This paper is concerned with the existence and multiplicity of solutions for the following variable $s(\cdot)$-order fractional $p(\cdot)$-Kirchhoff type problem \begin{equation*} \left\{\begin{array}{ll} M\left(\displaystyle\iint_{\mathbb R^{2N}}\frac{1}{p(x,y)}\displaystyle{\frac{|v(x)-v(y)|^{p(x,y)}}{|x-y|^{N+p(x,y)s(x,y)}}}dxdy\right)(-\Delta)^{s(\cdot)}_{p(\cdot)}v(x)+|v(x)|^{\overline{p}(x)-2}v(x) =\mu g(x,v)\ \ {\rm in}~\mathbb{R}^{N},\\ v\in W^{s(\cdot),p(\cdot)}(\mathbb{R}^{N}), \end{array}\right. \end{equation*} where $N>p(x,y)s(x,y)$ for any $(x,y)\in\mathbb{R}^{N}\times\mathbb{R}^{N}$, $(-\Delta)^{s(\cdot)}_{p(\cdot)}$ is a variable $s(\cdot)$-order $p(\cdot)$-fractional Laplace operator with $s(\cdot):\mathbb R^{2N}\to(0,1)$ and $p(\cdot):\mathbb R^{2N}\to(1,\infty)$, $\overline{p}(x)=p(x,x)$ for $x\in\mathbb{R}^{N}$, and $M$ is a continuous Kirchhoff-type function, $g(x,v)$ is a Carath\’{e}odory function, $\mu>0$ is a parameter. We obtain that there are at least two distinct solutions for the above problem by applying the generalized abstract critical point theorem. Under the weaker conditions, we also show the existence of one solution and infinitely many solutions by using the mountain pass lemma and fountain theorem, respectively. In particular, the new compact embedding result of the space $ W^{s(\cdot),p(\cdot)}(\mathbb{R}^{N})$ into $L^{q(\cdot)}_{a(x)}(\mathbb{R}^{N})$ will be used to overcome the lack of compactness in $\mathbb{R}^N$. The main feature and difficulty of this paper is the presence of a double non-local term involving two variable parameters.

A document by Fatma Taha. Click on the document to view its contents.

In this work, an energy stable numerical scheme is proposed to solve the PFC model with a nonlocal Lagrange multiplier. The construction of the numerical scheme is based on invariant energy quadratization (IEQ) technique to transform a nonlinear system into a linear system, while the time variables is discretized by second order scheme. The stability term in the new scheme can balance the influence of nonlinear term. Moreover, we obtain the results of unconditional energy stability, uniqueness and uniform boundedness of numerical solution, and the numerical scheme is convergent with order of $\mathcal{O}(\delta t^2)$. Several numerical tests are conducted to confirm the theoretical results.

We derive the fractional version of one-phase one-dimensional Stefan model. We assume that the diffusive flux is given by the time-fractional Riemann-Liouville derivative, i.e. we impose the memory effect in the examined model. Furthermore, we find a special solution to this problem.

In this paper we consider the initial boundary value problem for a nonlinear damping and a delay term of the form: $$ |u_t|^{l}u_{tt}-\Delta u (x,t) -\Delta u_{tt}+\mu_1|u_t|^{m-2}u_t\\+\mu_2|u_t(t-\tau)|^{m-2}u_t(t-\tau)=b|u|^{p-2}u, $$ with initial conditions and Dirichlet boundary conditions. Under appropriate conditions on μ₁,   μ₂, we prove that there are solutions with negative initial energy that blow-up finite time if p ≥ max{l + 2, m}.

In this paper, a discrete-time dynamic economic system, with exponential demand term and quadratic cost term, is established. We have spent great lot efforts in verifying the properties of existence and local stability of equilibrium points by Medium Theory and Zero-Point Theory. Immediately, the stability conditions are given in details. And then, by changing the valuesof parameters, the system shows some new and interesting phenomena in terms to stability and multi-stability, like different shape basin of coexisting attractors. Even some changes in the topological structure of basin have beenintuitively and more deeply analyzed by using numerical simulation. Finally, we utilize critical curves to analyze the reason of “hole” formation and to descript their evolution process. As a result, we can intuitively find that the generation of global bifurcation, like contact bifurcation or final bifurcation,is usually accompanied by the contact of critical curve and boundary.

