Background: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of longitudinal diastolic strain time (Dst) with the routine echocardiography diastolic parameters and to estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. Methods: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy were included. Echocardiography, including Global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity were determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. =diastolic time (ms) measured. Results: Among 69 patients, 67 (97.1%) were females with a mean age 52±13years. Diastolic strain timeDst measurement was significantly associated with the standard routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3 . Both in a univariate and a multivariate analyses the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (p<0.04). Conclusions: Among breast cancer patients, Dst time showed high correlation to standard the routine diastolic echocardiography parameters. Relative reductionChange in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

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African swine fever virus variants with different numbers of a 10-bp tandem repeat were isolated in South Korea soon after being identified in wild boar. The short emergence periods and sympatric distributions within a narrow geographical region suggest that the variants were sporadically generated in the pre-existing viral population.

Objectives: Although albuterol, the most frequently used bronchodilator, has been traditionally and generally delivered via nebulization (NEB) with compressed air/oxygen, the benefits of metered‐dose inhalers with a spacer (MDI+S) have been widely recognized as an alternative method for albuterol administration. The aim of this systematic review was to compare the response to albuterol delivered through NEB with albuterol delivered through MDI+S in pediatric patients with asthma exacerbations. Methods: We conducted an electronic search in MEDLINE/PubMed, EMBASE, Ovid and ClinicalTrials. To be included in the review, a study had to a randomized clinical trial comparing albuterol delivered via NEB versus MDI+S; and had to report the rate of hospital admission (primary outcome), or any of the following secondary outcomes: oxygen arterial saturation, heart rate (HR), respiratory rate, the pulmonary index score (PIS), adverse effects, and need for additional treatment. Results: Fifteen studies (n=2057) met inclusion criteria. No significant differences were found between the two albuterol delivery methods in terms of hospital admission (RR 0.89; 95% CI 0.55 to 1.46; I2=32%; p=0.65). There was a significant reduction in the PIS score (MD -0.63; 95% CI -0.91 to -0.35; I2=0%; p < 0.00001), and a significantly smaller increase in HR (better) (MD -6.47; 95% CI -11.69 to -1.25; I2=0%; p=0.02) when albuterol was delivered through MDI+S than when it was delivered through NEB. Conclusions: This review showed a significant reduction in the PIS and a significantly smaller increase in HR when albuterol was delivered through MDI+S than when it was delivered through NEB.

Background: Right ventricular failure (RVF) following Left Ventricular Assist Device (LVAD) implantation is associated with worse outcomes. Prediction and early identification of RVF with speckle-tracking echocardiography (STE) has been proposed. Methods: We queried multiple databases for articles reporting on pre-operative/intraoperative global longitudinal strain (GLS) and free-wall strain (FWS) in LVAD recipients. We performed a systematic review and meta-analysis of published literature. The standard mean difference (SMD) in GLS and FWS in patients with and without RVF postoperatively was pooled using random effects model. Results: Fifteen studies, with a total of 967 LVAD recipients were included. There was statistically significant difference in GLS among patients who did and did not develop RVF; SMD= -3.09 (95% CI: -4.62 to -1.57; p-value <0.0001). There was significant difference in FWS between two groups; SMD: -2.75 (95% CI: -3.72 to -1.79; p-value <0.0001). Upon subgroup analysis of imaging modality, transthoracic echocardiography (TTE)-derived GLS and FWS remained predictive for RVF with SMD of -3.97 (95% CI: -5.40 to -2.54; p-value <0.001) and -3.05 (95% CI: -4.11 to -1.99; p-value <0.001), respectively. However, there was no significant difference between RVF and non-RVF groups upon using transesophageal echocardiography (TEE) to assess GLS and FWS. Conclusion: GLS and FWS assessment of the RV by STE is a useful tool to predict postoperative RVF in LVAD recipients. While the predictive role of TTE was robust, the TEE-derived measures seemed to be less predictive. Future studies need to specify the strain cut-off value that can predict the adverse outcome of RVF

Background : To evaluate the long-term results of implantation of homogeneous large size of pulmonary homograft (PH) for reconstruction of the right ventricular outflow tract (RVOT). Methods : Between January 2000 and December 2017, 107 patients were implanted with PH for reconstruction of the RVOT. Data were collected retrospectively in this single-center study. PH failure was defined as a peak of gradient > 40 mmHg and/or as a pulmonary regurgitation > grade 2. Primary endpoint was the re-operation of the RVOT during follow-up. Secondary endpoints were overall survival, occurrence of PH failure and the rate of re-operation for all cause. Results : Mean age of the recipients was 26.13  13.59 years. Mean size of PH was 23.02  6.87 mm. Re-operation of the RVOT occurred in 8 patients (7.8%). Time before re-operation was 2.74 years (Interquartile Range: 6.41). Freedom from re-operation for RVOT at 5 and 10 years was respectively 95.7% and 90.0%. Overall survival at 10 years was 95.2%. PH failure occurred in 13 patients (12.0%). Mean time before PH failure was 5.00  4.35 years. Freedom from PH failure at 10 years was 81.6%. Re-operation for PH failure occurred in 4 patients (3.9%). Concomitant tricuspid valve surgery (p=0.037), initial pulmonary stenosis (p=0.04), recipient of PH < 16 years old (p=0.043) were risk factors of late reoperation in univariate analysis. Multivariate analysis showed no independent risk factor of late reoperation. Conclusions : Implantation of large PH for RVOT reconstruction provides excellent mid-term results in terms of re-operation.

