Three COVID-19 patients who were received lopinavir/ritonavir plus favipiravir got to improved without any severe adverse events. Two patients harboring high fever, severe pneumonia and respiratory failure obtained dramatic improvement. The combination therapy might be a treatment option; earlier therapy onset may have needed to avoid lung sequela.
Due to it is potential application in the field of high energy density materials, how to stabilize cyclopentazolate anion (cyclo-N5-) has attracted many interests theoretically and experimentally. Therefore, a series of ion salts containing [cyclo-N5]- were synthesized and studied. The instability of [cyclo-N5]- is caused by the five lone pairs of electrons localized on five neighbored N atoms. In this work, we expect if the [cyclo-N5]- can be stabilized by the coordination with acidic ligands, by weakening the multi repulsion from the lone pairs to stabilize the [cyclo-N5]-. The two compounds of [N5(BH3)5]-, and [N5(AgCN)5]- have been designed and compared based on the Lewis acid-base theory. [N5(H2O)5]- is designed to evaluate the effect of hydrogen bond in the stabilization. For all the structures, we study the bonding properties and thermal stabilities based on the analysis of electronic structures and Car-Parrinello molecular dynamics (CPMD) simulations. The results indicate it is a effective method to stabilize [cyclo-N5]- by introducing the Lewis acid. Our insights on [cyclo-N5]- compounds with high thermal stability under ambient conditions will provide a new idea for the research and synthesis of new high energetic [cyclo-N5]- series compounds.
Dear Sir We congratulate Dr Guy and colleagues on their paper1which demonstrates that implementation of combined screening using the FMF algorithm2 is feasible in practice and is better than the existing NICE guidelines in prevention of preeclampsia, especially preterm preeclampsia with delivery before 34 weeks. We hope that this will lead to wider application of combined screening for prediction and prevention of preeclampsia.The authors acknowledge that treatment with aspirin will have led to underestimation of screening performance. We would like to highlight this and emphasise the importance of accounting for the effect of aspirin when assessing predictive performance. To make the point, consider the most extreme case with 100% compliance with a treatment that prevents 100% of cases. In the screen positive group, all cases would be prevented by the treatment and classified as false positives. Adopting the same analysis presented in this paper would result in a detection rate and positive predictive value of zero regardless of performance without treatment.In the data presented in this study, for the FMF algorithm with 99% compliance to aspirin at a dose of 150 mg / day and assuming 62% reduction in risk,3 99%×62% = 61.4% of cases of preterm preeclampsia would be prevented and classed as false positives. The remaining 100-61.4% = 38.6% would be classed as true positives so the 15 cases of preterm preeclampsia which led to the detection rate of 15/27 = 55.6% represent just 38.6% of the cases of preterm preeclampsia detected. An estimate of the number detected, including those prevented by aspirin is, 15/0.386 = 39. The estimated number of cases in total is therefore 39 + 12 = 51, obtained by adding the false negatives 27-15 = 12 to the estimated true positives. This gives a detection rate of 39/51 = 76% compared to the figure of 55.6% given in Table 2. Applying similar calculations to the positive predictive value (i.e. proportion of women in the screen positive group who would, without aspirin, have developed preterm preeclampsia) of 9.8%. This should be compared with the 3.8% presented in the paper. Applying the same arithmetic to the NICE group gives a detection rate of 41.6% and a positive predictive value of 2.4%. These are much closer to the figures in Table 2 of the paper because of the relatively low compliance in the NICE group. Other measures of screening performance presented on this paper including the likelihood ratios, negative predictive value the receiver operating characteristic (ROC) curve analysis are also affected by this problem.The arithmetic presented above is intended for illustration; for the SPREE study4 we applied Markov chain monte carlo (MCMC) methods for inferences about screening performance. These or similar methods should be applied in future studies of screening performance.Dave Wright,1 Kypros Nicolaides2Institute of Health Research, University of Exeter, Exeter, UKHarris Birthright Research Centre for Fetal Medicine, King’s College Hospital, London, UK.
