Global emergence and re-emergence of Porcine epidemic diarrhea virus (PEDV), an Alphacoronavirus which causes a highly contagious enteric disease, have led to several studies addressing its variability. The aim of this study was to characterize the infection of weaned pigs with Swine enteric coronavirus (SeCoV) -a chimeric virus most likely originated from a recombination event between PEDV and Transmissible gastroenteritis virus, or its mutant Porcine respiratory coronavirus-, and two PEDV G1b variants, including a recently described recombinant PEDV-SeCoV (rPEDV-SeCoV), as well as to determine the degree of cross-protection achieved against the rPEDV-SeCoV. For this purpose, forty-eight 4-week-old weaned pigs were randomly allocated into four groups of 12 animals; piglets in groups B, C and D were orally inoculated with a PEDV variant (B and D) or SeCoV (C), while piglets in group A were mock inoculated and maintained as controls. At day 20 post-infection all groups were exposed to rPEDV-SeCoV; thus, group D was subjected to a homologous re-challenge, groups B and C to a heterologous re-challenge (PEDV/rPEDV-SeCoV and SeCoV/rPEDV-SeCoV, respectively) and group A was primary challenged (-/rPEDV-SeCoV). Clinical signs, viral shedding, microscopic lesions and specific humoral and cellular immune responses (IgG, IgA, neutralizing antibodies and IgA and IFN-γ-secreting cells) were monitored. After primo-infection all three viral strains induced an undistinguishable mild-to-moderate clinical disease with diarrhea as the main sign and villus shortening lesions in the small intestine. In homologous re-challenged pigs, no clinical signs or lesions were observed, and viral shedding was only detected in a single animal. This fact may be explained by the significant high level of rPEDV-SeCoV-specific neutralizing antibodies found in these pigs before the challenge. In contrast, prior exposition to a different PEDV G1b variant or SeCoV only provided partial cross-protection, allowing rPEDV-SeCoV replication and shedding in feces.

Xenotransplantation with porcine organs has been recognized as a promising solution to alleviate the shortage of organs for human transplantation. Porcine endogenous retrovirus (PERV), whose proviral DNAs are buried in the genome of all pig breeds, is a main microbiological risk for xenotransplantation. Over the last decades, some advances on PERVs’ study have been achieved. Here we reviewed the current progress of PERVs including the classification, molecular structure, regulation , function in immune system and potential risk in xenotransplantation. We also discussed the problem of insufficient research on PERVs as well as the questions need to be answered in the future work.

The H9N2 subtype of avian influenza virus (H9N2 AIV) has caused significant losses in chicken flocks throughout China. Our previous research has showed that field isolates of H9N2 underwent antigenic drift to evolve into distinct groups with significant antigenic divergence from the commercially available vaccines. The present study sought to identify which single mutations that have naturally appeared in isolates from the past 5 years has driven antigenic drift. Six high-frequency mutation sites in/near the receptor binding site (RBS) region were screened by comparing amino acid alignments of the H9N2 AIVs isolated from China between 2014 and 2019. Two substitutions, (A168N and D201G) were demonstrated to have a significant impact on the antigenicity, but did not change the growth kinetics and cell tropism of the virus. It is worth noting that the D201G substitution not only significantly changed the antigenicity, but also caused immune escape of the parental virus. In conclusion, A168N and D201G substitution are newly discovered determinants that can significantly change the antigenicity of H9N2 AIV, which should be tracked during outbreaks.

