The COVID-19 epidemic was not the first coronavirus epidemic of this century and represents one of the increasing number of zoonoses from wildlife to impact global health. SARS CoV-2, the virus causing the COVID-19 epidemic is distinct from, but closely resembles SARS CoV-1, which was responsible for the severe acute respiratory syndrome (SARS) outbreak in 2002. SARS CoV-1 and 2 share almost 80% of genetic sequences and use the same host cell receptor to initiate viral infection. However, SARS predominantly affected individuals in close contact with infected animals and health care workers. In contrast, CoV-2 exhibits robust person to person spread, most likely by means of asymptomatic carriers, which has resulted in greater spread of disease, overall morbidity and mortality, despite its lesser virulence. We review recent coronavirus-related epidemics and distinguish clinical and molecular features of CoV-2, the causative agent for COVID-19, and review the current status of vaccine trials.

A document by Nicola Tarantino. Click on the document to view its contents.

Abstract: Fluidized bed technology plays a vital role in petrochemistry and coal separation. To enhance fluidization stability, the flow is periodically introduced into the gas-solid fluidized bed to form a pulsed gas-solid fluidized bed. As the main fluidization parameter, the minimum fluidization velocity (umf) can reflect the change of the critical state of particles in the pulsed gas-solid fluidized bed, directly affecting the study of two-phase distribution in the bed. Due to lack of theoretical study on umf in pulsed gas-solid fluidized bed, the work proposed a novel method to predict umf comibined with soft sphere model. Meanwhile, the spring-damping and the resonance force models were established under the action of pulsating airflow. A theoretical model of umf was then derived for pulsed gas-solid fluidized bed based on experimental stress analysis of particles. The novel correlation is basically agreement with almost available data in the literatures and present work.

Liquid-phase adsorption has hardly been established in micro-flow, although this constitutes an industrially vital method for product separation. A micro-flow UV-photo isomerization process converts cis-cyclooctene partly into trans-cyclooctene, leaving an isomeric mixture. Trans-cyclooctene adsorption and thus separation was achieved in a fixed-bed micro-flow reactor, packed with AgNO3/SiO2 powder, while the cis-isomer stays in the flow. The closed-loop recycling-flow has been presented as systemic approach to enrich the trans-cyclooctene from its cis-isomer. In-flow adsorption in recycling-mode has hardly been reported so that a full theoretical study has been conducted. This insight is used to evaluate three process design options to reach an optimum yield of trans-cyclooctene. These differ firstly in the variation of the individual residence times in the reactor and separator, the additional process option of refreshing the adsorption column under use, and the periodicity of the recycle flow.

In this study, PS was synthesized by gaseous SO3 sulfonation of distillate oil in a rotating packed bed. The chemical compositions of the prepared PS and its raw material (distillate oil) were obtained by the combined analysis of the double-bond equivalent and carbon number at the molecular level. In addition, the EOR performance of PS has been studied by measuring surface tension, interfacial tension (IFT), wettability alteration and core-flooding experiments. An ultra-low IFT value 1.327×10-3 mN/m between the crude oil and prepared PS solution was obtained at the critical micelle concentration (CMC) of PS solution. Core flooding experiments showed that additional oil recoveries of 28.10% and 30.77% were obtained at PS concentrations of 0.3% and 0.6% respectively after conventional water flooding, indicating the prepared PS has good performance on EOR.

Drag force is essential to dense flows, but accurate and robust drag model is still an open issue. Direct numerical simulations of a shallow and a deep bubbling bed of moving rigid spheres have been carried out in the present work by using an immersed boundary method, and big data are produced. It turns out that the drag force in fluidized beds is typically underestimated by traditional drag models which depend only on the particle Reynolds number and the void fraction. With two additional parameters representing the velocity fluctuation and position fluctuation of particles introduced, a drag model based on the artificial neural network is developed. Given the complicated structure of this model, a simplified drag model is also formulated by directly fitting the samples. The drag force predicted by both models agrees excellently with the DNS data and is much more accurate than that predicted by existing models.

