Aim Oral flucloxacillin may be co-administered with probenecid to increase flucloxacillin concentrations and increase attainment of pharmacokinetic-pharmacodynamic (PK-PD) targets. The aims of this study were to describe outcomes of patients treated with oral flucloxacillin plus probenecid as follow-on therapy from initial intravenous treatment, and to identify optimal dosing regimens when treating infections caused by susceptible Gram-positive organisms. Methods We performed a prospective observational study of adults treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly (with food) for proven or probable staphylococcal infections. We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, in order to estimate probability of PK-PD target attainment (fT>MIC), and used Monte Carlo simulation to explore optimal dosing regimens. Results The 45 patients (73% male) had a median (range) age of 49 years (20 – 74), weight of 90 kg (59 – 167), fat free mass (Janmahasatian) of 65 kg (38 – 89) and eGFR (CKD-EPI) of 89 mL/min/1.73m2 (41 – 124). The most common infections were osteomyelitis (n=18, 40%) and septic arthritis (n=12, 27%). Forty patients (89%) were cured 30 days after completion of therapy. 10 (22%) experienced nausea which did not require treatment alternation. Free flucloxacillin clearance depended on allometrically-scaled fat free mass, and increased by 1% for each unit increase in eGFR. Conclusion Oral flucloxacillin and probenecid was well-tolerated and efficacious. Patients with higher fat free mass and eGFR may require four times daily dosing and/or therapeutic drug monitoring to ensure PK-PD target attainment.

Preeclampsia causes various presentations by increased endothelial permeability and microvascular damages. Maternal ascites related severe preeclampsia is generally explained by increased capillary permeability due to endothelial cell dysfunction and reduced intravascular oncotic pressure. Here we report a patient with postpartum massive ascites associated with preeclampsia.

The association of Daunorubicin and Steven-Johnson Syndrome (SJS) has not been well-established. In this report, we describe a fatal case of a 2 years old boy with acute leukemia who developed Steven-Johnson Syndrome owing to Daunorubicin. Clinicians should consider the possible association of Daunorubicin with SJS.

In this paper, we consider two dimensional inverse problem for a fractional diffusion equation. The inverse problem is reduced to the equivalent integral equation. For solving this equation the contracted mapping principle is applied. The local existence and global uniqueness results are proven. Also the stability estimate is obtained.

Coronavirus disease 2019 (COVID-19) vaccine BNT162b2 received approval and within the first few days of public vaccination several severe anaphylaxis cases occurred. An investigation is taking place to understand the cases and their triggers. The vaccine will be administered to a large number of individuals worldwide and concerns raised for severe adverse events might occur. With the current information, the European Academy of Allergy and Clinical Immunology (EAACI) states its position for the following preliminary recommendations that are to be revised as soon as more data emerges. To minimize the risk of severe allergic reactions in vaccinated individuals, it is urgently required to understand the specific nature of the reported severe allergic reactions, including the background medical history of the individuals affected and the mechanisms involved. To achieve this goal all clinical and laboratory information should be collected and reported. Mild and moderate allergic patients should not be excluded from the vaccine as the exclusion of all these patients from vaccination may have a significant impact on reaching the goal of population immunity. Health care practitioners vaccinating against COVID-19 are required to be sufficiently prepared to recognise and treat anaphylaxis properly with the ability to administer adrenaline. A mandatory observation period after vaccine administration of at least 15 minutes for all individuals should be followed. The current guidelines, which exclude patients with severe allergies from vaccination with BNT162b2, should be re-evaluated after more information and experience with the new vaccine develops.

Abstract Background: The patient experience of atrial fibrillation (AF) involves several daily self-care behaviors and ongoing confidence to manage their condition. Currently, no standardized self-report measure of AF patient confidence exists. The purpose of this study is to establish the reliability and validity of a newly developed confidence in AF management measure. Methods: This study provides preliminary analysis of the Confidence in Atrial FibriLlation Management (CALM) scale, which was rationally developed to measure patient confidence related to self-management of AF. The scale was provided to a sample of AF patients N=120, (59% male) electronically through a patient education platform. Principle components analysis (PCA) and Cronbach’s alpha were employed to provide preliminary assessment of the validity and reliability of the measure. Results: PCA identified a four-factor solution. Internal consistency of the CALM was considered excellent with Cronbach’s α = .910. Additional PCA confirmed the value of a single factor solution to produce a total confidence score for improved utility and ease of clinical interpretation. Conclusions: Initial assessment of a novel scale measuring patient confidence in managing AF provided promising reliability and validity. Patient confidence in self-management of AF may prove useful as a key marker and endpoint of the patient experience beyond QOL.

Abstract Objectives: In most cases, suspension laryngoscopy (SL) is efficient, bloodless and with minimal post-procedure discomfort. We aimed to identify predictive patient factors for acceptable surgical views at SL as well as quantify our tertiary airway unit’s complication rates. Design: Prospective cohort study of 150 consecutive microlaryngoscopy procedures involving SL over an 8-month period between November 2019 and July 2020. Patients were assessed pre-operatively for pre-existing oral, temporomandibular, dental, pharyngeal or laryngeal pathology, interincisor distance and qualitative gross limitations to neck extension and forward head posture. Intraoperatively, the laryngoscopic view was graded by anesthetic and surgical teams, and complications were recorded on patient interview in recovery. Setting: Tertiary adult airway service for predominantly benign pathology. Results: Adequate surgical views were obtained in 149/150 procedures. BMI and limitations to chin and neck movement had mild positive correlations with more difficult views in their own rights, but did not correlate with a statistically significant increase in complications. There was a negative correlation between age and interincisor gap (p=0.014), and wider mouth opening correlated with a lower incidence of sore throat (p=0.023). Macroglossia showed a statistically significant positive correlation with tongue symptoms (p=1.611x10-8). Conclusion: In the context of an experienced airway unit with a high caseload of predominantly benign pathology, SL is very effective and safe with low associated morbidity and no mortality. Patient-reported neck and chin movement were found to correlate well with the surgical view obtained. The most common complication of SL is temporary sore throat and there remain recognized risks of temporary tongue and dental symptoms.

Aim: Dyspnea, a common symptom of novel coronavirus, can negatively affect sleep quality. The aim of this study was to evaluate the relationship between dyspnea severity and sleep quality in patients with COVID-19. Study Design: A cross-sectional design was used. Methods: Using the researcher’s mobile phone, data were collected via an online questionnaire from patients (n=100) who agreed to participate in the study. The data-collection form comprised three parts: a patient descriptive information form, the Dyspnea–12 Questionnaire, and the Richards–Campbell Sleep Questionnaire. Results: The mean age of patients was 46.39±12.61 years and 66.0% were male. Patients who were treated in the intensive care unit, had bachelor’s degree or more and patients with comorbid diseases had low mean scores from the RCSQ and high mean scores from the Dyspnea–12 Questionnaire (p<0.001, p<0.001; p=0.047, p<0.001;p<0.001, p<0.00,1,respectively).Patients who not receiving oxygen therapy had higher RCSQ mean scores and lower Dyspnea–12 Questionnaire scores (p<0.001, p<0.001; p<0.001, p<0.001, respectively). There was a strong negative relationship between the total scores obtained from the Richards–Campbell Sleep Questionnaire and the Dyspnea–12 Questionnaire(r= -701, p<.001). Conclusions: Sleep quality is affected by dyspnea severity in patients with COVID-19. Sleep quality and dyspnea severity are also influenced by quite different factors, and these should be addressed and eliminated by nurses as part of a holistic approach. The results of this study will help nurses, especially those providing treatment and care for patients with COVID-19, to identify the factors affecting dyspnea and sleep quality and to plan, implement, and evaluate nursing interventions that will reduce their workload.

Nickel alloys are widely used in the production of gas turbine parts. The alloys show resistance to mechanical and chemical degradation under severe long-term stress and high temperatures. One of the major mechanical properties of the alloys is the high-temperature rupture strength, which is measured after a specimen is heated to a certain temperature and held for a certain time considering deformation. Determining the influence of certain elements on the properties of an alloy is a complex scientific and engineering problem that affects the time and cost of developing new materials. Simulation is a great chance to cut costs. In this paper, we predict a high-temperature strength based on the composition of refractory elements in alloys using a deep learning artificial neural network. We build the model based on prior knowledge of the composition of the alloys, information on the role of alloying elements, type of crystallization, test temperature and time, and the tensile strength. Successful simulation results show the applicability of this method in practice.

