Publications by authors named "D Cullen"

654 Publications

Expanding on The Origins, Evolution, and Spread of Anesthesia Monitoring Standards.

Anesth Analg 2021 Jul;133(1):e14-e15

Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA.

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http://dx.doi.org/10.1213/ANE.0000000000005585DOI Listing
July 2021

Chemical vapour deposition of Fe-N-C oxygen reduction catalysts with full utilization of dense Fe-N sites.

Nat Mater 2021 Jun 10. Epub 2021 Jun 10.

Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA.

Replacing scarce and expensive platinum (Pt) with metal-nitrogen-carbon (M-N-C) catalysts for the oxygen reduction reaction in proton exchange membrane fuel cells has largely been impeded by the low oxygen reduction reaction activity of M-N-C due to low active site density and site utilization. Herein, we overcome these limits by implementing chemical vapour deposition to synthesize Fe-N-C by flowing iron chloride vapour over a Zn-N-C substrate at 750 °C, leading to high-temperature trans-metalation of Zn-N sites into Fe-N sites. Characterization by multiple techniques shows that all Fe-N sites formed via this approach are gas-phase and electrochemically accessible. As a result, the Fe-N-C catalyst has an active site density of 1.92 × 10 sites per gram with 100% site utilization. This catalyst delivers an unprecedented oxygen reduction reaction activity of 33 mA cm at 0.90 V (iR-corrected; i, current; R, resistance) in a H-O proton exchange membrane fuel cell at 1.0 bar and 80 °C.
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http://dx.doi.org/10.1038/s41563-021-01030-2DOI Listing
June 2021

First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial.

Lancet 2021 Jun 4. Epub 2021 Jun 4.

Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: First-line chemotherapy for advanced or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastro-oesophageal junction adenocarcinoma has a median overall survival (OS) of less than 1 year. We aimed to evaluate first-line programmed cell death (PD)-1 inhibitor-based therapies in gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma. We report the first results for nivolumab plus chemotherapy versus chemotherapy alone.

Methods: In this multicentre, randomised, open-label, phase 3 trial (CheckMate 649), we enrolled adults (≥18 years) with previously untreated, unresectable, non-HER2-positive gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma, regardless of PD-ligand 1 (PD-L1) expression from 175 hospitals and cancer centres in 29 countries. Patients were randomly assigned (1:1:1 while all three groups were open) via interactive web response technology (block sizes of six) to nivolumab (360 mg every 3 weeks or 240 mg every 2 weeks) plus chemotherapy (capecitabine and oxaliplatin every 3 weeks or leucovorin, fluorouracil, and oxaliplatin every 2 weeks), nivolumab plus ipilimumab, or chemotherapy alone. Primary endpoints for nivolumab plus chemotherapy versus chemotherapy alone were OS or progression-free survival (PFS) by blinded independent central review, in patients whose tumours had a PD-L1 combined positive score (CPS) of five or more. Safety was assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT02872116.

Findings: From March 27, 2017, to April 24, 2019, of 2687 patients assessed for eligibility, we concurrently randomly assigned 1581 patients to treatment (nivolumab plus chemotherapy [n=789, 50%] or chemotherapy alone [n=792, 50%]). The median follow-up for OS was 13·1 months (IQR 6·7-19·1) for nivolumab plus chemotherapy and 11·1 months (5·8-16·1) for chemotherapy alone. Nivolumab plus chemotherapy resulted in significant improvements in OS (hazard ratio [HR] 0·71 [98·4% CI 0·59-0·86]; p<0·0001) and PFS (HR 0·68 [98 % CI 0·56-0·81]; p<0·0001) versus chemotherapy alone in patients with a PD-L1 CPS of five or more (minimum follow-up 12·1 months). Additional results showed significant improvement in OS, along with PFS benefit, in patients with a PD-L1 CPS of one or more and all randomly assigned patients. Among all treated patients, 462 (59%) of 782 patients in the nivolumab plus chemotherapy group and 341 (44%) of 767 patients in the chemotherapy alone group had grade 3-4 treatment-related adverse events. The most common any-grade treatment-related adverse events (≥25%) were nausea, diarrhoea, and peripheral neuropathy across both groups. 16 (2%) deaths in the nivolumab plus chemotherapy group and four (1%) deaths in the chemotherapy alone group were considered to be treatment-related. No new safety signals were identified.

Interpretation: Nivolumab is the first PD-1 inhibitor to show superior OS, along with PFS benefit and an acceptable safety profile, in combination with chemotherapy versus chemotherapy alone in previously untreated patients with advanced gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Nivolumab plus chemotherapy represents a new standard first-line treatment for these patients.

Funding: Bristol Myers Squibb, in collaboration with Ono Pharmaceutical.
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http://dx.doi.org/10.1016/S0140-6736(21)00797-2DOI Listing
June 2021

Growth and renal function dynamics of renal oncocytomas on active surveillance.

BJU Int 2021 May 28. Epub 2021 May 28.

Division of Surgery and Interventional Science, University College London.

Objectives: To study the natural history of renal oncocytomas and address indications for intervention by determining how growth associates with renal function over time, the reasons for surgery and ablation, and disease-specific survival.

Patients And Methods: Retrospective cohort of consecutive patients with renal oncocytoma on active surveillance reviewed at the Specialist Centre for Kidney Cancer at Royal Free London NHS Foundation Trust (2012 to 2019). Comparison between groups was tested using the Mann-Whitney U and the Chi-square tests. A mixed-effects model with a random intercept for patient was used to study the longitudinal association between tumour size and estimated glomerular filtration rate (eGFR).

Results: Longitudinal data from 98 patients with 101 lesions was analysed. Most patients were male (68.3%), median age was 69 years (IQR 13). The median follow-up was 29 months (IQR 26). Most lesions were small renal masses, 24% measured over 4 cm. Over half (64.4%) grew at a median rate of 2 mm per year (IQR 4). No association was observed between tumour size and eGFR over time (p=0.871). Nine lesions (8.9%) were subsequently treated. Two deaths were reported, neither were related to the diagnosis of renal oncocytoma.

Conclusion: Natural history data from the largest active surveillance cohort of renal oncocytomas to date show that renal function does not seem to be negatively impacted by growing oncocytomas, and confirms clinical outcomes are excellent after a median follow up of over 2 years. Active surveillance should be considered the gold standard management of renal oncocytomas up to 7cm.
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http://dx.doi.org/10.1111/bju.15499DOI Listing
May 2021

Electrochemical ammonia synthesis via nitrate reduction on Fe single atom catalyst.

Nat Commun 2021 May 17;12(1):2870. Epub 2021 May 17.

Department of Chemical and Biomolecular Engineering, Rice University, Houston, TX, USA.

Electrochemically converting nitrate, a widespread water pollutant, back to valuable ammonia is a green and delocalized route for ammonia synthesis, and can be an appealing and supplementary alternative to the Haber-Bosch process. However, as there are other nitrate reduction pathways present, selectively guiding the reaction pathway towards ammonia is currently challenged by the lack of efficient catalysts. Here we report a selective and active nitrate reduction to ammonia on Fe single atom catalyst, with a maximal ammonia Faradaic efficiency of ~ 75% and a yield rate of up to ~ 20,000 μg h mg (0.46 mmol h cm). Our Fe single atom catalyst can effectively prevent the N-N coupling step required for N due to the lack of neighboring metal sites, promoting ammonia product selectivity. Density functional theory calculations reveal the reaction mechanisms and the potential limiting steps for nitrate reduction on atomically dispersed Fe sites.
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http://dx.doi.org/10.1038/s41467-021-23115-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128876PMC
May 2021