The frequent occurrence of disasters has prompted the development of efficient disaster-responding equipment. This study deals with the design of special-purpose machinery and its performance assessment. We defined scenarios through the environmental analysis of disaster situations and expert consulting. We also formulated a set of design specifications by analyzing the objectives of the tasks that must be performed at disaster sites, based on simulated scenarios and existing disaster response machinery. The disaster-responding special-purpose machinery was designed to perform various tasks and display rapid movement in disaster situations. And this paper presents the control structure configured to operate the developed machinery. The performance of the special-purpose machinery was assessed through different scenario tests. 

Aim: Dapagliflozin improves glycaemic control in patients with type 2 diabetes mellitus (T2DM) and is approved in European and Japanese patients with type 1 diabetes mellitus (T1DM) with inadequate glycaemic control. The objectives of this work were to characterise the dapagliflozin pharmacokinetics (PK) in patients with T1DM, assess the influence of covariates on dapagliflozin PK, and compare dapagliflozin systemic exposure between patients with T1DM and T2DM. Methods: Population PK analysis was performed using a non-linear mixed-effect modelling approach. The analysis included 5,793 dapagliflozin plasma concentrations from 1,150 adult patients with T1DM, collected from one phase 2 (NCT01498185) and two phase 3 studies (DEPICT-1, NCT02268214; DEPICT-2, NCT02460978). Covariate effects were investigated using stepwise covariate modelling. Model-derived area under the concentration-time curve (AUC) was compared with AUC in patients with T2DM. Results: The final two-compartmental model adequately described the dapagliflozin concentrations in patients with T1DM. The estimated apparent clearance was 20.5 L/h. Model-predicted systemic exposure for 5 mg and 10 mg of dapagliflozin indicated dose-proportionality and was comparable between patients with T1DM and T2DM. The identified covariate relationships showed that patients with better renal function (measured as estimated glomerular filtration rate), males, and heavier patients had lower dapagliflozin systemic exposure. Among the covariates studied, no covariates affected dapagliflozin systemic exposure to a clinically relevant extent. Conclusions: Dapagliflozin PK in patients with T1DM was adequately described by the population PK model and no clinically relevant covariates were identified. Dapagliflozin systemic exposure was comparable between patients with T1DM and T2DM. NCT01498185, NCT02268214, NCT02460978

Animals like mink, cats and dogs are susceptible to SARS-CoV-2 infection. In the Netherlands, 69 out of 127 mink farms were infected with SARS-CoV-2 between April and November 2020 and all mink on infected farms were culled after SARS-CoV-2 infection to prevent further spread of the virus. On some farms, (feral) cats and dogs were present. This study provides insight into the prevalence of SARS-CoV-2 positive cats and dogs in ten infected mink farms and their possible role in transmission of the virus. Throat and rectal swabs of 101 cats (12 domestic and 89 feral cats) and 13 dogs of ten farms were tested for SARS-CoV-2 using PCR. Serological assays were performed on serum samples from 62 adult cats and all 13 dogs. Whole Genome Sequencing was performed on one cat sample. Cat-to-mink transmission parameters were estimated using data from all ten farms. This study shows evidence of SARS-CoV-2 infection in twelve feral cats and two dogs. Eleven cats (19%) and two dogs (15%) tested serologically positive. Three feral cats (3%) and one dog (8%) tested PCR-positive. The sequence generated from the cat throat swab clustered with mink sequences from the same farm. The calculated rate of mink-to-cat transmission showed that cats on average had a chance of 12% (95%CI 10% to 18%) of becoming infected by mink, assuming no cat-to-cat transmission. As only feral cats were infected it is most likely that infections in cats were initiated by mink, not by humans. Whether both dogs were infected by mink or humans remains inconclusive. This study presents one of the first reports of interspecies transmission of SARS-CoV-2 that does not involve humans, namely mink-to-cat transmission, which should also be considered as a potential risk for spread of SARS-CoV-2.

