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Mechanization is the way of life for the office of the future and it is rapidly approaching, according to the author. She discusses the business and office skills necessary for this future office and approaches that business teachers might take to keep their curricula current with business trends. (MF)

Background Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tiss...

PURPOSE: The objective of this work was to evaluate phantom dosimetry of a novel kilovoltage (kV) x-ray source, which employs a stationary tungsten anode and a linearly swept scanning electron-beam. The source utilizes converging x-ray collimation along with orthogonal mechanical rotation to distribute surface flux over large area. In this study, this was investigated as a potential solution to fast-falloff limitations expected with kV radiotherapy. This was done with the aim of future clinical development of a lower-cost radiotherapy alternative to megavoltage (MV) linac systems. METHODS: Radiochromic film was employed for dosimetry on the kV x-ray source of the Linear-Converging Radiotherapy System (LCRS). The source utilizes charge particle optics to magnetically deflect and focus an electron beam along a stationary, reflection tungsten target in an ultra-high-vacuum stainless-steel chamber. Resulting x-rays were collimated into converging beamlets that span a large planar angle and converge at the system isocenter. In this study, radiochromic film dosimetry was done at 140 and 145 kVp for a designated planning treatment volume (PTV) of 4-cm diameter. An acrylic phantom was employed for dose distribution measurements of stationary and rotational delivery. Film dosimetry was evaluated in planes parallel to the source x-ray window at various depths, as well as in the plane of gantry rotation. RESULTS: At 140 and 145 kVp and using a collimated 4-cm square field at depth, lesion-to-skin dose ratio was shown to improve with additional beams from different relative source positions, where the different beams are focused at the same isocenter and do not overlap at the phantom surface. It was only possible to achieve a 1:1 D(max)-to-surface ratio with four delivery beams, but the ratio improved to 4:1 with 12 beams, focused at the same isocenter depth of 7.8 cm in an acrylic phantom. For the tests conducted, the following D(max)-to-surface ratios were obtained: 0.4:1 lesion-to-skin ratio for stationary delivery from one entry beam, 0.71:1 lesion-to-skin ratio was obtained for two beams, 1.07:1 ratio for four beams, and 4:1 for 12 beams. Dose-depth profiles were evaluated for stationary and rotational dosimetry. Additionally, rotational dosimetry was measured for a case more analogous to a clinical scenario, where the isocenter was located at an off-center simulated lesion. CONCLUSIONS: The results demonstrate potential dose-depth improvements with kV arc therapy by distributing the surface flux with a wide converging beam along with perpendicular mechanical source rotation of the LCRS. The system delivered tolerable dose to a large surface area when a threshold of multiple, separated beams was reached. The radiochromic film data supports the feasibility of the construct of the LCRS kV radiotherapy system design.

Desmoplastic small round cell tumor is a rare sarcoma with 5-year overall survival of 15%. An 8-year-old female presented with diffuse abdominal/pelvic desmoplastic small round cell tumor including numerous liver metastasis. She underwent neoadjuvant chemotherapy followed by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Residual disease was found shortly after CRS/HIPEC which was resected, followed by whole abdomen/pelvic radiation and autologous hematopoietic cell transplant. Previous papers have reported dismal survival in patients with liver metastasis and residual disease arguing against CRS/HIPEC. Our patient remains disease-free over 6 years after completing therapy indicating long-term survival is achievable with aggressive multimodal therapy.

Clinical genetic testing enables the detection of specific gene mutations and variants that predispose individuals and their family members to disease. In recent years, tremendous strides have been made in the variety of clinically useful tests. Targeted testing for specific mutations that cause well-known syndromes enables the efficient diagnosis of genetic diseases with cutaneous manifestations. Testing for specific genes, however, may not always reveal a diagnosis. Expanded options are available. This review outlines the major types of available technology with a focus on those tests most useful for pediatric dermatologists.

Little is known about health professions students’ awareness and attitudes regarding public health in the United States. Therefore, the purpose of this study was to assess medical and pharmacy students’ knowledge and interest in the Healthy People initiative as well as perceptions of public health content in their curricula. An electronic survey was distributed in March 2021 in seven schools across Ohio, participation was incentivized through a USD 5 donation to the Ohio Association of Foodbanks to aid in COVID-19 relief efforts (maximum USD 1000) for each completed survey. A total of 182 medical students and 233 pharmacy students participated (12% response rate). Less than one-third of respondents reported familiarity with Healthy People and correctly identified the latest edition. However, nearly all respondents agreed public health initiatives are valuable to the American healthcare system. Almost all students expressed a desire to practice interprofessionally to attain public health goals. Both medical and pharmacy students recognized core public health topics in their curricula, and nearly 90% wanted more information. These findings indicate that the majority of medical and pharmacy students in Ohio believe public health initiatives to be important, yet knowledge gaps exist regarding Healthy People. This information can guide curricular efforts and inform future studies of health professions students.

Cosmic microwave background (CMB) measurements are fundamentally limited by photon statistics. Therefore, ground-based CMB observatories have been increasing the number of detectors that are simultaneously observing the sky. Thanks to the advent of monolithically fabricated transition edge sensor (TES) arrays, the number of on-sky detectors has been increasing exponentially for over a decade. The next-generation experiment CMB-S4 will increase this detector count by more than an order of magnitude from the current state-of-the-art to ~500,000. The readout of such a huge number of exquisitely precise sub-Kelvin sensors is feasible using an existing technology: frequency-domain multiplexing (fMux). To further optimize this system and reduce complexity and cost, we have recently made significant advances including the elimination of 4 K electronics, a massive decrease of parasitic in-series impedances, and a significant increase in multiplexing factor., Comment: 7 pages, 6 figures, Submitted to the JLTP for LTD-18

