A photo- and electrochemically-active porphyrin–fullerene dyad electropolymer

A hole- and electron-conducting polymer has been prepared by electropolymerization of aporphyrin–fullerene monomer. The porphyrin units are linked by aminophenyl groups to form a linear chain in which the porphyrin is an integral part of the polymer backbone. The absorption spectrum of a film formed on indium-tin-oxide-coated glass resembles that of a model porphyrin–fullerene dyad, but with significant peak broadening. The film demonstrates a first oxidation potential of 0.75 V vs. SCE, corresponding to oxidation of the porphyrin polymer, and a first reduction potential of -0.63 V vs. SCE, corresponding to fullerene reduction. Time-resolved fluorescence studies show that the porphyrin first excited singlet state is strongly quenched by photoinduced electron transfer to fullerene. Transient absorption investigations reveal that excitation generates mobile charge carriers that recombine by both geminate and nongeminate pathways over a large range of time scales. Similar studies on a related polymer that lacks the fullerene component show complex, laser-intensity-dependent photoinduced electron transfer behavior. The properties of the porphyrin–fullerene electropolymer suggest that it maybe useful in organic photovoltaic applications, wherein light absorption leads to charge separationwithin picoseconds in a “molecular heterojunction” with no requirement for exciton migration.Fil: Gervaldo, Miguel Andres. Universidad Nacional de Río Cuarto. Facultad de Ciencias Exactas Fisicoquímicas y Naturales. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Tecnologías Energéticas y Materiales Avanzados; ArgentinaFil: Liddell, Paul A.. Arizona State University; Estados UnidosFil: Kodis, Gerdenis. Arizona State University; Estados UnidosFil: Brennan, Bradley J.. Arizona State University; Estados UnidosFil: Johnson, Christopher R.. Arizona State University; Estados UnidosFil: Bridgewater, James W.. Arizona State University; Estados UnidosFil: Moore, Ana L.. Arizona State University; Estados UnidosFil: Moore, Thomas A.. Arizona State University; Estados UnidosFil: Gust, Devens. Arizona State University; Estados Unido

A comparison of outcomes between bovine pericardial and porcine valves in 38 040 patients in England and Wales over 10 years

OBJECTIVES: Biological valves are the most commonly implanted prostheses for aortic valve replacement (AVR) surgery in the UK. The aim of this study was to compare performance of porcine and bovine pericardial valves implanted in AVR surgery with respect to survival and reintervention-free survival in a retrospective observational study. METHODS: Prospectively collected clinical data for all first-time elective and urgent AVRs with or without concomitant coronary artery bypass graft (CABG) surgery performed in England and Wales between April 2003 and March 2013 were extracted from the National Institute for Cardiovascular Outcomes Research database. Patient life status was tracked from the Office for National Statistics. Time-to-event analyses were performed using log-rank tests and Cox proportional hazards regression modelling with random effects/grouped frailty for responsible cardiac surgeons. RESULTS: A total of 38 040 patients were included (64.9 % bovine pericardial; 35.1 % porcine). Patient characteristics were similar between the groups. The median follow-up was 3.6 years. There was no statistically significant difference in survival (P = 0.767) (the 10-year surviva

British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations

Reexamination of Lead(II) Coordination Preferences in Sulfur-Rich Sites: Implications for a Critical Mechanism of Lead Poisoning

Recent studies suggest that the developmental toxicity associated with childhood lead poisoning may be attributable to interactions of Pb(II) with proteins containing thiol-rich structural zinc-binding sites. Here, we report detailed structural studies of Pb(II) in such sites, providing critical insights into the mechanism by which lead alters the activity of these proteins. X-ray absorption spectroscopy of Pb(II) bound to structural zinc-binding peptides reveals that Pb(II) binds in a three-coordinate Pb(II)-S3 mode, while Zn(II) is known to bind in a four-coordinate mode in these proteins. This Pb(II)-S_3 coordination in peptides is consistent with a trigonal pyramidal Pb(II)-S_3 model compound previously reported by Bridgewater and Parkin, but it differs from many other reports in the small molecule literature which have suggested Pb(II)-S_4 as a preferred coordination mode for lead. Reexamination of the published structures of these “Pb(II)-S_4” compounds reveals that, in almost all cases, the coordination number of Pb is actually 5, 6, or 8. The results reported herein combined with this new review of published structures suggest that lead prefers to avoid four-coordination in sulfur-rich sites, binding instead as trigonal pyramidal Pb(II)-S_3 or as Pb(II)-S_(5-8). In the case of structural zinc-binding protein sites, the observation that lead binds in a three-coordinate mode, and in a geometry that is fundamentally different from the natural coordination of zinc in these sites, explains why lead disrupts the structure of these peptides and thus provides the first detailed molecular understanding of the developmental toxicity of lead

Reply to Comment on "The UK consensus position on the treatment of pancreatic cancer during the COVID-19 pandemic".