Root hair elongation (RHL), which expands the absorptive surface area of the root, is a crucial adaptation in plants for survival under magnesium (Mg) deficient soil. Despite the significance of this trait, the molecular mechanism in Mg starvation regulating RHL is elusive. We demonstrated that karrikins regulate RHL under a limited supply of Mg via crosstalk with auxin, ethylene, and NO. We used KAI2-KL-signalling mutants, auxin, ethylene, and NO-related genes mutants Arabidopsis and pharmacological method to investigate the role of KAI2-KL-signalling, and its interaction with ethylene, auxin, and NO in the process of RHL in Mg deficient conditions. Mg deficiency could not enhance RHL in positive regulators of KAI2-KL-signalling genes such as kai2 and max2 mutant Arabidopsis. Exogenous application of ethylene, nitric oxide, or auxin recovered RHL of kai2 and max2 under Mg deficiency. In contrast, exogenous supplementation of KAR 1 could not rescue RHL in auxin, ethylene, and NO-related mutants Arabidopsis. In conclusion, we suggest that karrikins signalling might regulate the RHL in response to low Mg by acting as an upstream signalling pathway of auxin, ethylene, and NO signalling.

The event-free survival of pediatric low-grade gliomas is poor, and patients often require multiple treatment strategies. While MEK and RAF inhibitors are efficacious in early-phase trials, not all patients respond and many experience progression following completion of therapy. Evaluating combination therapies that may enhance efficacy or prolong disease stabilization is warranted. We report our institutional experience using concurrent trametinib and lenalidomide in the treatment of primary pediatric central and peripheral nervous system tumors. Two of four patients using this combination therapy experienced severe thromboembolic events necessitating discontinuation of therapy. This combination requires further investigation, and we urge caution if used.

Human–wildlife conflict (HWC) threatens the existence of precious wildlife in nature. This study assesses human–black-bear conflicts in Guthichaur Rural Municipality of Jumla district, Nepal. A household questionnaire survey (n=84), key informants survey (n=5), and focus group discussion (n=8) were conducted to collect the wildlife-conflict information during the period 2009–2019. Results reveal that 85% of the respondents suffered from crop damage in the year 2019. Five people were attacked, and livestock depredation was observed to be 55% during the decade, 2009–2019. The black bear was responsible for livestock depredation, with the most frequently depredated livestock being the cow and ox (70.12%). The depredation was high from April to August due to the transhumance grazing system. Of the total number of attacks on livestock, 94% was found to occur in forest and rangeland; moreover, these attacks occurred at night, constituting about 47% of the total number of events. Local people were supportive of black-bear conservation. This study is aimed at those aware, local communities that support the ecological value of black bears in the environment.

This case report presents an 8 year old male patient from southcentral Somalia with clinical feature of visceral leishmaniasis but negative rk39 test, which possess a major challenge for the diagnosis and treatment of Visceral leishmania. After we ruled out other differential diagnosis, we successfully treated him with amphotericinB

Herbivory serves as a critical top-down mechanism within plant communities by regulating biodiversity, productivity, and ecosystem function. While top-down impacts of mammalian herbivores have garnered significant attention in the literature, fewer studies have investigated the role of herbivorous reptiles in regulating plant communities, which can serve as crucial herbivores in some ecosystems. In Southeastern United States coastal plain long-leaf pine forests, the gopher tortoise (Gopherus polyphemus) is a keystone species that may suppress plant productivity and promote local diversity within hyper-diverse understory plant communities. In January 2019, we established tortoise-exclusion plots within an active gopher tortoise population at Splinter Hill Bog Preserve in southwest Alabama, USA. We measured the response of plant species diversity, composition. and productivity through a single growing season to quantify the short-term impacts of tortoise-excluded plots on understory plant communities. We found that plots excluded tortoises had 35% more plant cover with a 15% reduction in plant richness, 6% reduction in evenness, and 12% reduction in Shannon’s diversity relative to control plots. Within a single growing season, we found that tortoise exclusion explained 5% of the variation within overall plant community composition. Our results provide clear evidence on the role of gopher tortoise herbivory for the maintenance of plant diversity within the species-rich longleaf pine forests of the Southeastern United States, even at short time scales and in an heterogeneous environment.