During the course of a pressure relief discharge from a vessel containing a multicomponent liquid mixture, composition changes occur that affect the properties vessel contents. In this work, a model of the dynamic relief process for ternary, non-ideal, homogeneous mixtures is developed, under the assumption of vapour-only venting. Opening/re-closing of the relief valve introduces state-events which require re-initialization of the model at each state transition. The relationship between the pressure relief model and the concept of residue curves, which describe simple-distillation processes, is demonstrated. It is known that the presence of azeotropes and distillation boundaries in mixtures restricts the composition trajectories of simple-distillation processes, as well as continuous distillation columns at total reflux. In this work, the residue-curve analogy is extended to vapour-only pressure-relief, where vapour composition changes directly affect the operation of the pressure-relief device. Examples of dynamic relief processes are developed for ternary mixtures with varying non-ideality.

This study deals with the MHD convective flow of Walters-B memory viscoelastic fluid over an accelerating permeable surface under the influence of Soret and Dufour. The modeled equations are set of partial differential equations. These equations are transformed into coupled nonlinear ordinary differential equations with the use of suitable similarity transformation. The thermal radiative heat flux is modeled using the Roseland approximation. Hence, the fluid considered in this study is optically thin. The numerical solution was profound to the transformed equations using spectral homotopy analysis method (SHAM) and results are presented in graphs and tables. The influence of Soret and Dufour are investigated separately. Results hereby revealed that the effect of Soret and Dufour on temperature and concentration profiles is the opposite.

Background: Ticks have the propensity to transmit plethora of pathogens that have zoonotic potentials. Their distribution, diversity and the pathogens they transmit differs from one ecological location to another. SFG (spotted fever group) rickettsiae which are predominantly transmitted by different Ixodes ticks are responsible for emerging zoonotic diseases globally. Ticks were collected from domesticated animals in Raymond Nkandla Municipality, Eastern Cape, South Africa. The ticks were identified morphologically prior to DNA extraction and were molecularly identified by randomly selecting ticks from the morphologically delineated groups. To assess for the presence of tick-borne pathogens belonging to Rickettsia spp. by PCR (polymerase chain reaction) we used specific primer pairs targeting the gltA, ompA and ompB genes. The selected amplified ticks (according to morphological delineations), all positive ompB and forty three ompA amplicons were sequenced in a commercial sequencing facility. The obtained nucleotide sequences were edited and subjected to BLASTn for homology search and phylogenetic analyses were performed with MEGA 7 Version for evolutionary relationships with curated reference sequences in GenBank. Results: A total of 953 ticks collected in the study were delineated into three genera consisting of Amblyomma, Rhipicephalus and Hyalomma in decreasing order of abundance. The presence of Rickettsia DNA was detected in 60/953 (6.3%) from the three genera of ticks screened. Genetic analyses of the DNA sequences obtained showed that they have phylogenetic relationship to members of spotted fever group rickettsiae with R. africae, R. parkeri and R.tamurae being the SFGR (spotted fever group rickettsiae) detected in the screened ticks. Conclusion: This report shows that R. africae is the predominant spotted fever group rickettsiae in ticks collected from domestic animals in the study area and the human health impacts are not known.

In this study, the digital droplet polymerase chain reaction (ddPCR) was used to quantify circulating bovine papillomavirus (BPV; genus: Deltapapillomavirus) levels in blood samples from 25 healthy cows and 15 cows with chronic enzootic hematuria due to papillomavirus-associated bladder tumors. ddPCR detected the BPV DNA in 95% of all the samples (i.e., in 24 of the healthy cows and 14 of the diseased animals), whereas quantitative real time PCR (qPCR) detected it in only 57.5% of the same blood samples, with the percentage differences between ddPCR and qPCR being statistically significant (P value  0.05), according to the 2 test of Campbell and Richardson. Furthermore, ddPCR detected BPV infections by a single genotype and by multiple genotypes in 37% and 63% of the cows, respectively, whereas qPCR detected these in 16% and 16%, respectively. Of the two assays, ddPCR was the more sensitive and accurate clinical diagnostic tool, allowing the detection of otherwise undetectable BPV genotypes, and consequently, a higher number of BPV co-infections. qPCR failed to detect many BPV co-infections by multiple genotypes. Therefore, ddPCR may be an essential tool for improving diagnostic procedures, allowing the identification of the genotypic distribution of BPV and a better understanding about the territorial divergence, if any, of the BPV prevalence in different areas. No significant differences in the blood viral load estimations were observed between the two animal groups, suggesting that the bloodstream could be a site of primary infection. Finally, as BPV DNA was detected in cows affected by noninvasive urothelial tumors, including papilloma and papillary urothelial neoplasms of low malignant potential, the circulating BPVs appeared to be independent of the status of urothelial neoplasms. Therefore, unlike in humans, circulating BPVs cannot be an actual prognostic marker of urothelial tumors in cows.