Funder: DH | National Institute for Health Research (NIHR); doi: https://doi.org/10.13039/501100000272Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/50110000028

Ornamental plants: annual reports and research reviews, 2002

Ohio State University Extension Nursery, Landscape, and Turf Team directory: 2003 / Jack Kerrigan -- Floriculture Industry Roundtable of Ohio: 2003 / Charles Behnke -- Ohio State University Extension 2002 Buckeye Yard and Garden Line evaluation survey / Amy K. Stone and James A. Chatfield -- Weather, environmental, and cultural problems of ornamental plants in Ohio: 2002 / Pamela J. Bennett -- Infectious disease problems of ornamental plants in Ohio: 2002 / James A. Chatfield, Nancy A. Taylor, Erik A. Draper, and Joseph F. Boggs -- A biological calendar for predicting pest activity: six years of plant and insect phenology in Secrest Arboretum / Daniel A. Herms -- Biological suppression of foliar diseases of ornamental plants with composted manures, biosolids, and Trichoderma hamatum 382 / Harry A. J. Hoitink, Carol A. Musselman, Terry L. Moore, Leona E. Horst, Charles R. Krause, Randy A. Zondag, and Hannah Mathers -- Growth and water use by four leguminous tree species in containers on a gravel surface or embedded in mulch / Michael Knee, Daniel K. Struve, Michael H. Bridgewater, and Joseph W. Phillips -- The effects of sprayer configuration on efficacy for the control of scab on crabapple / Charles R. Krause, Richard C. Derksen, Leona E. Horst, Randall Zondag, Ross D. Brazee, Michael G. Klein, and Michael E. Reding -- Update on honeylocust knot / Pierluigi Bonello, Maria Bellizzi, and Harry A. J. Hoitink -- Control of phytophthora and other major diseases of Ericaceous plants / Harry A. J. Hoitink, Steven T. Nameth, and James C. Locke -- Is your landscape mulch going up in smoke? / Larry G. Steward, T. Davis Sydnor, and Bert Bishop -- IR-4 ornamental trials conducted by USDA-ARS in Ohio: 2002 / Betsy A. Anderson, Michael E. Reding, Michael G. Klein, and Charles R. Krause -- Research on black vine weevil and white grubs in ornamental nurseries-in Ohio by USDA-ARS / Michael E. Reding, Michael G. Klein, Ross D. Brazee, and Charles R. Krause -- Herbaceous ornamental field trial results in Clark County, Ohio – 2002 / Pamela J. Bennett -- Results of annual trial gardens at the Cincinnati Zoo and Botanical Garden for 2002 / Dave Dyke -- Ohio State University Learning Garden annual cultivar trials / Monica M. Kmetz-Gonzalez and Claudio C. Pasian -- A collection of crabapple knowledge from Secrest Arboretum: 1993-2002 / Erik A. Draper, James A. Chatfield, and Kenneth D. Cochran -- Key results of the 2001 Ohio Green Industry Survey / Gary Y. Gao, John J. Smith, James A. Chatfield, Joseph F. Boggs, Erik A. Draper, and Hannah Mathers -- The USDA/Agricultural Research Service research weather network in Lake County, Ohio - 2002 update / R. D. Brazee, R. C. Derksen, C. R. Krause, K. A. Williams, D. Lohnes, M. G. Klein, M. Reding, R. Lyons, W. Hendricks, R. Zondag, R. D. Fox, and D. Herms -- The OSU Chadwick Arboretum Learning Gardens / Dr. Steven Still and Annette Duetz -- Choosing soil testing labs / Gary Y, Gao, Maurice E. Watson, Joseph F. Boggs, and James A. Chatfield -- Top horticultural references for a green industry professional's library / Gary Y. Gao and Pamela J. Bennett -- The maples of Secrest Arboretum / Gary W. Graham, James A. Chatfield, and Kenneth D. Cochran -- Deck the halls with boughs from Ollie! / Kenneth D. Cochran and James A. Chatfiel