Metallic magnetic calorimeters (MMCs) combine the excellent energy resolution of cryogenic gamma ray detectors with a very small nonlinearity and a reproducible response, owing to their magnetization-based sensor and their metallic heat flow path. These attributes make MMCs well suited for photon and particle spectroscopy applications requiring the highest accuracy. We are developing high-resolution MMC gamma ray detectors with the goal of improving the quality of key nuclear decay data for nuclear safeguards and fundamental science. Our exploratory “integrated” (SQUIDs and sensors on the same chip) 14-pixel MMC designs recently demonstrated energy resolution of 37.5 eV at 60 keV. Here, we describe the design and optimization for a new generation of MMC detectors using both “integrated” and “split” designs (SQUIDs and sensors on separate chips). The new designs are expected to have an energy resolution

With ever-increasing laser power, the requirements for ultraviolet (UV) coatings increase continuously. The fundamental challenge for UV laser-resistant mirror coatings is to simultaneously exhibit a high reflectivity with a large bandwidth and high laser resistance. These characteristics are traditionally achieved by the deposition of laser-resistant layers on highly reflective layers. We propose a “reflectivity and laser resistance in one” design by using tunable nanolaminate layers that serve as an effective layer with a high refractive index and a large optical bandgap. An Al2O3–HfO2 nanolaminate-based mirror coating for UV laser applications is experimentally demonstrated using e-beam deposition. The bandwidth, over which the reflectance is >99.5%, is more than twice that of a traditional mirror with a comparable overall thickness. The laser-induced damage threshold is increased by a factor of ~1.3 for 7.6 ns pulses at a wavelength of 355 nm. This tunable, nanolaminate-based new design strategy paves the way toward a new generation of UV coatings for high-power laser applications.

There is a long history of collaboration between artists and geographers, with creative forms of research and dissemination of findings taking shape as artworks. In addition, there has been significant push from academia for researchers to maximise their research in ways that cater to, and engage with, broader public audiences. Art and creative practices tap into this through formats such as exhibitions, performances and participatory workshops which draw upon arts-based research methodologies with which geographers are becoming increasingly engaged. However, with this enthusiasm to adopt art practices for research dissemination purposes, tensions can arise in determining the levels of collaboration and authorship between artists and geographers, especially when the artist is employed as a research assistant on the project. In this ‘In Practice’ article, we explore the tensions and challenges that creative collaborations produce with respect to copyright and authorship, specialist skills and the delicate balance of doing creative research as part of a research team. We argue that geographers and artists need to address these issues from the outset and revisit them throughout the research process, and we offer some suggestions for how art–geography research collaborations might best be negotiated.

BACKGROUND: Pediatric lung lesions are a group of mostly benign pulmonary anomalies with a broad spectrum of clinical disease and histopathology. Our objective was to evaluate the characteristics of children undergoing resection of a primary lung lesion and to identify preoperative risk factors for malignancy. METHODS: A retrospective cohort study was conducted by using an operative database of 521 primary lung lesions managed at 11 children’s hospitals in the United States. Multivariable logistic regression was used to examine the relationship between preoperative characteristics and risk of malignancy, including pleuropulmonary blastoma (PPB). RESULTS: None of the 344 prenatally diagnosed lesions had malignant pathology (P < .0001). Among 177 children without a history of prenatal detection, 15 (8.7%) were classified as having a malignant tumor (type 1 PPB, n = 11; other PPB, n = 3; adenocarcinoma, n = 1) at a median age of 20.7 months (interquartile range, 7.9–58.1). Malignancy was associated with the DICER1 mutation in 8 (57%) PPB cases. No malignant lesion had a systemic feeding vessel (P = .0427). The sensitivity of preoperative chest computed tomography (CT) for detecting malignant pathology was 33.3% (95% confidence interval [CI]: 15.2–58.3). Multivariable logistic regression revealed that increased suspicion of malignancy by CT and bilateral disease were significant predictors of malignant pathology (odds ratios of 42.15 [95% CI, 7.43–340.3; P < .0001] and 42.03 [95% CI, 3.51–995.6; P = .0041], respectively). CONCLUSIONS: In pediatric lung masses initially diagnosed after birth, the risk of PPB approached 10%. These results strongly caution against routine nonoperative management in this patient population. DICER1 testing may be helpful given the poor sensitivity of CT for identifying malignant pathology.

PURPOSE Low-grade serous ovarian carcinomas (LGSOCs) have historically low chemotherapy responses. Alterations affecting the MAPK pathway, most commonly KRAS/BRAF, are present in 30%-60% of LGSOCs. The purpose of this study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multiple cancers, in LGSOC. METHODS This was a 2:1 randomized study of binimetinib (45 mg twice daily) versus physician’s choice chemotherapy (PCC). Eligible patients had recurrent measurable LGSOC after ≥ 1 prior platinum-based chemotherapy but ≤ 3 prior chemotherapy lines. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR); additional assessments included overall survival (OS), overall response rate (ORR), duration of response (DOR), clinical-benefit rate, biomarkers, and safety. RESULTS A total of 303 patients were randomly assigned to an arm of the study at the time of interim analysis (January 20, 2016). Median PFS by BICR was 9.1 months (95% CI, 7.3 to 11.3) for binimetinib and 10.6 months (95% CI, 9.2 to 14.5) for PCC (hazard ratio,1.21; 95%CI, 0.79 to 1.86), resulting in early study closure according to a prespecified futility boundary after 341 patients had enrolled. Secondary efficacy end points were similar in the two groups: ORR 16% (complete response [CR]/partial responses[PRs], 32) versus 13% (CR/PRs, 13); median DOR, 8.1 months (range, 0.03 to ≥ 12.0 months) versus 6.7 months (0.03 to ≥ 9.7 months); and median OS, 25.3 versus 20.8 months for binimetinib and PCC, respectively. Safety results were consistent with the known safety profile of binimetinib; the most common grade ≥ 3 event was increased blood creatine kinase level (26%). Post hoc analysis suggests a possible association between KRAS mutation and response to binimetinib. Results from an updated analysis (n = 341; January 2019) were consistent. CONCLUSION Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study did not meet its primary end point, binimetinib showed activity in LGSOC across the efficacy end points evaluated. A higher response to chemotherapy than expected was observed and KRAS mutation might predict response to binimetinib.

The system presented herein consists of a custom 200 kV electron tube with deflection magnets and stationary water-cooled targets for radiotherapy (RT) and imaging. The electron beam is deflected and dwelled along 41 discrete anode locations equally spaced by 1 cm in a line, at equivalent speeds of 1000 cm/s, to create a focused radiotherapy source. The treatment beam is collimated into a triangular polyhedron shape, producing a 4 cm focal spot at the isocenter and corresponding planning-treatment-volume (PTV). This beam shape would allow entry dose to be distributed over large areas for skin sparing. The source is mounted on a ring gantry that rotates at speeds up to 1.5 rpm. Preliminary dose rate measurements were collected in air at 140 kV beam energy, up to 80 mA beam current. Radiographic film was used to collect an image of the treatment beam at isocenter. Results are presented and can be extrapolated to a dose rate of 2 Gy/min for a 140 kV, 200 mA beam. The electron beam can be deflected within 1 ms from therapy path to an additional array of 19 imaging targets, which provides hardware capabilities for real-time tomosynthesis and image-guided RT. Onboard cone beam CT for patient positioning is also available. The utilization of 200 kV beam treatment energies compared to MV greatly reduces the required shielding (4-6 mm lead vs. 1-2 m concrete) and the cost of radiotherapy system installations. Systems can be mounted onto standard mobile trailers for use at remote locations.

Metallic magnetic microcalorimeters (MMCs) achieve energy resolution comparable to transition-edge sensors (TESs) but rely on different measurement physics that may allow MMCs to surpass TESs in some future applications. We have recently completed fabrication of new MMC γ-ray detector arrays using several exploratory sensor designs. All designs integrate the SQUID and sensor on the same chip and use a superconducting cap layer on the paramagnet, but explore different combinations of combined/separate sensing and magnetization coils and direct/flux transformer coupling to the input SQUIDs. This report describes the design and initial testing of one of these devices, which has so far demonstrated an energy resolution of 38 eV at 60 keV near 10 mK using natural-abundance silver–erbium paramagnet.

A healthy 14-year-old, male neutered, Miniature Poodle was found to have a persistent erythrocyte macrocytosis and reticulocytosis with a normal and stable HCT. The hematologic features of macrocytosis, increased Howell-Jolly bodies, and metarubricytosis, in the absence of anemia or other cytopenias, combined with the cytologic evidence of bone marrow erythroid dysplasia, including megaloblastosis, binuclearity, increased mitotic activity, and nuclear fragmentation, are consistent with previous reports of congenital dyserythropoiesis termed poodle macrocytosis. We speculate that the additional presence of persistent reticulocytosis in the absence of an identifiable stimulus for accelerated erythropoiesis may represent a phenotypic variation of this inherited condition, and the morphologic abnormalities of the dyserythropoiesis are described.

We are developing metallic magnetic calorimeters for high-resolution gamma-ray spectroscopy for non-destructive assay of nuclear materials. Absorbers for these higher-energy photons can require substantial thickness to achieve adequate stopping power. We developed a new absorber fabrication process using dry-film photoresists to electroform cantilevered, thick absorbers. Gamma detectors with these absorbers have an energy resolution of 38 eV FWHM at 60 keV. In this report, we summarize modifications to STARCryo’s “Delta 1000” process for our devices and describe the new absorber fabrication process.

Purpose This study reviews contemporary management and follow-up of pediatric ovarian torsion. Methods This is a retrospective series of patients from birth to 19 years undergoing operative management of ovarian torsion from 2012 to 2016. Results We studied 43 girls who underwent 51 operations for ovarian torsion. The median age was 8.3 years. Ultrasound was utilized for diagnosis in 24/29 patients (83%) evaluated in a children's hospital. In contrast, computed tomography was used initially in 7 cases (50%) in children imaged at non–children's hospitals before transfer. Initial operation for ovarian torsion was completed laparoscopically in 38 (88%). Overall, ovarian preservation was performed in 37 (86%) patients, while 6 (13%) underwent oophorectomy. Indications for oophorectomy included 5 infants with in utero torsion and an 18-year-old with a suspected malignancy. In girls with acute ovarian torsion, the oophorectomy rate was reduced to 2%. Postoperatively, 1 patient developed a small bowel obstruction requiring operation after laparoscopic ovarian detorsion. Recurrent torsion occurred in 3 patients (7%). In total, 34 patients underwent postoperative ovarian imaging. A total of 25 (74%) had follicles visualized in the previously torsed ovary. Conclusion Ovarian-sparing operations for acute torsion are safe and result in ovarian salvage and preservation of follicular development in more than 70% of children and adolescents.

Background Neurofibromatosis type 1 (NF1) is a genetic disorder characterized by a predisposition to develop multiple benign tumors. A major feature of NF1 is the development of localized cutaneous neurofibromas. Cutaneous neurofibromas manifest in > 99% of adults with NF1 and are responsible for major negative effects on quality of life. Previous reports have correlated increased burden of cutaneous neurofibromas with age and pregnancy, but longitudinal data are not available to establish a quantitative natural history of these lesions. The purpose of this study is to conduct a prospective natural history study of 22 adults with NF1 over an 8-year period to quantify cutaneous neurofibroma number and size. Results The average monthly increase in volume for cutaneous neurofibromas was 0.37 mm3 in the back region (95% CI (0.23, 0.51), p

Background Early diagnosis and timely surgery are critical to treat children with testicular torsion. Only 33% of patients met the hospital goal of ‘critical diagnosis to operating room time of 60 minutes or less [CDOR60]’ prior to starting the QI project. Objectives The objective of the quality improvement project was to increase the utilization of TWIST score, a validated clinical scoring system from 0% to 80% over 12 months period for children evaluated for testicular torsion, as a means of increasing the number of patients with CDOR60. Methods Deploying the Institute for Healthcare Improvement Model for Improvement, we formulated an aim statement and identified key drivers. Of our interventions, successful implementation of the TWIST score in the emergency department (ED), with a guideline to support earlier notification of urology for high risk patients with testicular pain, was determined to be the highest impact intervention. We educated providers and gave biweekly feedback about guideline adherence, created order panels and documentation tabs in our electronic medical record to encourage documentation. Results Between September 2018 and April 2019, TWIST score documentation improved to >80% and was sustained at that rate for 4 months. After implementation of the guideline, the critical diagnosis to OR time of 60 minutes or less was achieved in 12 out of 16 patients diagnosed with testicular torsion in the ED [75%] compared to our baseline of 33%. Conclusions A quality improvement project to improve the timeliness of care for children with testicular torsion resulted in delivery of expedited surgical care for these patients.

