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Carotenoids play an essential role in photoprotection, interacting with other pigments to safely dissipate excess absorbed energy as heat. In cyanobacteria, the short time scale photoprotective mechanisms involve the photoactive orange carotenoid protein (OCP), which binds a single carbonyl carotenoid. Blue-green light induces the photoswitching of OCP from its ground state form (OCPO) to a metastable photoproduct (OCPR). OCPR can bind to the phycobilisome antenna and induce fluorescence quenching. The photoswitching is accompanied by structural and functional changes at the level of the protein and of the bound carotenoid. Here, we use broadband two-dimensional electronic spectroscopy to study the differences in excited state dynamics of the carotenoid in the two forms of OCP. Our results provide insight into the origin of the pronounced vibrational lineshape and oscillatory dynamics observed in linear absorption and 2D electronic spectroscopy of OCPO and the large inhomogeneous broadening in OCPR, with consequences for the chemical function of the two forms.

Two-dimensional electronic-vibrational spectroscopy is used to study the excited state evolution of the carotenoid β-apo-8'-carotenal in solution. This new multidimensional spectroscopy is unique in its ability to directly follow the electronic and nuclear degrees of freedom simultaneously. © 2014 OSA.

Background: Effective therapeutics given early to high-risk ambulatory patients with coronavirus disease 2019 (COVID-19) could improve outcomes and reduce overall healthcare burden. However, conducting site visits in non-hospitalised patients, who should remain isolated, is problematic. Aim: To evaluate the feasibility of a purely remote (virtual) study in non-hospitalised patients with COVID-19; and the efficacy and safety of nebulised recombinant interferon-β1a (SNG001) in this setting. Design & setting: Randomised, double-blind, parallel-group study, which was conducted remotely. Method: Eligible patients aged ≥65 years (or ≥50 years with risk factors) with COVID-19 and not requiring hospital admission were recruited remotely. They were randomised to SNG001 or placebo once-daily via nebuliser for 14 days. The main outcomes were assessments of feasibility and safety, which were all conducted remotely. Results: Of 114 patients treated, 111 (97.4%) completed 28 days of follow-up. Overall compliance to study medication was high, with ≥13 doses taken by 89.7% and 92.9% of treated patients in the placebo and SNG001 groups, respectively. Over the course of the study, only two patients were hospitalised, both in the placebo group; otherwise there were no notable differences between treatments for the efficacy parameters. No patients withdrew owing to an adverse event, and a similar proportion of patients experienced on-treatment adverse events in the two treatment groups (64.3% and 67.2% with SNG001 and placebo, respectively); most were mild or moderate and not treatment-related. Conclusion: This study demonstrated that it is feasible to conduct a purely virtual study in community-based patients with COVID-19, when the study included detailed daily assessments and with medication administered via nebuliser. [ABSTRACT FROM AUTHOR]

BackgroundInternet-based self-help interventions for individuals with depressive symptoms, in which the main component is often a web-based self-help program, have been shown to be efficacious in many controlled trials. However, there are also trials on self-help programs showing no significant effect when delivered in routine care, and some studies report high dropout and low adherence rates. Research suggests that these findings do not emerge primarily due to the specific content of a self-help program. It seems more important how a program is embedded in the context of human and automated support before and during the use of a self-help program. ObjectiveThis study aims to better understand the effects of 4 supportive contextual factors on outcomes of and adherence to a web-based self-help program for depressive symptoms. In a factorial experiment, 2 of 4 supportive factors, for which there is evidence for their role on outcomes and adherence, are realized during the intervention—personal guidance and automated email reminders. The other 2 factors are realized before the intervention—a diagnostic interview and a preintervention module aimed at increasing the motivation to use the program with motivational interviewing techniques. MethodsThe study is a full factorial randomized trial. Adults with mild to moderate depressive symptoms (Patient Health Questionnaire–9 score: 5-14) are recruited from the community through the internet and conventional media. All participants receive access to a web-based self-help program based on problem-solving therapy. They are randomized across 4 experimental factors, each reflecting the presence versus absence of a supportive factor (guidance, automated reminders, diagnostic interview, preintervention module) resulting in a 16-condition balanced factorial design. The primary outcome is depressive symptoms at 10 weeks post assessment. Secondary outcomes include adherence to the program, anxiety, stress, health-related quality of life, possible negative effects, and treatment satisfaction. Potential moderators and mediators (eg, treatment expectancy, problem-solving skills, working alliance with the study team) will also be investigated. ResultsEthical approval was received on January 20, 2020. The study was initiated in February 2020, and 240 participants have been enrolled in the study as of November 1, 2020. Recruitment for a total of 255 participants is ongoing. Data collection is expected to be completed by May 2021. ConclusionsA better understanding of relevant supportive factors in the dissemination of web-based interventions is necessary to improve outcomes of and adherence to web-based self-help programs. This study may inform health care systems and guide decisions to optimize the implementation context of web-based self-help programs for depressive symptoms. Trial RegistrationClinicalTrials.gov NCT04318236; https://clinicaltrials.gov/ct2/show/NCT04318236 International Registered Report Identifier (IRRID)DERR1-10.2196/21207