In this article, we study the blow-up of the damped wave equation in the \textit{scale-invariant case} and in the presence of two nonlinearities. More precisely, we consider the following equation: \begin{displaymath} \d u_{tt}-\Delta u+\frac{\mu}{1+t}u_t=|u_t|^p+|u|^q, \quad \mbox{in}\ \R^N\times[0,\infty), \end{displaymath} with small initial data.\\ For $\mu < \frac{N(q-1)}{2}$ and $\mu \in (0, \mu_*)$, where $\mu_*>0$ is depending on the nonlinearties’ powers and the space dimension ($\mu_*$ satisfies $(q-1)\left((N+2\mu_*-1)p-2\right) = 4$), we prove that the wave equation, in this case, behaves like the one without dissipation ($\mu =0$). Our result completes the previous studies in the case where the dissipation is given by $\frac{\mu}{(1+t)^\beta}u_t; \ \beta >1$ (\cite{LT3}), where, contrary to what we obtain in the present work, the effect of the damping is not significant in the dynamics. Interestingly, in our case, the influence of the damping term $\frac{\mu}{1+t}u_t$ is important.

We consider the generalized Stokes resolvent problem in an infinite layer with Neumann boundary conditions. This problem arises from a free boundary problem describing the motion of incompressible viscous one-phase fluid flow without surface tension in an infinite layer bounded both from above and from below by free surfaces. We derive a new exact solution formula to the generalized Stokes resolvent problem and prove the $$-boundedness of the solution operator families with resolvent parameter $\lambda$ varying in a sector $$ for any $\gamma_0>0$ and $0<\varepsilon<\pi/2$, where $ =\{ \lambda\in\setminus\{0\} \mid \arg\lambda\leq\pi-\varepsilon, \ \lambda>\gamma_0 \}$. As applications, we obtain the maximal $L_p$-$L_q$ regularity for the nonstationary Stokes problem and then establish the well-posedness locally in time of the nonlinear free boundary problem mentioned above in $L_p$-$L_q$ setting. We make full use of the solution formula to take $\gamma_0>0$ arbitrarily, while in general domains we only know the $$-boundedness for $\gamma_0\gg1$ from the result by Shibata. As compared with the case of Neumann-Dirichlet boundary condition studied by Saito, analysis is even harder on account of higher singularity of the symbols in the solution formula.

The paper studies the global existence and general decay of solutions using Lyaponov functional for a nonlinear wave equation, taking into account the fractional derivative boundary condition and memory term. In addition, we establish the blow up of solutions with nonpositive initial energy.

In this work, a class of fractional delay differential equations with four-point boundary condition and p-Laplacian operator are discussed. Based on the Avery-Peterson theorem, the existence of at least triple positive solutions are derived. An simple example are given to show the validity of the conditions of our main theorem.

In this article, we study two extended higher-order KdV-type models, namely, the extended Sawada-Kotera (eSK) and the extended Lax (eLax) equations. These models successfully describe propagation of dimly nonlinear long waves in fluids, ion-acoustic waves in harmonic sparklers. We firstly derive multi-soliton solutions of the models. We then construct interection solutions in-terms of hyperbolic and sinusoidal functions using the multi-soliton solutions with appropriate complex conjugate parameters. Such parameters influence and control the phase shifts, propagation direction and energies of the waves. In particularly, we present their collision solutions in the identical plane with different parametric constraints, which degenerate to the line rogue waves, x-shaped rogue waves, cnoidal periodic waves, interactions of rogue and bell waves, line breather and double breather waves. The dynamical characteristics of the wave solutions has been plotted by choosing particular values of the parameters in graphically.

The main goal of this paper is to study the asymptotic behavior of a coupled Klein-Gordon-Schr¨odinger system in three dimensional unbounded domain. We prove the existence of a global attractor of the systems of the nonlinear Klein-Gordon-Schr¨odinger (KGS) equations in H1(R3) × H1(R3) ×L2(R3) and more particularly that this attractor is in fact a compact set of H^2(R^3) × H^2(R^3) × H1(R^3).