Race is a Modifier between Parental Allergy and Food Allergy in OffspringAmy A. Eapen, MD, MS*1, Erica Ridley MD*1, Alexandra R. Sitarik MS2, Christine Joseph PhD2, Christian Nageotte, MD1, Rana Misiak, MD1, Dennis Ownby MD3, Christine Johnson PhD2, Edward Zoratti MD1, Haejin Kim MD1.1Division of Allergy and Clinical Immunology, Henry Ford Health System, Detroit, Michigan2Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan3Department of Pediatrics, Augusta University, Augusta, Georgia.*Dr. Eapen and Dr. Ridley are listed as co-first authorsCorresponding author: Amy A. Eapen, MD, One Ford Place, 4B Detroit, MI 48202; Telephone (313) 971-6182; Fax (313) 876-2094; E-mail: aeapen1@hfhs.orgFunding: Grants from the National Institute of Allergy and Infectious Diseases (R01 A1051598 and P01 A1089473) and the Fund for Henry Ford Hospital.Financial disclosure : There are no financial disclosures of conflicts of interest.Word count: 1191Keywords : Food allergy, race, parental allergy, total IgETo the Editor,Studies indicate associations between maternal allergy and development of food allergy in their offspring1, with higher food allergy risk among those with more than one first degree relative with allergic disease2. However, unnecessary food avoidance among children of allergic parents has important implications since diverse diets in children may decrease risk for food allergy, and early food introduction with foods such as peanut, can be protective for food allergy3. We sought to assess the association between parental allergic markers and offspring food sensitization and clinical allergy to milk, egg, or peanut.We analyzed data from the racially and socioeconomically diverse population birth cohort, Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS) that enrolled pregnant women between 21 to 45 years of age and their offspring following recruitment between September 2003 to December 2007. Details regarding the cohort have been previously published4,5. Institutional Review Board (IRB) approval was obtained for all aspects of the study.Parental factors assessed included questionnaire responses regarding history of allergy or asthma; maternal total IgE and maternal serum allergen specific IgE (sIgE) levels during pregnancy or one month postpartum were also evaluated. Atopy was defined as at least one sIgE ≥ 0.35 IU/mL to eight allergens (dust mite, dog, cat, grass, ragweed,Alternaria , egg, cockroach). Maternal asthma, atopic dermatitis, and food allergy were determined by questionnaire. Due to a paucity of paternal data, only paternal asthma was assessed.Offspring sensitization to milk, egg, or peanut was determined at 2 years of age by sIgE≥ 0.35 IU/mL and also skin prick testing (SPT; wheal size ≥3 mm larger than the saline control defined a positive test). As sensitization to foods does not translate to clinical allergy in all cases, we formed an algorithm to determine those most likely to have true IgE-mediated food allergy6. A consensus panel of allergists determined food allergy status in offspring based on review of the aforementioned data and abstracted chart informations as previously described7. Briefly, infant data were forwarded to the panel only if more than one of the following criteria were met for milk, egg, or peanut allergens: (1) 1 sIgE ≥0.35 IU/mL; (2) a positive SPT; or (3) parental report of infant symptoms potentially related to food allergy plus at least one specific IgE greater than 0.10 IU/mL. To enhance standardization in classifying infants to the presence of IgE- mediated food allergy (IgE-FA), physicians were asked to combine professional experience with investigator-developed protocols based on the Guidelines for the Diagnosis and Management of Food Allergy in the United States8. A third allergist independently reviewed and ruled on discordant decisions.Logistic regression models of parental variables with each outcome were fit. Interaction terms were added to logistic regression models to assess differences in associations based on race, (p<0.10 was considered a significant interaction). Predicted probabilities were used to construct receiver operating characteristic (ROC) curves and calculate area-under-the-curve (AUC) values.Of 1258 maternal-child pairs, 761 had sufficient data for analysis (Supplemental Figure el). Participant characteristics indicated that families not lost to follow up had higher household incomes, as well as higher maternal education, and a higher proportion of mothers who were married, kept pets, and breastfed the child. rates (Table e1).Associations between parental variables and physician panel determination of food allergy are shown in Table 1. After adjusting for child race, seven out of eight parental characterics of the were significant or of borderline signficance. However, the maximum AUC for ROC curves for any individual variable was 0.54 (maternal total IgE), indicating poor prognostic value (Supplemental Table e2). Maternal atopy, multi-sensitization, and total IgE significantly interacted with race (p=0.012, 0.092, 0.068, respectively) indicating strong associations among African American (AA) children only (Table 1). For example, maternal atopy in non-AA children was not associated with food allergy, but was highly associated among AA children (OR [95% CI]=3.56 [1.55, 9.66], p=0.006).Maternal current asthma was also associated with childhood food allergy (OR [95% CI]=2.27 [1.02, 4.71], p=0.034), and patterns varied by race with history of maternal asthma associated with food allergy only in non-AA children (OR [95% CI]= 4.92 [1.22, 17.14], p=0.015), and current asthma among AA children (OR [95% CI]=2.64 [1.10, 5.92], p=0.022; Table 1).Combined, parental variables only modestly impacted food allergy ROC analyses resulting in an AUC of 0.66. However, the ROC curves differed by race (non-AA AUC 0.36 vs AA AUC 0.71, p=0.002) as shown in Figure 1.Apart from food allergy, parental variables were analysed for associations with offspring sensitization (positive sIgE or SPT) to peanut, milk, or egg at age 2 years. Maternal atopy, multi-sensitization, and total IgE were associated with offspring positive food sIgE sensitization to at least one food. Analysis stratified by race indicated these associations were significant only among AA children. (Supplemental Table e3). Furthermore, maternal current asthma was associated with food sIgE sensitization only among non-AA children (OR [95% CI]=4.90 [1.69, 16.20], p=0.005). ROC curves were significantly different between AA and non-AA children (p=0.036) but predictive ability remained poor in both (AUC 0.55 and 0.44 respectively as in supplemental Figure e2).Maternal multisensitization, total IgE and current asthma, and paternal asthma were statistically significantly associated with any positive food SPTs only among AA children. (Supplemental Table e4). Additionally, race modified the relationship between maternal atopy and SPTs (p=0.039); AA children of atopic mothers had elevated odds of food SPT positivity (OR [95% CI]=1.96 [1.15, 3.45], p=0.016). Despite ROC differences by race (p=0.015; Figure e3), parental variables again had minimal predictive ability.The importance of genetic factors in food allergy is supported by twin studies showing higher concordance of peanut allergy among monozygotic compared with dizygotic twins (64.3% and 6.8%, respectively)9. In addition, heritability among parents and offspring for overall food sensitization have been reported1. However, our report indicates parental variables related to allergy have poor predictive ability for offspring food sensitization. The results from the physician panel demonstrate a moderate degree of risk and capability of predicting food allergy in offspring from parents having clinical characteristics of allergy.We previously reported similar food allergy prevalence for milk, egg, and peanut in AA and non-AA children7. We report here that the inherited risk as measures by parental allergic variables and predictive ability of parental allergic variables on food allergy development in offspring varies by race and is more strongly associated with clinical food allergy versus sensitization, among AA children. The potential mechanisms behind this racial discrepancy are require further studies.Potential study limitations include the physician panel to determine clinical food allergy status as opposed to performing oral food challenges. These challenges are time consuming and impractical to implement in large epidemiological studies10. Another limitation is that non-AA children included multiple ethnicites, which was done to preserve sample size. These groups may have different incidences of disease, and risk may vary. Finally, included and excluded WHEALS participants differed by demographic variables, so findings may not be generalizable to the target population.Parental allergy and atopy, although associated with offspring food allergy, is only a weak predictor and depends upon race. Further studies of familial factors contributing to food allergy and these disparities are needed to precisely identify children at risk for food allergy.Amy A. Eapen, MD, MS*1, Erica Ridley MD*1, Alexandra R. Sitarik MS2, Christine Joseph PhD2, Christian Nageotte, MD1, Rana Misiak, MD1, Dennis Ownby MD3, Christine Johnson PhD2, Edward Zoratti MD1, Haejin Kim MD1.1Division of Allergy and Clinical Immunology2Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan3Department of Pediatrics, Augusta University, Augusta, Georgia.*Dr. Eapen and Dr. Ridley are listed as co-first authors