Background: A tremendous research on signal transducer and activator of transcription (STAT3) pertaining to cancer. It regulated the gene expressions like normal cellular process includes differentiation, cell development, proliferation, survival, maturation and immune perform. There are many drugs are clinically approved derivatives are used as STAT3 for cancer therapy suffer from many limitations related to stability and toxicity. Experiment: In order to envisage structurally diverse novel chemical entity as STAT3 poison with better efficacy, Ligand-based-pharmacophore model was developed using 3D QSAR pharmacophore generation (HypoGen algorithm) methodology in Discovery studio 4.1 clients. The chemical features of 48 different derivatives were taken as the training set. The selected pharmacophore model Hypo1 was further validated by 15 test set molecules and used as a query model for further screening of 1,45,000 drug-like molecules from SPECS databases. These molecules were subjected to several assessments such as Lipinski rule of 5, verber’s rule and SMART filtration. The molecule obtained after filtration was further scrutinized by molecular docking analysis on the active site of STAT3 crystal structure. Result: 19 potential inhibitory molecules have been selected by analysing the binding interaction and Ligand- Pharmacophore mapping with the validated pharmacophore model. These 19 hits are further subjected to TOPKAT program for toxicity assessment. These 19 hit molecules can be utilized for designing future class of potential STAT3 inhibitor. Conclusion: From the result of all of these studies compounds Specs 1, Specs 9, Specs 13, Specs 17, Specs 28 and Specs 37 was finalised for further studies.

Background: To investigate the comparative effects of Renin-Angiotensin System (RAS) Blockades and other antihypertensive agents on insulin sensitivity, metabolic cytokines and glycemic control in non-diabetic patients. Methods: We searched for the relevant articles published on MEDLINE, EMBASE, Cochrane Library and Web of Science. 29 randomized control trials that investigated the use of Angiotensin-converting enzyme inhibitors (ACEI) or Angiotensin receptor blockers (ARB) versus active comparator or placebo to determine the effects on insulin sensitivity and glycemic index in non-diabetics were included. Subgroup and meta-regression analyses were performed to explore potential sources of heterogeneity. Results: RAS Blockades significantly decreased the homeostasis model assessment of insulin resistance and fasting plasma glucose (WMD −0.69, 95% CI −1.01 to −0.38, p < 0.001; WMD −0.09 mmol/L, 95% CI −0.15 to −0.03, p = 0.003, respectively), while increased the quantitative insulin sensitivity check index (WMD 0.02, 95% CI 0.01 to 0.03, p < 0.001) among non-diabetic patients. Besides, RAS Blockades significantly decreased hsCRP and TNF-α (WMD −0.41 mg/L, 95% CI −0.70 to −0.11, p = 0.007; WMD −0.21 ng/mL, 95% CI −0.30 to −0.13, p < 0.001, respectively), while increased adiponectin and potassium (WMD 0.46 μg/mL, 95% CI 0.14 to 0.78, p = 0.005; WMD 0.24 mmol/l, 95% CI 0.10 to 0.39, p = 0.001, respectively). Conclusions: RAS Blockades are superior to other antihypertensive agents in improving insulin sensitivity, glycemic control and some metabolic cytokines in non-diabetic patients, indicating a better antihypertensive choice, which probably delays the onsets of diabetes.

The data used in the analysis were obtained from an ecologically restored plant community. The basic idea presented in this study is that the conventionally defined chemical potential μi can be used as a growth potential index for a species for evaluating the biotic effect on its realized niche. An ecological niche defines a suitable environment for a species to live while μi defines the adaptability of a species to a given environment. The deviation from the fundamental niche of a plant species due to changes in its living environment will thus be reflected by the changes in its μi value. The μi factor is a function of μi0 (the standard chemical potential) and N (the species number). Similar to the fundamental niche, μi0 is uniquely determined by abiotic factors. Increasing N will reduce μi and thus, similar to the realized niche, μi takes into account the biotic effect.

