Current Strategies to Enhance Recovery following Radical Cystectomy: Single Centre Initial Experience

A radical cystectomy (RC) with pelvic lymph node dissection is the gold standard treatment for muscle-invasive bladder carcinoma. The morbidity associated with RC is clearly lower than that in the previous decades; it still continues to remain higher than 30% in the early postoperative period associated with and remains the most effective method for local control. We present current strategies being developed to further enhance recovery in patients undergoing RC and stratifying these into pre, intra, and post operative. We present our current strategies to enhance revcovery in patients undergoing RC which includes a combination of a through preoperative assessment with cardiopulmonary exercise (CPX), preoperative carbohydrate loading drinks, and intraoperative fluid monitoring with the trans-oesophageal Doppler probe (TODP) that may enhance recovery following radical cystectomy. We conclude that using these strategies may not only help in reducing peri/post operative morbidity and the duration of inpatient stay but may also help in enhancing the patient's long-term recovery

Fast and Accurate Retrieval of Methane Concentration From Imaging Spectrometer Data Using Sparsity Prior

The strong radiative forcing by atmospheric methane has stimulated interest in identifying natural and anthropogenic sources of this potent greenhouse gas. Point sources are important targets for quantification, and anthropogenic targets have the potential for emissions reduction. Methane point-source plume detection and concentration retrieval have been previously demonstrated using data from the Airborne Visible InfraRed Imaging Spectrometer-Next Generation (AVIRIS-NG). Current quantitative methods have tradeoffs between computational requirements and retrieval accuracy, creating obstacles for processing real-time data or large data sets from flight campaigns. We present a new computationally efficient algorithm that applies sparsity and an albedo correction to matched the filter retrieval of trace gas concentration path length. The new algorithm was tested using the AVIRIS-NG data acquired over several point-source plumes in Ahmedabad, India. The algorithm was validated using the simulated AVIRIS-NG data, including synthetic plumes of known methane concentration. Sparsity and albedo correction together reduced the root-mean-squared error of retrieved methane concentration-path length enhancement by 60.7% compared with a previous robust matched filter method. Background noise was reduced by a factor of 2.64. The new algorithm was able to process the entire 300 flight line 2016 AVIRIS-NG India campaign in just over 8 h on a desktop computer with GPU acceleration

Fast and Accurate Retrieval of Methane Concentration from Imaging Spectrometer Data Using Sparsity Prior

The strong radiative forcing by atmospheric methane has stimulated interest in identifying natural and anthropogenic sources of this potent greenhouse gas. Point sources are important targets for quantification, and anthropogenic targets have potential for emissions reduction. Methane point source plume detection and concentration retrieval have been previously demonstrated using data from the Airborne Visible InfraRed Imaging Spectrometer Next Generation (AVIRIS-NG). Current quantitative methods have tradeoffs between computational requirements and retrieval accuracy, creating obstacles for processing real-time data or large datasets from flight campaigns. We present a new computationally efficient algorithm that applies sparsity and an albedo correction to matched filter retrieval of trace gas concentration-pathlength. The new algorithm was tested using AVIRIS-NG data acquired over several point source plumes in Ahmedabad, India. The algorithm was validated using simulated AVIRIS-NG data including synthetic plumes of known methane concentration. Sparsity and albedo correction together reduced the root mean squared error of retrieved methane concentration-pathlength enhancement by 60.7% compared with a previous robust matched filter method. Background noise was reduced by a factor of 2.64. The new algorithm was able to process the entire 300 flightline 2016 AVIRIS-NG India campaign in just over 8 hours on a desktop computer with GPU acceleration.Comment: 13 pages, 11 figure

Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing

AbstractOBJECTIVESThis study examined the effect of physiologic pacing on the development of chronic atrial fibrillation (CAF) in the Canadian Trial Of Physiologic Pacing (CTOPP).BACKGROUNDThe role of physiologic pacing to prevent CAF remains unclear. Small randomized studies have suggested a benefit for patients with sick sinus syndrome. No data from a large randomized trial are available.METHODSThe CTOPP randomized patients undergoing first pacemaker implant to ventricular-based or physiologic pacing (AAI or DDD). Patients who were prospectively found to have persistent atrial fibrillation (AF) lasting greater than or equal to one week were defined as having CAF. Kaplan-Meier plots for the development of CAF were compared by log-rank test. The effect of baseline variables on the benefit of physiologic pacing was evaluated by Cox proportional hazards modeling.RESULTSPhysiologic pacing reduced the development of CAF by 27.1%, from 3.84% per year to 2.8% per year (p = 0.016). Three clinical factors predicted the development of CAF: age ≥74 years (p = 0.057), sinoatrial (SA) node disease (p < 0.001) and prior AF (p < 0.001). Subgroup analysis demonstrated a trend for patients with no history of myocardial infarction or coronary disease (p = 0.09) as well as apparently normal left ventricular function (p = 0.11) to derive greatest benefit.CONCLUSIONSPhysiologic pacing reduces the annual rate of development of chronic AF in patients undergoing first pacemaker implant. Age ≥74 years, SA node disease and prior AF predicted the development of CAF. Patients with structurally normal hearts appear to derive greatest benefits

Zinc is essential for high-affinity DNA binding and recombinase activity of φC31 integrase

The mechanism through which the large serine recombinases bind DNA is poorly understood. Alignments of ϕC31 integrase (Int) and its relatives indicate the presence of a conserved motif containing four cysteines resembling a zinc finger. Inductively coupled plasma–mass spectrometry (ICP–MS) confirmed that an Int monomer contains one atom of zinc. Pre-incubation of Int with ethylenediaminetetraacetic acid (EDTA) was detrimental for both recombination activity and DNA binding affinities but full activity could be restored by adding back Zn2+. Mutations in the cysteines and other highly conserved residues yielded proteins that were hypersensitive to proteases, suggesting that without zinc the domain is unfolded. Substitutions in the highly charged region between the conserved cysteines led to lowered DNA binding affinities while circular dichroism revealed that these variant Ints were not greatly affected in overall folding. Int was protected from inhibition by EDTA when DNA containing an attachment site was present suggesting that the zinc finger and the DNA are in close proximity. A truncated mutant of Int, hInt V371SUGA, lacking the putative zinc finger could bind DNA with low affinity. The data are consistent with there being at least two DNA binding motifs in Int one of which is the zinc finger-like motif

International nonproprietary names for monoclonal antibodies: an evolving nomenclature system

Appropriate nomenclature for all pharmaceutical substances is important for clinical development, licensing, prescribing, pharmacovigilance, and identification of counterfeits. Nonproprietary names that are unique and globally recognized for all pharmaceutical substances are assigned by the International Nonproprietary Names (INN) Programme of the World Health Organization (WHO). In 1991, the INN Programme implemented the first nomenclature scheme for monoclonal antibodies. To accompany biotechnological development, this nomenclature scheme has evolved over the years; however, since the scheme was introduced, all pharmacological substances that contained an immunoglobulin variable domain were coined with the stem -mab. To date, there are 879 INN with the stem -mab. Owing to this high number of names ending in -mab, devising new and distinguishable INN has become a challenge. The WHO INN Expert Group therefore decided to revise the system to ease this situation. The revised system was approved and adopted by the WHO at the 73rd INN Consultation held in October 2021, and the radical decision was made to discontinue the use of the well-known stem -mab in naming new antibody-based drugs and going forward, to replace it with four new stems: -tug, -bart, -mig, and -ment. Keywords: International Nonproprietary Name (INN); antibodies; antibody-based drugs; antibody-drug conjugates; biological drugs; biologics; nomenclature scheme; pharmaceuticals; safety; therapeutic antibodies