Background: Food allergy is a disease with a diverse and variable natural history, and some patients may react to two or more food antigens. This study aimed to classify and characterize the long-term prognosis of infantile-onset, immediate-type food allergies in children, focusing on three major antigens in Japan: egg, milk, and wheat. Methods: All children visited to our hospital with food allergies, including suspected cases, were prospectively registered in our medical database. From this database, infants who had immediate-type symptoms or were sensitized to above three antigens were included. Cox regression analysis and repeated-measures latent class analysis were performed to reveal risk factors and tolerance patterns for food allergies. Results: Of 2,830 patients registered in the database, we included 915 patients with immediate-type food allergy symptoms and 276 sensitized asymptomatic patients in this study. The number of patients with immediate-type symptoms to egg, milk, and wheat was 609, 443, and 235, respectively. The number of patients with multiple food allergies was 302. Ratios of acquiring tolerance to egg, milk, and wheat at the age of 6 years were 74%, 69%, and 75%, respectively. Latent class analysis revealed 10 classes of prognosis for food allergies, including five with multiple food allergies. The largest class was transient egg allergy alone (21.4%), and there were severe cases of persistent allergy to three major allergens (3.2%). Conclusions: This study demonstrated the prognosis of food-allergy classes in Japan, including multiple food allergies, with 10 classes with its own characteristics.

