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Background Postoperative atrial fibrillation (POAF) is a frequent adverse event after thoracic surgery with associated morbidity, mortality, and healthcare costs. It has been shown to be preventable with prophylactic amiodarone, which is only recommended in high-risk individuals due to the potential associated side effects. Risk factors for POAF have been identified and incorporated into a prediction model to identify high-risk patients. Further evaluation in the form of a multicenter clinical trial is required to assess the effectiveness of prophylaxis specifically in this high-risk population. The feasibility of such a trial first needs to be assessed. Methods The PREP-AF trial is a double-blind randomized controlled feasibility trial. Individuals undergoing major thoracic surgery who are identified to be high-risk by the POAF prediction model will be randomized 1:1 to receive a short course of amiodarone vs. placebo in the immediate postoperative period. The primary outcome is feasibility, which will be measured by the number of eligible patients identified, consented, and randomized; intervention adherence; and measurement of future outcomes of a full trial. Discussion This study will determine the feasibility of a randomized controlled trial to assess the effectiveness of prophylactic amiodarone, in high-risk patients undergoing major thoracic surgery. This will inform the development of a multi-center trial to establish if prophylactic amiodarone is safe and effective at reducing the incidence of POAF. Preventing this adverse event will not only improve outcomes for patients but also reduce the associated health resource utilization and costs. Trial registration ClinicalTrials.gov NCT04392921. Registered on 19 May 2020.

Multicentric approaches are widely used in clinical trials to assess generalizability of findings, however they are novel in preclinical experimentation. We synthesized characteristics of multilaboratory studies and quantitatively compared them to single laboratory studies. We systematically identified sixteen in vivo interventional multilaboratory studies and matched them to 100 single laboratory studies by intervention and disease. Differences in standardized mean differences (DSMD) were calculated to compare treatment effects based on study design. The multilaboratory study design was applied across a range of diseases (e.g. stroke, diabetes, trauma). The median number of labs was 4 (range 2-6) and the median sample size was 111 (range 23-384). Multilaboratory studies adhered to practices that reduce risk of bias and were transparently reported. These studies demonstrated significantly smaller treatment effects than single lab studies (DSMD 0.72 [95% confidence interval 0.43-1]). Preclinical multilaboratory studies demonstrate trends that have been well recognized in clinical research (i.e. smaller treatment effects with greater rigour in study design). This approach may provide a method to robustly assess interventions and reproducibility of findings between laboratories.

The efficacy of convalescent plasma for COVID-19 is unclear. While most randomized controlled trials have shown negative results, uncontrolled studies have suggested that the antibody content may influence patient outcomes.We conducted an open-label, randomized controlled trial of convalescent plasma for adults with COVID-19 receiving oxygen within 12 days of respiratory symptom onset. Patients were allocated 2:1 to 500 mL of convalescent plasma or standard of care. The composite primary outcome was intubation or death by 30 days. The effect of convalescent plasma antibodies on the primary outcome was assessed by logistic regression.The trial was terminated at 78% of planned enrollment after meeting stopping criteria for futility. 940 patients were randomized and 921 patients were included in the intent-to-treat analysis. Intubation or death occurred in 199/614 (32.4%) in the convalescent plasma arm and 86/307 (28.0%) in the standard of care arm; relative risk (RR) 1.16 (95% confidence interval (CI) 0.94-1.43; p=0.18). Patients in the convalescent plasma arm had more serious adverse events (33.4% vs. 26.4%; RR=1.27, 95% CI 1.02-1.57, p=0.034). The antibody content significantly modulated the therapeutic effect of convalescent plasma. In multivariate analysis, each standard log increase in neutralization or antibody-dependent cellular cytotoxicity independently reduced the potential harmful effect of plasma (OR=0.74; 0.57-0.95 and OR=0.66; 0.50-0.87, respectively), while IgG against the full transmembrane Spike protein increased it (OR=1.53, 95% CI 1.14-2.05).Convalescent plasma did not reduce the risk of intubation or death at 30 days among hospitalized patients with COVID-19. Transfusion of convalescent plasma with unfavourable antibody profiles may be associated with worse clinical outcomes compared to standard care.Trial registrationCONvalescent Plasma for Hospitalized Adults With COVID-19 Respiratory Illness (CONCOR-1); NCT04348656; https://www.clinicaltrials.gov/ct2/show/NCT04348656