Systemic chemotherapy with or without cetuximab in patients with resectable colorectal liver metastasis (New EPOC): long-term results of a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: The interim analysis of the multicentre New EPOC trial in patients with resectable colorectal liver metastasis showed a significant reduction in progression-free survival in patients allocated to cetuximab plus chemotherapy compared with those given chemotherapy alone. The focus of the present analysis was to assess the effect on overall survival. METHODS: New EPOC was a multicentre, open-label, randomised, controlled, phase 3 trial. Adult patients (aged ≥18 years) with KRAS wild-type (codons 12, 13, and 61) resectable or suboptimally resectable colorectal liver metastases and a WHO performance status of 0-2 were randomly assigned (1:1) to receive chemotherapy with or without cetuximab before and after liver resection. Randomisation was done centrally with minimisation factors of surgical centre, poor prognosis cancer, and previous adjuvant treatment with oxaliplatin. Chemotherapy consisted of oxaliplatin 85 mg/m2 administered intravenously over 2 h, l-folinic acid (175 mg flat dose administered intravenously over 2 h) or d,l-folinic acid (350 mg flat dose administered intravenously over 2 h), and fluorouracil bolus 400 mg/m2 administered intravenously over 5 min, followed by a 46 h infusion of fluorouracil 2400 mg/m2 repeated every 2 weeks (regimen one), or oxaliplatin 130 mg/m2 administered intravenously over 2 h and oral capecitabine 1000 mg/m2 twice daily on days 1-14 repeated every 3 weeks (regimen two). Patients who had received adjuvant oxaliplatin could receive irinotecan 180 mg/m2 intravenously over 30 min with fluorouracil instead of oxaliplatin (regimen three). Cetuximab was given intravenously, 500 mg/m2 every 2 weeks with regimen one and three or a loading dose of 400 mg/m2 followed by a weekly infusion of 250 mg/m2 with regimen two. The primary endpoint of progression-free survival was published previously. Secondary endpoints were overall survival, preoperative response, pathological resection status, and safety. Trial recruitment was halted prematurely on the advice of the Trial Steering Committee on Nov 1, 2012. All analyses (except safety) were done on the intention-to-treat population. Safety analyses included all randomly assigned patients. This trial is registered with ISRCTN, number 22944367. FINDINGS: Between Feb 26, 2007, and Oct 12, 2012, 257 eligible patients were randomly assigned to chemotherapy with cetuximab (n=129) or without cetuximab (n=128). This analysis was carried out 5 years after the last patient was recruited, as defined in the protocol, at a median follow-up of 66·7 months (IQR 58·0-77·5). Median progression-free survival was 22·2 months (95% CI 18·3-26·8) in the chemotherapy alone group and 15·5 months (13·8-19·0) in the chemotherapy plus cetuximab group (hazard ratio [HR] 1·17, 95% CI 0·87-1·56; p=0·304). Median overall survival was 81·0 months (59·6 to not reached) in the chemotherapy alone group and 55·4 months (43·5-71·5) in the chemotherapy plus cetuximab group (HR 1·45, 1·02-2·05; p=0·036). There was no significant difference in the secondary outcomes of preoperative response or pathological resection status between groups. Five deaths might have been treatment-related (one in the chemotherapy alone group and four in the chemotherapy plus cetuximab group). The most common grade 3-4 adverse events reported were: neutrophil count decreased (26 [19%] of 134 in the chemotherapy alone group vs 21 [15%] of 137 in the chemotherapy plus cetuximab group), diarrhoea (13 [10%] vs 14 [10%]), skin rash (one [1%] vs 22 [16%]), thromboembolic events (ten [7%] vs 11 [8%]), lethargy (ten [7%] vs nine [7%]), oral mucositis (three [2%] vs 14 [10%]), vomiting (seven [5%] vs seven [5%]), peripheral neuropathy (eight [6%] vs five [4%]), and pain (six [4%] vs six [4%]). INTERPRETATION: Although the addition of cetuximab to chemotherapy improves the overall survival in some studies in patients with advanced, inoperable metastatic disease, its use in the perioperative setting in patients with operable disease confers a significant disadvantage in terms of overall survival. Cetuximab should not be used in this setting. FUNDING: Cancer Research UK

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies