In December 2019, the coronavirus disease-19 (COVID-19) outbreak emerged in Wuhan, China. On March 11, 2020, the WHO (World Health Organization) officially declared it a pandemic. Reports indicated that the associated mortality of the infection is quite higher in the elderly, patients with specific comorbidities (like diabetes mellitus), and generally the ones with a compromised immune system. A cohort study of 452 patients with laboratory-confirmed COVID-19 in Wuhan, China, reported a dysregulated immune response in these patients. As a result of this suppressed immune response, the increase of neutrophil to lymphocyte ratio (NLR), T lymphopenia, and decrease of CD4+ T cells was considered as common laboratory findings, especially in severe cases. On the other hand, there is also clear evidence of T cell exhaustion in severely ill patients. So, the immune system seems to play an important role in disease prognosis and pathogenesis. This study aims to review the evidence on the immune response dysregulation in COVID-19 infection and the potential role of immunoregulatory treatments such as immune checkpoint inhibitors, interferons, and CD200 inhibitors in altering disease prognosis, especially in critically ill patients.

A document by Adrian Gaspar. Click on the document to view its contents.

Anopheles hinesorum is a mosquito species with variable host preference. Throughout New Guinea and northern Australia, An. hinesorum feeds on humans (it is opportunistically anthropophagic) while in the southwest Pacific’s Solomon Archipelago, the species is abundant but has rarely been found biting humans (it is exclusively zoophagic in most populations). There are at least two divergent zoophagic (non-human biting) mitochondrial lineages of An. hinesorum in the Solomon Archipelago. Since zoophagy is a derived (non-ancestral) trait in this species, this leads to the question: has zoophagy evolved independently in these divergent lineages? Or conversely: has nuclear gene flow or connectivity resulted in the transfer of zoophagy? Although we cannot conclusively answer this, we find close nuclear relationships between Solomon Archipelago populations indicating that recent nuclear gene flow has occurred between zoophagic populations from the divergent mitochondrial lineages. Recent work on isolated islands of the Western Province (Solomon Archipelago) has also revealed an anomalous, anthropophagic island population of An. hinesorum. We find a common shared mitochondrial haplotype between this Solomon Island population and another anthropophagic population from New Guinea. This finding suggests that there has been recent migration from New Guinea into the only known anthropophagic population from the Solomon Islands. Although currently localized to a few islands in the Western Province of the Solomon Archipelago, if anthropophagy presents a selective advantage, we may see An. hinesorum emerge as a new malaria vector in a region that is now working on malaria elimination.

The relation between intellect and revelation is one of the critical questions of theology, with roots extending back to both Muslim, Christian, and Jews. It has been mentioned that "The concept of ʿaql, "intellect," is one of the most controversial in the history of Muslim thought. Also, it is well known that in Islamic history, there have been different approaches toward understanding religious texts and the correlation between intellect and revelation. Understanding Ṣadrā 's conception of the relation between intellect and revelation and the way in which he explains their interaction is the concern of this essay.

A document by SeyedAmirHossein Asghari. Click on the document to view its contents.

Since 2000s, most of West-African countries and particularly Benin have experienced an increased frequency of extreme flood events. In this study we focus on the case of the Ouémé-river basin in Benin for the period 2008-2010. To investigate on how to early warn flood events in this basin, the coupled atmosphere-hydrology model system WRF-Hydro is selected. Such a coupled model allows to explore the contribution of atmospheric components into the flood event, and its ability to simulate and predict accurate streamflow. The potential of WRF-Hydro in correctly simulating streamflow in the Ouémé-river basin is assessed by forcing the model with operational analysis datasets from the ECMWF. Atmospheric and land surface processes are resolved at a spatial resolution of 5km. The additional surface and subsurface water flow routing is computed at a resolution 1:10. Key parameters of the hydrological module of WRF-Hydro are calibrated offline, and tested online with the coupled WRF-Hydro. The uncertainty of atmospheric modeling on coupled results is assessed with the stochastic kinetic-energy backscatter scheme (SKEBS). WRF-Hydro is able to simulate the discharge in Ouémé river on offline and fully-coupled modes with a Kling-Gupta Efficiency (KGE) around 0.70 and 076 respectively. In fully-coupled mode the model captures the flood event that occurred in 2010. A stochastic perturbation ensemble of 10 members for three rain seasons shows that the coupled model performance in terms of KGE is from 0.14 to 0.79. This ability in realistically reproducing observed discharge in the Ouémé-river basin demonstrates the potential of the coupled WRF-Hydro modeling system for future flood forecasting applications.