Objectives: To measure medical journal Editor-in-Chiefs’ perceptions regarding including patients as (co-)authors on research publications and to measure their views on the application of the ICMJE authorship criteria to patient partners.Design: Cross-sectional survey co-developed with a patient partner Participants: Editor-in-Chiefs of medical journals were identified via a random sample of journals obtained from the Scopus source list, which contains all MEDLINE and EMBASE content. We restricted the Scopus source list to journals with a classification code of ‘Medicine’ and that were listed as active. Editor-in-Chiefs contact names and contact details were manually extracted from journal websites or obtained via online searching. Main outcome measures: The key outcome measures were whether Editor-in-Chiefs believed: 1) patient partners should be (co-)authors and; 2) whether they felt the ICMJE criteria for authorship required modification for use with patient partners. We also measured Editor-in-Chiefs description of how their journal’s operations incorporate patient partner perspectives. Results: 112 Editor-in-Chiefs responded to our survey (18.7% response rate; 66.69% male). Participants were able to skip any questions they did not want to answer, so there is missing data for some items. 69.2% (N = 74) of Editor-in-Chiefs indicated it was acceptable for patient partners to be authors or co-authors on published biomedical research articles, with the remaining 30.8% (N = 33) indicating this would not be appropriate. When asked specifically about the ICMJE authorship criteria, and whether this should be revised to be more inclusive of patient partners, 35.8% (N = 39) indicated it should be revised, 35.8% (N = 39) indicated it should not be revised, and 28.4% (N = 31) were unsure about a revision. Acceptability of the individual components of the ICMJE authorship criteria by Editor-in-Chiefs varied. 67.9% (N=74) of Editor-in-Chiefs felt a patient partner would likely be able to “give final approval a manuscript to be published” but only 42.6% (N = 46) of Editor-in-chiefs felt patient partners could be “accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved”. 74.1% (N = 80) of Editor-in-Chiefs did not think patients should be required to have an academic affiliation to published while 16.7% (N = 18) and 9.3% (N = 10) indicated they should or were unsure, respectively. 3.6% (N = 4) of Editor-in-Chiefs indicated their journal had a policy that specifies how patients or patient partners should be considered as authors. Conclusions: We found that a substantial proportion of medical journal Editor-in-Chiefs do not agree that patient partners should act as authors on publications, and that there is little consensus as to whether the ICMJE authorship criteria is appropriate for use with patient partners. Further, few journals involve patient or patient partners in the operations of their journal or have independent policy guidance around how authorship might apply to these groups. Access to, and awareness of, appropriate authorship criteria is an important right for patient partners to recognize contributions to research. Our findings highlight gaps that may act as barriers to patient partner participation in research.

A series of PF-8380 analogs, a recently developed autotaxin inhibitor, was explored. Inhibition of autotaxin by these analogs, as well as by all PF-8380 synthetic intermediates, shows the importance of meta-dichlorobenzyl and benzo[d]oxazol-2(3H)-one fragments. However, analogs 8 and 9, bearing only the benzo[d]oxazol-2(3H)-one moiety, are more cytotoxic on the LN229 glioblastoma cell line than PF-8380 and temozolomide (TMZ).

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by unpredictable clinical behaviors that suggest distinct molecular subtypes. With the tumor metabolic phenotype being one of the hallmarks of cancer, we have set upon to investigate whether GBMs show differences in their metabolic profiles. 1H NMR analysis was performed on metabolite extracts from a selection of nine glioblastoma cell lines. Analysis was performed directly on spectral data and on relative concentrations of metabolites obtained from spectra using a multivariate regression method developed in this work. Both qualitative and quantitative sample clustering have shown that cell lines can be divided into four groups for which the most significantly different metabolites have been determined. Analysis shows that some of the major cancer metabolic markers (such as choline, lactate, and glutamine) have significantly dissimilar concentrations in different GBM groups. The obtained lists of metabolic markers for subgroups were correlated with gene expression data for the same cell lines. Metabolic analysis generally agrees with gene expression measurements, and in several cases, we have shown in detail how the metabolic results can be correlated with the analysis of gene expression. Combined gene expression and metabolomics analysis have shown differential expression of transporters of metabolic markers in these cells as well as some of the major metabolic pathways leading to accumulation of metabolites. Obtained lists of marker metabolites can be leveraged for subtype determination in glioblastomas.

Hierarchical porous titanium dioxide is of great interest as a potential photocatalyst material because of its enhanced mass transfer capability and light capture efficiency. Tuning of these nanostructures allows for the design of new photocatalysts with improved performance. In this study, we report the synthesis of hierarchically meso–macroporous TiO 2 materials through a template-free aqueous technique. Controlled porous textures and crystalline structures of TiO 2 were obtained by varying the pH of the starting aqueous solution and the method of crystallization. The catalytic efficiency of these materials was investigated using photodegradation of methyl orange and the results show that specific surface area, pore volume and crystallinity play a key role in the photocatalytic performance. The hierarchical titania prepared by the hydrothermal method at a pH of 2 has the highest efficiency with an apparent reaction rate of 9.10 × 10 −2 min −1 , surpassing that of Degussa P25, hence showing its promising potential in environmental remediation.