Background and purpose: Paclitaxel is a widely used anti-neoplastic agent but has low oral bioavailability due to gut extrusion by P-glycoprotein (P-gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut specific P-gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80mg/m2. Experimental approach: We conducted a multi-centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615mg/m2 divided over three days and encequidar 15mg orally one-hour prior, followed by IVP 80mg/m2, or the reverse sequence. PK blood samples were taken up to day 9 for oPac+E and day 5 for IVP. Key Results: 42 pts were enrolled; 35 completed both treatment periods. AUC0-∞was 5033.5 +/- 1401.1 ng.h/mL for oPac+E and 5595.9 +/- 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.5% (90% CI 83.9-95.5). Mean absolute bioavailability of oPac+E was 12%. PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment emergent adverse events occurred in 7 (18%) pts with oPac+E and 2 (5%) with IVP. 75% of pts preferred oPac+E over IVP. Conclusion and Implications: GMR for AUC was within the predefined acceptable range of 80%-125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P-gp induction with repeat administration. With further study, oPac+E is a candidate to replace IVP.

Mapping and monitoring the Trees outside Forests (ToF) is gaining significance in the scientific community as they provide critical ecosystem services such as protecting soil and water resources, wildlife habitat, energy efficiency etc. Also, quantifying ToF can provide useful information on emissions estimation in the Agriculture, Forests, and Other Land Use (AFOLU) category of the Intergovernmental Panel for Climate Change (IPCC). Despite the importance of quantifying ToF, very few studies have attempted to quantify them in India’s natural resource inventory programs. In this study, we focus on Haryana state, India, to map ToF using very high-resolution (VHR) Indian Remote Sensing (IRS) satellite data. Haryana’s landscape is highly interspersed with croplands and ToF, thus providing a challenging environment to test VHR satellite data’s ability to quantify the diversified landscape structure. We specifically used Cartosat-1 panchromatic (2.5m) and Multispectral LISS IV (5.8m) datasets to quantify the vegetation and build a much-needed database on ToF. We used a novel classification scheme based on the geometry, i.e., point, polygon, or polygon formations, to quantify ToF at 1:10,000 scale. Our results suggest ToF with the point, area, and linear block formations of about 2,774,531, 20.51, and 128.83 sq. km, respectively, accounting for ~3.38% of the total study area . Our study highlights the usefulness of VHR satellite data and fused imagery to quantify ToF in highly diverse landscapes, with the case study in Haryana State, India. The results will help address vital ecosystem services from ToF, including greenhouse gas emissions quantification from the AFOLU category.

Saline-alkali soils are widely distributed in China, affecting plant growth and sustainable development of ecosystems. This study characterized the effects of planting Melia azedarach L. on chemical properties and microbial communities in saline-alkali soils [bare (CK), bulk (BS) and rhizosphere soil (RS)]. Compared with the bare soil, planting Melia azedarach L. lowered salt content and concentrations of extractable Na, K, Ca, Mg and Cl-, but significantly increased organic matter, total nitrogen, total phosphorus, available phosphorus, soil urease activity and alkaline phosphatase activity in the rhizosphere soil. High-throughput sequencing results indicated that bacterial richness and diversity decreased in the order RS>BS>CK. The richness of fungi was ranked RS>CK>BS, and their diversity decreased in the order CK>RS>BS. The three dominant bacterial phyla were Proteobacteria, Actinobacteria and Bacteroidetes, and the three dominant fungal phyla were Ascomycota, Basidiomycota and Glomeromycota. Redundancy analysis indicated that total phosphorus concentration and alkaline phosphatase activity significantly influenced bacterial diversity, whereas soil Ca and Mg concentrations were closely related to the fungal community diversity. In conclusion, planting Melia azedarach L. improved soil properties, increased the diversity and richness of soil microbial communities, and thus ameliorated the saline-alkali soil.

In this paper, we consider the artificial neural networks for solving the differential equation with boundary layer, in which the gradient of the solution changes sharply near the boundary layer. The solution of the boundary layer problems poses a huge challenge to both traditional numerical methods and artificial neural network methods. By theoretical analyzing the changing rate of the weights of first hidden layer near the boundary layer, a mapping strategy is added in traditional neural network to improve the convergence of the loss function. Numerical examples are carried out for the 1D and 2D convection-diffusion equation with boundary layer. The results demonstrate that the modified neural networks significantly improve the ability in approximating the solutions with sharp gradient.

