Central Venous Catheter Confirmation by Ultrasonography: A Novel Instructional Protocol

Central Venous Catheter Confirmation by Ultrasonography: A Novel Instructional Protoco

Truncated mass divergence in a Mott metal

The Mott metal–insulator transition represents one of the most fundamental phenomena in condensed matter physics. Yet, basic tenets of the canonical Brinkman-Rice picture of Mott localization remain to be tested experimentally by quantum oscillation measurements that directly probe the quasiparticle Fermi surface and effective mass. By extending this technique to high pressure, we have examined the metallic state on the threshold of Mott localization in clean, undoped crystals of NiS2. We find that i) on approaching Mott localization, the quasiparticle mass is strongly enhanced, whereas the Fermi surface remains essentially unchanged; ii) the quasiparticle mass closely follows the divergent form predicted theoretically, establishing charge carrier slowdown as the driver for the metal–insulator transition; iii) this mass divergence is truncated by the metal–insulator transition, placing the Mott critical point inside the insulating section of the phase diagram. The inaccessibility of the Mott critical point in NiS2 parallels findings at the threshold of ferromagnetism in clean metallic systems, in which criticality at low temperature is almost universally interrupted by first-order transitions or novel emergent phases such as incommensurate magnetic order or unconventional superconductivity

Nitric Oxide Synthase Inhibition Enhances the Antitumor Effect of Radiation in the Treatment of Squamous Carcinoma Xenografts

This study tests whether the nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine (L-NNA), combines favorably with ionizing radiation (IR) in controlling squamous carcinoma tumor growth. Animals bearing FaDu and A431 xenografts were treated with L-NNA in the drinking water. IR exposure was 10 Gy for tumor growth and survival studies and 4 Gy for ex vivo clonogenic assays. Cryosections were examined immunohistochemically for markers of apoptosis and hypoxia. Blood flow was assayed by fluorescent microscopy of tissue cryosections after i.v. injection of fluorospheres. Orally administered L-NNA for 24 hrs reduces tumor blood flow by 80% (p<0.01). Within 24 hrs L-NNA treatment stopped tumor growth for at least 10 days before tumor growth again ensued. The growth arrest was in part due to increased cell killing since a combination of L-NNA and a single 4 Gy IR caused 82% tumor cell killing measured by an ex vivo clonogenic assay compared to 49% by L-NNA or 29% by IR alone. A Kaplan-Meyer analysis of animal survival revealed a distinct survival advantage for the combined treatment. Combining L-NNA and IR was also found to be at least as effective as a single i.p. dose of cisplatin plus IR. In contrast to the in vivo studies, exposure of cells to L-NNA in vitro was without effect on clonogenicity with or without IR. Western and immunochemical analysis of expression of a number of proteins involved in NO signaling indicated that L-NNA treatment enhanced arginase-2 expression and that this may represent vasculature remodeling and escape from NOS inhibition. For tumors such as head and neck squamous carcinomas that show only modest responses to inhibitors of specific angiogenic pathways, targeting NO-dependent pro-survival and angiogenic mechanisms in both tumor and supporting stromal cells may present a potential new strategy for tumor control

Tubulin-binding dibenz[c,e]oxepines: Part 2 Structural variation and biological evaluation as tumour vasculature disrupting agents

5,7-Dihydro-3,9,10,11-tetramethoxybenz[c,e]oxepin-4-ol 1, prepared from a dibenzyl ether precursor via Pd-catalysed intramolecular direct arylation, possesses broad-spectrum in vitro cytotoxicity towards various tumour cell lines, and induces vascular shutdown, necrosis and growth delay in tumour xenografts in mice at sub-toxic doses. The biological properties of 1 and related compounds can be attributed to their ability to inhibit microtubule assembly at the micromolar level, by binding reversibly to the same site of the tubulin αβ-heterodimer as colchicine 2 and the allocolchinol, N-acetylcolchinol 4

Effects of platinum/taxane based chemotherapy on acute perfusion in human pelvic tumours measured by dynamic MRI

Dynamic contrast enhanced MRI (DCE-MRI) is being used increasingly in clinical trials to demonstrate that vascular disruptive and antiangiogenic agents target tumour microcirculation. Significant reductions in DCE-MRI kinetic parameters are seen within 4–24 and 48 h of treatment with vascular disruptive and antiangiogenic agents, respectively. It is important to know whether cytotoxic agents also cause significant acute reductions in these parameters, for reliable interpretation of results. This study investigated changes in transfer constant (Ktrans) and the initial area under the gadolinium curve (IAUGC) following the first dose of chemotherapy in patients with mostly gynaecological tumours. A reproducibility analysis on 20 patients (using two scans performed on consecutive days) was used to determine the significance of DCE-MRI parameter changes 24 h after chemotherapy in 18 patients. In 11 patients who received platinum alone or with a taxane, there were no significant changes in Ktrans or IAUGC in either group or individual patient analyses. When the remaining seven patients (treated with a variety of agents including platinum and taxanes) were included (n=18), there were also no significant changes in Ktrans. Therefore, if combination therapy does show changes in DCE-MRI parameters then the effects can be attributed to antivascular therapy rather than chemotherapy