Changes across metabolic networks are emerging as an integral part of cancer development and progression. Increasing comprehension of the importance of metabolic processes as well as metabolites in cancer is stimulating exploration of novel, targeted treatment options. Arachidonic acid (AA) is a major component of phospholipids. Through the cascade catalyzed by cyclooxygenases and lipoxygenases, AA is also a precursor to cellular signaling molecules as well as molecules associated with a variety of diseases including cancer. 5-Lipoxygenase catalyzes the transformation of AA into leukotrienes (LT), important mediators of inflammation. High-throughput analysis of metabolic profiles was used to investigate the response of glioblastoma cell lines to treatment with 5-lipoxygenase inhibitors. Metabolic profiling of cells following drug treatment provides valuable information about the response and metabolic alterations induced by the drug action and give an indication of both on-target and off-target effects of drugs. Four different 5-lipoxygenase inhibitors and antioxidants were tested including zileuton, caffeic acid, and its analogues caffeic acid phenethyl ester and caffeic acid cyclohexethyl ester. A NMR approach identified metabolic signatures resulting from application of these compounds to glioblastoma cell lines, and metabolic data were used to develop a better understanding of the mode of action of these inhibitors.

Glioblastoma multiforme (GBM) is the most common form of malignant glioma, characterized by unpredictable clinical behaviors that suggest distinct molecular subtypes. With the tumor metabolic phenotype being one of the hallmarks of cancer, we have set upon to investigate whether GBMs show differences in their metabolic profiles. (1)H NMR analysis was performed on metabolite extracts from a selection of nine glioblastoma cell lines. Analysis was performed directly on spectral data and on relative concentrations of metabolites obtained from spectra using a multivariate regression method developed in this work. Both qualitative and quantitative sample clustering have shown that cell lines can be divided into four groups for which the most significantly different metabolites have been determined. Analysis shows that some of the major cancer metabolic markers (such as choline, lactate, and glutamine) have significantly dissimilar concentrations in different GBM groups. The obtained lists of metabolic markers for subgroups were correlated with gene expression data for the same cell lines. Metabolic analysis generally agrees with gene expression measurements, and in several cases, we have shown in detail how the metabolic results can be correlated with the analysis of gene expression. Combined gene expression and metabolomics analysis have shown differential expression of transporters of metabolic markers in these cells as well as some of the major metabolic pathways leading to accumulation of metabolites. Obtained lists of marker metabolites can be leveraged for subtype determination in glioblastomas.

Background Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in clinical practice. The safety and efficacy of these agents in peritoneal dialysis (PD) patients are unclear. Objectives We conducted a systematic review to study the safety and efficacy of ACEI and ARB use in PD patients. Primary outcome measures were mortality and cardiovascular (CV) events; secondary outcome measures were renal function, proteinuria, hyperkalemia, and erythropoietin requirement at 3 months. Methods We searched Medline, EMBASE, Cochrane Central Register of Controlled Trials, trial registry Web sites, reference lists of eligible and review articles, as well as abstracts from the American Society of Nephrology and Canadian Society of Nephrology meetings. To be eligible, studies had to be randomized controlled trials that allocated PD patients to ACEI and ARB use or to placebo or other antihypertensive medications, included adult patients, and reported on at least one of the outcome measures. Results 418 citations were identified. Four met the eligibility criteria. Three examined CV events and mortality, of which two studies did not have any events. The third showed no statistically significant difference between control and treatment groups in either CV events or mortality: odds ratio 1.56 [95% confidence interval (CI) 0.24 – 10.05] for mortality and odds ratio 1.00 (95% CI 0.19 – 5.40) for CV events. Two studies reported renal function at 12 months and the weighted mean difference was 0.91 mL/minute/1.73 m2 (95% CI 0.14 – 1.68), favoring ACEI and ARB use. Conclusions In PD patients, evidence for the use of ACEIs and ARBs for reduction of mortality and CV events is lacking. Limited data suggest that they slow the loss of residual renal function.

The Multiple Kill Vehicle (MKV) system, which is being developed by the US Missile Defense Agency (MDA), is a midcourse payload that includes a carrier vehicle and a number of small kill vehicles. During the mission, the carrier vehicle dispenses the kill vehicles to address a complex threat environment and directs each kill vehicle toward the intercept point for its assigned threat object. As part of the long range carrier vehicle sensor development strategy, MDA and project leaders have developed a pathfinder sensor and are in the process of developing two subsequent demonstration sensors to provide proof of concept and to demonstrate technology. To increase the probability of successful development of the sensor system, detailed calibration measurements have been included as part of the sensor development. A detailed sensor calibration can provide a thorough understanding of sensor operation and performance, verifying that the sensor can meet the mission requirements. This approach to instrument knowledge will help ensure the program success and reduce cost and schedule risks. The Space Dynamics Laboratory at Utah State University (SDL) completed a calibration test campaign for the pathfinder sensor in April 2008. Similar calibration efforts are planned in 2009 for the two demonstration sensors. This paper provides an overview of calibration benefits, requirements, approach, facility, measurements, and preliminary results of the pathfinder calibration.