Early signaling events in response to elicitation include reversible protein phosphorylation and re-localization of plasma membrane (PM) proteins. Oligogalacturonides (OGs) are a class of Damage-Associated Molecular Patterns (DAMPs) that act as endogenous signals to activate the plant immune response. Previous data on early phosphoproteome changes in Arabidopsis thaliana upon OG perception uncovered the immune-related phospho-regulation of several membrane proteins, among which PCaP1, a PM-anchored protein with actin filament-severing activity, was chosen for its potential involvement in OG- as well as flagellin-triggered responses. Here we demonstrate that PCaP1 is required for late, but not early, responses induced by OGs and flagellin. Moreover, pcap1 mutants, unlike the wild type, are impaired in the recovery of full responsiveness to a second treatment with OGs performed 24 h after the first one. Localization studies on PCaP1 upon OG treatment in plants expressing a functional PCaP1-GFP fusion under the control of PCaP1 promoter revealed fluorescence on the PM, organized in densely packed punctate structures, previously reported as microdomains. Fluorescence was found to be associated also with endocytic vesicles, the number of which rapidly increased after OG treatment, suggesting both an endocytic turnover of PCaP1 for maintaining its homeostasis at the PM and an OG-induced endocytosis.

Chronic myeloid leukemia (CML) is a myeloproliferative disorder due to translocation between chromosomes (9, 22), known as the “Philadelphia chromosome.” In 2016, the World health organization (WHO) introduced a new clinical entity of de novo acute myeloid leukemia (AML). Both diseases share some commonalities, therefore, create a challenge to diagnose.

Cd1-xZnxS thin films were deposited by chemical bath deposition (CBD) on glass substrate to study the influence of cadmium sulfate concentration on the structural characteristics of the thin film. The SEM results show that the thin film surfaces under the cadmium sulfate concentration of 0.005 M exhibit better compactness and uniformity. Due to the less Cd2+ involved in the reaction and little precipitation in the solution. The distribution diagrams of thin film elements illustrate that the film growth rate changes on the increase, decrease, and increase with the increase of cadmium sulfate concentration. XRD studies exhibit the crystal structure of the film is hexagonal phase, and there are obvious diffraction peaks and better crystallinity when the concentration is 0.005 M. Spectrophotometer test results demonstrate that the relationship between zinc content x and optical band gap value Eg can be expressed by the equation Eg(x)=0.59x2+0.69x+2.43. Increasing the zinc content can increase the optical band gap, the absorbance of the thin film can be improved by decreasing the cadmium sulfate concentration, however, all of them have good transmittance. At a concentration of 0.005 M, the thin film has good absorbance in the 300 - 800 nm range, 80% transmittance, and band gap value of 3.24 eV, which is suitable for use as a buffer layer for solar cells.

A document by Francesco Lo Re. Click on the document to view its contents.

The usage of preprint servers in ecology and evolution is increasing, as it allows for research to be rapidly disseminated and available through open access at no cost. This is relevant for Early Career Researchers (ECRs), who must demonstrate research ability for funding opportunities, scholarships, grants, or faculty positions in short temporal windows in order to advance their careers. Concurrently, limited experience with the peer review process can make it challenging for those who are in the early stages of their research career to build publication records. Therefore, ECRs face different challenges relative to researchers with permanent positions and established research programs and have different requirements in terms of research output and timelines. These challenges might also vary according to institution size and country, which are associated with the availability of funding for open access journals. Herein, we hypothesize that career stage and institution size impact relative usage of preprint servers among researchers in ecology and evolution. Using data collected from 500 articles (100 from each of two open access journals, two closed access journals, and a preprint server), we demonstrate that ECRs generate more preprints relative to non-ECRs, for both first and last authors. We speculate that this pattern is reflective of the advantages of quick and open access research that is disproportionately beneficial to ECRs. There is also a marginal effect of first author institution size on preprint usage, whereby the number of preprints tends to increase with institution size for ECRs, although the interaction between ECR status and institution size was not significant. The United States and United Kingdom contributed the greatest number of preprints by early career researchers, whereas non-western countries contributed relatively fewer preprints. This research provides empirical evidence regarding motivations of preprint usage and barriers surrounding large-scale adoption of preprinting in ecology and evolution.