Recent work attempted to demonstrate the global best minimum in complex problems. This paper proposes a population and direct-based swarm optimization algorithm called as HPO algorithm. The HPO algorithm is designed by inspired of personal behaviorand demonstrated in the 30 and 100 dimensionson benchmark functions. The model have four concepts: what you want?, what you have?, what others have?, what is happened?. These concepts take into account the balancing between exploration and exploitation operator and demonstrate its efficiency, robustness and stability insynthetic and real problems.In experiment, we consider 15 benchmark functions include unimodal and multimodal characteristic of functions.For compression, our algorithm and some well-known algorithms with 30 times run and applied on the benchmark functions and compared with statistical value and Wilcoxon signed-rank test. As a consequence, the performance and convenient ofour work aredemonstratedbetter than the others. 1-INTRUDOCTION Many real-world applications include the complexity problem that should be optimize and then applied on the real work. The purpose of optimization is the minimization or maximization of fitness function for real problem such as energy consumption, designing, routing, transportation et al. The performance, efficiency and sustainability of optimization algorithms are important in solving complex problem. In many case, optimization problem is highly complex and nonlinear function, whom scientist attempts to solve the problem by using popular methods of soft computing. In recent years, metaheuristic algorithms have been used and applied on the real problems in engineering field [1-5]. The advantage of metaheuristic algorithm rather than the deterministic algorithm is scape of trap from local minimum state. There are two popular methodology such as Evolutionary Algorithms (EA) and Swarm Intelligence (SI), which have new landscape for the complex problem in the metaheuristics optimization algorithm. The advantages of them are the power of based-population solution and providea new solutionby considering the balance of exploration and exploitation.Thepoint of view of efficiency and balancing of them should be se the best solution by escaping from many local minimum.By inspired of Darwin's theory the Evolutionary Optimization techniques are presented and used in real problems. The principle of mechanism includes selection, mutation and crossover operation. Genetic algorithm is one of EA which is popular in metaheuristic algorithm (GA) and have rigorous mathematical analyses [6-7].And some works with based on this paradigm is tabu search [9], simulated annealing [10], forest optimization algorithm [11], biogeography-based optimizer (BBO) [12], Evolutionary Programing (EP) [13], Evolution Strategy (ES) [14].Beni and Wang in 1993 presented concept of swarm intelligence, which include simulation of behavior of living creature [15]. Scientist attempt to find local rule between creatures and then convert to aalgorithm for using in soft computing.The other algorithmsare computational method, which based on directed best agent. The framework of them are repeatedlytrying to improve a nomineesolution in relation toa given measure of quality fitness.Examples of SI-based approaches are particle swarm optimization [16], Glowworm algorithm [17] Intelligent water drops [18], Cat

For 50 years, researchers have considered how time-dependent environmental effects can be included in cycle-dependent corrosion fatigue (CF) crack growth rate (CGR) models. Common assumptions are that cycle- and time-dependent contributions are separable, operate in parallel, are non-interacting and that total environmental CGR can be obtained by linear summation of cycle-dependent fatigue and time-dependent (SCC) CGRs. However, considered here are data and analyses that show that environmental CGRs may be greater than predicted by superposition models. A phenomenological model is developed to quantify the effect of crack-tip strain-rate due to fatigue stress-cycles on electrochemical activity at a crack tip and thereby synergistically increase crack growth rates by a cyclic-stress corrosion-cracking (C-SCC) mechanism.

Aim Oral flucloxacillin may be co-administered with probenecid to increase flucloxacillin concentrations and increase attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets. The aims of this study were to describe outcomes of patients treated with oral flucloxacillin plus probenecid as follow-on therapy from initial intravenous treatment, and to identify optimal dosing regimens when treating infections caused by susceptible Gram-positive organisms. Methods We performed a prospective observational study of adults treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly (with food) for proven or probable staphylococcal infections. We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, in order to estimate probability of PK-PD target attainment (fT>MIC), and used Monte Carlo simulation to explore optimal dosing regimens. Results The 45 patients (73% male) had a median (range) age of 49 years (20 – 74), weight of 90 kg (59 – 167), fat free mass (Janmahasatian) of 65 kg (38 – 89) and eGFR (CKD-EPI) of 89 mL/min/1.73m2 (41 – 124). The most common infections were osteomyelitis (n=18, 40%) and septic arthritis (n=12, 27%). Forty patients (89%) were cured 30 days after completion of therapy. 10 (22%) experienced nausea which did not require treatment alternation. Free flucloxacillin clearance depended on allometrically-scaled fat free mass, and increased by 1% for each unit increase in eGFR. Conclusion Oral flucloxacillin and probenecid was well-tolerated and efficacious. Patients with higher fat free mass and eGFR may require four times daily dosing and/or therapeutic drug monitoring to ensure PK-PD target attainment.