He's frequency formulation suggests the fast identification of the amplitude-frequency relationship of a nonlinear oscillator. This paper applies the formulation to the Duffing-harmonic oscillator with great success. A modification of He's frequency formulation and the variational iteration method are also used for comparison.

This study provides the optimization of thermophysical properties of Cu/engine oil nanofluid. In this optimization, the objective functions were determined with the experimental data of viscosity and TC of nanofluid using RSM. Two equations for predicting thermal conductivity (TC) and viscosity data were presented which can accurately predict these properties. The NSGA-II method was used for multi-objective optimization (Mo-O) and Pareto’s front was introduced to study optimal viscosity and TC responses. According to the results, the highest TC and the lowest viscosity occurs when the temperature and solid volume fraction (SVF) of the nanoparticle are at their maximum values. Among the results, those with the highest TC and the lowest viscosity are referred to as optimal points.

To the Editor In allergic diseases, not only ‘allergic inflammation’, but also ‘epithelial barrier impairment’ play important roles in their development1. Allergen penetration through epithelium to the body is essential for allergen sensitizations, which are the most critical risk factors for the development of allergic diseases. In children with atopic dermatitis (AD), in which epithelial barrier impairment is one of its famous features, the prevalences of allergen sensitization and food allergy (FA) are known to be very high1. Concerning about the assessment of epithelial barrier function, while transepidermal water loss (TEWL) is a clinically useful marker in AD skin, it is quite difficult to evaluate barrier function in gastrointestinal tracts.Zonulin (pre-haptoglobin 2), an epithelial tight-junction regulator, plays an important role in the regulation of epithelial barrier function2,3. Recently, zonulin was reported to play a pathogenic role in celiac disease and other chronic inflammatory diseases23. Sturgeon et al reported that zonulin transgenic mice, as a result of zonulin-dependent small intestinal barier impairment and altered gut permeability, increased morbidity and mortality in the DSS colitis model4.Because allergen sensitization and chronic inflammation are important in the pathogenesis of allergic diseases, zonulin has potential to play significant roles in allergic diseases. However, there are few reports about zonulin levels in pediatric allergic patients. So, the objectives of this study are to assess whether i) serum zonulin levels in allergic children are higher than those in children without allergic diseases and ii) serum zonulin levels are different among allergic diseases.To evaluate them, we measured serum zonulin levels in infants and school-age children (with or without allergic diseases) using zonulin enzyme-linked immunosorbent assay kit. All infants (9 months old) were selected from Katsushika cohort study5. Allergic infants (‘AD infants’) were defined as infants who had doctor-diagnosed AD, and whose total IgE levels were above normal levels and Eczema area and severity index (EASI) were above zero. ‘Healthy infants’ were defined as infants who did not have AD, FA, bronchial asthma (BA), nor allergic rhinitis (AR), and whose serum total IgE levels were below measureable limits and EASI were zero. There were significant differences in total IgE levels and EASI score between groups (AD infants vs. healthy infants) (Table S1). Allergic school-age children were recruited in our outpatient clinic in Chiba University hospital and were defined as children who had doctor-diagnosed FA or BA or both, and whose total IgE levels were above normal levels. ‘healthy school-age children’ 6 were defined as school-age children who did not have AD, FA, nor BA and their serum total IgE levels were below measureable limits. The details of study subjects are shown in online supplementary methods and table S1-S3.Our first question was whether or not serum zonulin levels in allergic children are higher than those in children without allergic diseases. In infants, median zonulin levels in AD infants and healthy infants were 28.1 ng/ml (interquartile range (IQR): 23.8-32.3) and 15.3 ng/ml (IQR: 10.0-23.7), so serum zonulin levels were significantly higher in allergic infants than those in healthy infants (p<0.01) (Figure 1). To confirm this result in other age group, we evaluated zonulin levels in school-age children. Same as in infants, serum zonulin levels in school-age children were significantly higher in allergic children with FA and BA than those in healthy children without FA, BA, nor AD (Median (IQR): 29.5 ng/ml (22.6-41.9) and 10.6 ng/ml (9.4-12.2), p<0.001) (Figure 2a). Those results suggest that zonulin levels are higher in allergic children than in non-allergic children, regardless of their age.To assess our second question, we compared serum zonulin levels in BA patients with those in FA patients. In this analysis, we selected asthmatic patients as children who had BA but not FA, and FA patients as children who had FA but not BA, and there were no significant differences in total IgE and age between groups (Table S3). Serum zonulin in FA patients was significantly higher than those in BA patients (Median (IQR): 38.5 ng/ml (35.0-46.7) and 31.0 ng/ml (13.6-34.0), p<0.05) (Figure 2b). Those results suggest that zonulin levels are higher in FA patients than those in BA patients.Sheen et al reported that Serum zonulin levels were elevated in children with AD7, and this result was confirmed in our present paper. On the other hand, zonulin primarily reflects epithelial permeability in the gastrointestinal tract, it is important to examine Zonulin levels in other age groups and in patients with other allergic diseases. As we showed in this paper, in school-age children, zonulin levels are higher in allergic children than in healthy children, and higher in food allergy children than in asthmatic children. In general, many AD infants also have FA and intestinal permeability is repoted to be increased in younger children with AD but not in older children with AD 8. Those facts might influence the serum zonulin levels in infants with AD.Zonulin regulates intestinal barrier function through the regulation of tight junctional 2. This suggests that zonulin may affect allergen permeability in epithelia of the intestinal tract. Zonulin may contribute to the development of allergic diseases through allergen sensitization and affect the appearance of allergic symptoms via their effect on allergen exposure.There were several limitations in this study. First, the number of study subjects was small. And secondly, we did not compare zonulin levels in allergic children to those in children with other non-allergic diseases. So it is not clear whether serum zonulin is an “allergic marker”, and zonulin plays a role in the “development” of allergic diseases.In conclusion, serum zonulin levels are significantly higher in allergic children than in healthy children. In addition, those levels are significantly higher in food allergy patients than in asthmatic patients. Based on the knowledge about the role of zonulin in the intestinal epithelial barrier regulation, zonulin may play a role in the development of allergic diseases, especially in FA.

Violence in Rakhine, Myanmar forcibly displaced nearly one million Rohingya who took refuge in Cox’s Bazar–Teknaf peninsula of Bangladesh. Initially, nearly 2,000 ha of forested lands had to be cleared to accommodate them in an area, that is ecologically very sensitive. Fuelwood collection and illegal logging have become widespread since their arrival, causing severe environmental degradation, including loss of a vast amount of forest cover. To devise conservation strategies of a highly sensitive ecosystem, it is imperative to understand the degree of forest cover deterioration and associated impacts related to Rohingya emigration. This study employed satellite images to monitor and model spatiotemporal pattern of forest cover degradation, and loss of ecosystem function in the peninsula. Supervised classification method was used to derive multidate land use/cover data which was then utilized to monitor spatiotemporal pattern of forest cover change from 2017–2019. Dynamic modelling was performed to predict changes in the forest covers using markov cellular automata. Analysis revealed that 3,130 ha of different forested covers were transformed into either refugee camps or degraded forest cover between 2017 and 2019. Prediction showed that around 5,115 ha of forest may experience loss from 2019–2027. Furthermore, above ground biomass and carbon stock estimation indicated a consistent loss, which is likely to swell if present rate of deforestation continues. The findings of this work have considerable implications in developing conservation decisions, priority interventions and public policies to save an ecologically sensitive area.