Novel Scoring Scale for Quality Assessment of Lung Ultrasound in the Emergency Department

Introduction: The use of a reliable scoring system for quality assessment (QA) is imperative to limit inconsistencies in measuring ultrasound acquisition skills. The current grading scale used for QA endorsed by the American College of Emergency Physicians (ACEP) is non-specific, applies irrespective of the type of study performed, and has not been rigorously validated. Our goal in this study was to determine whether a succinct, organ-specific grading scale designed for lung-specific QA would be more precise with better interobserver agreement.Methods: This was a prospective validation study of an objective QA scale for lung ultrasound (LUS) in the emergency department. We identified the first 100 LUS performed in normal clinical practice in the year 2020. Four reviewers at an urban academic center who were either emergency ultrasound fellowship-trained or current fellows with at least six months of QA experience scored each study, resulting in a total of 400. The primary outcome was the level of agreement between the reviewers. Our secondary outcome was the variability of the scores given to the studies. For the agreement between reviewers, we computed the intraclass correlation coefficient (ICC) based on a two-way random-effect model with a single rater for each grading scale. We generated 10,000 bootstrapped ICCs to construct 95% confidence intervals (CI) for both grading systems. A two-sided one-sample t-test was used to determine whether there were differences in the bootstrapped ICCs between the two grading systems.Results: The ICC between reviewers was 0.552 (95% CI 0.40–0.68) for the ACEP grading scale and 0.703 (95% CI 0.59–0.79) for the novel grading scale (P &lt; 0.001), indicating significantly more interobserver agreement using the novel scale compared to the ACEP scale. The variance of scores was similar (0.93 and 0.92 for the novel and ACEP scales, respectively).Conclusion: We found an increased interobserver agreement between reviewers when using the novel, organ-specific scale when compared with the ACEP grading scale. Increased consistency in feedback based on objective criteria directed to the specific, targeted organ provides an opportunity to enhance learner education and satisfaction with their ultrasound education

Emergency Physician-performed Transesophageal Echocardiography in Simulated Cardiac Arrest

Introduction: Transesophageal echocardiography (TEE) is a well-established method of evaluatingcardiac pathology. It has many advantages over transthoracic echocardiography (TTE), including theability to image the heart during active cardiopulmonary resuscitation. This prospective simulation studyaims to evaluate the ability of emergency medicine (EM) residents to learn TEE image acquisitiontechniques and demonstrate those techniques to identify common pathologic causes of cardiac arrest.Methods: This was a prospective educational cohort study with 40 EM residents from two participatingacademic medical centers who underwent an educational model and testing protocol. All participantswere tested across six cases, including two normals, pericardial tamponade, acute myocardial infarction(MI), ventricular fibrillation (VF), and asystole presented in random order. Primary endpoints were correctidentification of the cardiac pathology, if any, and time to sonographic diagnosis. Calculated endpointsincluded sensitivity, specificity, and positive and negative predictive values for emergency physician (EP)-performed TEE. We calculated a kappa statistic to determine the degree of inter-rater reliability.Results: Forty EM residents completed both the educational module and testing protocol. This resultedin a total of 80 normal TEE studies and 160 pathologic TEE studies. Our calculations for the abilityto diagnose life-threatening cardiac pathology by EPs in a high-fidelity TEE simulation resulted in asensitivity of 98%, specificity of 99%, positive likelihood ratio of 78.0, and negative likelihood ratio of0.025. The average time to diagnose each objective structured clinical examination case was as follows:normal A in 35 seconds, normal B in 31 seconds, asystole in 13 seconds, tamponade in 14 seconds,acute MI in 22 seconds, and VF in 12 seconds. Inter-rater reliability between participants was extremelyhigh, resulting in a kappa coefficient across all cases of 0.95.Conclusion: EM residents can rapidly perform TEE studies in a simulated cardiac arrest environmentwith a high degree of precision and accuracy. Performance of TEE studies on human patients in cardiacarrest is the next logical step to determine if our simulation data hold true in clinical practice. [West JEmerg Med. 2017;18(5)830-834.