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

Goosegrass control options in bermudagrass are limited. Topramezone is one option that offers excellent control of mature goosegrass, but application to bermudagrass results in unacceptable symptoms of bleaching and necrosis typical of hydroxyphenylpyruvate dioxygenase inhibitors. Previous research has shown that adding chelated iron reduced the phytotoxicity of topramezone without reducing the efficacy of the herbicide, resulting in safening when applied to bermudagrass. Our objective was to examine additional iron sources to determine whether similar safening effects occur with other sources. Field trials were conducted in the summers of 2016 to 2018 (Auburn University). Mixtures of topramezone and methylated seed oil were combined with six different commercial iron sources, including sodium ferric ethylenediamine di-o-hydroxyphenyl-acetate (FeEDDHA), ferrous diethylenetriamine pentaacetic acid (FeDTPA), iron citrate, FeSO4, and a combination of iron oxide/sucrate/sulfate, some of which contained nitrogen. Bermudagrass necrosis and bleaching symptoms were visually rated on a 0% to 100% scale. Reflectance (normalized difference vegetation index) and clipping yield measurements were also collected. Application of FeDTPA and FeSO4 reduced symptoms of bleaching and necrosis when applied with topramezone. Other treatments that contained nitrogen did not reduce injury but did reduce bermudagrass recovery time following the appearance of necrosis. Inclusion of small amounts of nitrogen often negated the safening effects of FeSO4. The iron oxide/sucrate/sulfate product had no effect on bleaching or necrosis. Data suggest that the iron source had a differential effect on bleaching and necrosis reduction when applied in combination with topramezone to bermudagrass. Overall, FeSO4 and FeDTPA safened topramezone the most on bermudagrass.

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.

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.

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.

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.

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 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.

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.

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

Background: Little is known of the hematology of the dugong (Dugong dugon), a secretive and endangered coastal marine mammal. Objectives: This paper reports hematologic reference intervals (RI) for dugongs and characterizes morphologic, cytochemical, and ultrastructural features of dugong leukocytes. Methods: Blood was collected from live, apparently healthy dugongs and analyzed using Cell-Dyn 3700 or Sysmex XT-2000iV hematology analyzers. Blood films were subjected to a series of cytochemical stains, and leukocyte structure was examined using transmission electron microscopy. Results: Reference intervals were established for 14 hematologic variables, total solids, and fibrinogen for 92 dugongs. Significant differences in some variables were found for animal size class, sex, and pregnancy status, and between analyzers. Subadults had higher leukocyte and lymphocyte counts than adults. Males had higher total solids and fibrinogen than females. Pregnant females had higher HCT, MCV, and circulating nucleated RBC, and lower platelet counts than nonpregnant females. Lymphocytes were usually the predominant circulating leukocyte. Heterophil cytoplasmic granules were abundant, fine, round to ovoid, and intensely eosinophilic, and round to ovoid or rod-shaped, and variably electron dense in electron microscopy. Eosinophils contained larger round eosinophilic to orange cytoplasmic granules, which ultrastructurally were bicompartmental with a round eccentric electron-dense core. Cytochemical staining of dugong heterophils suggests biochemical similarity to those of manatees and elephants, and for eosinophils, similarity to those of elephants, ruminants, and equids. Conclusions: Generation of hematologic RI and characterization of leukocyte morphology improves evaluation of dugong health across this population and serves as a reference for other populations outside southern Queensland.

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

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.

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.

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.

Based on promising results with adults, Acceptance and Commitment Therapy (ACT) presents as a treatment opportunity for depressed adolescents. We present a pilot study that compares ACT with treatment as usual (TAU), using random allocation of participants who were clinically referred to a psychiatric outpatient service. Participants were 30 adolescents, aged M = 14.9 (SD = 2.55), with 73.6% in the clinical range for depression. At posttreatment on measures of depression participants in the ACT condition showed significantly greater improvement statistically (d = 0.38), and 58% showed clinically reliable change with a response ratio of 1.59 in favor of ACT. Outcomes from 3-month follow-up data are tentative due to small numbers but suggest that improvement increased in magnitude. Measures of global functioning showed statistically significant improvement for both conditions, although clinical change measures favored only the ACT condition. The results support conducting a larger trial of ACT for the treatment of adolescent depression.