Then novel coronavirus disease (COVID-19) epidemic was considered to be the worst and complex virus outbreak, which caused 56,985 deaths as of April 22, 2020 already. The epidemic infectious may cause mental health crisis. Meanwhile, little is known about the specific psychological status of the COVID-19 survivors and healthcare workers. This cross-sectional study surveyed the mental health among 20 COVID-19 survivors, 54 nurses, and 24 hygienists in Wuhan, China and analyze the possible impact factors using the Symptom Check List 90 - Revised (SCL90-R) questionnaire. 3 indices and 9 dimensions were compared among job, education level, gender, age, marriage classification. This study found that mental distress among participants was not very serious in general. The survivors presented a highest score, then the hygienists, and the lowest in nurses. Low-educated and women showed significant increase. No significant difference was noted in age and marriage classification. Our study indicated that the survivors need psychological support immediately. Meanwhile, healthcare workers warrant more attention, especially low-educated and women. Comprehensive emergency response plan was warranted.

Background Increased uterine activity (UA) may not allow adequate recovery time for foetal oxygenation. Objectives To determine if increased UA during labour is associated with an increased risk of either short- or long-term neurological injury in term neonates, or with neonatal proxy measures of intrapartum hypoxia-ischemia. Search Strategy MEDLINE, CINAHL, and ClinicalTrials.gov using terms uterine activity, Excessive Uterine Activity, XSUA, Uterine hyperstimulation, and Tachysystole. Selection Criteria Any study that analysed the relationship between UA during term labour and neurological outcomes/ selected proxy neurological outcomes was eligible for inclusion. Data Collection and Analysis Outcomes from individual studies were reported in tables and presented descriptively with odds ratios (OR) and 95% confidence intervals (CI) for dichotomous outcomes and means with standard deviations for continuous outcomes. Where group numbers were provided, ORs and CIs were calculated according to Altman. Main Results Twelve studies met the inclusion criteria. Seven studies featured umbilical artery pH as an individual outcome. Umbilical artery base excess and Apgar scores were both reported as individual outcomes in four studies. No study examined long term neurodevelopmental outcomes and only one study reported on encephalopathy as an outcome. The evidence for a relationship between UA and adverse infant outcomes was inconsistent. The reported estimated effect size varied from non-existent to clinically significant. Conclusions There is some evidence that increased UA may be a non-specific predictor of depressed neurological function in the newborn, but it is inconsistent and insufficient to support the conclusion that an association generally exists.