To the Editor, Severe asthma (SA) is a chronic disease affecting around 3-8% of adult asthma population in Europe, with the refractory form estimated to occur in 0.1% of the general population (1,2). SA is characterized by increased use of healthcare resources (i.e. emergency room/hospital admissions, access to intensive care units (ICU), use of biologics) due to exacerbations compared to the less severe form. In the current SARS-CoV-2 pandemic, there is an ongoing debate on the role of asthma and use of immunomodulating drugs, like corticosteroids and biologics, on COVID-19 outcomes. According to available data on COVID-19 hospitalizations, asthma seems to play little role on the clinical severity or access to health resources, unlike other chronic conditions such as hypertension, obesity and chronic obstructive pulmonary disease (3). However, to date, no information is available on the burden of SA on COVID-19 severity and hospitalization rates.A questionnaire was submitted to the Italian Registry of Severe Asthma (IRSA) network (4), assessing the prevalence and clinical characteristics of patients with SA who contracted COVID-19 during the outbreak in Italy (February 24th - May 18th 2020), and 41 out of 78 centers distributed evenly among different Italian regions participated to the survey (Figure 1a).Among the 558 subjects surveyed, 7 subjects contracted COVID-19 (1.25% of the national sample), with an average age of 54.5 years: 5 isolated at home/received home care (71.5%), while 2 subjects were admitted to the hospital (28.5%), none required accessed to ICU and no deaths were reported. All COVID-19 subjects with SA came from 2 regions of Northern Italy (6 Lombardy, 1 Emilia-Romagna, 3.7% of the regional population), all showing one or more comorbidities, and were treated with high-dose inhaled corticosteroids plus long-acting beta-2 agonists (ICS-LABA) and biologics (see Table 1).We then compared our results with data provided by the Italian Department for Civil Protection in the same time period from the affected geographic areas (5), and we observed that the frequency of COVID-19 among subjects referred to IRSA centers strongly correlated with the prevalence of SARS-CoV-2 infection in the corresponding province (Figure 1b). Furthermore, the hospitalization rate in COVID-19-SA subjects was not significantly different from the general population (24.1%, 23.6-24.6 95% C.I.; p=0.25, Chi-squared test). Lastly, we could not observe a significantly increased COVID-19 frequency in subjects undergoing high-dose ICS-LABA and biologics compared to SA treated with ICS-LABA alone (p=0.09, Fisher exact test).These findings from the IRSA registry offer some insights on the susceptibility to SARS-CoV-2 infection, access to healthcare resources and mortality by SA patients.Given the low prevalence of SA in Italy (2), we expected less COVID-19-SA cases per region than what reported by the IRSA survey. However, we observed that the geographic location of COVID-19-SA patients mostly reflected the bimodal distribution of the COVID-19 outbreak in Italy, mainly clustered in Lombardy and neighboring regions, where the highest cumulative COVID-19 cases were recorded (>500/100000 cases per inhabitants) (5). In these areas, the prevalence of positive cases by province also strongly correlated with the frequency of COVID-19-SA patients observed in each IRSA center (Figure 1b), suggesting that patients with SA most likely contract the infection when high circulation of the virus within the area of residence is present. The lack of positive cases reported in Southern regions further proves this hypothesis, and demonstrates the efficacy of the lockdown measures adopted to contain the further spread of the virus.Our results also suggest no increased risk of contracting COVID-19 in SA treated with biologics compared to ICS-LABA alone. Although there is currently no strong evidence that biologics used in asthma might affect the risk of contracting COVID-19, new evidence suggests a protective effect of inhaled corticosteroids against viral entry by ACE2 receptor downregulation, that are usually prescribed at a high dose in SA (6), thus a possible explanation to the lack of observed differences in our cohort.Despite the severity of asthma and reported comorbidities, no ICU admissions were reported, and hospital admissions in COVID-19-SA subjects did not differ from the median rate observed in the same geographic areas (5). Furthermore, we could observe no difference in the median monthly hospitalization rate of SA patients in 2019 compared to 2020 in Lombardy region where both hospital-admitted subjects reside (0.97 vs 0.9%, IRSA data).Our result is consistent with recent literature, showing that asthma in Western countries was not associated with an increased hospitalization rate and ICU admissions due to COVID-19 (3,8). It is still debated if a protective effect of Th2-inflammation in a significant proportion of asthma sufferers (7), or concomitant anti-inflammatory therapy could be the reasons for such outcomes (6). However, if asthma patients with COVID-19 require intubation, the duration of hospitalization was shown to be longer than average (8).As for the role of biologics in COVID-19 disease progression, we could not observe an increase in hospital admissions in patients with SA treated with biologics compared to the general population, with the majority isolating at home and requiring no additional treatment. Considering that, in areas with high prevalence of SARS-CoV-2 infection, 68.2% of SA subjects were treated with either omalizumab or mepolizumab, our observations further prove the safety of biologics during the COVID-19 pandemic.Lastly, we did not observe any deaths in our cohort, but we speculate that this outcome is most likely due to the small sample size and younger average age. In fact, advanced age seems to be the most determining risk factor on mortality due to COVID-19 compared to other causes. (9)Taken together, our results point at a neutral role of SA in the COVID-19 disease course and hospital admissions. One major strengths of our study is that, by using a fast and inexpensive tool, we could outline the salient features of severe asthma and COVID-19 at a national level, while the major weakness is the limited number of SA subjects diagnosed with COVID-19, that could lead to sampling bias and low accuracy. Further confirmation of these results with an increased sample size is therefore warranted