Background Patients with chronic hepatitis C genotype 1 (HCV-1) and difficult-to-treat characteristics respond poorly to pegylated interferon alfa and ribavirin (RBV), and could benefit from an interferon with increased activity (consensus interferon or CIFN), favorable viral kinetics from daily dosing, and a longer duration of therapy. The purpose of this pilot study was to determine the efficacy and safety of daily CIFN + RBV for initial treatment of patients with HCV-1 infection. Methods Patients with difficult-to-treat characteristics (92% male, 33% African American, 78% Veterans Affairs [VA]; 67% high viral load, 59% stage 3–4 fibrosis, and mean weight of 204 lbs) were enrolled at seven VA and two community medical centers. They were randomized to daily CIFN (15 mcg/day SQ) and RBV (1–1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52–72 weeks (from time of viral response +48 weeks) (group B, n = 31). Results Intention to treat analysis for treatment groups A and B demonstrated 33% (11/33) and 32% (10/31) sustained virologic response (SVR), respectively. Only 2/31 patients in group B received more than 52 weeks of treatment. The overall group demonstrated a 31% (20/64) rapid virologic response rate (RVR), 54% (34/64) end of treatment virologic response and a 33% (21/64) SVR. Patients with RVR at 4 weeks, early virologic response from 8–12 weeks, and late virologic response from 16–24 weeks demonstrated SVR of 75% (15/20), 31% (4/13), and 22% (2/9), respectively. Overall early non-protocol discontinuation occurred in 26/64 (40%) patients. Conclusion Daily CIFN and ribavirin for initial treatment of HCV-1 patients has potential for achieving a relatively high RVR rate, but discontinuations are frequent and successful use of this regimen is highly dependent on adequate patient support to maintain adherence.

Background Cafe-au-lait macules (CALMs) in neurofibromatosis type 1 (NF1) are an early and accessible phenotype in NF1, but have not been extensively studied. Objective We sought to more fully characterize the phenotype of CALMs in patients with NF1. Methods In all, 24 patients with a diagnosis of NF1 confirmed through clinical diagnosis or molecular genetic testing were recruited from patients seen in the genetics department at the University of Alabama at Birmingham. CALM locations were mapped using standard digital photography. Pigment intensity was measured with a narrowband spectrophotometer, which estimates the relative amount of melanin based on its absorption of visible light. The major response was defined as the difference between the mean melanin from the CALM and the mean melanin from the surrounding skin. The major response for each spot was compared with spots within an individual and across individuals in the study population. Results There was significant variability of the major response, primarily attributable to intrapersonal variability (48.4%, P P Limitations The study was performed on a small population of patients and the method has not yet been used extensively for this purpose. Conclusions CALMs vary in pigment intensity not only across individuals, but also within individuals and this variability was unrelated to sun exposure. Further studies may help elucidate the molecular basis of this finding, leading to an increased understanding of the pathogenesis of CALMs in NF1.

The objective of this review is to summarise the evidence for mindfulness and acceptance approaches in the treatment of adolescent depression. The article begins by summarising the outcomes of three broad approaches to the treatment of adolescent depression — primary prevention, pharmacotherapy, and psychotherapy — in order to advocate for advances in treatment. With regard to psychotherapy, we restrict this to comparisons of meta-analytic studies, in order to cover the breadth of the outcome literature. In the second half of this article, we introduce the reader to mindfulness and acceptance-based psychotherapy, with a particular focus on Acceptance and Commitment Therapy (ACT) and the applicability with adolescents. We provide an overview of the philosophical arguments that underlie this approach to psychotherapy and consider how each of these might contribute to treatment approaches for adolescents with depression.

Pancreatic enzyme replacement therapy (PERT) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval.This study was conducted to compare the efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF.This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover, superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI. In each period, pancrelipase or identical placebo capsules were taken for 5 days. The primary outcome measure was the coefficient of fat absorption (CFA); secondary outcome measures were the coefficient of nitrogen absorption (CNA) and clinical symptoms. The latter were assessed based on patient-reported daily stool frequency, stool consistency (hard, formed/normal, soft, or watery), flatulence (none, mild, moderate, or severe), and abdominal pain (none, mild, moderate, or severe). Safety measures included vital signs, physical examinations, standard laboratory safety tests (hematology and biochemistry), and adverse events.Seventeen patients were randomized to treatment and 16 completed the study; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis. Patients' median age was 8.0 years (range, 7-11 years); 12 patients (70.6%) were male. CFA values were significantly greater for pancrelipase compared with placebo, with least squares mean (SE) values of 82.8% (2.7%) and 47.4% (2.7%), respectively (P0.001). The results were similar for CNA, with mean values of 80.3% (3.2%) and 45.0% (3.2%) (P0.001). Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA50% than in those with a placebo CFA50% (both parameters, P0.001 and P = 0.008, respectively). Significant improvements in stool fat, weight, and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo (all, P0.001). Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment, but worsened slightly during receipt of placebo. Treatment-emergent adverse events were reported in 5 patients (29.4%) during receipt of pancrelipase and in 9 patients (56.3%) during receipt of placebo; these were predominantly gastrointestinal events. There were no discontinuations due to treatment-emergent adverse events and no serious adverse events.In this study in children with EPI due to CF, the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA, CNA, stool properties, and EPI symptoms compared with placebo. Pancrelipase delayed-release capsules appeared to be well tolerated. ClinicalTrials.gov identifier: NCT00690820. (Clin Ther.

Neurofibromatosis type 1 (NF1) is an autosomal dominant, multisystem disorder affecting approximately 1 in 3500 people. Significant advances in the understanding of the pathophysiology of NF1 have been made in the last decade. While no medical therapies for NF1 are currently available, trials are ongoing to discover and test medical treatments for the various manifestations of NF1, primarily plexiform neurofibromas, learning disabilities, and optic pathway gliomas. In addition, mutational analysis has become available on a clinical basis and is useful for diagnostic confirmation in individuals who do not fulfill diagnostic criteria or when a prenatal diagnosis is desired. There are several disorders that may share overlapping features with NF1; in 2007, a disorder with cutaneous findings similar to NF1 was described. This paper addresses the dermatologist's role in diagnosis and management of NF1 and describes the variety of cutaneous and extracutaneous findings in NF1 to which the dermatologist may be exposed. Learning objectives After completing this learning activity, participants should be able to discuss the indications and limitations of genetic testing in neurofibromatosis type 1, distinguish common and uncommon cutaneous findings, and recognize the dermatologist's role in diagnosis and management.

Sense of belonging to a community offers protection against depression (Glover et al. 1998); however, rural adolescents with mental health issues often feel isolated, lonely and socially excluded (Aisbett et al. 2007). This is exacerbated by the stoic attitudes and fear of social stigma which prevent many rural adolescents from engaging with mainstream mental health programs (Boyd et al. 2006). With this knowledge, we aimed to engage atrisk rural adolescent males who would otherwise not seek psychological help in an innovative program which would link them to a broader sporting community. The project also aimed to strengthen leaders of this community to act as mentors for these young people. In this article, we describe the development and delivery of the mentoring component of this innovative program. The outcomes for the youth involved in this program are described in the subsequent article by Kemp and colleagues in the next edition of Children Australia.

The objectives of this article are to expand and comment upon a recent review in Australian Psychologist of the literature in relation to mental health problems in rural contexts by Jackson et al. (2007). In the present article we review recently published qualitative research on the help-seeking attitudes and experiences of rural Australian adolescents. While we agree on the utility of the Macintyre, Ellaway, and Cummins (2002) conceptual framework based on notions of health and place, we note that this framework specifically emphasises the importance of the collective dimension. We present a broader perspective on health and place than Jackson et al. (2007) by incorporating social geographic research. We argue that rural mental health research has been hampered by a simplistic view of social stigma of mental illness and that a more thorough conceptualisation of the phenomenon is needed. Finally, we make some further recommendations based on a broader perspective of mental health in rural contex...

We present the photometric calibration of the Swift UltraViolet/Optical Telescope (UVOT) which includes: optimum photometric and background apertures, effective area curves, colour transformations, conversion factors for count rates to flux, and the photometric zero points (which are accurate to better than 4 per cent) for each of the seven UVOT broadband filters. The calibration was performed with observations of standard stars and standard star fields that represent a wide range of spectral star types. The calibration results include the position dependent uniformity, and instrument response over the 1600-8000A operational range. Because the UVOT is a photon counting instrument, we also discuss the effect of coincidence loss on the calibration results. We provide practical guidelines for using the calibration in UVOT data analysis. The results presented here supersede previous calibration results.