In this paper, we consider two singular planar differential systems which can describe the evolution of the optical pulse width and chirp for the so-called dispersion-managed solitons. Based on the method of third order approximation in combination with some quantitative information obtained by the upper-lower solutions method and the averaging method, some results on the existence and Lyapunov stability of the periodic solutions are obtained. Moreover, the formula of the first twist coefficient and a stability criterion of a nonlinear differential equation are also established.

Background: Normal mature sperm have a considerably reduced number of mitochondria which provide the energy required for progressive sperm motility. Literature suggests that disorders of sperm motility may be linked to abnormal sperm mitochondrial number and function. Objectives: To summarise the evidence from literature regarding the association of mitochondrial DNA copy numbers and semen quality with a particular emphasis on the spermatozoa motility. Search strategy: Standard methodology recommended by Cochrane. Selection criteria: All published primary research reporting on differences in mitochondrial DNA copy numbers between the sperm of males with a normal and abnormal semen analysis. Data collection and analysis: Using standard methodology recommended by Cochrane we pooled results using a random effects model and the findings were reported as a standardised mean difference. Main results: We included 10 trials. The primary outcome was sperm mitochondrial DNA copy numbers. A meta-analysis including five studies showed significantly higher mitochondrial DNA copy numbers in abnormal semen analysis as compared to normal semen analysis(SMD 1.08, 95% CI 0.74-1.43). Three other studies not included in the meta-analysis showed a significant negative correlation between mitochondrial DNA copy numbers and semen parameters. The quality of evidence was assessed as good to very good in 60% of studies. Conclusions: Our review demonstrates significantly higher mitochondrial DNA in human sperm cells of men with abnormal semen analysis in comparison to men with normal semen analysis. PROSPERO registration: CRD42019118841 Funding None received

Introduction: We aimed to measure the dynamic thiol-disulfide balance and thioredoxin reductase (TrxR) enzyme levels in patients with chronic kidney disease (CKD). Material and Methods: Thirty hemodialysis (HD), 30 CKD patients (stage3-5) and 30 controls were included in the study. The dynamic thiol-disulfide balance was determined by the colorimetric method developed by Erel et al. TrxR levels were determined by ELISA. Results: Native and total thiol levels of CKD and HD patients were significantly lower than that of the control group (p=0.001for both). However, disulfide levels were significantly higher in the HD group (p=0.001), but there was no significant difference between control and CKD groups(p=0.547). A notable negative correlation was found between the native and total thiol levels and IMA(r=-0.628;-0.631),BUN (r=-0.747;-0.747),and creatinine(r=-0.732;-0.721). There was a significant positive correlation between GFR and the thiol levels (r=0.835;0.824). TrxR levels were significantly higher in the patient groups compared to the controls (p=0.001).CRP levels of the patient groups were significantly higher compared to the controls (p=0.001). Conclusions: We have demonstrated that measurement of dynamic thiol-disulfide levels by using colorimetric method can contribute to the diagnosis and follow-up of the disease as a marker, because, it is easily applicable in routine clinical biochemistry laboratories and related with disease severity in CKD patients. Also, we showed that volume correction due to dialysis process should be consider in studies dealing with plasma thiol values and the final results should be given after the correction process.