Abstract Background and Objectives: Better phenotyping of the heterogenous bronchiolitis syndrome may lead to targeted future interventions. This study aims to identify severe bronchiolitis profiles among hospitalised Australian Indigenous infants, a population at high-risk of bronchiectasis, using Latent Class Analysis (LCA). Methods: We included prospectively collected clinical, viral and nasopharyngeal bacteria data from 164 Indigenous infants hospitalised with bronchiolitis. We undertook multiple correspondence analysis (MCA) followed by LCA. The best-fitting model for LCA was based on adjusted Bayesian information criteria and entropy R2. Results: We identified five clinical profiles. Profile-A’s (23.8% of cohort) phenotype was previous preterm (90.7%), low birth-weight (89.2%) and weight-for-length z-score <-1 (82.7% from combining those with z-score between -1 and -2 and those in the z-score of <-2 group) previous respiratory hospitalisation (39.6%) and bronchiectasis on chest high-resolution computed tomography scan (35.4%). Profile-B (25.3%) was characterised by oxygen requirement (100%) and marked accessory muscle use (45.5%). Infants in profile-C (7.0%) had the most severe disease, with oxygen requirement and bronchiectasis in 100%, moderate accessory muscle use (85% vs 0-51.4%) and bacteria detected (93.1% vs 56.7-72.0%). Profile-D (11.6%) was dominated by rhinovirus (49.4%), mild accessory muscle use (73.8%) and weight-for-length z-score <-2 (36.0%). Profile-E (32.2%) included bronchiectasis (13.8%), RSV (44.0%), rhinovirus (26.3%) and any bacteria (72%). Conclusions: Using LCA in Indigenous infants with severe bronchiolitis, we identified 5 clinical profiles with one distinct profile for bronchiectasis. LCA can characterise distinct phenotypes for severe bronchiolitis and infants at risk for future bronchiectasis, which may inform future targeted interventions.
Dear Editor, With great interest, I read the article by Flécher et al1 and congratulate them on the quality of the review carried out on the history of surgical treatment of cardiac wounds. It is an exciting topic, so I would like to briefly comment on some facts narrated in this work.The well-known surgical approach to the heart, described by Larrey in the subxiphoid region, should not be placed in a close historical relationship with the pericardiotomy he performed in 1810 through a thoracotomy. It was not until 1824 that, after treating a soldier who had suffered a penetrating wound between the xiphoid appendix and the 7th costal cartilage, the French surgeon began experimenting on cadavers in search of a faster route to the heart. In 1829 he proposed his oblique subcostal incision which is currently practically not used.2During Milton’s service in Egypt, he surely performed several thoracic surgeries in extremis situation, but there is no evidence to support the claim that median longitudinal sternotomy (MLS) was created during an emergency approach3 or that has been designed for this type of procedure. When he decided to operate on a living human being on January 25, 1897, he used it for an elective total sternectomy in a patient with sternal tuberculosis and ruled out its use in patients with true mediastinal tumors, who needed more urgent surgeries.On the other hand, it can hardly be said that MLS is currently the gold standard for cardiac surgeons to safely and quickly manage a cardiac stab wound. In patients such as those shown in the article,1 an approach using a MLS would be very difficult since lateral mobilization of the costal wall during the necessary separation of the two halves of the sternum would displace the knife, causing probably fatal bleeding.In the emergency room, the gold standard for quickly managing a penetrating cardiac injury is anterolateral thoracotomy in the fifth intercostal space. A 1906 article on experimental surgery in dogs has led some authors to mistakenly consider Spangaro to be the creator of this incision.4 They forget that in 1893 Daniel Hale William performed his famous pericardioraphy (the second in history) precisely using that approach.5References1. Flécher E, Leguerrier A, Nesseler N. An odyssey of suturing cardiac wounds: Lessons from the past. J Card Surg. 2020;35(7):1597-9.2. López de la Cruz Y, Quintero Fleites YF. Modifications to the classic simple-longitudinal inferior pericardiotomy (Sauerbruch technique). CorSalud. 2019;11(3):225-32.3. Milton H. Mediastinal Surgery. Lancet. 1897;1:872 - 5.4. Pust GD, Namias N. Resuscitative thoracotomy. International Journal of Surgery. 2016;33:202-8.5. Buckler H. Doctor Dan. Pioneer in American surgery. Boston: Little, Brown and Company; 1954.Correspondence: “July 26” Ave., No. 306, Apt. 18. Santa Clara. Villa Clara. Cuba. Postal code: 50 200. E-mail: firstname.lastname@example.org
In this report we describe the clinical presentation, laboratory findings and outcomes of four patients that were referred for urgent cardiothoracic intervention and tested positive for COVID-19. Though the majority of the patients undergoing surgery had low Society of Thoracic Surgeons score and uneventful operating time, mortality was very high and driven primarily by the viral syndrome. Laboratory markers that have been associated with disease severity in the general population were also prognostic in our population. Our study shows that these patients have very high mortality, whereas prevention and preoperative screening is required in preventing nosocomial spreading of the disease.