Background: The liberal administration of hydroxychloroquine-sulphate (HCQ) to COVID-19 patients has raised concern regarding the risk of QTc prolongation and cardiac arrhythmias, particularly when prescribed with azithromycin. We evaluated the incidence of QTc prolongation among moderately and severely ill COVID-19 patients treated with HCQ and of the existence of concomitant alternative causes. Methods: All COVID-19 patients treated with HCQ (between Mar 1 and Apr 14, 2020) in a tertiary medical center were included. Clinical characteristics and relevant risk factors were collected from the electronic medical records. Individual patient QTc intervals were determined before and after treatment with HCQ. The primary outcome measure sought was a composite endpoint comprised of either an increase ≥ 60 milliseconds (ms) in the QTc interval compared with pretreatment QTc, and/or a maximal QTc interval >500 ms. Results: Ninety patients were included. Median age was 65 years (IQR 55-75) and 57 (63%) were male. Thirty-nine patients (43%) were severely or critically ill. Hypertension and obesity were common (n=23 each, 26%). QTc prolongation evolved in fourteen patients (16%). Age > 65 years, congestive heart failure, severity of disease, C-reactive protein level, hypokalemia and furosemide treatment, were all associated with QTc prolongation. Adjusted analysis showed that QTc prolongation was five times more likely with hypokalemia [OR 5, (95% CI, 1.3-20)], and three times more likely with furosemide treatment [OR 3 (95% CI, 1.01-13.7)]. Conclusion: In patients treated with HCQ, QTc prolongation was associated with the presence of traditional risk factors such as hypokalemia and furosemide treatment.

Objective: We aimed to investigate the demographic shifts in emergency service admissions, possible measures and room for improvement in emergency services during the Covid-19 pandemic. Methodology: Our study retrospectively analyzed the demographic features and clinical admission types of patients admitted to Batman District State Hospital Emergency Service at two different time periods, one prior to the Covid-19 pandemic and the other during the Covid-19 pandemic. The results were compared between the two periods designated as the pandemic period and the pre-pandemic period. Results: The number of patients admitted to emergency service was 47.681 in the pre-pandemic period and 9455 in the pandemic period (p<0.01). The number of patients admitted for trauma was 1247(2.61%) in the pre-pandemic period and 59(0.62%) in the pandemic period (p<0.01). The number of patients hospitalized to cardiology department or coronary care unit for acute coronary syndrome was 602(1.26%) in the pre-pandemic period and 29(0.3%) in the pandemic period (p<0.01). The number of patients hospitalized to neurological intensive care unit for acute cerebrovascular disease was 542(1.13%) in the pre-pandemic period and 22(0.2%) in the pandemic period (p<0.01). The number of patients hospitalized to pulmonary diseases department or intensive care unit for dyspnea was 622(1.21%) in the pre-pandemic period and 515 (5.4%) in the pandemic period (p <0.01). Conclusion: Measures taken to prevent the spread of Covid-19 infection have caused a significant drop in emergency service admissions. We are of the opinion that this will lead to an increase in deaths occurring at home, and we will soon encounter patients with worse prognosis and overcrowded emergency services. In order to prevent this problem, we believe that the public awareness about emergency conditions requiring emergency service admission should be heightened alongside of the ‘stay home’ calls.

Key Points: 1. Efforts to combat the large global burden of ear and hearing disorders are hampered by poor availability of expert diagnosis 2. We report the first study to directly compare prediction model, non-expert and tele-diagnosis of middle and external ear disorders. 3. A prediction model based upon a novel automated otological symptom questionnaire performed poorly, but absence of otorrhoea was found to reliably exclude a diagnosis of chronic suppurative otitis media. 4. Both on-site non-expert and expert tele-diagnosis had high diagnostic specificity, but low sensitivity. 5. Future work could explore how the validity of these diagnostic methods may be improved.