Given that soil erosion is a primary cause of land degradation globally, it has been receiving increasing attention in food production regions, such as the Mollisol region in northeastern China. This study assessed soil quality under soil erosion degradation using a novel optimal data set (ODS) approach and a comparative minimum data set (MDS) approach based on soil quality indices (SQIs) within an agriculture watershed in Bin County, Heilongjiang Province, China. SQIs selection was contingent on multiple soil factors. Soil erosion rates was determined using cesium-137 technique. Relationships between soil quality and erosion or deposition rates were also analyzed. Results showed that erosion primarily drove soil redistribution, and soil quality grades were generally extremely low (approx. 80% of sampling sites), based on results from both the MDS and ODS approaches. However, soil quality varied significantly between erosion and deposition sites, it increased from upstream to midstream to downstream areas. Moreover, changes in SQIs and erosion rates exhibited spatially opposite trends, indicative of the impact that soil erosion has on soil quality, which was also confirmed by comparing representative soil properties at soil erosion and deposition sites. The good correlation between the MDS and ODS approaches indicated the feasibility of the ODS approach in estimating soil quality. Finally, the ODS approach is a cause-related method applying a relatively strict indicator selection procedure, which, compared to the MDS approach, could theoretically obtain more reliable results. Further studies are nevertheless necessary to assess the feasibility of this novel approach in other cases.

Carcinosarcomas are aggressive biphasic neoplasms composed of high-grade, malignant, epithelial, and mesenchymal elements. They usually occur in the uterus and rarely involve the ovaries. Only 10% of them are bilateral. Their diagnosis relies on histological examination coupled with immunohistochemistry.

Despite being first described over 30 years ago, focal radiofrequency (RF) continues to be the most widely used energy modality for catheter ablation. The fact that it has managed to hold its own against stiff competition from alternative energy sources used for pulmonary vein isolation (PVI) is down to continuous evolution based on enhancements in our understanding of its biophysical principles. In particular, the advent of contact-force (CF) based integrated indices such as Ablation Index have improved both efficacy and safety. However, a significant limitation of this approach is the absence of tissue feedback during lesion creation, which results in a blunt ‘one-size-fits-all’ approach. This limitation has been further brought into focus by the recent appreciation of the much greater importance of circuit impedance rather than delivered power as a fundamental determinant of RF lesion size.

We have read with great interest the article “Efficacy of Catheter Ablation for Premature Ventricular Contractions (PVC) in Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)” by Assis F.R. et. al. PVC ablation in ARVC was previously studied by Aras D. et al and they presented successful results.In this study, we believe that the study should not be considered as unsuccessful since 2 patients showed a decrease in PVC burden by more than 80% and in the other three patients between 45-70%. The demonstration of a decrease in PVC burden with catheter ablation in ARVD patients indicates that a second ablation may increase the success rate and decrease symptoms. The fact that ARVC has a complex substrate and the disease can progress is undoubtedly the most important factor in achieving the desired success with PVC ablation. Epicardial ablation with endocardial ablation has increased the chance of success in this patient group. In addition, given that BCSD ablation and basal heart rate are guaranteed by ICD implantation, we think that administration of the maximum dose of antiarrhythmic medication may create a significant improvement in these patients. And another factor, contact force sensing plays an important role in evaluating the effectiveness of the process. We suggest that with the current treatment modalities, a pharmacoablative combination therapy and re-ablation when necessary would be appropriate for such a complicated disease.

Though generally self-limited, viral myocarditis can lead to acute cardiac failure or chronic dilated cardiomyopathy. We describe three cases of human herpes virus 6 (HHV6) associated -myocarditis unresponsive to conventional therapies, with detection of HHV-6 evidences and initiation of antiviral treatment, we observed significant improvement in clinical status of patients.

By integrating continuous cell cultures with continuous purification methods, process yields and product quality attributes were improved over the last 10 years for recombinant protein production. However, for the production of viral vectors such as Modified Vaccinia virus Ankara (MVA), no such studies have been reported although there is an increasing need to meet the requirements for a rising number of clinical trials against infectious or neoplastic diseases. Here, we present for the first time a scalable suspension cell (AGE1.CR.pIX cells) culture-based perfusion process in bioreactors integrating continuous virus harvesting through an acoustic settler with semi-continuous chromatographic purification. This allowed to obtain purified MVA particles with a space-time yield >600% higher for the integrated perfusion process (1.05 x 1011 TCID50/Lbioreactor/day) compared to the integrated batch process. Without further optimization, purification by membrane-based steric exclusion chromatography resulted in an overall product recovery of 50.5%. To decrease the level of host cell DNA prior to chromatography, a novel inline continuous DNA digestion step was integrated into the process train. A detailed cost analysis comparing integrated production in batch versus production in perfusion mode showed that the cost per dose for MVA was reduced by nearly one third using this intensified small-scale process.