Title: Real-life study in non-atopic severe asthma patients achieving disease control by omalizumab treatmentTo the Editor,Severe asthma is defined as asthma requiring treatment with guidelines-suggested medications for Global Initiative for Asthma (GINA) steps 4 or 5 or systemic corticosteroids for ≥50% of the previous year to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.1 Up to 34%–50% of severe asthmatic patients have non-atopic (also called non-allergic) asthma. 2 A significant proportion of these patients have severe uncontrolled asthma, which requires high doses of inhaled corticosteroids (ICS) or even oral corticosteroids (OCS).2 Until the advent of biologics, treatment options in these patients have been very limited. For many years, both the pathogenesis knowledge and the results of clinical trials supported the view that anti-IgE treatment is specifically effective in allergic asthma. Interestingly, recent molecular and clinical evidence suggests that anti-IgE treatment might also be effective in patients with non-allergic asthma.2 Omalizumab (Xolair®) is an anti-IgE monoclonal antibody that selectively binds to human IgE and prevents the binding of IgE to its receptors. Although omalizumab is indicated in Europe in patients with severe persistent allergic asthma, several case reports and short series have provided data on the value of omalizumab in patients with non-atopic asthma.3,4The observational, multicenter, retrospective, real-life FENOMA study specifically evaluated patients who achieved full asthma control after one year of treatment with omalizumab.5 The study included 345 patients, 80 (23.2%) of whom had non-atopic asthma. The present post-hoc sub-analysis aims to describe the clinical improvement of patients with non-atopic asthma. Socio-demographic and asthma-related characteristics were collected at baseline. Outcomes analyzed at baseline and after one year of treatment were those included in the definition of asthma control by GEMA guidelines.5 Medical records were reviewed between February 2015 and June 2016. For statistical comparisons, the 2-sided Wilcoxon signed-rank test was used. A P-value of <0.05 was considered to be statistically significant. All analyses were performed with the SAS statistical package (version 9.4; SAS Institute, Cary, NC).The primary outcome of this post-hoc sub-analysis was to describe the baseline characteristics and clinical improvement of non-atopic asthma patients who achieved full disease control after one-year of treatment with omalizumab through i) frequency of daytime symptoms, ii) changes in use of ICS or OCS iii) need for rescue therapy, iv) pulmonary function (forced expiratory volume in 1 second [FEV1]), v) number of non-severe exacerbations and vi) use of healthcare resources, i.e. unplanned visits to primary care or specialists and the number of days of school or workplace absenteeism due to asthma worsening. Non-severe asthma exacerbations were defined as those that did not require OCS, emergency assistance or hospitalization. Secondary outcomes include an assessment of the percentage of eosinophil blood count and exhaled nitric oxide fraction (FeNO) before and after treatment.Demographic, clinical characteristics and asthma history (before starting treatment with omalizumab) are shown in Table 1 . Mean (SD) age of patients was 58.7 (12.2) years and 65% were female. Almost all patients had daytime symptoms, 92% of patients needed rescue medication, and the mean (SD) initial dose of omalizumab was 338.7 (153.1) mg.After one year of treatment with omalizumab 50.0% (n=40) of patients had no daytime symptoms, while 37.5% (n=30) and 12.5% (n=10) had symptoms 1 and 2 days per week, respectively. Forty-one (51.2%) of the 54 patients who were receiving OCS at entry, stopped treatment (P<0.0001). Of those continuing on OCS, the average reduction of the daily dose was not statistically significant (P=0.2132). More than half of patients (53.7%, n=43) needed no rescue medication. Median FEV1 increase was 15% and there was a reduction in the number of non-severe asthma exacerbations. After one year of treatment with omalizumab, a great reduction in unplanned visits and absenteeism from school or workplace (P<0.0001; Table 2 ) was observed.Of note, the effectiveness of omalizumab was previously assessed in a Spanish multicenter registry, which evaluated 29 non-atopic severe asthma patients over 2 years.6 However, our series is the most extensive study in patients with non-atopic asthma published to date in Spain, and provides data on full disease control. There have been several potential suggestions to explain the effectiveness of omalizumab in non-atopic patients.7 In a proof-of-concept study in non-atopic asthma patients, treatment with omalizumab resulted – as per in atopic patients – in a significant reduction of high-affinity IgE receptor (FcεRI) expression on blood basophils and plasmacytoid dendritic cells (pDC2), which hampered IgE binding and the subsequent production on proinflammatory mediators.8 Additionally, omalizumab treatment was associated with an increase in FEV1 with a positive trend in some relevant clinical endpoints, such as asthma exacerbations.8 In another proof-of-concept trial, omalizumab therapy (but not placebo) reduced IgE expression and IgE sensitization of target cells within the bronchial mucosa, and increased FEV1 versus baseline despite withdrawal of conventional therapy.9 Interestingly, it has been hypothesized that patients labelled as ‘non-allergic’ might in fact have a localized allergy to an unrecognized allergen, with elevated concentrations of allergen-specific IgE antibodies in the airways.7Our study has several limitations. Its single-arm retrospective nature relies on the accuracy and completeness of the information entered into the clinical records. This has especially affected predictors of response such as FeNO and the level of eosinophils, which were not routinely assessed in the clinical practice at the time of the study. The benefits of omalizumab presented here are those observed in the population of non-atopic patients who achieved disease control after one year of treatment with omalizumab. It is unknown how many other patients classified as non-atopic in the clinical practice did not benefit from this treatment.In summary, in the population of patients with non-atopic severe asthma who achieved full disease control after one year of treatment with omalizumab, the clinical and pulmonary benefits were remarkable and similar to those described for atopic patients. A reduction in the use of healthcare resources was also documented. Large randomized controlled trials are warranted to confirm the value of omalizumab in this population of patients.