Abstract Objectives: To examine changes in surgeon volume over time and evaluate the influence of surgeon volume on complications of abdominal radical hysterectomy (ARH) and laparoscopic radical hysterectomy (LRH) for cervical cancer. Design: A retrospective cohort study. Setting: 42 hospitals in China. Population: 14536 patients undergoing ARH and 8148 patients underwent LRH. Methods: The influence of the surgeon volume of ARH and LRH on surgical complications was examined using multivariable logistic regression models. Main outcome measures: Intraoperative complications and postoperative complications. Results: In the ARH cohort, the mean surgeon case volume increased from 3.5 cases in 2004 to 8.7 cases in 2013 and then decreased to 4.9 cases in 2016. The number of surgeons performing LRH increased from 1 surgeon with 1 patient (mean cases=1) in 2004 to 183 surgeons who operated on 2,206 patients in 2016 (mean cases=12.1) (P< 0.01). In the ARH, patients treated by intermediate-volume surgeons had more postoperative complications (OR=1.55, 95% CI=1.11-2.15). In the laparoscopic surgery cohort, surgeon volume had no independent effect on intraoperative or postoperative complications (P=0.46; P=0.13). Conclusions: The performance of ARH by intermediate-volume surgeons is associated with an increased risk of postoperative complications. However, surgeon volume may have little effect on intraoperative or postoperative complications after LRH.

Background Acute pulmonary exacerbation (APE) in cystic fibrosis patients is frequent and associated with a decline in pulmonary function, quality of life and survival. Tobramycin is often used in regimens requiring activity against Pseudomonas aeruginosa, however, an important number of centers do not use official dosing recommendation. The current dosing strategy may be suboptimal. Methods This retrospective cohort analysis was performed on all adult cystic fibrosis patients that were admitted at a tertiary care facility for treatment of APE and with tobramycin between January 2015 and December 2019. The primary objective was to evaluate the predictive performance of previously published pharmacokinetic (PK) models and, secondly, to evaluate potential factors that impact clinical outcomes. Clinical outcomes were only evaluated in a sub-group of patients with cultures positive for P. aeruginosa. Results A total of 202 APEs from 51 patients were included in the PK analysis. Two population PK models were assessed and failed to fit our data. In all, 109 APEs from 32 patients were included in the clinical analysis. Factors that significantly impacted clinical outcome were the number of prior APE and concomitant antibiotics. Clinical success rate for regimens containing at least one active agent against P. aeruginosa according to its susceptibility was 67%. Conclusion Population PK models evaluated in this study cannot be used to perform simulations. A new model must be developed for our population. In patients positive for P. aeruginosa, Ceftazidime in combination to tobramycin may be a superior regimen. APE history remains predictive for outcomes in adult CF patients treated for an APE.