Reduced representation genome sequencing has popularized the application of single nucleotide polymorphisms (SNPs) to address evolutionary and conservation questions in non-model organisms. Patterns of genetic structure and diversity based on SNPs often diverge from those obtained with microsatellites to different degrees, but few studies have explicitly compared their performance under similar sampling regimes in a shared analytical framework. We compared range-wide patterns of genetic structure and diversity in two amphibians endemic to the Iberian Peninsula: Hyla molleri and Pelobates cultripes, based on microsatellite (18 and 14 loci) and SNP (15,412 and 33,140 loci) datasets of comparable sample size and spatial extent. Model-based clustering analyses with STRUCTURE revealed minor differences in genetic structure between marker types, but inconsistent values of the optimal number of populations (K) inferred. SNPs yielded more repeatable and less admixed ancestries with increasing K compared to microsatellites. Genetic diversity was weakly correlated between marker types, with SNPs providing a better representation of southern refugia and of gradients of genetic diversity congruent with the demographic history of both species. Our results suggest that the larger number of loci in a SNP dataset can provide more reliable inferences of patterns of genetic structure and diversity than a typical microsatellite dataset, at least at the spatial and temporal scales investigated.
With no end in sight to the convergence of COVID-19, countries are struggling with strategies to halt the “second wave” and mitigate economic decline. Estimated to account for around half of the infections, asymptomatic transmission of SARS-CoV-2 has been hampering the containment of the virus. A positive case rate of 10% was reported by Prabhu et al. among 625 pregnant women who were universally screened for SARS-CoV-2 on the day of admission for delivery at 3 institutions in New York City, of which 80% were asymptomatic at the time of testing including pre- and post-symptomatic patients. As evidence shows that virus sheds before symptoms appear and even after their cessation, these populations may have increased the chances of COVID-19 outbreak in the hospitals. Utilization of testing results for isolation practices was not mentioned in the report, possibly given the long turnaround time for the testing platforms at the time.While the risk of nosocomial transmission is affected by clinical settings, the intimate and prolonged nature of childbirth elevates the risk of cross-infection between midwives and women. The role of nosocomial transmission has been increasingly recognized, and its severity risk may be greater than those of community-acquired infections. A recent report has suggested facilities to consider testing pregnant women for SARS-CoV-2 at the time of admission (Rasmussen SA, et al. JAMA. 2020). International Confederation of Midwives has also called for governments to prioritize testing for all pregnant women and their care providers. Identification of infectious women prior to delivery could contribute to prevention of further transmission to patients and healthcare workers. Importance should also be emphasized on evaluating contact history due to the nature of false-negative PCR results (Woloshin S, et al. NEJM. 2020).Another significance of performing testing for SARS-CoV-2 on pregnant women is for the adequate medical management of the women and the fetuses. While outcome for mothers and neonates seems generally favorable, data suggest that pregnancy can be associated with increased risk for severity, including intensive care unit admission and receipt of mechanical ventilation (Ellington S, et al., MMWR Morb Mortal Wkly Rep 2020;69:769–775). Furthermore, a recent article has raised concerns over transplacental transmission of SARS-CoV-2 to the fetus (Vivanti AJ, et al. Nat Commun. 2020;11:3572). Collection of longitudinal data is crucial to understand the effects of SARS-CoV-2 infection on maternal and neonatal outcomes. Results of large-scale prospective cohort studies, such as INTERCOVID study, are expected to add high-quality evidence on the effects of COVID-19 in pregnancy on the health of the mothers, fetuses, and newborns.Screening a maternity population under a pandemic can be a way to provide a glimpse of the distribution of the population, since capacity constraints still impede widespread testing in many countries. Recent development of faster diagnostic testing could bring improvement, but test sensitivity will remain a challenge. Fundamental preventive measures and clinical management should be continued; that is, hygiene and social distancing practices for women themselves, and careful evaluation of each mother and fetus for care providers.