OBJECTIVES: Feasibility and results of cardiovascular hub-spoke networks to face COVID19 pandemic. The COVID-19 pandemic in Italy had the primary outbreak in the northern part of the country forcing the regional health care system to expand the availability of beds in the wards and intensive care units and to institute a Hub and Spoke hospital network to ensure assistance continuity for urgencies and emergencies. We report a descriptive analysis of the activity of the first 30 days of the Hub center. METHODS: Role of our Hub center was to guarantee 24/24h 7/7days cardiovascular surgical care for an area of 3.145.312 inhabitants’ area. Hub-spoke reorganization permitted a significant increase of ICU and ward beds availability for COVID patients needing hospitalization in all peripheral centers. Records of all consecutive patients admitted were collected and analyzed. RESULTS: a total of 100 patients were evaluated in the study period . Hub and spoke cooperation have been successful, all patients affected by cardiovascular urgencies or emergencies found a highly specialized hospital and was evaluated and treated. Global reduction of elective and non-deferrable interventions in spoke centers was achieved for both vascular and cardiac surgery while we detected a significant increase of urgent vascular interventions for acute limb ischemia. We did not observe an increase of in-hospital mortality in non-infected patients. CONCLUSION: Hub and spoke network for cardiovascular pathology is an effective way to face healthcare needs during the pandemic.