This report entails a case of an 11-year-old Chinese boy with cystic fibrosis (CF), who bears the c.1521_1523delCTT/c.3874-4522A>G genotype, which is extremely rare in Chinese population. Notably, the deep intron mutation c.3874-4522A>G was the first time identified among Chinese patients, which was reported mainly associated with mild phenotype. It is generally considered that a mild allele sustains CFTR function in a dominant fashion, even if paired with a severe allele. However, in the present report, the c.3874-4522A>G mutation was found related to severe pulmonary diseases, including early symptom onset, progressive bronchiectasis, recurrent airway P. aeruginosa combined with MRSA, rapid decline of lung function, and poor weight gain, which suggesting severe phenotype. Despite intensive chest care and optimized therapy, the child ultimately died of cardiopulmonary failure 3 months after discharge.

The paper is concerned with the SIZR mathematical model for an outbreak of zombie infection with time-dependent infection rate. This class of the SIZR model involves equations that relate the susceptible S(t), the infected I(t), the zombie Z(t), and removed population R(t). The well poseness of the model is presented. The proposed model is then outstretched to the fractional order mathematical model with three different derivative operators i.e., Caputo, Caputo-Fabrizio, and Atangana-Baleanu fractional derivative operator. The conditions under which the model has a unique solution are established for different derivative operators. Using the numerical scheme which was proposed by Atangana and Toufik the numerical solutions are presented for the different fractional derivative operators.

Background: Left atrial appendage occlusion (LAAO) has historically been performed using intraprocedural transesophageal echocardiography (TEE) and fluoroscopy. Multiple recent reports have described the feasibility and advantages of utilizing two-dimensional intracardiac echocardiography (ICE) for LAAO. However, in inexperienced hands, safe manipulation of the ICE catheter in the left atrium (LA) can be challenging. Objective: To assess the feasibility and efficacy of three-dimensional (3D) ICE mapping in guiding LAAO device implant compared to standard TEE imaging. Methods: We retrospectively included patients who underwent LAAO in our institution from January 2017 and October 2021. We compared baseline demographics, intraprocedural data, post-procedural complications, and outcomes. P= value of <0.05 was considered significant. A linear regression model was performed using ICE and TEE as dependent variables to model contrast dose. Results: 130 patients underwent LAAO device implantation, of which 57 underwent ICE guided LAAO and 73 underwent TEE guided implantation. There was no difference in baseline demographics or post-procedural outcomes between both groups. There was no difference in the total procedure time between ICE and TEE groups, 86 (72-107) and 83 (72-111) minutes (p=0.65), respectively. Conversely, total fluoroscopic time was significantly shorter in ICE arm 7.8 (5.6-11), compared to TEE arm 12.9 (10.5-17.6) (p= <0.001). In patients undergoing LAAO device implantation using 3D ICE technique, with each additional ICE-guided procedure, the contrast dose decreased by 0.87 mL (correlation r = -0.48, p<0.001). Conclusion: 3D ICE is safe and feasible in guiding LAAO device implantation. When compared to TEE technique, total fluoroscopic time was shorter. Additionally, with more procedures utilizing 3D ICE, contrast dose decreased in a linear fashion.

It is established $L^{p}$ estimates for the fractional $\Phi$-Laplacian operator defined in bounded domains where the nonlinearity is subcritical or critical in a suitable sense. Furthermore, using some fine estimates together with the Moser’s iteration, we prove that any weak solution for fractional $\Phi$-Laplacian operator defined in bounded domains belongs to $L^\infty(\Omega)$ under appropriate hypotheses on the $N$-function $\Phi$. Using the Orlicz space and taking into account the fractional setting for our problem the main results are stated for a huge class of nonlinear operators and nonlinearities.