Vegetation restoration can not only preserve soil and water and reduce soil erosion, but also improve soil properties and quality significantly. However, different vegetation types have different effects on soil organic carbon fractions and enzyme activities. In this study, we examined the response of soil organic carbon fractions and enzyme activities to different types of vegetation (i.e., Xanthoceras sorbifolia (XS), Hippophae rhamnoides (HR), Caragana korshinskii (CK), Grassland (GL)) on the northern Loess Plateau. The contents of soil organic carbon (SOC), microbial biomass carbon (MBC), easily oxidized carbon (EOC) and particulate organic carbon (POC) and the enzyme activities (i.e., amylase, catalase, urease and surase) were investigated at the end of plant growth. We found that the content of soil SOC fractions and enzyme activities upper > lower layer in each vegetation types except for MBC and catalase activity. There was no significant difference in MBC content and catalase activity between soil layers. The EOC and amylase of GL vegetation were significantly higher than other vegetation types. POC, SOC, urease and sucrase were significantly higher in SX vegetation than other vegetation types. The maximum soil MBC content was found in HR vegetation, and among the four vegetation types, the MBC content showed significant differences in lower layer, but no significant difference in the surface soil. Correlation analysis showed that the MBC significant influenced on the catalase activities; POC significant affected urease and sucrase activities; SOC extremely significant influenced on the urease and sucrase activities. Therefore, vegetation type was an important factor affecting the change of soil enzyme activities and carbon fractions on the Loess Plateau.

An equation of the threshold stress intensity factor range was proposed for the fatigue crack growth using a nonlinear region of unique fatigue fracture. The following phenomena, peculiar to the peening specimen with a pre-crack, were analyzed using previous experiment results based on the proposed equation. As a result, the following ① to ④ phenomena could be evaluated quantitatively whereas ⑤ was evaluated qualitatively. ① Pre-crack size that can be rendered harmless by peening; ② Fatigue limit of pre-crack specimen that cannot be rendered harmless; ③ A phenomenon that fatigue fracture appears from outside the pre-cracked part on most of the harmless pre-crack specimen; ④ Non-propagating crack condition of stage II (tensile type), observed in most specimen showing fatigue limit; and ⑤ Qualitative analysis for initiation of non-propagating stage II crack (tensile type) in the peening specimen based on the reference regarding to a micro distribution of residual stress due to peening.

Sir,We read with great interest the recent study by Misra et al.evaluating different surgical interventions for the treatment of pain associated with endometriosis.1 We understand the importance of this research to inform our clinical practice and extend our gratitude to the researchers, the women who participated in the study, and the research funder.BJOG: An International Journal of Obstetrics and Gynaecology has been at the forefront of reducing research waste by implementing several important interventions including the requirement to prospectively register randomised trials, implementing the Consolidated Standards of Reporting Trials (CONSORT) statement, and mandating the reporting of core outcome sets.2Reflecting upon this recent study presents an opportunity to consider the impact of implementing such initiatives on selective outcome reporting. The authors prospectively registered their trial (ISRCTN50928834) and reported their pre-specified primary outcome as pelvic pain. This differs from the primary outcome reported in the final publication. A secondary outcome, dyspareunia, reported in the final publication, was not prospectively registered. The CONSORT statement commits researchers to report all prespecified primary and secondary outcomes. When new outcomes are added this should be made clear in the final publication and a comprehensive explanation provided. It would be useful for the authors to clarify the discrepancies between the prospective registry record and the published trial report.Core outcomes aim to address the challenges of poorly selected, collected, and reporting outcomes, including tackling outcome reporting bias.3 We are grateful to the authors for acknowledging the development of a core outcome set for endometriosis research within their study report. The core outcome set for endometriosis has recently been published and was developed using formal consensus methods involving 116 healthcare professionals, 32 researchers, and 206 women with endometriosis from 29 countries.4 The core outcomes include overall pain, improvement in most troublesome symptom, quality of life, adverse events, and patient satisfaction with treatment. It would be useful for the authors to clarify if the core outcomes had been collected as part of the trial and report available data.Over eight speciality journals, including the Cochrane Gynaecology and Fertility Group, have committed to supporting the development, dissemination, and implementation of the core outcome set for endometriosis. The collaboration who have developed the core outcome set for endometriosis are now assisting with implementation and are systematically examining published endometriosis trials. Where inconsistencies between the trial registry record and the outcomes reported in the published trial report are identified or when the core outcome set has not been fully reported we are writing to the authors seeking clarification. Our progress can be followed at https://twitter.com/EndoOutcomes where we will be posting the prospective registry record, final publication, and response to this letter.