Background: Bicuspid aortic valve (BAV) is the most common congenital heart defect and it is responsible for an increased risk of developing aortic valve and ascending aorta complications. In case of mild to moderate BAV disease in patients undergoing supracoronary ascending aorta replacement, it is unclear whether a concomitant aortic valve replacement should be performed. Methods: From June 2002 to January 2020, 75 patients with mild-to-moderate BAV regurgitation (± mild-to-moderate stenosis) who underwent isolated supracoronary ascending aorta replacement were retrospectively analyze. Clinical and echocardiographic follow-up was 100% complete (mean: 7.4±3.9 years, max 16.4). Kaplan Meier estimates were employed to analyze long-term survival. Cumulative incidence function for time to re-operation, recurrence of aortic regurgitation (AR)≥3+ and aortic stenosis (AS) greater than moderate, with death as competing risk, were computed. Results: There was no hospital mortality and no cardiac death occurred. Overall survival at 12 years was 97.4±2.5%, 95% CI [83.16-99.63]. At follow-up there were no cases of aortic root surgery whereas 3 patients underwent AV replacement. At 12 years the CIF of reoperation was 2.6±2.5%, 95% CI [0.20-11.53]. At follow up, AR 3+/4+ was present in 1 pt and AS greater than moderate in 3. At 12 years the CIF of AR>2+/4+ was 5.1±4.98% and of AS>moderate 6.9±3.8%. Conclusions: In our study mild to moderate regurgitation of a BAV did not significantly worse at least up to 10 years after isolated supracoronary ascending aorta replacement.

Gravel augmentation has become common practice to mitigate the effects of decline in upstream sediment supply in gravel-bed rivers. However, the functional aspects of river systems are often left out of rehabilitation monitoring programmes. Despite temperature being a fundamental parameter determining the general health of rivers, a limited number of studies have tested whether gravel augmentation can aid restoring thermal functions. Using airborne thermal infrared (TIR) imagery, this paper explores potential positive outcomes through the monitoring of gravel augmentation actions on 3 rivers in France using hydro-morphological indicators within a trajectory-based Before-After Control-Impact (BACI) framework. This design, combining long-term geomorphic evolution with TIR-based CI strategy, indicated that restoring forms was not sufficient to restore thermal functions in their spatial dimension. Despite forms showing various degrees of recovery, the thermal regime of rehabilitated reaches (i.e. temperature gradient, cold-water patches density, etc.) failed to recover. Nonetheless, hydro-morphological indices can be used to estimate long-term evolution of groundwater-surface water interactions. We emphasise the benefits of trajectory-based BACI assessment to identify current conditions, understand the past evolution (trajectory) of the system to define the framework within which rehabilitation can be objectively assessed, especially when assessing hydrological (here thermal) processes. From a hydrological perspective, the gap between restored forms and restored thermal processes stems from the alteration of connectivity pathways, which potentially require more time (or efforts) to be recovered than forms do. With an increasing number of rehabilitation schemes and increasing pressure of global changes on rivers, we suggest that monitoring of water temperature becomes a routine part of rehabilitation projects.

We report a case of cardiac hibernoma, which is a very rare type of benign lipomatous tumour. They are usually asymptomatic and therefore remain undetected or are found incidentally. When symptomatic, they vary and depend on location of heart involved. The patient had a hibernoma on right atrial wall invading the intra-atrial groove and extending over superior vena cava (SVC), causing significant symptoms of SVC obstruction and tamponade. The patient therefore underwent emergency operation, in which the tumour was resected and the right atrium was reconstructed with Bovine pericardial patch. He was discharged home well.

Changing and moving toward online shopping has made it necessary to customize customers' needs and provide them more selective options. The buyers search the products' features before deciding to purchase items. The recommender systems facilitate the searching task for customers via narrowing down the search space within the specific products that align the customer needs. Clustering, as a typical machine learning approach, is applied in recommender systems. As an information filtering method, a recommender system clusters user's data to indicate the required factors for more accurate predictions by calculating the similarity between members of a cluster. In this study, using the Gaussian mixture model clustering and considering the scores distance and the value of scores in the Pearson correlation coefficient, a new method is introduced for predicting scores in machine learning recommender systems. To study the proposed method's performance, a Movie Lens data set is evaluated, and the results are compared to some other recommender systems, including the Pearson correlation coefficients similarity criteria, K-means, and fuzzy C-means algorithms. The simulation results indicate that our method has less error than others by increasing the number of neighbors. The results also illustrate that when the number of users increases, the proposed method's accuracy will increase. The reason is that the Gaussian mixture clustering chooses similar users and considers the scores distance in choosing similar neighbors to the active user.

Title: COVID-19 vaccine anaphylaxis: IgE, complement or what else? A reply to: “COVID-19 vaccine anaphylaxis: PEG or not?”