Visuo-spatial ability in colonoscopy simulator training

Visuo-spatial ability is associated with a quality of performance in a variety of surgical and medical skills. However, visuo-spatial ability is typically assessed using Visualization tests only, which led to an incomplete understanding of the involvement of visuo-spatial ability in these skills. To remedy this situation, the current study investigated the role of a broad range of visuo-spatial factors in colonoscopy simulator training. Fifteen medical trainees (no clinical experience in colonoscopy) participated in two psycho-metric test sessions to assess four visuo-spatial ability factors. Next, participants trained flexible endoscope manipulation, and navigation to the cecum on the GI Mentor II simulator, for four sessions within 1 week. Visualization, and to a lesser degree Spatial relations were the only visuo-spatial ability factors to correlate with colonoscopy simulator performance. Visualization additionally covaried with learning rate for time on task on both simulator tasks. High Visualization ability indicated faster exercise completion. Similar to other endoscopic procedures, performance in colonoscopy is positively associated with Visualization, a visuo-spatial ability factor characterized by the ability to mentally manipulate complex visuo-spatial stimuli. The complexity of the visuo-spatial mental transformations required to successfully perform colonoscopy is likely responsible for the challenging nature of this technique, and should inform training- and assessment design. Long term training studies, as well as studies investigating the nature of visuo-spatial complexity in this domain are needed to better understand the role of visuo-spatial ability in colonoscopy, and other endoscopic techniques

A multi-instrumental approach for calibrating real-time mass spectrometers using high-performance liquid chromatography and positive matrix factorization

Obtaining quantitative information for molecular species present in aerosols from real-time mass spectrometers such as an extractive electrospray time-of-flight mass spectrometer (EESI) and an aerosol mass spectrometer (AMS) can be challenging. Typically, molecular species are calibrated directly through the use of pure standards. However, in some cases (e.g., secondary organic aerosol (SOA) formed from volatile organic compounds (VOCs)), direct calibrations are impossible, as many SOA species can either not be purchased as pure standards or have ambiguous molecular identities. In some cases, bulk OA sensitivities are used to estimate molecular sensitivities. This approach is not sufficient for EESI, which measures molecular components of OA, because different species can have sensitivities that vary by a factor of more than 30. Here, we introduce a method to obtain EESI calibration factors when standards are not available, and we provide a thorough analysis of the feasibility, performance, and limitations of this new technique. In this method, complex aerosol mixtures were separated with high-performance liquid chromatography (HPLC) followed by aerosol formation via atomization. The separated aerosols were then measured by an EESI and an AMS, which allowed us to obtain sensitivities for some species present in standard and SOA mixtures. Pure compounds were used to test the method and characterize its uncertainties, and obtained sensitivities were consistent within ±20 % when comparing direct calibrations vs. HPLC calibrations for a pure standard and within a factor of 2 for a standard mixture. In some cases, species were not completely resolved by chromatography, and positive matrix factorization (PMF) of AMS data enabled further separation. This method should be applicable to other real-time MS techniques. Improvements in chromatography are possible that would allow better separation in complex mixtures.</p

Reconciling Assumptions in Bottom-Up and Top-Down Approaches for Estimating Aerosol Emission Rates From Wildland Fires Using Observations From FIREX-AQ

Accurate fire emissions inventories are crucial to predict the impacts of wildland fires on air quality and atmospheric composition. Two traditional approaches are widely used to calculate fire emissions: a satellite-based top-down approach and a fuels-based bottom-up approach. However, these methods often considerably disagree on the amount of particulate mass emitted from fires. Previously available observational datasets tended to be sparse, and lacked the statistics needed to resolve these methodological discrepancies. Here, we leverage the extensive and comprehensive airborne in situ and remote sensing measurements of smoke plumes from the recent Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) campaign to statistically assess the skill of the two traditional approaches. We use detailed campaign observations to calculate and compare emission rates at an exceptionally high-resolution using three separate approaches: top-down, bottom-up, and a novel approach based entirely on integrated airborne in situ measurements. We then compute the daily average of these high-resolution estimates and compare with estimates from lower resolution, global top-down and bottom-up inventories. We uncover strong, linear relationships between all of the high-resolution emission rate estimates in aggregate, however no single approach is capable of capturing the emission characteristics of every fire. Global inventory emission rate estimates exhibited weaker correlations with the high-resolution approaches and displayed evidence of systematic bias. The disparity between the low-resolution global inventories and the high-resolution approaches is likely caused by high levels of uncertainty in essential variables used in bottom-up inventories and imperfect assumptions in top-down inventories