One hundred Hampshire x Duroc cross-bred pigs (HD) and 100 NE Index line (I) pigs were infected with porcine reproductive and respiratory syndrome (PRRS) virus and evaluated for resistance/susceptibility. Controls (100/line) were uninfected littermates to the infected pigs. Viremia, change in weight (WTdelta), and rectal temperature at 0, 4, 7, and 14 d postinfection were recorded. Lung, bronchial lymph node (BLN), and blood tissue were collected at necropsy (14 d postinfection). The first principal component from principal component analyses of all variables was used to rank the pigs for phenotypic response to PRRS virus. Low responders (low PRRS burden) had high WTdelta, low viremia, and few lung lesions; high responders (high PRRS burden) had low WTdelta, high viremia, and many lesions. The RNA was extracted from lung and BLN tissue of the 7 highest and 7 lowest responders per line and from each of their littermates. Expression of 11 innate and T helper 1 immune markers was evaluated with cDNA in a 2 x 2 x 2 factorial design. Significant upregulation in lung, lymph, or both of infected pigs relative to controls occurred for all but one gene. Expression differences were greater in HD than I pigs. Significant downregulation for certain immune genes in low pigs, relative to littermate controls, was detected in lung and BLN, particularly in line I. Serum levels of the immune cytokines affirmed the gene expression differences. High preinfection serum levels of IL 8 were significantly associated with PRRS virus-resistant, low pigs. After infection, low expression of interferon gamma in cDNA and in serum was also correlated with PRRS virus resistance. Important genetic associations were revealed for fine mapping of candidate genes for PRRS virus resistance and determining the causative alleles.

We report the chromosomal localization, mutant gene identification, ophthalmic appearance, histology, and functional analysis of two new hereditary mouse models of retinal degeneration not having the Pde6brd1("r", "rd", or "rodless") mutation. One strain harbors an autosomal recessive mutation that maps to mouse chromosome 5. Sequence analysis showed that the retinal degeneration is caused by a missense point mutation in exon 13 of the beta-subunit of the rod cGMP phosphodiesterase (beta-PDE) gene (Pde6b). The gene symbol for this strain was set as Pde6brd10, abbreviated rd10 hereafter. Mice homozygous for the rd10 mutation showed histological changes at postnatal day 16 (P16) of age and sclerotic retinal vessels at four weeks of age, consistent with retinal degeneration. Retinal sections were highly positive for TUNEL and activated caspase-3 immunoreactivity, specifically in the outer nuclear layer (ONL). ERGs were never normal, but rod and cone ERG a- and b-waves were easily measured at P18 and steadily declined over 90% by two months of age. Protein extracts from rd10 retinas were positive for beta-PDE immunoreactivity starting at about the same time as wild-type (P10), though signal averaged less than 40% of wild-type. Interestingly, rearing rd10 mice in total darkness delayed degeneration for at least a week, after which morphological and functional loss progressed irregularly. With the second strain, a complementation test with rd1 mice revealed that the retinal degeneration phenotype observed represents a possible new allele of Pde6b. Sequencing demonstrated a missense point mutation in exon 16 of the beta-subunit of rod phosphodiesterase gene, different from the point mutations in rd1 and rd10. The gene symbol for this strain was set as Pde6bnmf137, abbreviated nmf137 hereafter. Mice homozygous for this mutation showed retinal degeneration with a mottled retina and white retinal vessels at three weeks of age. The exon 13 missense mutation (rd10) is the first known occurrence of a second mutant allele spontaneously arising in the Pde6b gene in mice and may provide a model for studying the pathogenesis of autosomal recessive retinitis pigmentosa (arRP) in humans. It may also provide a better model for experimental pharmaceutical-based therapy for RP because of its later onset and milder retinal degeneration than rd1 and nmf137.

The aim of this study was to explore the prevalence of eating disorders in primary care in the Ballarat region and to highlight the role of GPs in the detection and management of eating disorders in regional Australia. We used anonymous data previously collated by the Ballarat and District Division of General Practice on the prevalence of eating disorders and patterns of referral of eating disorder patients among GPs in their Division. Over half of GPs surveyed indicated that they treat patients with eating disorders within their practice rather than referring patients to other services. In referring on, GPs were more likely to refer to mental health professionals and dietitians. A notable finding was that these regional GPs were more likely to refer to metropolitan specialist services than local hospitals if their patients required an admission. GPs in regional Australia do significant work to detect and manage patients with clinical eating disorders in the absence of locally-based, specialist services. In this context, we recommend the establishment of linkage partnerships between GPs and mental health practitioners to facilitate early intervention for rural and regional eating disorder patients. Further research into the current treatment practices of regional GPs is also needed to ascertain their specific training needs with respect to this patient population.