To the Editor Since the end of February 2020 Italy, first non- Asian Country, has reported an ever increasing number of COronaVIrus Disease 19 (COVID-19) patients, which has reached over 200,000 confirmed Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infected subjects and resulted in more than 34000 deaths (data updated to June 19th, 20201).Patients with asthma are potentially more severely affected by by SARS-CoV-2 infection 2 and it is well established that respiratory viral infections are associated with severe adverse outcomes in patients with asthma, including increased risk of asthma exacerbation episodes 3. Nonetheless, according to the epidemiological studies published so far, chronic pulmonary diseases are not amongst the most common clinical conditions in COVID-19 patients4About 5-10% of entire asthma population, are severe asthmatics5 and one would expect increased vulnerability to SARS-CoV-2 infection, but no data is so fare available ti confirm this hypothesis.We investigated the incidence of COVID-19, describing its clinical course, in the population of the Severe Asthma Network in Italy (SANI), one of the largest registry for severe asthma worldwide6, and in an additional Center (Azienda Ospedaliero Univeristaria di Ferrara, Ferrara, Italy). All centers, have been contacted and inquired to report confirmed (i.e. patients with positive test result for the virus SARS-CoV-2 from analysis of nasopharyngeal or oropharyngeal swab specimens) or highly suspect cases of COVID-19 (i.e. patients with symptoms, laboratory findings and lung imaging typical of COVID-19 but without access to nasopharyngeal or oropharyngeal swab specimens because of clinical contingencies/emergency) among their cohorts of severe asthma. Demographic and clinical data of the entire cohort of severe asthmatics enrolled in the study and all reported cases of confirmed or suspect cases of COVID-19, have been obtained from the registry platform and collected from the additional Center. Additional data about COVID-19 symptoms, treatment and clinical course have been collected for all cases reported.Ethical issues and statistical analysis are reported in the online supplementary material.Twenty-six (1.73%) out of 1504 severe asthmatics had confirmed (11 out of 26) or highly suspect COVID-19 (15 out 26); eighteen (69.2%) were females and mean age was 56.2 ± 10 years. The geographical distribution of COVID-19 cases is presented in Figure 1.Nine (34.6%) infected patients experienced worsening of asthma during the COVID-19 symptomatic period; four of them needed a short course of oral corticosteroids for controlling asthma exacerbation symptoms.The most frequent COVID-19 symptoms reported were fever (100% of patients), malaise (84.6%), cough (80.8%), dyspnea (80.8%), headache (42.3%) and loss of smell (42.3%). Four patients (15.3%) have been hospitalized, one of which in intensive care unit; among hospitalized patients, two (7.7%) died for COVID-19 interstitial pneumonia. No deaths have been reported among the non-hospitalized patients.Severe asthmatics affected by COVID-19, had a significantly higher prevalence of non-insulin-dependent diabetes mellitus (NIDDM) compared to non-infected severe asthma patients (15.4% vs 3.8%, p=0.002; odds ratio: 4.7). No difference was found in other comorbidities (including rhinitis, chronic rhinosinusitis with or without nasal polyps, bronchiectasis, obesity, gastroesophageal reflux, arterial hypertension, cardiovascular diseases).Twenty-one patients with COVID-19 were on biological treatments: 15 (71%) were on anti-IL-5 or anti-IL5R agents (Mepolizumab n= 13; Benralizumab n=2 - counting for the 2.9% of all severe asthmatics treated with anti-IL5 in our study population) and 6 (29%) were on anti IgE (Omalizumab - 1.3% of all severe asthmatics treated with omalizumab in our study population).Table I summarizes demographic and clinical characteristics of the 26 COVID-19 patients.In conclusion, in our large cohort of severe asthmatics, COVID-19 was infrequent, not supporting the concept of asthma as a particularly susceptible condition to SARS-COV2 infection 2. This is in line with the first published large epidemiological data on COVID-19 patients, in which asthma is under-reported as comorbidity4. The COVID-19 related mortality rate in our cohort of patients was 7.7%, lower than the COVID-19 mortality rate in the general population (14.5% in Italy 1). These findings suggest that severe asthmatics are not at high risk of the SARS-CoV-2 infection and of severe forms of COVID-19. There are potentially different reasons for this. Self-containment is the first, because of the awareness of virus infections acting as a trigger for exacerbations, and therefore they could have acted with greater caution, scrupulously respecting social distancing, lockdown and hygiene rules of prevention, and being more careful in regularly taking asthma medications.Another possible explanation stands in the intrinsic features of type-2 inflammation, that characterizes a great proportion of severe asthmatics. Respiratory allergies and controlled allergen exposures are associated with significant reduction in angiotensin-converting enzyme 2 (ACE2) expression 7, the cellular receptor for SARS-CoV-2. Interestingly, ACE2 and Transmembrane Serine Protease 2 (TMPRSS2) (another protein mediating SARS-CoV-2 cell entry) have been found highly expressed in asthmatics with concomitant NIDDM8, the only comorbidity that was more frequent reported in our COVID-19 severe asthmatics.The third possible explanation refers to the possibility that inhaled corticosteroids (ICS) might prevent or mitigate the development of Coronaviruses infections. By definition, patients with severe asthma are treated with high doses of ICS 5 and this may have had a protective effect for SARS-CoV-2 infection.Noteworthy, among the patients of our case-series of severe asthmatics with COVID-19, the proportion of those treated anti-IL5 biologics was higher (71%) compared to the number of patients treated with anti-IgE (29%). Although the number of cases is too small to draw any conclusion, it is tempting to speculate that different biological treatments can have specific and different impact on antiviral immune response. In addition we may speculate of the consequence of blood eosinophils reduction: eosinopenia has been reported in 52-90% of COVID-19 patients worldwide and it has been suggested as a risk factor for more severe COVID-19 9.In conclusion, in our large cohort of severe asthmatics only a small minority experienced symptoms consistent with COVID-19, and these patients had peculiar clinical features including high prevalence of NIDDM as comorbidity. Further real-life registry-based studies are needed to confirm our findings and to extend the evidence that severe asthmatics are at low risk of developing COVID-19.