The concept of cell type is key for modeling biology. Recent technological advances are prompting us to rethink what we understand by cell type and how we classify them. There is currently no consensus for a definition of cell type, which makes it hard to integrate knowledge across life sciences. We propose here that a cell type should represent any class of cell that (1) is explicitly defined; (2) is identifiable within a taxon; and (3) is theoretically useful. We also present four classes of cell types: sensu stricto cell types, archetypes, infratypes, and technotypes. They respectively specify cell type concepts applied to a single species, multiple species, populations below the species level, and particular experiments. The flexible and rigorous framework we propose can base annotation of single-cell omics datasets, and reconcile knowledge about cells across all different domains of science.

The transcriptional regulators of arsenic-induced gene expression remain largely unknown; however, arsenic exposure rapidly depletes cellular glutathione levels increasing demand for thiol compounds from the sulfur assimilation pathway. Thus, sulfur assimilation is tightly linked with arsenic detoxification. To explore the hypothesis that the key transcriptional regulator of sulfur assimilation, SLIM1, is involved in arsenic-induced gene expression, we evaluated the response of slim1 mutants to arsenic treatments. We found that slim1 mutants were sensitive to arsenic in root growth assays. Furthermore, arsenic treatment caused high levels of oxidative stress in the slim1 mutants, and slim1 mutants were impaired in both thiol and sulfate accumulation. We also found enhanced arsenic accumulation in the roots of slim1 mutants. Furthermore, microarray analyses identified genes from a highly co-regulated gene cluster (the O-acetylserine gene cluster), as being significantly upregulated in the slim1-1 mutant background in response to arsenic exposure. The present study identified the SLIM1 transcription factor as an important component in arsenic-induced gene expression and arsenic tolerance. Our results suggest that the severe arsenic sensitivity of the slim1 mutants is a result of both altered redox status as well as mis-regulation of key genes.

Preeclampsia causes various presentations by increased endothelial permeability and microvascular damages. Maternal ascites related severe preeclampsia is generally explained by increased capillary permeability due to endothelial cell dysfunction and reduced intravascular oncotic pressure. Here we report a patient with postpartum massive ascites associated with preeclampsia.

The association of Daunorubicin and Steven-Johnson Syndrome (SJS) has not been well-established. In this report, we describe a fatal case of a 2 years old boy with acute leukemia who developed Steven-Johnson Syndrome owing to Daunorubicin. Clinicians should consider the possible association of Daunorubicin with SJS.

Aim: To investigate the effect of primary (pSS) on skeletal muscle architecture and strength. Method: 19 pSS patients and 19 age, body mass index and sex matched healthy controls were included. Symptoms of subject’s were assessed with ESSPRI (The EULAR Sjogren’s Syndrome Patient Reported Index), anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), fatigue with Multidimensional Assessment of Fatigue scale (MAF), functionality with HAQ. Ultrasonographic evaluations were performed with a multifrequency linear probe from quadriceps femoralis, gastrocnemius and soleus of the bilateral lower extremity. Muscle thickness, pennation angle and fascicle length were measured. Isokinetic knee muscle strength tests were performed at 60 and 180°/s. Isokinetic ankle muscle strenght tests were performed at 30 and 120°/s. Result: In pSS group, mean ESSPRI was 7.70±1.17. Scores of depression (10.05 ± 3.09 vs 4.47 ± 2.29 p<0.0001), anxiety (8.26 ± 4.28 vs 3.79 ± 2.42 p<0.0001), functionality (0.94 ± 0.78 vs 0.22 ± 0.26, p<0.0001), fatigue (37.69 ± 5.47 vs 17.69 ± 5.26, p<0.0001) were significantly higher in patients with pSS than healthy controls. In dominant leg, pennation angle of vastus medialis was significantly greater in healthy controls than in patients with pSS (p=0.049). The other ultrasonographic measurements were similar between the two groups. Peak torque/body weight of knee and ankle muscle were found to be similar. Conclusion: Although patients with pSS have some minor structural changes on ultrasonographic evaluation, isokinetic muscle strength were similar between groups. In patients with pSS, disease activity and fatigue level were negatively correlated with isokinetic muscle strength measurement.

In this paper, we consider two dimensional inverse problem for a fractional diffusion equation. The inverse problem is reduced to the equivalent integral equation. For solving this equation the contracted mapping principle is applied. The local existence and global uniqueness results are proven. Also the stability estimate is obtained.