Emergency department (ED) computed tomography (CT) use has increased substantially in recent years, resulting in increased radiation exposure for patients. Few studies have assessed which parties contribute to CT ordering in the ED. The objective of this study was to determine the proportion of CT scans ordered due to explicit requests by various stakeholders in ED patient care. This is a prospective, observational study performed at three university hospital EDs. CT scans ordered during research assistant hours were eligible for inclusion. Attending emergency physicians (EPs) completed standardized data forms to indicate all parties who had explicitly requested that a specific CT be performed. Forms were completed before the CT results were known in order to minimize bias. Data were obtained from 77 EPs regarding 944 CTs. The parties most frequently requesting CTs were attending EPs (82.0 %, 95 % CI 79.4-84.3), resident physicians (28.6 %, 95 % CI 25.8-31.6), consulting physicians (24.4 %, 95 % CI 21.7-27.2), and admitting physicians (3.9 %, 95 % CI 2.9-5.4). In the 168 instances in which the attending EP did not explicitly request the CT, requests most commonly came from consulting physicians (51.2 %, 95 % CI 43.7-58.6), resident physicians in the ED (39.9 %, 95 % CI 32.8-47.4), and admitting physicians (8.9 %, 95 % CI 5.5-14.2). EPs were the sole party requesting CT in 46.2 % of cases while multiple parties were involved in 39.0 %. Patients, families, and radiologists were uncommon sources of such requests. Emergency physicians requested the majority of CTs, though nearly 20 % were actually not desired by them. Admitting, consulting, and resident physicians in the ED were important contributors to CT utilization.

Langerhans cell histiocytosis (LCH) with involvement of the gastrointestinal tract is rare and typically identified in patients with systemic disease. We describe a 16-month-old girl who initially presented with bilious vomiting, failure to thrive and a rash. An upper gastrointestinal (GI) examination revealed loss of normal mucosal fold pattern and luminal narrowing within the duodenum, prompting endoscopic biopsy. Langerhans cell histiocytosis of the digestive tract was confirmed by histopathology. A skeletal survey and skin biopsy identified other systemic lesions. Although uncommon, it is important to consider LCH in the differential diagnosis for gastrointestinal symptoms of unclear origin, especially when seen with concurrent rash. Findings of gastrointestinal involvement on upper GI examination include loss of normal mucosal fold pattern and luminal narrowing in the few published case reports.

We present ultraviolet and optical light curves in six broadband filters and grism spectra obtained by Swift's Ultraviolet/Optical Telescope for the Type Ia supernova SN2005am. The data were collected beginning about four days before the B-band maximum, with excellent coverage of the rapid decline phase and later observations extending out to 69 days after the peak. The optical and near UV light curve match well those of SN1992A. The other UV observations constitute the first set of light curves shorter than 2500 Angstroms and allow us to compare the light curve evolution in three UV bands. The UV behavior of this and other low redshift supernovae can be used to constrain theories of progenitor evolution or to interpret optical light curves of high redshift supernovae. Using Swift's X-Ray Telescope, we also report the upper limit to SN2005am's X-ray luminosity to be 1.77 x 10^40 erg s^-1 in the 0.3--10 keV range from 58,117 s of exposure time., 15 pages, including 3 figures and 2 tables, submitted to Astrophysical Journal