Introduction Left bundle branch pacing (LBBP) has emerged in recent years as a new pacing modality, providing patients with a narrower paced QRS than conventional pacing and stable pacing parameters. At the same time, there is a growing concern about the use of fluoroscopy in pacemaker implantations, given its harmful effects to both patients and operators. However, there are no prior experiences of zero fluoroscopy in LBBP procedure. Methods We conducted an observational prospective study recruiting consecutive patients that underwent zero fluoroscopy LBBP pacemaker implantation. A 6-month follow-up visit was programmed for every patient. The main goal of our study was to assess the efficacy, feasibility and safety of the procedure. Results From January 2021 to February 2022, we included 10 patients, 8 males. The average age was 63 ± 4 years. The procedure was successful in all patients. We observed a significant reduction in paced QRS width compared with basal QRS width (149 ms vs 116 ms, p= 0.02). All device parameters remained stable at 6-month follow-up: no significant differences in mean impedance (700.5 vs 494 Ohm, p=0.09), capture threshold (0.67 vs 0.83V @ 0.4ms, p=0.27) or R-wave amplitude (10.6 vs 13.92 mV, p= 0.19). No complications were reported in any case. Conclusion Zero fluoroscopy LBBP is feasible and safe, and it may be considered an optimal election in cases where radiation exposure is contraindicated or especially undesirable and as an alternative in all other cases.

In the present paper we investigate the qualitative behaviour of a fractional SEIR model with general incidence rate function and time delay where the fractional derivative is defined in the Caputo sense. The basic reproduction number $\mathcal{R}_{0}$ is derived using the method of next generation matrix and we give a complete study of local stability of both free and endemic equilibrium. Using Liapunov method we prove the global stability of free and endemic equilibrium under some hypotheses on the parameters of the system. Finally to illustrate our results, we use the model to predict the first peak of the COVID-19 epidemic in Algeria.

In this paper we study the partial differential equation with piecewise constant argument of the form : \[ \begin{array}{lll} x_t(t,s)=&A(t)x(t,s)+B(t,s)x([t],s)+C(t,s)x(t,[s])+\\[0.5cm] &D(t,s)x([t],[s])+f(x(t,[s])),\ \ t,s\in \R^{+}=(0,\infty) \end{array} \] where $A(t)$ is a $k\times k$ invertible and continuous matrix function on $\R^{+}$, $B(t,s)$, $C(t,s)$, $D(t,s)$ are $k \times k$ continuous and bounded matrix functions on $\R^{+}\times \R^{+}$, $[t]$, $[s]$ are the integral parts of $t,s$ respectively and $f:\R^k\rightarrow \R^k$ is a continuous function. More precisely under some conditions on the matrices $A(t)$, $B(t,s)$, $C(t,s)$, $D(t,s)$ and the function $f$ we investigate the asymptotic behaviour of the solutions of the above equation. \end{abstract}

Background: Randomized controlled trials (RCTs) are the gold-standard for benefit-risk assessments during drug approval processes. Real-word data (RWD) and the resulting real-world evidence (RWE) are becoming increasingly important for assessing the effectiveness of drug products after marketing authorization showing how RCT results are transferred into real life care. The effectiveness of allergen immunotherapy (AIT) has been assessed in several RWE studies based on large prescription databases. Methods: We performed a literature search for retrospective cohort assessments of prescription databases in Europe to provide an overview on the methodology, long-term effectiveness outcomes and adherence to AIT. Results: 13 respective publications were selected. AIT was more effective in reducing the progression of allergic rhinitis (AR) compared to a non-AIT control group receiving only symptomatic treatment for AR for up to 6 years. The development and progression of asthma was hampered for most endpoints in patients treated with most preparations compared to the non-AIT group, receiving only anti-asthmatic medication. The results for “time to onset” of asthma were inconsistent. Adherence to AIT decreased during the recommended 3-years treatment period, however in most studies higher adherence to subcutaneous than to sublingual AIT was shown. Conclusion: The analysis of long-term effectiveness outcomes of the RWE studies based on prescription databases confirms the long-term efficacy of AIT demonstrated in RCTs. Progression of rhinitis and asthma symptoms as well as delayed onset of asthma triggered by different allergens, real life adherence to the treatment shows differences in particular application routes.