The aim of this study was to demonstrate the applicability of a novel magnetically-assisted external-loop airlift bioreactor (EL-ALB), equipped with RMF generators for the preparation of Komagataeibacter xylinus inoculum during three-cycle repeated fed-batch cultures, further used for bacterial cellulose (BC) production. The fermentation carried out in the RMF-assisted EL-ALB allowed to obtain an inoculum of more than 200x higher cellular density compared to classical methods of inoculum preparation. The inoculum obtained in the RMF-assisted EL-ALB was characterized by a high and stable metabolic activity during repeated batch fermentation process. The application of the RMF-assisted EL-ALB for K. xylinus inoculum production did not induce the formation of cellulose-deficient mutants. It was also confirmed that the ability of K. xylinus to produce BC was at the same level (7.26 g/L of dry mass), regardless of inoculum age. Additionally, the BC obtained from the inoculum produced in the RMF-assisted EL-ALB was characterized by reproducible mechanical strength, nanostructure and total crystallinity index. The results obtained in this study may find multiple applications in any biotechnological processes requiring a high-quality bacterial inoculum.

Approval of direct-acting oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation (AF) was an important milestone, providing widened treatment choices along with the possibility for inter-drug switching after initiation. In addition to improved utilisation of oral anticoagulants (OACs) for stroke prevention, reports of switching among OACs are growing in the literature. Switching may influence clinical outcomes, healthcare costs and patient satisfaction. This review aimed to summarise the current literature on the pattern of OAC switching in patients with AF, including reasons for switching and clinical consequences following switching. We included articles published after 2013, following the introduction of apixaban; searched on June 27, 2020 from PubMed, Scopus and Embase. The review found that switching among OACs was common in clinical practice, significantly varying with the type of OAC. Studies reporting the reason for switching and clinical outcomes were comparatively limited. The reasons were often related to safety issues, poor anticoagulation control and ease of use. Factors that can increase the risk of bleeding and stroke were found to be associated with switching from vitamin K antagonists, but less for DOAC switching. Findings regarding bleeding outcomes following switching were inconsistent, possibly confounded with the type of OAC, reasons for switching and switching protocol. Despite the limited number of studies included and their relatively short follow-up periods, our review revealed that switching had minimal impact on stroke and other related thrombotic outcomes. Further prospective studies are needed to better understand possible reasons for switching and its influence on clinical outcomes.

The potential developed on a membrane with fixed charge plays crucial roles in many biological and engineering systems. The classic Teorell-Meyer-Siever (TMS) theory gives an analytical expression of the membrane potential only for limited cases of simple solutions. A numerical method that can be applied to the general cases was developed in this study. With a boundary updating scheme, a numerical solution to the Nernst-Planck-Poisson equations was obtained rigorously without the commonly used simplifications and assumptions in previous studies. The features of the membrane potentials with different fixed charges were investigated with this numerical method under various conditions. The validity of this numerical method was verified by identical values of Donnan potential obtained with well-established analytical methods. The suitability and applicability of analytical TMS model were assessed by comparison to the numerical method.

Additive manufacturing is increasingly being used to develop innovative packings for absorption and desorption columns. Since distillation has not been in focus so far, this paper aims to fill this gap. The objective is to obtain a miniaturized 3D printed packed column with optimized properties in terms of scalability and reproducibility, which increases process development efficiency. For this purpose, a flexible laboratory scale test rig is presented combining standard laboratory equipment with 3D printed components such as innovative multifunctional trays or the column wall with packing. The test rig offers a particularly wide operating range (F=0.15 Pa0.5…1.0 Pa0.5) for column diameters between 20 mm and 50 mm. First results regarding the time to reach steady-state, operational stability and separation efficiency measurements are presented using a 3D printable version of the Rombopak 9M. Currently, innovative packings are being characterized, which should exhibit a optimized bevavior regarding scalability, reproducibility and separation efficiency.

