The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice.
During the academic years 2013 to 2014 and ...2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported.
Sixty-six chief residents completed the survey in 2013 to 2014 (53% response rate), and 69 completed the survey in 2014 to 2015 (64% response rate). Forty to 85% percent of residents reported inadequate exposure to high-dose rate and low-dose rate brachytherapy. Nearly all residents in both years (>90%) reported adequate clinical experience for the following disease sites: breast, central nervous system, gastrointestinal, genitourinary, head and neck, and lung. However, as few as 56% reported adequate experience in lymphoma or pediatric malignancies. More than 90% of residents had participated in retrospective research projects, with 20% conducting resident-led prospective clinical trials and 50% conducting basic science or translational projects. Most chief residents reported working 60 or fewer hours per week in the clinical/hospital setting and performing fewer than 15 hours per week tasks that were considered to have little or no educational value. There was more than 80% compliance with Accreditation Council for Graduate Medical Education (ACGME) work hour limits. Fifty-five percent of graduating residents intended to join an established private practice group, compared to 25% who headed for academia. Residents perceive the job market to be more competitive than previous years.
This first update of the ARRO chief resident survey since the 2007 to 2008 academic year documents US radiation oncology residents' experiences and conditions over a 2-year period. This analysis may serve as a valuable tool for those seeking to improve training of the next generation of oncology leaders.
Extracellular adenosine (ADO), present in high concentrations in the tumor microenvironment (TME), suppresses immune function via inhibition of T cell and NK cell activation. Intratumoral generation ...of ADO depends on the sequential catabolism of ATP by two ecto-nucleotidases, CD39 (ATP → AMP) and CD73 (AMP → ADO). Inhibition of CD73 eliminates a major pathway of ADO production in the TME and can reverse ADO-mediated immune suppression. Extensive interrogation of structure–activity relationships (SARs), structure-based drug design, and optimization of pharmacokinetic properties culminated in the discovery of AB680, a highly potent (K i = 5 pM), reversible, and selective inhibitor of CD73. AB680 is further characterized by very low clearance and long half-lives across preclinical species, resulting in a PK profile suitable for long-acting parenteral administration. AB680 is currently being evaluated in phase 1 clinical trials. Initial data show AB680 is well tolerated and exhibits a pharmacokinetic profile suitable for biweekly (Q2W) iv-administration in human.
Solid tumors are often associated with high levels of extracellular ATP. Ectonucleotidases catalyze the sequential hydrolysis of ATP to adenosine, which potently suppresses T-cell and NK-cell ...functions via the adenosine receptors (A
and A
). The ectonucleotidase CD73 catalyzes the conversion of AMP to adenosine. Thus, increased CD73 enzymatic activity in the tumor microenvironment is a potential mechanism for tumor immune evasion and has been associated with poor prognosis in the clinic. CD73 inhibition is anticipated to restore immune function by skirting this major mechanism of adenosine generation. We have developed a series of potent and selective methylenephosphonic acid CD73 inhibitors via a structure-based design. Key binding interactions of the known inhibitor adenosine-5'-(α,β-methylene)diphosphate (AMPCP) with hCD73 provided the foundation for our early designs. The structure-activity relationship study guided by this structure-based design led to the discovery of
, which exhibits excellent potency against CD73, exquisite selectivity against related ectonucleotidases, and a favorable pharmacokinetic profile.
The autothermal reforming and partial oxidation of hexadecane via Pt/Ni bimetallic nanoparticles on various ceria-based supports were investigated. Nanoparticles with Pt/Ni molar ratios ranging from ...0/100 to 10/90 were loaded on ceria-based supports including cerium oxide, gadolinium-doped cerium oxide and cerium-doped zirconium oxide. The effect of the Pt/Ni molar ratio and the promotional effect of the support were studied by comparing the hydrogen yield. TPR and XPS analysis showed that there was a strong interaction between Ni and the CeO2–ZrO2 support, which led to the enhancement of catalyst performance when the Pt/Ni ratio was low. In the case of bimetallic catalysts loaded on Gd2O3–CeO2, no significant improvement of the catalytic activity of auto-thermal reforming was achieved until the Pt/Ni ratio reached 10/90.
•High yields of H2 were produced via reforming of hexadecane.•Pt/Ni bimetallic nanocatalysts on different ceria-based supported were investigated.•Generally, catalytic performance was enhanced with increasing Pt/Ni ratio.•Strong interaction between Ni and CeO2–ZrO2 was demonstrated.•Low Pt/Ni ratios led to improvement in hydrogen yield on Ni CeO2–ZrO2.