There has been a recent increase in recognition of lung disease related to the use of electronic cigarettes (called “vaping”). These patients present with acute respiratory illness following exposure to vaporized cannabis or nicotine products and sometimes require hospitalization and intensive care. We describe the imaging findings of this disease entity in the pediatric population. To describe the radiologic findings of lung injury associated with electronic cigarette use (vaping) in the adolescent pediatric population. We identified all adolescents with acute respiratory illness and a history of electronic cigarette use who presented at our institution within a 3-month period (June 2019 through August 2019). We excluded adolescents with potential intercurrent pulmonary disease. We reviewed the charts for symptomatology and laboratory and pathology data. In addition, we reviewed the chest radiographs and chest CTs of these adolescents. The review group consisted of 12 teenage pediatric patients (10 boys and 2 girls; mean age 16.9 years, range 16.0–17.7 years) with acute respiratory illness found to have a temporal association with electronic cigarette use for cannabis products, nicotine, or both. Other etiologies for illness in these adolescents had been excluded by clinical and laboratory evaluation. All of the adolescents were admitted to the hospital for treatment. The clinical presentations included dyspnea, abdominal pain and constitutional symptoms. Pulmonary function testing that was performed in all patients during admission or follow-up demonstrated reduced diffusion capacity in 4/12 (33%), an obstructive ventilatory pattern in 4/12 (33%), a restrictive pattern in 1/12 (8%), and a mixed obstructive and restrictive pattern in 2/12 (17%) adolescents. Bronchoalveolar lavage studies, performed in 9 of the 12 adolescents, revealed inflammatory cells and lipid-laden macrophages. All of the patients underwent CT of the chest; the findings were notable for centrilobular ground-glass nodules (11/12; 92%) and confluent ground-glass opacities (12/12; 100%), with frequent subpleural sparing (9/12; 75%). Additionally, 6/12 (50%) adolescents demonstrated small pleural effusions; 6/12 (50%) had mild bronchial wall thickening; 9/12 (75%) had enlarged hilar or mediastinal lymph nodes; and 2/12 (17%) had a small pericardial effusion. As seen in our teenage population, e-cigarette, or vaping, product use-associated lung injury (EVALI) is characterized by centrilobular ground-glass nodules and ground-glass opacities with subpleural sparing. The imaging findings are most consistent with acute lung injury resulting from toxic inhalation. Because adolescent pediatric patients might not be forthcoming with their history of electronic cigarette use, it is important for the pediatric radiologist to be aware of the imaging patterns of this disease.

Percutaneous feeding tubes are generally considered a safe option for enteral feeding and are widely used in children who require long-term nutritional support. However, complications are not infrequent and can range from bothersome to life-threatening. Radiologists should be familiar with the imaging appearances of potential complications for optimal patient care. In this review, we discuss radiologic appearances of common complications and less frequent but serious complications related to percutaneous feeding tubes. Additionally, as fluoroscopic feeding tube evaluation is often requested as the initial imaging study, we also discuss the fluoroscopic appearances of some uncommon complications.

The aim of this study was to investigate the protective effects of systemically administered N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-2-oxopiperidine-3-carboxamide (HIOC) or tauroursodeoxycholic acid (TUDCA) in an optic nerve crush (ONC) mouse model. HIOC (50 mg/kg) or TUDCA (500mg/kg) were intraperitoneally (i.p.) injected into adult C57BL/6 mice three times per week. Two weeks after treatment (6 injections), unilateral optic nerve crush was conducted followed by treatment at the same day. The treatment was continued until 1 week or 2 weeks after ONC. A control cohort was identically treated with drug vehicle (phosphate-buffered saline; PBS). Retinas were harvested for whole mount immunofluorescence staining with RGC markers and imaged by fluorescent confocal microscopy at 40x magnification. Fluorescing cells were counted by computer-assisted automated identification and counting software (CellProfiler). Cohort sampling sizes were N=4 and statistical tesing was by the Wilcoxon-Mann-Whitney Test. Significant loss (80%’85%) occurred in the PBS-injected group 1 and 2 weeks after ONC. This loss was partially but significantly prevented in drug-treated cohorts (P < 0.05). Delivery of HIOC or TUDCA by i.p. injection increased survival of RGCs after ONC. Protection was similar between treatment with either drug. These data suggest that it is worthwhile to further explore possible protective effects of HIOC or TUDCA on RGC subtypes with regards to structure and function and in additional disease models that involve RGC loss.

There are three sets of arms control negotiations which could have a long range political impact on Europe. These are the Conference on Security and Cooperation in Europe (CSCE), the Mutual and Balanced Force Reduction (MBFR) talks, and Theater Nuclear Forces/Intermediate-Range Nuclear Forces (TNF/INF) talks. In each set of negotiations, there are factors encouraging arms control as well as impediments to arms control. The weight of these factors and impediments directly affect the prospects for mutual understanding and ultimate agreement.

Purpose: The intent of this work was to evaluate the ability of our 200 kV kilovoltage arc therapy (KVAT) system to treat realistic lung tumors without exceeding dose constraints to organs-at-risk (OAR). Methods and Materials: Monte Carlo (MC) methods and the McO optimization framework generated and inversely optimized KVAT treatment plans for 3 SABR lung cancer patients. The KVAT system was designed to treat deep-seated lesions with kilovoltage photons. KVAT delivers dose to roughly spherical PTVs and therefore non-spherical PTVs were divided into spherical sub-volumes. A prescription dose of 12 Gy/fx × 4 fractions was planned to 90% of the PTV volume. KVAT plans were compared to VMC++ calculated, 6 MV stereotactic ablative radiotherapy (SABR) treatment plans. Dose distributions, dose volume histograms, gradient index (GI), planned mean doses and plan treatment times were calculated. Dose constraints for organs-at-risk (OAR) were taken from RTOG 101. Results: All plans, with the exception of the rib dose calculated in one of the KVAT plans for a peripheral lesion, were within dose-constraints. In general, KVAT plans had higher planned doses to OARs. KVAT GI values were 5.7, 7.2 and 8.9 and SABR values were 4.6, 4.1, and 4.7 for patient 1, 2 and 3, respectively. KVAT plan treatment times were 49, 65 and 17 min for patients 1, 2 and 3, respectively. Conclusions: Inverse optimization and MC methods demonstrated the ability of KVAT to produce treatment plans without exceeding TG 101 dose constraints to OARs for 2 out of 3 investigated lung cancer patients.

Retrospective kV x-ray 4DCT treatment planning for lung cancer MV linac treatment is becoming a standard-of-care for this widely used procedure for the largest cancer cause-of-death in the US. It currently provides the best estimate of a fixed-in-time but undulating and closed 3D "shell" to which a minimum curative-intent radiation dose should be delivered to provide the best estimated patient survival and the least morbidity, usually characterized by quantitative dose-volume-histograms (DVHs). Unfortunately this closed shell volume or internal target volume (ITV) currently has to be increased enough to enclose the full range of respiratory lesion motion (plus set-up etc. uncertainties) which cannot yet be accurately determined in real time during treatment delivery. With accurate motion-tracking, the planning target volume (PTV) or outer “shell” may be reduced by up to 40%. However there is no single 2D plane that precisely follows the reduced-PTV-volume’s 3D respiratory motion, currently best estimated by the retrospective hand contouring by a trained and experienced MD radiation oncology MD using the full 3D-time information of 4DCT. Once available, 3D motion tracking in real time has the potential to substantially decrease DVH doses to surrounding organs-at-risk (OARs), while maintaining or raising the curative-intent dose to the lesion itself. The assertion argued here is that, the 3D volume-rendered imaging of lung cancer lesion-trajectories in real-time from TumoTrak digital x-ray tomosythesis, has the potential to provide more accurate 3D motion tracking and improved dose delivery at lower cost than the real time, 2D single slice imaging of MRI-guided radiotherapy.

5519 Background: Lower responses to chemotherapy and the unique molecular profile of LGSO led to the adoption of MEK-inhibitors for this disease. Updated analysis from the MILO/ENGOT-ov11 phase III study of binimetinib vs PCC in recurrent LGSOC showed response rate of 24% in those treated with binimetinib (JCO, 2020; NCT01849874). Here we present results of the post-hoc tumor tissue biomarker analysis performed with MILO/ENGOT-ov11. Methods: Mutational/copy number analysis was performed via Foundation Medicine on archival tissue obtained prior to randomization. Unbiased univariate analysis was used to test association between mutation status and outcomes in binimetinib and PCC treated patients. Outcomes examined were progression free survival (PFS), binary response by local RECIST 1.1 (complete or partial response [CR/PR] vs. stable [SD] or progressive disease [PD]), and ordinal response. Kaplan-Meier was used to estimate PFS. Cox regression, binary logistic regression, and ordinal logistic regression were used to examine relationship between mutation status and outcomes. Results: MILO/ENGOT-OV11 enrolled 341 patients from June, 2013 to April, 2016. Patients were randomized 2:1 to binimetinib or PCC. Based on January 1, 2020 data cut-off the data is as-is, amongst those patients treated with binimetinib with molecular results available, PFS data is available for 144 and response rate (RR) data for 135. There were 47 mutations detected in ≥5% of patients, most commonly KRAS (33%). Patients harboring a KRAS mutation had 3.4 times the odds of responding to treatment with binimetinib as patients without KRAS mutation (95% CI 1.57,7.67; p-value 0.002). There was no difference in effect of KRAS G12V mutation vs other KRAS mutation on PFS (PFS HR 1.06; 95% CI:0.53, 2.12; p value 0.9). In the 135 patients with binimetinib RR data, other MAPK mutations were identified as follows; NRAS in 11(8.1%), BRAFV600E in 8(5.9%), RAF1 in 2 (1.5%), NF1 in 7 (5.2%). In patients with MAPK mutation (as defined above) the RR was 41% vs 13% in those without MAPK mutation. PFS was significantly better in patients treated with binimetinib harboring MAPK mutation vs those without (HR 0.5; 95% CI 0.31, 0.79; p = 0.003). In patients treated with PCC there was a nonsignificant trend towards improved PFS in those with MAPK mutation vs those without (HR 0.82; 95% CI 0.43,1.59; p = 0.6). A test for interaction between treatment and MAPK pathway was not significant by Cox regression model (p = 0.32). Conclusions: While this hypothesis generating analysis is limited by multiple testing, higher response rates and longer PFS were seen in those patients with LGSOC treated with binimetinib who harbored MAPK mutations, most commonly in KRAS. Somatic tumor testing should be routinely performed in patients with recurrent LGSOC to aid in clinical decision making. Clinical trial information: NCT01849874.

An optical picowatt calorimeter at 4 K is demonstrated to measure absorption spectra from 330 nm to 1700 nm of optical samples. The minimum detectable absorbed power is 10 pW, resulting in absorption sensitivities of 0.3 ppm for 30 µW of incident power from a tunable source and 0.6 ppb for 15 mW laser excitation. Active temperature stabilization of main components of the cryogen-free cryostat and the use of paramagnetic temperature sensors with superconducting quantum interference device readout provided a low noise environment (700 nK temperature rms) and nK temperature resolution.

HfO2/SiO2 bilayer coatings and multilayer high-reflection coatings without and with a modified co-evaporated interface (MCEI) have been prepared. An MCEI is designed to be evaporated at an oxygen-deficient environment to achieve higher absorption than the conventional discrete interface. Capacitance-voltage measurements and absorption measurements demonstrate that an MCEI increases the trap density and leads to higher absorption. The laser-induced damage threshold and nano-indenter test results indicate that the MCEI multilayer coating exhibits better laser resistance and mechanical property, despite the larger absorption. The experimental results suggest that adhesive force between layers plays a more important role in nanosecond laser damage resistance than interface absorption.

Through personal experience and study I am a patient expert in the area of communication between clinicians and patients in clinical situations. Therefore I am in a position to provide constructive suggestions on how this interpersonal relationship can be improved As a patient with systemic RA, fibromyalgia, raynaud9s, IBD and non-obstructive sleep apnoea I have extensive experience in dealing with HCPs in clinical settings. I studied communications and media at university and post-graduate level and I am a sought-after speaker on communications models on a national and European level. I will seek to give examples of both positive and negative patient experiences with clinicians. I will explain communications models such as Shannon9s and Berlo9s as they pertain to clinical settings. I will then look to suggest changes and improvements that can be made in clinical situations by both clinicians and patients. By using the communication models I will illustrate the personal experiences I have had in clinical settings – both positive and negative. Improving communication is a joint effort between both the clinician and the patient. At the conclusion of the presentation, delegates will have a clearer understanding of the relevant communications models. They will also have an understanding of techniques to implement which will be of assistance in clinical settings. Despite this lecture being about clinicians improving communication, it is important to recognise that the patient plays just as important a role in the relationship. A patient must be willing to meet the clinician in the middle and ensure positive communication is a two-way enterprise. The clinician may be able to take the lead to a greater extent but the essence of communication requires a minimum of two people. Disclosure of Interest None declared

The combinations of a 60 fps kV x-ray flat panel imager, a 19 focal spot kV x-ray tube enabled by a steered electron beam, plus SART or SIRT sliding reconstruction via GPUs, allow real time 6 fps 3D-rendered digital tomosynthesis tracking of the respiratory motion of lung cancer lesions. The tube consists of a “U” shaped vacuum chamber with 19 tungsten anodes, spread uniformly over 3 sides of a 30 cm x 30 cm square, each attached to a cylindrical copper heat sink cooled by flowing water. The beam from an electron gun was steered and focused onto each of the 19 anodes in a predetermined sequence by a series of dipole, quadrupole and solenoid magnets. The imager consists of 0.194 mm pixels laid out in 1576 rows by 2048 columns, binned 4x4 to achieve 60 fps projection image operation with 16 bits dynamic range. These are intended for application with free breathing patients during ordinary linac C-arm radiotherapy with modest modifications to typical system hardware or to standard clinical treatment delivery protocols. The sliding digital tomosynthesis reconstruction is completed after every 10 projection images acquired at 60 fps, but using the last 19 such projection images for each such reconstruction at less than 8 mAs exposure per 3D rendered frame. Comparisons, to “ground truth” optical imaging and to diagnostic 4D CT (10 phase) images, are being used to determine the accuracy and limitations of the various versions of this new “19 projection image x-ray tomosynthesis fluorooscopy” motion tracking technique.

Integrating the SQUIDs and sensing coils of magnetic microcalorimeters onto the same die is a promising approach for maximizing flux coupling and signal/noise. However, new challenges in microfabrication must be overcome, because the underlying SQUID devices are sensitive to chemical attack and elevated processing temperatures. In this report, we describe development and details of a microfabrication process for integrated SQUID/sensor gamma-ray magnetic microcalorimeters with electroformed gold absorbers, starting from a modified version of the STAR Cryoelectronics “Delta 1000” Josephson Junction process.

The electrode in a cochlear implant (CI) system is a key factor in hearing performance as it is the interface between the device and the auditory pathway of the recipient. The first CI electrodes were straight and thus adopted a lateral wall position. Subsequent innovations include: perimodiolar electrodes designed to lie adjacent to the modiolar wall and thus to provide more spatially-focused stimulation of the spiral ganglion cells; shorter atraumatic straight electrodes for combined electric and acoustic (hybrid) stimulation. This paper explores the relative merits of straight and perimodiolar electrodes in the search for the optimal electrode design with reference to electrodes from Cochlear(®).

OBJECTIVE This study sought to learn the wishes of young adolescents via an open-ended survey question and to determine the association of these wishes with sociodemographic variables. METHODS We performed a cross-sectional study of consecutive adolescents aged 11-14 years who had a well-child visit at a clinic with a diverse patient population, who completed a Guidelines for Adolescent Preventive Services (GAPS) previsit health questionnaire, and who answered the question, "If you could have three wishes come true, what would they be?" Responses to this question were double-coded according to thematic content and whether wishes were for self, others, or both. RESULTS Among 96 respondents, wishes for others were listed more frequently by girls than by boys (54% versus 31%; P = .02). Girls also had more family-oriented wish themes (27% versus 10%; P = .04). Boys were more likely to wish for success (17% versus 4%; P = .05). Among respondents with private insurance, 45% wished for the good for the world, with responses such as "world peace"; only 12% of respondents with Medicaid wished for the good of the world (P = .01). No statistically significant differences were identified by race/ethnicity or age. Positive future orientation themes such as career were not as prioritized as previously suggested in the literature. LIMITATIONS The sample population derives from a single university-based clinic in North Carolina; while diverse, this population may not be representative of larger groups. CONCLUSIONS Many wishes seemed predictable (ie, for wealth, athleticism), but occasionally wishes were poignant and original ("to have papers for my parents to pass the border"); this finding reinforces the value of listening to adolescents' wishes. Both sex and insurance status were related to wish themes. Further research should determine how knowledge of adolescents' wishes can be used to best direct individual care.

OBJECTIVES: Constipation is a common diagnosis in the pediatric emergency department (ED). Children diagnosed with constipation may undergo an abdominal radiograph (AXR) as part of their diagnostic workup despite studies that suggest that an AXR in a patient suspected of being constipated is unnecessary and potentially misleading. We aimed to decrease the percentage of low-acuity patients aged between 6 months and 18 years diagnosed with constipation who undergo an AXR in our pediatric ED from 60% to 20% over 12 months. METHODS: We conducted an interventional improvement project at a large, urban pediatric ED by using the Institute for Healthcare Improvement’s Model for Improvement. The primary outcome was the proportion of patients ultimately diagnosed with constipation who had an AXR during their ED visit. Analysis was performed by using rational subgrouping and stratification on statistical process control (SPC) charts. RESULTS: Process analysis was performed by using a cause-and-effect diagram. Four plan-do-study-act cycles were completed over 9 months. Interventions included holding Grand Rounds on constipation, sharing best practices, metrics reporting, and academic detailing. Rational subgrouping and stratification on SPC charts were used to target the interventions to different ED provider groups. Over 12 months, we observed a significant and sustained decrease from a mean rate of 62% to a mean rate of 24% in the utilization of AXRs in the ED for patients with constipation. CONCLUSIONS: The use of rational subgrouping and stratification on SPC charts to study different ED provider groups resulted in a substantial and sustained reduction in the rate of AXRs for constipation.

Background EULAR Young PARE9s strategy for 2020 is to establish and strengthen groups for young people with rheumatic and musculoskeletal diseases (RMDs) across Europe, by developing a collaborative network. We aim to empower youth leaders to ensure the voice of young people with RMDs is heard. To facilitate this, the 2nd EULAR Young PARE Conference was held in Retie, Belgium in October 2016. Objectives To empower and educate EULAR Young PARE youth liaisons, focusing on developing academic and interpersonal skills to best support young people across Europe living with RMDs. This was achieved through a series of practical, skills-based workshops and plenary sessions. Methods The EULAR Young PARE working group reflected on the conference during a debrief meeting. A post-conference evaluation was completed by liaisons. A five-point Likert scale (1= very bad, 5= very good) was used alongside open questions. In addition, there was an informal meeting to generate discussions and receive input from participants regarding the future direction and focus of EULAR Young PARE in 2017 and 2018. Results The conference was attended by 22 youth liaisons from 20 organisations. The programme was well received with the face-to-face interactions favoured to establish and grow collaborative networks. Through a series of digital poster presentations, each liaison had the opportunity to share recent work in their national organisations. This session was evaluated positively and encouraged liaisons to identify opportunities for collaboration and new national activities, using the VKC as a platform for the sharing of best practices. Workshops were delivered in collaboration with EMEUNET and a EULAR member organisation representative and we piloted a series of six walk-in workshops. While these workshops were evaluated positively, a lack of structure and the need for time constraints was a consistent finding. Conclusions The “Change the Future” conference was a successful meeting of youth liaisons from across Europe, who were highly satisfied with the programme and mechanism of delivery. Meeting in person facilitated the growth and continued involvement within the EULAR Young PARE network. The activities of EULAR, and specifically the Standing Committee of PARE, were shared with liaisons, encouraging liaisons to become involved in a wider number of EULAR activities. Theoretical and practical skills were developed, while best practices and experiences were shared and highly valued. Furthermore, in future conferences, bitesize workshops will replace walk-in workshops for structure and clarity. Despite living in a digitally connected world, face-to-face interactions cannot be replaced. Learning can be enhanced and actions implemented when motivated individuals are physically united, demonstrating the need for the use of multiple meeting methods to drive innovation. Following the conference, everyone felt inspired, empowered and motivated to implement concrete and tangible steps to inform ongoing and future work. Together, we can change the future for young people living with RMDs. Disclosure of Interest None declared

Background In a recent European youth survey, 53% reported that rheumatic and musculoskeletal diseases (RMDs) affected their ability to work, while 75% reported that RMDs interrupted their education. Therefore, in 2017 and 2018, while continuing to achieve the objectives reached in 2015 and 2016, EULAR Young PARE will focus on two key points from EULAR Young PARE9s strategic objectives: work and education. Objectives In 2017, in line with EULAR9s efforts to raise awareness of the needs of people with RMDs among employers and other stakeholders, the specific and still unmet needs of young people with RMDs will be highlighted, so that employers and other stakeholders will be more aware of the needs of young people with RMDs and young people will receive better support to find a suitable job. In 2018, education for young people with RMDs will be in focus, so that educational institutions across Europe will be more flexible and assistive in supporting high quality education for young people with RMDs. Methods In 2017, we will support EULAR9s lobbying activities by raising awareness among employers and other stakeholders about the needs of young people with RMDs. We will also provide information to support young people in finding suitable jobs and to be aware of their rights in the workplace. Best practices concerning ergonomics, support programmes, career counselling and suitable jobs will be collected and shared. In 2018, we will support educational institutions across Europe to be more flexible and assistive in providing high quality education for young people with RMDs by offering training and support to national youth leaders. Results Thanks to the results achieved in 2015 and 2016, it is anticipated that structures will be in place to continuously raise awareness among employers, medical staff in schools, teachers and unions about the competencies and limitations of young people with RMDs. These activities enable EULAR Young PARE to expand and strengthen the active network of youth groups across Europe. Every PARE organisation will have a PARE youth liaison person, who will be encouraged and supported to take active roles in their national organisations and in the EULAR community. Conclusions The objectives reached by EULAR Young PARE in 2015 and 2016 are closely related to its future aims and achievements, allowing EULAR Young PARE to grow stronger and continue its work by the side of young people with RMDs, in order to improve their quality of life. References EULAR Young PARE. Available from: http://www.youngpare.org[accessed on 30 January 2017]. Acknowledgements Special thanks to EULAR and EULAR PARE for supporting the vision of EULAR Young PARE. EULAR Young PARE would also like to acknowledge all of the patient organisations that they continue to work with. Disclosure of Interest None declared

This paper examines the interactive effects of apology source (i.e., whether an apology is given by a chief executive officer or employee) and apology components (i.e., acknowledgment, remorse, and compensation) on forgiveness. Results revealed a significant source by component interaction. A remorseful employee apology was more successful than a remorseful CEO apology because consumers felt more empathy for the employee. Furthermore, a compensatory CEO apology was more effective than a compensatory employee apology because CEOs could significantly affect consumer perceptions of justice. No significant differences were found between apology source and the apology component of acknowledging violated rules and norms.