Response to sunitinib in combination with proton beam radiation in a patient with chondrosarcoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Chondrosarcoma is well-known to be primarily resistant to conventional radiation and chemotherapy.</p> <p>Case presentation</p> <p>We present the case of a 32-year-old Caucasian man with clear cell chondrosarcoma who presented with symptomatic recurrence in his pelvis and metastases to his skull and lungs. Our patient underwent systemic therapy with sunitinib and then consolidation with proton beam radiation to his symptomatic site. He achieved complete symptomatic relief with a significantly improved performance status and had an almost complete and durable metabolic response on fluorine-18-fluorodeoxyglucose positron emission tomography.</p> <p>Conclusions</p> <p>Our findings have important clinical implications and suggest novel clinical trials for this difficult to treat disease.</p

Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins

<p>Abstract</p> <p>Background</p> <p>Sunitinib malate (SUTENT^®) is an oral, multitargeted tyrosine kinase inhibitor, approved multinationally for the treatment of advanced RCC and of imatinib-resistant or – intolerant GIST. The purpose of this study was to explore potential biomarkers of sunitinib pharmacological activity via serial assessment of plasma levels of four soluble proteins from patients in a phase II study of advanced RCC: VEGF, soluble VEGFR-2 (sVEGFR-2), placenta growth factor (PlGF), and a novel soluble variant of VEGFR-3 (sVEGFR-3).</p> <p>Methods</p> <p>Sunitinib was administered at 50 mg/day on a 4/2 schedule (4 weeks on treatment, 2 weeks off treatment) to 63 patients with metastatic RCC after failure of first-line cytokine therapy. Predose plasma samples were collected on days 1 and 28 of each cycle and analyzed via ELISA.</p> <p>Results</p> <p>At the end of cycle 1, VEGF and PlGF levels increased >3-fold (relative to baseline) in 24/54 (44%) and 22/55 (40%) cases, respectively (P < 0.001). sVEGFR-2 levels decreased ≥ 30% in 50/55 (91%) cases and ≥ 20% in all cases (P < 0.001) during cycle 1, while sVEGFR-3 levels were decreased ≥ 30% in 48 of 55 cases (87%), and ≥ 20% in all but 2 cases. These levels tended to return to near-baseline after 2 weeks off treatment, indicating that these effects were dependent on drug exposure. Overall, significantly larger changes in VEGF, sVEGFR-2, and sVEGFR-3 levels were observed in patients exhibiting objective tumor response compared with those exhibiting stable disease or disease progression (P < 0.05 for each analyte; analysis not done for PlGF).</p> <p>Conclusion</p> <p>Sunitinib treatment in advanced RCC patients leads to modulation of plasma levels of circulating proteins involved in VEGF signaling, including soluble forms of two VEGF receptors. This panel of proteins may be of value as biomarkers of the pharmacological and clinical activity of sunitinib in RCC, and of angiogenic processes in cancer and other diseases.</p

Phase II Trial of Concurrent Sunitinib and Image-Guided Radiotherapy for Oligometastases

BACKGROUND: Preclinical data suggest that sunitinib enhances the efficacy of radiotherapy. We tested the combination of sunitinib and hypofractionated image-guided radiotherapy (IGRT) in a cohort of patients with historically incurable distant metastases. METHODS: Twenty five patients with oligometastases, defined as 1-5 sites of active disease on whole body imaging, were enrolled in a phase II trial from 2/08 to 9/10. The most common tumor types treated were head and neck, liver, lung, kidney and prostate cancers. Patients were treated with the recommended phase II dose of 37.5 mg daily sunitinib (days 1-28) and IGRT 50 Gy (days 8-12 and 15-19). Maintenance sunitinib was used in 33% of patients. Median follow up was 17.5 months (range, 0.7 to 37.4 months). RESULTS: The 18-month local control, distant control, progression-free survival (PFS) and overall survival (OS) were 75%, 52%, 56% and 71%, respectively. At last follow-up, 11 (44%) patients were alive without evidence of disease, 7 (28%) were alive with distant metastases, 3 (12%) were dead from distant metastases, 3 (12%) were dead from comorbid illness, and 1 (4%) was dead from treatment-related toxicities. The incidence of acute grade ≥ 3 toxicities was 28%, most commonly myelosuppression, bleeding and abnormal liver function tests. CONCLUSIONS: Concurrent sunitinib and IGRT achieves major clinical responses in a subset of patients with oligometastases. TRIAL REGISTRATION: ClinicalTrials.gov NCT00463060

Sizing response of the Ultra-High Sensitivity Aerosol Spectrometer (UHSAS) and Laser Aerosol Spectrometer (LAS) to changes in submicron aerosol composition and refractive index

We evaluate the sensitivity of the size calibrations of two commercially available, high-resolution optical particle sizers to changes in aerosol composition and complex refractive index (RI). The Droplet Measurement Technologies Ultra-High Sensitivity Aerosol Spectrometer (UHSAS) and the TSI, Inc. Laser Aerosol Spectrometer (LAS) are two commonly used instruments for measuring the portion of the aerosol size distribution with diameters larger than nominally 60–90 nm. Both instruments illuminate particles with a laser and relate the single-particle light scattering intensity and count rate measured over a wide range of angles to the size-dependent particle concentration. While the optical block geometry and flow system are similar for each instrument, a significant difference between the two models is the laser wavelength (1054 nm for the UHSAS and 633 nm for the LAS) and intensity (about 100 times higher for the UHSAS), which may affect the way each instrument sizes non-spherical or absorbing aerosols. Here, we challenge the UHSAS and LAS with laboratory-generated, mobility-size-classified aerosols of known chemical composition to quantify changes in the optical size response relative to that of ammonium sulfate (RI of 1.52+0i at 532 nm) and NIST-traceable polystyrene latex spheres (PSLs with RI of 1.59+0i at 589 nm). Aerosol inorganic salt species are chosen to cover the real refractive index range of 1.32 to 1.78, while chosen light-absorbing carbonaceous aerosols include fullerene soot, nigrosine dye, humic acid, and fulvic acid standards. The instrument response is generally in good agreement with the electrical mobility diameter. However, large undersizing deviations are observed for the low-refractive-index fluoride salts and the strongly absorbing nigrosine dye and fullerene soot particles. Polydisperse size distributions for both fresh and aged wildfire smoke aerosols from the recent Fire Influence on Regional to Global Environments Experiment and Air Quality (FIREX-AQ) and the Cloud, Aerosol, and Monsoon Processes Philippines Experiment (CAMP2Ex) airborne campaigns show good agreement between both optical sizers and contemporaneous electrical mobility sizing and particle time-of-flight mass spectrometric measurements. We assess the instrument uncertainties by interpolating the laboratory response curves using previously reported RIs and size distributions for multiple aerosol type classifications. These results suggest that, while the optical sizers may underperform for strongly absorbing laboratory compounds and fresh tailpipe emissions measurements, sampling aerosols within the atmospherically relevant range of refractive indices are likely to be sized to better than ±10 %–20 % uncertainty over the submicron aerosol size range when using instruments calibrated with ammonium sulfate.</p