter of debate. These changes are closely related to the normal degenerative process affecting the lumbar spine, and their prevalence increases with age. However, the exact pathogenesis underlying these changes and their relation to segmental instability of the lumbar spine and to low back pain remain unclear. In this paper, we review the literature relevant to this topic and discuss the currently available evidence regarding the pathologic and clinical significance of Modic changes.