Objectives
Patients presenting with dysphagia can encounter a pathway to therapy and relief that is expensive and frustrating. High resolution impedance planimetry (HRIP) is a new mechanism for ...enhancing and possibly hastening that process. A balloon with integrated pressure sensors is utilized to measure luminal geometry and pressure by volume-controlled distention. Esophagogastric junction (EGJ) distensibility and body contractility are assessed at the time of other endoscopic procedures. Here we describe a single-center experience utilizing HRIP in the endoscopic evaluation of patients presenting with dysphagia.
Methods
A prospectively maintained registry of patients undergoing impedance planimetry assessments at an academic medical center was queried for demographics, procedural details, and patient-reported outcomes.
Results
Data was reviewed for 122 procedures performed by two providers. HRIP was performed in 63 (52%) patients for initial dysphagia assessment, 36 (30%) for follow-up assessment, and 20 (16%) as a procedural adjunct at the time of other planned procedures. HRIP contractile response was characterized as normal in 36%, absent in 32%, and diminished/disorganized in 14%. These results motivated clinical planning for surgical referral in 7 (5%) patients, 31 (26%) additional testing, and 82 (68%) continued medical management and follow-up.
Discussion
HRIP is an emerging endoscopic modality which can streamline diagnostic work-up and therapeutic planning for patients with symptomatic dysphagia. Using functional esophageal assessment at the time of other diagnostic and therapeutic procedures, HRIP may expedite care and lead to improved patient satisfaction and clinical outcomes.
A diphenylacetylene containing two different end groups (isonitrile and thioacetate) was synthesized, showing that the chemistry used to install each end group is compatible with that of the others. ...The isonitrile group binds preferentially to platinum, and the thiol group binds preferentially to gold. However, the selectivity was different when nanoparticles were compared to planar substrates.
Mycoplasma gallisepticum cell membranes were used to immunize mice to produce monoclonal antibodies to cell surface proteins. Three monoclonal antibodies were chosen for further characterization. All ...three reacted in immunoblots with an M. gallisepticum protein band of Mr approximately 67,000 (designated pMGA). By using immunoelectron microscopy, pMGA was shown to be located on the cell surface. When M. gallisepticum whole cells were treated with up to 250 micrograms of trypsin per ml for 30 min, the only major protein lost from the cell surface as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by Western immunoblot transfer was pMGA. Two of the pMGA-specific monoclonal antibodies inhibited hemagglutination of chicken erythrocytes by M. gallisepticum S6, suggesting a role for pMGA in the attachment of M. gallisepticum to chicken erythrocytes. Sequencing the amino terminus of pMGA yielded 17 amino acids with no significant homology with the Mycoplasma pneumoniae attachment protein P1 or any other protein in the GenBank, Swiss-Prot, and EMBL data bases
A 40-kDa protein from Corynebacterium pseudotuberculosis has been previously identified as a protective antigen against ovine caseous lymphadenitis. From genomic DNA libraries of C. ...pseudotuberculosis, we have cloned and sequenced the 40-kDa protein gene, which was found to contain an open reading frame of 1,137 bp encoding a protein of 379 amino acids. No significant homology with previously published DNA or amino acid sequence data was found in databases, suggesting that this is a novel protein. Recombinant 40-kDa protein was overexpressed as a fusion protein to 15% of total cell proteins in Escherichia coli. Biochemical analysis of native and recombinant 40-kDa proteins has revealed associated proteolytic activity, which was shown to be of the serine protease type through the use of specific inhibitors. We suggest that this novel protective antigen be termed corynebacterial protease 40 (CP40)
A 40-kDa protein antigen from Corynebacterium pseudotuberculosis has been identified by application of a strategy that employs locally derived antibody-secreting cells (ASC). ASC probes generated by ...culture of ASC obtained from the lymph node draining the site of infection showed a specificity restricted to a 40-kDa antigen. Analysis of immunoblots with sequential serum samples taken from sheep during the course of experimental primary infection with C. pseudotuberculosis also revealed the 40-kDa antigen as an early immunodominant antigen. Sheep vaccinated with two 100-microgram doses of a 40-kDa antiagen preparation in aluminium hydroxide adjuvant were protected against infection with C. pseudotuberculosis, with an 82% reduction in the proportion of infected sheep and a 98% reduction in lung lesions. Sera from vaccinated sheep exhibited a strong response only to the 40-kDa antigen on immunoblots. These results strongly suggest that the 40-kDa antigen plays a major role in immunity to caseous lymphadenitis
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