Based on the combination of novel carbon material graphynes (GYs) and superalkalis (OM3), a class of graphyne superalkali complexes, OM3+@(GY/GDY/GTY)– (M = Li, Na, and K), have been designed and investigated by density functional theory method. Computational results reveal that these complexes with high stability can be regarded as novel superalkali salts of graphynes due to electron transfer from OM3 to GYs. For second order nonlinear optical response, these superalkali salts exhibit large first hyperpolarizabilities (β0). Two important effects on β0 values are found, namely the atomic number of alkali atom in superalkali and the pore size of graphyne. Integrating the two effects, the selected combination of OLi3 with large pore size GTY can bring the considerable β0 value (6.5×105 au), which is a new record for superatom-doped graphynes. In the resulting complex, the OLi3 molecule is located at the center of the pore of GTY, forming a planar structure with the highest stability among these salts. Besides large β0 values, these superalkali salts of graphynes have deep-ultraviolet working region, hence can be considered as a new kind of high-performance deep-ultraviolet NLO molecules.

Sore throat (acute pharyngitis) is globally one of the most frequent reasons for seeking healthcare. Its etiology is mostly viral. In 15-30% of cases, group A streptococci (GAS) are detected, which may cause acute rheumatic fever. We have done a worldwide systematic review to compare diagnostic and therapeutic guidelines across countries and regions. Previous reviews of sore throat guidelines were limited to specific regions and/or language; this is the first global review. Searches were performed in MEDLINE, EMBASE and COCHRANE (key words: sore throat, pharyngitis, tonsillitis or pharyngotonsillitis, and management, guidance, guideline or recommendation) and on the web sites of major health authorities and associated institutions from Africa, Asia, Europe, Middle East, North America, Oceania and South America. Thirty-six guidelines were identified from 26 countries. Most common are recommendations relying on the symptom- and age-based Centor or McIsaac scores. However, antibiotic treatment may be based on other symptomatic criteria; in the most extreme approach just sore throat in children. The recommendation of GAS-specific diagnostic tests is mainly limited to countries where such tests are readily available, although some countries choose not to use them. Penicillins are consistently recommended as first-line antibiotics. By contrast, guidance for symptomatic treatment is variable and mostly sparse or missing. African countries without sore throat guidelines and Asian countries bypassing them are afflicted by rising antibiotic resistance. The availability of sore throat guidelines varies considerably by region and country. Moreover, important divergence is found among the guidelines regarding diagnostic and treatment criteria. This may be explained by the historical background or adoption of external guidelines, rather than the local incidences of GAS infections or acute rheumatic fever. Absence of recommendations on symptomatic treatment in many guidelines is concerning, and raises issues about antimicrobial stewardship, as this is the mainstay of sore throat management, rather than antibiotics.

As science and student populations continue to diversify, it is important for ecologists, evolutionary scientists, and educators to foster inclusive environments in their research and teaching. Academics are often poorly trained in diversity, equity, and inclusion best practices and may not know where to start to make scientific environments more welcoming and inclusive. We propose that by approaching research and teaching with empathy, flexibility, and a growth mindset, scientists can be more supportive and inclusive of their colleagues and students. This paper provides guidance, explores strategies, and directs scientists to resources to better cultivate an inclusive environment in three common settings: the classroom, the research lab, and the field. As ecologists and evolutionary scientists, we have an opportunity to adapt our teaching and research practices in order to foster an inclusive educational ecosystem for students and colleagues alike.

Rationale, aims and objectives New therapies are increasingly approved by regulatory agencies such as the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) based on testing in non-randomized clinical trials. These treatments have typically displayed “dramatic effects” (i.e., effects that are considered large enough to obviate the combined effects of bias and random error). The agencies, however, have not identified how large these effects should be to avoid the need for further testing in randomized controlled trials (RCTs). We investigated the effect size that would circumvent the need for further RCTs testing by the regulatory agencies. We hypothesized that the approval of therapeutic interventions by regulators is based on heuristic decision-making whose accuracy can be best characterized by the application of signal detection theory (SDT). Methods We merged the EMA and FDA database of approvals based on non-RCT comparisons. We excluded duplicate entries between the two databases. We included a total of 134 approvals of drugs and devices based on non-RCTs. We integrated Weber-Fechner law of psychophysics and recognition heuristics within SDT to provide descriptive explanations of the decisions made by the FDA and EMA to approve new treatments based on non-randomized studies without requiring further testing in RCTs. Results Our findings suggest that when the difference between novel treatments and the historical control is at least one logarithm (base 10) of magnitude, the veracity of testing in non-RCTs seems to be established. Conclusion Drug developers and practitioners alike can use the change in one logarithm of effect size as a benchmark to decide if further testing in RCTs should be pursued, or as a guide to interpreting the results reported in non-randomized studies. However, further research would be useful to better characterize the threshold of effect size above which testing in RCTs is not needed.

