pulmonary hypertension in left heart disease

Elevated left ventricular filling pressures are a general feature and hallmark of heart failure resulting from cardiac dysfunctions, essentially arising from and affecting the left ventricle [1, 2]. These disorders include heart failure due to diastolic and/or systolic malfunctions, as such heart failure with preserved (HFpEF) and without preserved; reduced (HFrEF) ejection fraction; valvular diseases; congenital cardiomyopathies; and congenital and acquired afflictions of left heart inflow and/or outflow tract [2, 3]. Thereby, the pressure of the left atrium will be elevated, either subsequently due to the increased LV-filling pressure [1, 4] or even initially, primarily in case of mitral stenosis [5]. In any case, left heart disease (LHD) is generally characterized by elevated left-sided filling pressures [4, 6]. The left-sided filling pressures are transmitted backwards, downstream, thereby causing an increase in pulmonary venous pressures [1, 5–7], a condition "of passive or congestive nature" as associated with pulmonary venous congestion [6]. In the literature this issue has in the past been called pulmonary venous hypertension (PvH) [8], or post-capillary pulmonary hypertension [9] or passive pulmonary hypertension [10]. Consequently, with the rise in pulmonary venous pressure, pulmonary artery pressure (PAP) also increases [11]

Development of certain novel N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)-benzamides and 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones as CFM-1 analogs: design, synthesis, QSAR analysis and anticancer activity.

The reaction of N-(2-(hydrazinecarbonyl)aryl)benzamides 2a, b with indoline-2,3-diones 4ae in acidified ethanolic solution furnished the corresponding N-(2-(2-(2-oxoindolin-3-ylidene)hydrazinecarbonyl)phenyl)benzamides 5aj, respectively. Furthermore, 3-(2-oxoindolin-3-ylideneamino)-2-substituted quinazolin-4(3H)-ones 6aj were prepared by the reaction of 3-amino-2-arylquinazolin-4(3H)-one 3a, b with 4ae. Six derivatives of the twenty newly synthesized compounds showed remarkable antitumor activity against most of the tested cell lines, Daoy, UW228-2, Huh-7, Hela and MDA-MB231. Although these six compounds were more potent than the standard drug (CFM-1), indeed compounds 5b, 5d and 6b were the best candidates with IC50 values in the range 1.866.87, 4.4210.89 and 1.468.60 μg/ml and percentage inhibition in the range 77.188.7, 59.4184.8 and 75.488.0%, respectively. QSAR analyses on the current series of derivatives also have been performed for all five cancer cell lines and thus 10 statistically significant models were developed and internally cross validated

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Indexing Scientific Data

The ability to extract information from collected data has always driven science. Today.s large computers and automated sensing technologies collect terabytes of data in a few weeks. Extracting information from such large amounts of data is like trying to find a needle in a haystack. For efficient information extraction, we need disk-based indexing schemes that can efficiently handle queries restricting ranges on dozens of attributes. Unfortunately, the unique characteristics of scientific data and queries cause traditional indexing techniques to have poor performance on scientific workloads, occupy excessive space, or both. Bitmap indexes were proposed as a solution to these problems. However, in experiments with scientific data and queries, we found that previously proposed variations of bitmap indexes either were quite slow or required excessive storage for processing the large-range query conditions our scientists used. Scientists also told us that bitmap indexes, though smaller than traditional indexes, were too large for scientific data warehouses. Our scientists also wanted an efficient method to consolidate the data points returned by the indexes into larger, more meaningful regions of interest. To address these three problems, we introduced multi-resolution bitmap indexes, which group data into bins at multiple granularities. We achieved a query performance which is 10 times faster than traditional bitmap indexes by using bitmap indexes built at these multiple granularities. To address the issue of size, we introduced an adaptive version of multi-resolution bitmap indexes. The adaptive index adds and drops auxiliary indexes as needed for the query workload and is a fraction of the size of the data being indexed. We achieved a performance improvement of a factor of 6, compared to an ordinary multi-resolution bitmap index of the same size. We also introduced a novel algorithm to consolidate data points into regions of interest. By exploiting the special properties of compressed bitmap indexes and scientific meshes we achieved sublinear running times, with respect to the number of points in the query result, for both the index lookup and region consolidation

Entity Retrieval over Structured Data

Entity retrieval is the problem of finding information about a given real-world entity (e.g., director Peter Jackson) from one or a set of data sources. This problem is fundamental in numerous data management settings, but has received little attention. We define the general entity retrieval problem, then discuss the limitations of current information systems (e.g. relational databases, search engines) in solving it. Next, we focus on the specific problem of entity retrieval over structured data (as opposed to text or Web pages). We show that it is inherently more general and difficult than the actively-studied problem of entity matching (i.e. record linkage). We then develop the ENRICH system, which significantly extends entity matching solutions to perform entity retrieval. In particular, ENRICH employs clustering techniques to obtain a global picture on how many entities are "out there" and which data fragment should best be assigned to which entity. It also constructs profiles that capture important characteristics of the target entity, then uses the profiles to help the assignment process. Finally, it leverages "query expansion", an idea commonly used in the information retrieval community, to further improve retrieval accuracy. We apply ENRICH to several real-world domain, and show that it can perform entity retrieval with high accuracy