L’ ANALYTIC HIERARCHY PROCESS, nasce dal matematico Thomas Saaty, negli anni Settanta per organizzare ed analizzare decisioni complesse.La metodologia consente di confrontare più alternative in relazione ad una pluralità di criteri, di tipo quantitativo o qualitativo, e ricavare una valutazione globale per ciascuna di esse. Ciò permette di:ordinare le alternative secondo un asse di preferenza;selezionare l'alternativa globalmente migliore;assegnare le alternative a sottoinsiemi predefiniti.I punti di forza principali sono il confronto a coppie delle alternative decisionali e la separazione fra importanza del criterio e impatto sulla decisione.Il metodo è basato su una  scala di comparazione, suddivisa in nove livelli, la cui base teorica è data dal teorema di Perron-Frobenius.Riportiamo a seguire la documentazione relativa alla realizzazione del corridoio Tirreno -Brennero sul quale è stato applicato il metodo AHP, relativamente al confronto dei diversi corridoi stradali e la successiva scelta di quello a minimo impatto ambientale.

Despite the advent of a vaccine, broadening the arsenal of drugs effective in the treatment and prevention of COVID-19 disease remains critical in the global effort to control the SARSCoV2 pandemic. Opioids and opioid antagonists may have a role in treating and in the prevention of this disease based on a number of observations: an unexpectedly low incidence of COVID-19 has been observed in patients treated for opioid dependency with long acting opioid drugs such as methadone; opioids bind to the ACE2 transmembrane protein, a molecule that is widely considered to be main host cell receptor for SARS CoV2 cell entry; opioids have systemic immunomodulatory effects which may influence the response to the virus; studies aimed at repurposing drugs for treatment of COVID-19 have identified that opioids have therapeutic potential and finally there are ongoing trials of some of these drugs. The interaction of long acting opioids or opioid antagonists with the ACE2 receptor and the possible effects on TLR4 function in SARS CoV2 infection should be given serious consideration when developing effective therapies. Note an updated version of this preprint is under review with the British Journal of Anaesthesia

Coronavirus disease 2019 (COVID-19) vaccine BNT162b2 received approval and within the first few days of public vaccination several severe anaphylaxis cases occurred. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and concerns raised for severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerges. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of population immunity. Health care practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognise and treat anaphylaxis properly with the ability to administer adrenaline. A mandatory observation period after vaccine administration of at least 15 minutes for all individuals should be followed. The current guidelines, which exclude patients with severe allergies from vaccination with BNT162b2, should be re-evaluated after more information and experience with the new vaccine develops.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019 is rapidly spreading worldwide. Scientists are searching to find an effective treatment for coronavirus disease 2019 (COVID-19). Several antiviral drugs are currently undergoing clinical trial studies to evaluate their safety and efficacy in the treatment of COVID-19. SARS-CoV-2 is a positive-sense single-stranded RNA virus. Previous studies showed the efficacy of anti-RNA virus, single strand RNA inhibiting antisense RNAs (asRNAs), on silencing of virus replication, in vitro. To transfer the anti-SARS-CoV-2 asRNAs to human respiratory epithelium, exosomes can be suggested as a promising candidate. Mesenchymal stem cells (MSCs) secret exosomes and they can be loaded by anti-RNA virus asRNAs. MSCs-secreted exosomes as a nano-cargo of anti-SARS-CoV-2 asRNAs have other therapeutic potentials such as immunomodulatory effects of their cytokine contents, affinity to respiratory epithelial attachment, anti-fibrotic activity in lung, non-toxicity for normal cells, and do not trigger an immune response. Inhalation of anti-SARS-CoV-2 asRNAs may stop SARS-CoV-2 replication. Producing a specific anti-SARS-CoV-2 asRNAs by targeting the genome of virus and their delivery by MSCs exosomes is suggested and discussed. This approach potentially sheds light on gene therapy of the other human lung diseases via inhalational delivery using exosomes in future.

Aims: This study to evaluate the efficacy and complications of Argon Plasma Coagulation (APC) therapy to treat post-RYGB weight regain compared to a sham control group. Methods: 41 Patients with minimum regain of 10 kg and minimal postoperative time of 36 months was randomized into two groups. Results: In the APC group (n=21), the mean initial weight 100.4 kg, and mean regained weight of 24.94 kg. In the Sham group (n=20), the mean initial weight of 103.65 kg, and mean regained weight of 25.18 kg. Only happened anastomosis stenosis after the first APC session. The comparative results between the APC versus the Sham were percentage recovered weight loss (63.95 x-2.65), weight loss in kg (15.02 x-0.57), percentage total weight loss (14.46 x-0.62), % excess weight loss (54.32 x-2.34), and BMI reduction (5.38 x-0.21), with a p<0.0001 for all the comparisons. There was a significant reduction in the APC group of HbA1c (5.66% to 4.96%) and triglycerides (153.20mg/dL to 132.20mg/dL). Conclusion: This study proves that APC outlet pouch reduction is much superior compared to sham in promoting weight loss for patients that presented weight regain after de RYGB.