Purpose.--Clinical use of analytical tests to assess genomic variants in circulating tumor DNA (ctDNA) is increasing. This joint review from the American Society of Clinical Oncology and the College of American Pathologists summarizes current information about clinical ctDNA assays and provides a framework for future research. Methods.--An Expert Panel conducted a literature review on the use of ctDNA assays for solid tumors, including preanalytical variables, analytical validity, interpretation and reporting, and clinical validity and utility. Results.--The literature search identified 1338 references. Of those, 390, plus 31 references supplied by the Expert Panel, were selected for full-text review. There were 77 articles selected for inclusion. Conclusions.--The evidence indicates that testing for ctDNA is optimally performed on plasma collected in cell stabilization or EDTA tubes, with EDTA tubes processed within 6 hours of collection. Some ctDNA assays have demonstrated clinical validity and utility with certain types of advanced cancer; however, there is insufficient evidence of clinical validity and utility for the majority of ctDNA assays in advanced cancer. Evidence shows discordance between the results of ctDNA assays and genotyping tumor specimens, and supports tumor tissue genotyping to confirm undetected results from ctDNA tests. There is no evidence of clinical utility and little evidence of clinical validity of ctDNA assays in early-stage cancer, treatment monitoring, or residual disease detection. There is no evidence of clinical validity or clinical utility to suggest that ctDNA assays are useful for cancer screening, outside of a clinical trial. Given the rapid pace of research, reevaluation of the literature will shortly be required, along with the development of tools and guidance for clinical practice. doi: 10.5858/arpa.2018-0901-SA, INTRODUCTION The use of assays that assess genomic variants in circulating tumor DNA (ctDNA) is increasing in the oncology clinical setting, despite uncertainties surrounding preanalytical considerations, analytical validity, and clinical [...]

ContextLung cancer is the leading cause of cancer death. Most patients are diagnosed with advanced disease, resulting in a very low 5-year survival. Screening may reduce the risk of death from lung cancer.ObjectiveTo conduct a systematic review of the evidence regarding the benefits and harms of lung cancer screening using low-dose computed tomography (LDCT). A multisociety collaborative initiative (involving the American Cancer Society, American College of Chest Physicians, American Society of Clinical Oncology, and National Comprehensive Cancer Network) was undertaken to create the foundation for development of an evidence-based clinical guideline.Data sourcesMEDLINE (Ovid: January 1996 to April 2012), EMBASE (Ovid: January 1996 to April 2012), and the Cochrane Library (April 2012).Study selectionOf 591 citations identified and reviewed, 8 randomized trials and 13 cohort studies of LDCT screening met criteria for inclusion. Primary outcomes were lung cancer mortality and all-cause mortality, and secondary outcomes included nodule detection, invasive procedures, follow-up tests, and smoking cessation.Data extractionCritical appraisal using predefined criteria was conducted on individual studies and the overall body of evidence. Differences in data extracted by reviewers were adjudicated by consensus.ResultsThree randomized studies provided evidence on the effect of LDCT screening on lung cancer mortality, of which the National Lung Screening Trial was the most informative, demonstrating that among 53,454 participants enrolled, screening resulted in significantly fewer lung cancer deaths (356 vs 443 deaths; lung cancer−specific mortality, 274 vs 309 events per 100,000 person-years for LDCT and control groups, respectively; relative risk, 0.80; 95% CI, 0.73-0.93; absolute risk reduction, 0.33%; P = .004). The other 2 smaller studies showed no such benefit. In terms of potential harms of LDCT screening, across all trials and cohorts, approximately 20% of individuals in each round of screening had positive results requiring some degree of follow-up, while approximately 1% had lung cancer. There was marked heterogeneity in this finding and in the frequency of follow-up investigations, biopsies, and percentage of surgical procedures performed in patients with benign lesions. Major complications in those with benign conditions were rare.ConclusionLow-dose computed tomography screening may benefit individuals at an increased risk for lung cancer, but uncertainty exists about the potential harms of screening and the generalizability of results.