Identifying the etiology of acute pelvic pain in girls is often clinically challenging. Particularly in young girls, it is often difficult to determine if acute pelvic symptoms are originating from a gynecologic source or from a genitourinary or gastrointestinal etiology based on the childʼs clinical examination alone. Therefore, imaging plays a key role in establishing a diagnosis and in directing medical and surgical treatment. Pediatric gynecologic conditions, which can present acutely with pain or mass or both include ovarian torsion, hematometrocolpos, pelvic inflammatory disease, inguinal hernias containing an ovary or the uterus or both, adnexal cysts, pregnancy, vaginal foreign bodies, and ovarian vein thrombosis. Sources of pelvic pain in girls from nongynecologic etiologies include appendicitis, distal ureterolithiasis, and Crohn’s disease. Owing to the lack of ionizing radiation, widespread availability, and lack of need for sedation, gray scale, with color Doppler ultrasound examination is often the initial imaging obtained when there is suspicion of gynecologic pathology. Radiographs of the abdomen and pelvis are commonly used in the acute setting, when there is concern for a bowel obstruction or free intraperitoneal air. Cross-sectional imaging with computed tomography or magnetic resonance imaging is used, when the diagnosis remains unknown and to clarify findings found on ultrasound and radiographs. Correctly identifying and diagnosing the causes of acute pelvic pain in girls is crucial for the care of these patients. Here, we review the spectrum of causes of acute pelvic pain in female infants to teens with emphasis on imaging approach and age-related characteristics. Objectives • Review the normal anatomy, key anatomical relationships, and age-related changes of the uterus and ovaries. • Discuss the appropriate choice of imaging for girls with acute pelvic pain. • Review the imaging of pelvic pathologic conditions presenting in girls in the emergent clinical setting. • Differentiation of surgical from nonsurgical entities.

We propose an Automatic Threat Detection (ATD) algorithm for Explosive Detection System (EDS) using our multistage Segmentation Carving (SC) followed by Support Vector Machine (SVM) classifier. The multi-stage Segmentation and Carving (SC) step extracts all suspect 3-D objects. The feature vector is then constructed for all extracted objects and the feature vector is classified by the Support Vector Machine (SVM) previously learned using a set of ground truth threat and benign objects. The learned SVM classifier has shown to be effective in classification of different types of threat materials. The proposed ATD algorithm robustly deals with CT data that are prone to artifacts due to scatter, beam hardening as well as other systematic idiosyncrasies of the CT data. Furthermore, the proposed ATD algorithm is amenable for including newly emerging threat materials as well as for accommodating data from newly developing sensor technologies. Efficacy of the proposed ATD algorithm with the SVM classifier is demonstrated by the Receiver Operating Characteristics (ROC) curve that relates Probability of Detection (PD) as a function of Probability of False Alarm (PFA). The tests performed using CT data of passenger bags shows excellent performance characteristics.

Two simulated sets of digital tomosynthesis images of the lungs, each acquired at a 90 degree angle from the other, with 19 projection images used for each set and SART iterative reconstructed, gives dual tomosynthesis slice image quality approaching that of spiral CT, and with a data acquisition time that is 3% of that of cone beam CT. This fast kV acquisition, should allow near real time tracking of lung tumors in patients receiving SBRT, based on a novel TumoTrakTM multi-source X-ray tube design. Until this TumoTrakTM prototype is completed over the next year, its projected performance was simulated from the DRR images created from a spiral CT data set from a lung cancer patient. The resulting dual digital tomosynthesis reconstructed images of the lung tumor were exceptional and approached that of the gold standard Feldkamp CT reconstruction of breath hold, diagnostic, spiral, multirow, CT data. The relative dose at 46 mAs was less than 10% of what it would have been if the digital tomosynthesis had been done at the 472 mAs of the CT data set. This is for a 0.77 fps imaging rate sufficient to resolve respiratory motion in many free breathing patients during SBRT. Such image guidance could decrease the magnitudes of targeting error margins by as much as 20 mm or more in the craniocaudal direction for lower lobe lesions while markedly reducing dose to normal lung, heart and other critical structures. These initial results suggest a wide range of topics for future work.

The case recounts an incident of theft at a CEOs home during a company party. The rogue may well be an employee, and the CEO considers his options: should he let the matter pass and preserve the good will generated by the party, or should he stand on principle and engage the issue frontally? Three commentators provide perspective on an optimal response. They consider whether the CEOs true intent is to show appreciation or showcase opulence. In addition, the aberrant behavior at this celebratory event suggests some measures that management might take in the workplace.

PurposeEnvironmental uncertainty threatens many companies. This paper seeks to offer a strategic model to help imperiled firms overcome employee inertia, counter competitive forces, and speed organizational renewal.Design/methodology/approachThe paper presents a change model which outlines five major steps, each comprised of three elements. Examples from the field illustrate sequential stages of the cycle.FindingsThis framework aligns human resources and organizational processes. By adhering to this approach, leaders can become transformational change agents.Practical implicationsThe proposed strategic format evolved from face‐to‐face discussions with exemplary turnaround leaders. In their visits to the author's classroom over the last six years, they offered insights that should prove beneficial to other leaders in turnaround situations.Originality/valueThe paper extends existing business models by providing a comprehensive set of action steps to engage all organizational members.

Purpose Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity. Patients and Methods Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m2/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS). Results Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%). Conclusion To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.