In this study a series of GO-based adsorbents were assembled via impregnation method using N-resources: 3-aminopropyl-triethoxysilane (APTS) as primary amio-silane, Piperazine (PIP) as secondary cyclic diamine, and ethanolamine (EA) as primary amine. The influence of amine type, adsorption temperature and pressure were undertaken to obtain the best CO2 adsorption performance. The characterizing techniques including FTIR, SEM, TGA, BET, BJH, and MP confirmed well impregnation of amine functionalities to the GO framework and high thermal stability of adsorbents. GO/APTS showed the maximum CO2 uptake (43.114 mmol/g) predicted by the Sips isotherm model and the highest CO2 ¬(15% V, balanced N2) selectivity (33.7 %) estimated by the ideal adsorbed solution theory. The experimental adsorption capacity of GO/APTS is 2.3 times higher than pristine GO. This behavior highlights the role of electron-donor amine and methyl groups and high molecular weight of APTS as well as high interfacial area of GO/APTS in CO2 capture.

Background: Children with metastatic neuroblastoma have inferior survival despite therapeutic advances. Myeloablative chemotherapy followed by stem cell transplantation, accepted as the current standard of care, is not accessible to patients in many developing countries due to resource constraints. We share our experience of treating metastatic neuroblastoma in a non-transplant facility with conventional chemotherapy, surgery, and radiotherapy. Method - Retrospective study of children 1-14years of age treated for metastatic neuroblastoma in our center from January 2008 to December 2017 Results – Eighty-nine patients with metastatic neuroblastoma received treatment. Mean age was 3.5years and male:female ratio was 1.1:1. The commonest primary site was suprarenal(55%) and commonest site of metastasis was bone marrow(76%). 40% patients had multiple metastatic sites. Mean baseline LDH was 3724 U/L(range303-16609 U/L) and most(65%) patients had LDH>750U/L.53 patients(59.6%)had good response to chemotherapy as evidenced by clearance of metastatic disease, but out of them, 43 patients (81%) progressed subsequently. 26 patients underwent surgery and 12 patients received maintenance therapy. 74 patients(86%) developed recurrence and all but one died. Median time to recurrence and death were 9months(range 0-120months) and 10months(range 1-123months) respectively. At a median follow-up of 72months(range15-135months), 16 patients are alive, with 5-year disease-free survival and overall survival of 17.6% and 18.4% respectively. Age, baseline LDH, chemotherapy regimen and response to treatment affected survival. Conclusion: Outcome of non-infant metastatic neuroblastoma remains dismal in a non-transplant setting. Younger age, lower baseline LDH and good response to chemotherapy appear to confer survival advantage, and may be used for risk-stratification in developing countries.

Cancer cachexia is one of the most common causes of death among cancer patients, no effective anti-cachectic treatment is currently available. In experimental cachectic animal models, aberrant activation of STAT3 in skeletal muscle has been found to contribute to muscle wasting. However, its clinical association, the factors regulating STAT3 activation, and the molecular mechanisms remain incompletely understood. Here, we show that an enhanced interaction between activated STAT3 and HSP90, which were observed in the skeletal muscle of cancer cachexia patients, is a crucial event for the development of cachectic muscle wasting. Administration of HSP90 inhibitors 17DMAG and PU-H71 alleviated the muscle wasting in C26 tumor-bearing cachectic mice or the myotube atrophy of C2C12 cells induced by C26 conditional medium. A mechanistic study indicated that in cachectic skeletal muscle, prolonged STAT3 activation transactivated FOXO1 by binding directly to its promoter and triggered the muscle wasting in a FOXO1-dependent manner; Our results demonstrate that the HSP90/STAT3/FOXO1 axis plays a critical role in the cachectic muscle wasting, which might serve as potential therapeutic target for the treatment of cancer cachexia.