Over time, populations of species can expand, contract, and become isolated, creating subpopulations that can adapt to local conditions. Understanding how species adapt following these changes is of great interest, especially as the current climate crisis has caused range shifts for many species. Here, we characterize how Drosophila innubila came to inhabit and adapt to its current range: mountain forests in southwestern USA separated by large expanses of desert. Using population genomic data from more than 300 wild-caught individuals, we examine four distinct populations to determine their population history in these mountain-forests, looking for signatures of local adaptation to establish a genomic model for this spatially-distributed system with a well understood ecology. We find D. innubila spread northwards during the previous glaciation period (30-100 KYA), and has recently expanded even further (0.2-2 KYA). Surprisingly, D. innubila shows little evidence of population structure, though consistent with a recent migration, we find signatures of a population contraction following this migration, and signatures of recent local adaptation and selective sweeps in cuticle development and antifungal immunity. However, we find little support for recurrent selection in these genes suggesting recent local adaptation. In contrast, we find evidence of recurrent positive selection in the Toll-signaling system and the Toll-regulated antimicrobial peptides.

Binswanger's disease is a type of vascular leukoencephalopathy that can lead to cognitive impairment and neurological deficits and is sometimes difficult to diagnose. We present a case of Binswanger's disease with an interesting differential diagnosis based on clinical aspects, laboratory findings and imaging studies.

Having proper correlations for hydrodynamic forces is essential for successful CFD-DEM simulations of a fluidized bed. For spherical particles in a fluidized bed, efficient correlations for predicting the drag force, including the crowding effect caused by surrounding particles, are already available and well tested. However for elongated particles, next to the drag force, the lift force and hydrodynamic torque also gain importance. In this work we apply recently developed multi-particle correlations for drag, lift and torque in CFD-DEM simulations of a fluidized bed with spherocylindrical particles of aspect ratio 4 and compare them to simulations with widely used single-particle correlations for elongated particles. Simulation results are compared with previous magnetic particle tracking (MPT) experimental results. We show that multi-particle correlations improve the prediction of particle orientation and vertical velocity. We also show the importance of including hydrodynamic torque.

Introduction: Studies have shown an association between outcome in cardiac resynchronization therapy (CRT) and longer interventricular delay at the site of the left ventricular (LV) lead. Targeted LV lead placement at the latest electrically activated segment increases LV function further as compared with standard treatment. We aimed to determine reproducibility and repeatability of identifying latest electrically activated segment during mapping of all available CS branches in patients receiving CRT. Methods: We included 35 patients who underwent CRT implantation with protocolled mapping guided LV lead implantation aiming for the site of latest electrical activation. Three different doctors experienced in electrophysiology and implantation of CRT devices independently measured time interval from the local bipolar right ventricular (RV) electrogram (EGM) to the local unipolar LV EGM at all mapped sites (RV-LV). The segment with the latest electrical activation was defined as target segment (TS) and the CS tributary containing TS was defined as target vein (TV). Weighted Kappa statistics with 95% confidence intervals were computed to assess intra-and inter-observer agreement for TS and TV. Results: We mapped 258 segments within 131 veins. Weighted kappa values for repeatability were 0.85 (0.81-0.89) for TS and 0.92 (0.89-0.93) for TV, and weighted kappa values of inter-observer agreement ranged from 0.70 (0.61-0.73) to 0.80 (0.76-0.83) for TS and 0.73 (0.64-0.78) to 0.86 (0.83-0.89) for TV among all three observers. Conclusion: The reproducibility and repeatability of identifying latest electrically activated segment during mapping of all available CS branches in patients receiving CRT ranges from good to very good.

Objectives. We compared the common pathway components C3a, C5a and membrane attack complex (MAC), also known as C5b-9, and the alternative pathway components factor B and properdin in patients with ANCA-associated vasculitis (AAV) and healthy controls, and conducted a meta-analysis of the available clinical evidence for the role of complement activation in the pathogenesis of AAV. Methods. Complement components were evaluated in 59 patients with newly diagnosed or relapsing granulomatosis with polyangiitis or microscopic polyangiitis and 36 healthy volunteers. In 28 patients, testing was repeated in remission. Next, we performed a meta-analysis by searching databases to identify studies comparing complement levels in AAV patients and controls. A random-effects model was used for statistical analyses. Results. The median concentrations of MAC, C5a, C3a, and factor B were higher in active AAV patients (p<0.001). Achievement of remission was associated with reductions in C3a (p=0.005), C5a (p=0.035), and factor B levels (p=0.045), whereas MAC and properdin levels did not change. In active AAV, there were no effects of ANCA specificity, disease phenotype, previous immunosuppression, or disease severity on complement levels. A total of 1122 articles were screened, and five studies, including this report, were entered in the meta-analysis. Plasma MAC, C5a, and factor B in patients with active AAV were increased compared to patients in remission (excluding factor B) and controls. Changes in C3a were of borderline significance. Conclusion. Our findings and the results of the meta-analysis support activation of the complement system predominantly via the alternative pathway in AAV patients.