Objectives: Short-term outcomes for those with a prolonged length of stay (LOS) in intensive care (ITU) following cardiac surgery are poor, with higher rates of in-hospital mortality and morbidity. Consequently, discharge from hospital has been considered the key measure of success. However, there has been a shift towards long-term outcomes, functional recovery and quality of life (QoL) as measures of surgical quality. The aim of this review is to compare and critique the findings of multiple studies in order to determine the long-term effects of prolonged ITU stay post-cardiac surgery. Methods: A computerised literature search of CINAHL, EMBASE and Google Scholar databases, based on keywords ‘long-term effects’; ‘prolonged ITU stay’; ‘cardiac surgery’, with rigorous CASP critique, was undertaken. Results: The search yielded 12 papers meeting the inclusion criteria, with eight retrospective and four prospective studies. Eight of these 12 papers identified inferior long-term survival or higher mortality rates for those who had prolonged LOS in ITU in comparison to ‘normal’ LOS or a control. The greatest burden of mortality was six months to one year post-discharge. Three papers found that quality of life was adversely affected or worse for those who had experienced prolonged LOS in ITU. Conclusions: Further research is required to provide better quality evidence into QoL, following prolonged stay in ICU post cardiac surgery. The evidence reviewed suggests that the risk of mortality in this demographic of patients is higher, especially within the first year and, therefore, more frequent medical surveillance of these patients is recommended.
Typically, the Crack Tip Opening Displacement (CTOD) is used only to quantify the crack closure phenomenon. However, more information about crack tip phenomena can be extracted from the CTOD curves, which can be used for a better understanding of fatigue crack growth. The main objective here is the development of a numerical tool for the automatic analysis of CTOD plots, which can be obtained either numerically using the Finite Element Method (FEM) or experimentally using Digital Image Correlation (DIC). The parameters extracted are the elastic and plastic CTOD in loading and unloading regimes, the corresponding load ranges, the crack opening and closure levels and the dissipated energy. This tool is expected to promote a fast and efficient analysis of DIC and FEM results, facilitating the implementation of CTOD analysis in the fatigue community.
Introduction Childhood cancer survivors (CSs) might face an increased lifelong risk of lung function impairment. The Lung Clearance Index (LCI) has been described as being more sensitive than spirometry in the early stages of some lung diseases. The aim of this study was to evaluate this index in a cohort of patients with a history of childhood cancer for the first time. Materials and Methods We evaluated 57 off-treatment CSs aged 0–18 years old and 50 healthy controls (HCs). We used the multiple breath washout (MBW) method to study LCI and spirometry. Results CSs did not show any differences from the controls in ventilation homogeneity (LCI 6.78 ± 1.35 vs. 6.32 ± 0.44, P: ns) or lung function (FEV1 99.9 ± 11.3% vs. 103.0 ± 5.9% of predicted, P: ns; FVC 98.2 ± 10.3% vs. 101.1 ± 3.3% of predicted). LCI significantly correlated with the number of years since the last chemotherapy (r = 0.35, P < 0.05). Conclusions Our study describes the trend of LCI in a cohort of CSs and compares it with the results obtained from healthy controls. The results show that patients maintain both good values of respiratory function and good homogeneity of ventilation during childhood. Moreover, the LCI identifies the tendency toward pulmonary fibrosis, which is typical of adult CSs, at an earlier time than spirometry.