Treatment of refractory Evans syndrome (ES) remains a challenge in Hematology practice. Due to rarity of this condition, evidence-based approaches are limited and often treatment choices stem from small case series or anectodal experiences. Here, we describe three very refractory pediatric ES cases treated on bortezomib without adverse effects. Two of the three patients had dramatical and long-lasting recovery that started following the first doses of the drug. Clinical trials to assess bortezomib role in ES treatment are warrented and results may lead to inclusion of this drug as an option, even as a first-line therapy.

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The authors of “Outcomes of truncus arteriosus repair and predictors of mortality” carried out a retrospective analysis of more than 3000 infants with truncus arteriosus using the National Inpatient Sample dataset of the Healthcare Cost and Utilization Project database. Logistic regression was used to identify factors associated with in-hospital mortality. The authors also identified a seemingly protective effect of 22q11.2 deletion. But do these findings offer a complete understanding of surgical risk factors for patients with truncus arteriosus?

Background: During COVID-19 pandemic, as the prime care is directed towards the management of infected cases, patients with non-communicable diseases are subject to lack of attention. Pediatric Hematology Oncology patients demand holistic care therefore might get affected tremendously during this pandemic. Procedure: An online cross-sectional survey was carried out among the Pediatric Hematologists-Oncologists from all over Pakistan in order to assess the pandemic effects. Responses were received online and data analyzed in SPSS 16.0. Results: Survey was sent to 96 Pediatric Hematologists-Oncologists from 14 different centers with 50% response rate. Majority (62%) were working in public sector hospitals, 14% reported to have stopped registering new patients, 68% reported reduced overall number of patients and 64% reported reduction of patients for scheduled chemotherapies; 78% reported affected supportive care services while 70% reported closure of various units of the department. Affected supplies, specialized investigations, tumor boards, oncological surgeries, radiation therapies, stem cell transplant and academic activities were also reported. Availability of PPE was satisfactory, 62% reported unavailability of isolated febrile neutropenia rooms, 58% reported inability to exercise social distancing in ward while 90% reported to exercise short staff rosters. Significant level of personal and family health concern (M>2.5) and stress (>3.0) during the pandemic were reported by pediatric hematologists/oncologists. Conclusion: Apart from overwhelming issues of COVID-19 patients and their doctors, patients with non-communicable diseases and their treating physicians are also tremendously affected during the pandemic and interrupted management of pediatric hematology oncology patients during pandemic may lead to devastating long term effects.

Saline migrants into freshwater habitats constitute among the most destructive invaders in aquatic ecosystems throughout the globe. However, evolutionary and physiological mechanisms underlying such habitat transitions remain poorly understood. To explore mechanisms of freshwater adaptation and distinguish between adaptive (evolutionary) and acclimatory (plastic) responses to salinity change, we examined genome-wide patterns of gene expression between ancestral saline and derived freshwater populations of the Eurytemora affinis species complex, reared under two different common-garden conditions (0 vs. 15 PSU). We found that evolutionary shifts in gene expression (between saline and freshwater inbred lines) showed far greater changes and were more widespread than acclimatory responses to salinity (0 vs. 15 PSU). Most notably, many genes showing evolutionary shifts in gene expression across the salinity boundary were associated with ion transport function, with inorganic cation transmembrane transport forming the largest Gene Ontology category. Of particular interest was the sodium transporter, the Na+/H+ antiporter (NHA) gene family, which was discovered in animals relatively recently. A few key ion regulatory genes, such as NHA paralog #7, demonstrated concordant evolutionary and plastic shifts in gene expression, suggesting the evolution of ion transporter plasticity and function during rapid invasions into novel salinities. Moreover, freshwater invasions were associated with the evolution of reduced plasticity in the freshwater population, again for the same key ion transporters, consistent with the predicted evolution of canalization following adaptation to stressful conditions. Our results have important implications for understanding invasion mechanisms by some of the most widespread invaders in aquatic habitats.