Background: Objective data on chemosensitive disorders during COVID-19 are lacking in the Literature.Methods: Multicenter cohort study that involved four Italian hospitals. 345 COVID-19 patients underwent objective chemosensitive evaluation.Results:  Chemosensitive disorders self-reported by 256 patients (74.2%) but the 30.1% of the 89 patients who did not report dysfunctions proved objectively hyposmic. 25% of patients presented serious long-lasting complaints. All asymptomatic patients had a slight lowering of the olfactory threshold. No significant correlations were found between the presence and severity of chemosensitive disorders and the severity of the clinical course. On the contrary there is a significant correlation between the duration of the olfactory and gustatory symptoms and the development of severe COVID-19.Conclusions: patients under-report the frequency of chemosensitive disorders. Contrary to recent reports, such objective testing refutes the proposal that the presence of olfactory and gustatory dysfunction may predict a milder course, but instead suggests that those with more severe disease neglect such symptoms in the setting of severe respiratory disease.

Background: PCR used for SARS‐CoV‐2 diagnosis is variable and unstable. Lung ultrasound has good safety and accuracy in pneumonia. We aim to evaluate the ability of bedside lung ultrasound in suspecting the diagnosis and/or predicting the prognosis of Covid 19 infection. Patients & Methods: We recruited any case with pulmonary symptoms necessitating admission in intermediate care and/or ICU during the period between 27th March and 11th April 2020 in 3 international centres. Patients were stratified according to Covid 19 PCR results. All patients underwent chest X ray, CT, lung ultrasound, echocardiography and laboratory analysis. Results: Eighty-two cases were recruited. Fifty cases (61%) were negative for SARS‐CoV‐2 while 32 cases (39%) were positive. Sixty-four cases (78%) were recovered while 18 cases (22%) died. Covid 19 patients had more A profile and more abnormal A lines than non-Covid 19 group (p<0.001). Smoking, congestion in X ray, A profile and abnormal A lines in lung ULS are independent predictors for Covid 19 infection. A scoring system for prediction of Covid 19 using clinical and radiological data was calculated with a sensitivity of 93.8% and a specificity of 58%. Mortality in Covid 19 patients is significantly correlated with age, duration of fever, presence of cardiac disease, B profile and abnormal A lines by lung ULS. However, it is negatively correlated with initial O2 saturation and EF by echocardiography Conclusion: Lung ULS could predict SARS‐CoV‐2 infection among patients with pulmonary symptoms necessitating admission. Lung ULS can also predict the outcome of Covid 19 infected patients.

Treatment of patients with concomitant patent foramen ovale (PFO), atrial septal aneurysm (ASA), and multi fenestrated ASDs (mfASD) poses many challenges and may need several devices placed across the atrial septum which is more challenging, problematic and expensive. This is done by careful interrogation of the atrial septum by color doppler echocardiography, preferably by transoesophageal or three-dimensional transesophageal echocardiography (3D TEE) at the time of catheterization. We report one case who referred for PFO closures that were found to have an atrial septal aneurysm and multiple small holes. we used one occluder device Uni occlutech to close the PFO and fenestrations that this technique was with high success and without complication.

COVID-19 Clinical trials: quality matters more than quantity

Objective: to establish a prognostic model informing optimal timing of delivery in women with late preterm preeclampsia. Design: development and validation of a prognostic model Setting: prospective cohort study, nested in the PHOENIX trial, in 36 maternity units across England and Wales. Population: women with late preterm pre-eclampsia (34+0-36+6 weeks’ gestation) Methods: prospective recruitment of women in whom blood samples for Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) testing was obtained, alongside clinical data, for use within the ‘Prediction of complications in early-onset pre-eclampsia’ (PREP)-S model. Candidate variables were compared using standard methods (sensitivity, specificity, Receiver Operator Curve areas). Estimated probability of early delivery from PREP-S was compared to actual event rates by calibration. Main Outcome Measures: clinically indicated need for delivery for pre-eclampsia within seven days. Results: PlGF testing had high sensitivity (97.9%) for delivery within seven days, but negative predictive value was only 71.4%, with low specificity (8.4%). The area under the curve for PREP-S was 0.64 (standard error (SE) 0.03), for PlGF was 0.60 (SE 0.03), and 0.65 (0.03), and 0.64 (0.03) for PREP-S in combination with PlGF and sFlt-1:PlGF, respectively. Conclusions: PlGF-based testing does not add to clinical assessment to determine need for delivery in late preterm pre-eclampsia. Existing models developed in women with early onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. Funding: NIHR HTA Monitoring Add on Studies Programme (reference 15/59/06). Keywords: placental growth factor, preeclampsia, prognosis