Modern healthcare requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of the distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions on the efficacy of the current management of allergic diseases requires further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen-immunotherapy with a special emphasis on specific IgE, microbiome and epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.
Case report A 74-year-old man presented with frequent palpitations, described as “the heart beating on the neck.” He also had a history of two syncope episodes; the most recent was more than six months before his admission. By careful history taking, we found that the syncope episodes did not seem to occur as a result of vasovagal reflex. The patient’s resting electrocardiogram (ECG) showed a right bundle branch block (RBBB) pattern (Figure 1 ). Holter monitoring and exercise tests revealed a bundle branch block alternating between the right and left bundles. His echocardiogram was normal with preserved ejection fraction (EF) (66%).After this initial evaluation, he was subjected to an electrophysiological study (EPS) and the basic intervals measured were as follows: PR, 186 ms; QRS, 153 ms (RBBB); AH, 86 ms (basal); and HV, 60 ms. Atrial electrical stimulation (AES) induced a wide QRS complex tachycardia (Figure 2A ), with predominantly RBBB morphology, some of the QRS having a left bundle branch block (LBBB) pattern, and some atrial beats being blocked to the ventricles below the bundle of His (Figure 2B ).
Authors’ reply re: ’Maternal transmission of SARS-COV-2 to the neonate, and possible routes for such transmission: A systematic review and critical analysis (Response to BJOG-20-1416)Kate F Walker1, Keelin O’Donoghue2, Nicky Grace3, Jon Dorling4, Jeannette L Comeau4, Wentao Li5 Jim G Thornton11Division of Child Health, Obstetrics and Gynaecology, School of Medicine, University of Nottingham2The Irish Centre for Maternal and Child Health, University College Cork, Cork University Maternity Hospital, Cork, Ireland3 School of English, University of Nottingham4Department of Pediatrics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada5Department of Obstetrics and Gynaecology, Monash University, Clayton, AustraliaThank you for the opportunity to comment on the letter by Dr Xue from Shanghai Jiao Tong University. We agree there are many weaknesses in the data we reviewed. Dr Xue has identified one. Others are the incomplete reporting of infant feeding and mother-child interactions, and the frequent lack of infant testing to confirm or refute the possibility of vertical transmission of COVID-19. Finally, although we simply provided summary totals, it would be statistically preferable to combine series using the Mantel-Haenszel method and calculate a relative risk. We judged that doing this in light of the uncertainties around the data which Dr Xue has identified, might give a spurious precision to our results. As he says, more work is needed. For now we think it remains reasonable to not regard COVID-19 in itself, as an indication for Caesarean, artificial feeding or separation, in the mother and baby’s interest.
Optical cables are enormous transmission media which carries high-speed data across transatlantic, intercontinental, international boundaries and cities. The optical cable is essential in data communication. The cable has become an indispensable component in optical communications infrastructure; hence, conscious efforts are always adopted to prevent or minimize faults in the optical network infrastructure. Typically, tracing fault in the underground optical network has been difficult even though optical time-domain reflectometer (OTDR) has been used to measure the distance of faults in the underground fiber cable. The methodologies deployed in the reviewed literature indicate a vast gap between the fault distance measured by the OTDR and the actual distance of fault. This paper observed the difficulties involved in tracing the actual spot of fault in the underground optical networks. The difficulty of tracing these underground faults mostly result in an undue delay and loss of revenue. This research presents a machine learning (ML) approach to predict the actual location of a fiber cable fault in an underground optical transmission link. Linear regression in the python sci-kit learn library was used to predict the actual location of a fault in an underground optical network. The MSE and MAE evaluation matrix used provided good accuracy results of 0.061291 and 0.080143, respectively. The result obtained in this paper indicates that faults in underground optical networks can be found quickly to avoid the delays in the fault tracing process, which leads to an excessive revenue loss.
Crecutzfeldt-Jakob disease (CJD) is a rare, fatal, and devastating neurodegenerative disease，It is not well recognized and increasingly underdiagnosed due to its variant clinical presentations. Here we report a case of probable sporadic CJD in a woman with dizziness as initial symptom and misdiagnosed as acute cerebral infarction.