Purpose Efaproxiral (RSR13) reduces hemoglobin oxygen–binding affinity, facilitates oxygen release, and increases tissue pO2. We conducted a phase II multicenter study that assessed the efficacy and safety of efaproxiral when administered with thoracic radiation therapy (TRT), following induction chemotherapy, for treatment of locally advanced non–small-cell lung cancer (NSCLC). Patients and Methods Fifty-one patients with locally advanced NSCLC were enrolled at 13 sites. Treatment comprised two cycles of paclitaxel (225 mg/m2) and carboplatin (area under the curve, 6), 3 weeks apart, followed by TRT (64 Gy/32 fractions) with concurrent efaproxiral (50 to 100 mg/kg). Survival results were compared with results of study Radiation Therapy Oncology Group (RTOG) 94-10. Results Overall response rate was 75% (37 of 49 patients). Complete and partial response rates were 6% (three of 49 patients) and 69% (34 of 49 patients), respectively. Median survival time (MST) was 20.6 months (95% CI, 14.0 to 24.2); overall survival rates at 1- and 2-years were 67% and 37%, respectively. Survival results were compared with the sequential (S-CRT) and concurrent (C-CRT) chemoradiotherapy arms of RTOG 94-10. MSTs for cases matched by stage, Karnofsky performance status, and age were: RT-010, 20.6 months; S-CRT, 15.1 months; and C-CRT, 17.9 months. Grade 3 to 4 toxicities related to efaproxiral that occurred in more than one patient included transient hypoxemia (19%), radiation pneumonitis (11%), and fatigue (4%). Conclusion Addition of efaproxiral to S-CRT represents a promising approach in NSCLC treatment, and a randomized study should be pursued. The low incidence of grade 3 to 4 toxicities suggests that the use of efaproxiral instead of a cytotoxic agent, as a radiation sensitizer, may be advantageous.

Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signalling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT or 5-HTT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. It has been speculated that such functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhoea predominant IBS (dIBS) phenotype. Subjects: A total of 194 North American Caucasian female dIBS patients and 448 female Caucasian controls were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analysed by polymerase chain reaction based technologies for nine SERT polymorphisms, including the insertion/deletion polymorphism in the promoter (SERT-P) and the variable tandem repeat in intron 2. Statistical analysis was performed to assess association of any SERT polymorphism allele with the dIBS phenotype. Results: A strong genotypic association was observed between the SERT-P deletion/deletion genotype and the dIBS phenotype (p = 3.07×10 −5 ; n = 194). None of the other polymorphisms analysed was significantly associated with the presence of disease. Conclusions: Significant association was observed between dIBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for dIBS in women.

Depression is a highly complex mental disorder that for many years was believed to be absent in children and adolescents. It is now accepted that depression not only exists in this age group, but also is a major mental health problem (Weller & Weller, 2000a). Research suggests that the prevalence of depression in Australian children and adolescents is around 14% (Boyd, Kostanski, Gullone, Ollendick, & Shek, 2000). As depression appears to be highly prevalent, it is essential that efficacious treatments are identified, and that effective treatment strategies are established that best alleviate depressive symptoms in children and adolescents. In light of this need, this article details the criteria used to identify depression in children and adolescents, and examines the available evidence for the use of pharmacological and psychotherapeutic approaches in the treatment of depression in children and adolescents.

TPS870 Background: Approximately 96% of CRCs have an MSS phenotype, which results in more immunologically quiescent tumors for which immunotherapies are largely ineffective (Lee et al. 2015; Overman et al. 2016). Pts with MSS CRC and activating RAS mutation (35%–45% of CRCs) have treatment options limited still further because anti-EGFR monoclonal antibodies (eg, cetuximab) are ineffective owing to dominant activation of RAS in the MAPK pathway (Douillard et al. 2014). However, preclinical and preliminary clinical data suggest that MAPK pathway inhibition enhances antigen presentation and T-cell cytotoxicity to positively modulate the efficacy of checkpoint inhibitors (Brea et al. 2016; Bendell et al. 2014). The main objective of this open-label multicenter phase 1b/2 study is to evaluate whether the potential positive modulation of NIVO or NIVO plus IPI, when combined with BINI, translates into clinically meaningful overall response in pts with MSS mCRC and RAS mutation. Methods: The study will enroll ~90 previously treated pts (1 or 2 prior regimens), ~42 in phase 1b and ~48 in phase 2. The primary objective of phase 1b will be to determine the recommended phase 2 dose (RP2D) of BINI in combination with NIVO ± IPI. Dose finding in the doublet arm will begin with BINI 45 mg BID + NIVO 480 mg Q4W; the triplet arm will begin with the BINI RP2D from the doublet arm + NIVO 480 mg Q4W + IPI 1 mg/kg Q8W. In phase 2, pts will be randomized 1:1 to doublet or triplet arms, incorporating the BINI RP2Ds found in phase 1b; treatment will continue in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, initiation of subsequent anticancer therapy, loss to follow-up, or death. The primary objective for phase 2 will be to assess response by RECIST version 1.1. The study will also characterize safety and PK. CT.gov Identifier: Clinical trial information: NCT03271047.