Introduction: Currently, 30% of the world's population is overweight or obese. Roux-en-Y gastric bypass (BGYR) and vertical gastrectomy are the most commonly performed techniques in Brazil and worldwide. Objective: Conduct a meta-analysis of the results of using argon plasma coagulation (APC), suture (SUT), and surgery (SUR), to clarify the safety and efficacy of using argon plasma to other procedures. Methods: The quality of the evidence was classified as high, moderate, low, or very low, according to the risk of bias. The Variance (α2) and One-Way (ANOVA) test were applied, adopting the α level less than 0.05 with a statistically significant difference for the 95% CI. The value of R-sq (R2) was analyzed to discover the imprecision or heterogeneity of the analyzes. Results: A total of 34 studies were found, eight to APC, twenty to SUT, and six to SUR. For relapsed weight loss (RWL), the means for APC, SUT, and SUR were respectively 19.39 ± 10.94, 26.06 ± 16.71, and 17.05 ± 9.85, and for SR, the means were respectively 89.75 ± 16.75, 86.80 ± 11.44, and 76.00 ± 21.57. There was a small difference between the values of APC averages with SUT and SUR, both in relation to RWL and SR, with p>0.05, with a high association (R2 ≥ 50%). Conclusion: It was shown that the APC technique showed excellent results in terms of RWL and SR compared to the other techniques, with no statistically significant difference. Thus, the results of the APC strongly point to its potential use.

Objective: To determine maternal and neonatal morbidity associated with induction of labor at 39 weeks compared with expectant management through 42 weeks. Design: Cohort study Setting & Population: Low risk American women who delivered between 39 and 42 weeks in 2015 to 2017. Methods: Data was abstracted from the national vital statistics database. Multivariable log-binomial regression analysis was conducted to estimate the relative risk of morbidity. Main Outcome Measures: Maternal morbidity included Triple I, blood transfusion, ICU admission, uterine rupture, cesarean hysterectomy, and cesarean delivery. Neonatal morbidity included 5 minute Apgar ≤3, prolonged ventilation, seizures, NICU admission, and neonatal death. Results: A total of 1,885,694 women were included for analysis. Women undergoing induction of labor at 39 weeks were less likely to develop Triple I (p-value < 0.001; aRR 0.66; 95% CI [0.64-0.68]) and require a cesarean section (p-value <0.01; aRR 0.69l 95% CI [0.68-0.69]) than the expectant management group. There was a small, but significant increase in cesarean hysterectomy in the induction group (p-value <0.01; aRR 1.32; 95% CI [1.05-1.65]). Neonates of the induction group were less likely to have 5 minute Apgar ≤3 (p-value < 0.01; aRR 0.69; 95% CI [0.64-0.74]), prolonged ventilation (p-value < 0.01; aRR 0.77; 95% CI [0.72-0.82]), NICU admission (p-value < 0.01; aRR 0.80; 95% CI [0.79-0.82]), and/or neonatal seizures (p-value <0.01; aRR 0.80; 95% CI [0.66-0.98]) compared to the expectant management group. Conclusions: Induction of labor at 39 weeks gestation compared with expectant management is not harmful and has maternal and neonatal benefits.

Il rapporto ambientale sulla valutazione ambientale strategica (VAS), è il documento che individua tutti gli impatti positivi e negativi sul territorio del piano, sviluppando delle possibili alternative di miglioramento, tenendo in considerazione le esigenze del territorio stesso. Questo documento permette di avere una panoramica dedicata ai contenuti principali del piano ed un’analisi dell’opzione ‘’0’’, intesa come l’evoluzione del territorio senza l’attuazione del piano. L’analisi vera e propria consiste nell’esaminare le caratteristiche ambientali, culturali e paesaggistiche per poi verificarne gli impatti provocati dal P.U.C. sull’ambiente, con l’obiettivo di mitigarli. È importante non trascurare i processi di monitoraggio sulla mitigazione degli impatti negativi, affinché vengano rispettati gli standard qualitativi e quantitativi degli obiettivi preposti.

A document by Aude Belbezier. Click on the document to view its contents.