We reported one of the rare, documented cases of a girl with LVNC associated jSLE with a past history of Hashimoto's thyroiditis.Thus, the association between jSLE, and LVNC should be considered, and requires further research in order to find the probable mechanism joining both entities.

In this paper, we investigate the existence and attractivity of mild solutions to fractional evolution equations with Caputo fractional derivative on an infinite interval. Our methods are based on fractional calculus, semigroup theory, compactness methods and the measure of noncompactness. Several sufficient conditions for the existence of solutions to the given problem are proposed. Examples illustrating the main results are presented.

The three lowest spin states (S=0,1,2) of twelve representative Na13+ isomers have been studied using both, KS-DFT via three hybrid density functionals, and benchmark multireference CASSCF and CASPT2 methods with a couple of Dunning’s correlation consistent basis sets. CASSCF(12,12) geometry optimizations were carried out. Since 12 electrons in 12 active orbitals span the chemically-significant complete valence space, the results of the present study provide benchmarks for Na13+. The CASPT2(12,12)/cc-pVTZ* lowest energy structures are three nearly degenerate singlets (S=0): an isomer formed from two pentagonal bipyramids fused together (PBPb), a capped centered-squared antiprism [CSAP-(1,3)] and an optimum tetrahedral OPTET(II) structure, the last two lying 0.88 and 1.63 kcal/mol above the first, respectively. The lowest triplet (S=1) and quintet (S=2) states lie 4.33 and 3.77 kcal/mol above the singlet global minimum, respectively. The latter is a deformed icosahedron while the former is a CSAP-(1,3). The flatness of the potential energy surface of this cluster suggests a rather strong dynamical character at finite temperature. Prediction of the lowest energy structures and electronic properties is crucially sensitive both to non-dynamical and dynamical electron correlation treatment. The CASPT2 vertical ionization energy is 3.66 eV, in excellent agreement with the $3.6 \pm 0.1$ eV experimental figure. All the isomers are found to have a strong multireference character, thus making Kohn-Sham density functional theory fundamentally inappropriate for these systems. Only large multiconfigurational complete active space self-consistent field (CASSCF) wavefunctions provide a reliable zeroth-order description; then the dynamic correlation effects must be properly taken into account for a truly accurate account of the structural and energetic features of alkali-metal clusters.

The ghost condensation of the early universe in a pre-big bang phase has been presented in this paper through duration of a non-singular bounce. The undergoing universe contracts and passes smoothly in an expanding universe via a post-big bang phase. Initially developing and then taming any ghost like instabilities, the Null Energy Condition (NEC) is explicitly violated through the curvature mechanism of an adiabatic perturbed metric. The vacuum state of the ongoing phase is stabilized via a La-grangian that in essence stabilizes the vacuum state under the higher order derivatives. The violation of the NEC regards a catastrophic vacuum instability, which re-emerges with a correction valid at small energies and momenta, below the UV-cutoff scale that, could potentially be problematic if one tries to construct a UV-completed theory of this Ekpyrotic model. The scale-invariant curvature perturbation, that arises and is sourced out of the scale-invariant entropy perturbations sourced by 2-Ekpyrotic scalar fields, that, in contrast, becomes constant on the super-horizon limits, due to the non-singular nature of the background geometry. Apart, from the ghost condensates, this theory addresses the new Ekpyrotic theory which in order becomes a distinguishable alternative to inflation theory for the birth of the universe. As per the recent WMAP data, the Ekpyrotic model has a spectral red tilt that shows the bounced scalar potential falling through a negative phase shift during the matter-fluid fluctuations in the hot big bang phase.