Salvage Fractionated Stereotactic Re-irradiation (FSRT) for Patients with Recurrent High Grade Gliomas Progressed after Bevacizumab Treatment

Purpose/Objectives: Bevacizumab failure is a major clinical problem in the manage- ment of high grade gliomas (HGG), with a median overall survival of less than 4 months (m). This study evaluated the efficacy of fractionated stereotactic re-irradiation (FSRT) for patients with HGG after progression on Bevacizumab. Materials/Methods: Retrospective review was conducted of patients treated with FSRT after progression on bevacizumab. A total of 36 patients were identified. FSRT was most commonly delivered in 3.5 Gy fractions to a total dose of 35 Gy. Survival from initial diagnosis, as well as from recurrence and re-irradiation, were utilized as study endpoints. Univariate and multivariate analysis was performed. Results: Among the 36 patients, 31 patients had recurrent glioblastoma, and 5 patients had recurrent anaplastic astrocytoma. The median time from initial bevacizumab treatment to FSRT was 8.5 m (range 2.3 – 32.0 m). The median plan target volume for FSRT was 27.5 cc (range 1.95 – 165 cc). With a median follow up of 20.4 m, the overall survival of the patients since initial diagnosis was also 24.9 m. The median overall survival after initiation of bevacizumab was 13.4 months. The median overall survival from FSRT was 4.8 m. FSRT treatment was well tolerated with no Grade \u3e3 toxicity. Conclusions: Favorable outcomes were observed in patients with recurrent HGG who received salvage FSRT after bevacizumab failure. The treatment was well tolerated. Prospective study is warranted to further evaluate the efficacy of salvage FSRT for selected patients with recurrent HGG amenable to FSRT, who had failed bevacizumab treatment

Smartphone Mobile Application to Enhance Diagnosis of Skin Cancer: A Guide for the Rural Practitioner

Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier access to dermatologists. Recent expansion in smartphone mobile application technology offers simple ways for rural practitioners to address these problems. More than 100,000 health related applications are currently available, with over 200 covering dermatology. This review will evaluate the newest and most useful of those applications offered to enhance the prevention and early diagnosis of skin cancer, particularly in the rural population

Phase I Study of Ipilimumab Combined with Whole Brain Radiation Therapy or Radiosurgery for Melanoma Patients with Brain Metastases

Purpose: We performed a phase I study to determine the maximum tolerable dose (MTD) and safety of ipilimumab with stereotactic radiosurgery (SRS) or whole brain radiotherapy (WBRT) in patients with brain metastases (BM) from melanoma. Methods: Based on intracranial (IC) disease burden, patients were treated with WBRT (Arm A) or SRS (Arm B). Ipilimumab starting dose was 3 mg/kg (every 3 weeks, starting on day 3 of WBRT or 2 days after SRS). Ipilimumab was escalated to 10 mg/kg using a two-stage, 3+3 design. The primary endpoint was to determine the MTD of ipilimumab combined with radiotherapy. Secondary endpoints were overall survival (OS), IC and extracranial (EC) control, progression free survival (PFS), and toxicity. This trial is regis- tered with ClinicalTrials.gov, number NCT01703507. Results: Characteristics of the 16 patients enrolled between 2011 and 2014 were: mean age, 60; median BM, 2 (1 to \u3e10); number with EC disease, 13 (81%). Treatment included WBRT (n=5), SRS (n=11), ipilimumab 3mg/kg (n=7), 10 mg/kg (n=9). Median follow-up was 8 months (Arm A) and 10.5 months (Arm B). There were 21 grade 1-2 neuro- toxic effects with no dose-limiting toxicities (DLTs). One patient experienced grade 3 neurotoxicity prior to ipilimumab administration. Ten additional grade 3 toxicities were reported with gastrointestinal (n=5, 31%) as the most common. There were no grade 4/5 toxicities. Median PFS and OS, respectively, in Arm A were 2.5 months and 8 months, and in Arm B were 2.1 months and not reached. Conclusion: Concurrent ipilimumab 10 mg/kg with SRS is safe. The WBRT arm was closed early due to slow accrual, but demonstrated safety with ipilimumab 3 mg/kg. No patient experienced DLT. Larger studies with ipilimumab 10 mg/kg and SRS are warranted

Spectrum of Renal Biopsy Findings in TRIDENT Cohort

Introduction: Diabetic kidney disease is the most common cause of chronic end stage renal failure in the USA. Kidney biopsy is the gold standard diagnostic criteria; however, it is an invasive procedure; not everyone undergoes diagnostic biopsy. The relationship between histological and clinical parameters and prognosis in DKD is incompletely understood. TRIDENT, (Transformative research in diabetic nephropathy) plans to enroll 400 diabetic subjects undergoing clinically indicated renal biopsies and performs multi-omics characterization of subjects to identify pathways associated with kidney function decline. Genetic studies indicated that podocytes influence albuminuria and diabetic kidney disease development. We seek to understand whether podocyte and basement membrane changes correlate with kidney function, degree of albuminuria, and histopathologic features of diabetic nephropathy using electron microscopy and digital light microscopy. Methods: I performed quantitative characterization of podocyte foot process morphology using TRIDENT subject biopsies. Podocyte foot process width (FPW) was measured using electron micrographs in ImageJ and calculated: FPW = (π/4) × (ΣGBM length/Σfoot process). Results: In our cohort, the average FPW was 1.624μm, and the glomerular basement membrane (GBM) average thickness was 773.27μm. The average FPW and GBM thickness ranged from 519μm-4.806μm and 200μm-3230μm per patient, respectively. Using a Pearson’s correlation coefficient: GBM thickness positively correlates with RPS Class (.424240229), %interstitial fibrosis (.203720183), arteriolar hyalinosis (0.307801899), proteinuria (.639114291). Discussion: Podocyte features such as FPW and GBM thickness showed stronger correlation with proteinuria than other parameters. Some samples were collected in patients with advanced DKD; collecting samples earlier in the disease process may represent more accurate correlations between EM findings and disease severity. Overall podocyte structural changes strongly correlate with proteinuria, indicating the key role of podocytes in proteinuria

Countering Home-Grown Terrorists in Australia: An Overview of Legislation, Policy and Actors Since 2001

This article explores the impact of counter-terrorism legislation and policy in Australia. In particular it explores how legislation facilitated prosecution and conviction of persons involved in home-grown terrorism, including analysis of investigation and prosecution policy surrounding the ul-Haque and Haneef cases. Particular attention is given to the terrorism trials involving Benbrika & Ors and Elomar & Ors. What makes these trials intriguing is the fact that most of those convicted could be more easily described as more vulnerable than menacing. Sentencing of those convicted was cognate with no policies for rehabilitation. The small number of convictions under the legislation when considered against the increased funding of counter-terrorism, loss of traditional rights and privileges and Australia’s involvement in Afghanistan and Iraq raises issues about adequate policy setting in this area

Cytoreductive surgery for patients with recurrent epithelial ovarian carcinoma.

OBJECTIVE: This study aims to identify favorable preoperative characteristics and examine the impact of secondary cytoreductive surgery on survival for patients with recurrent epithelial ovarian carcinoma. METHODS: Patients who underwent cytoreductive surgery for recurrent epithelial ovarian cancer were identified in our surgical database for the period 1988-2004. Patient charts were reviewed and data collected regarding patient demographics, surgical management, preoperative evaluation, perioperative complications, and oncologic outcome. RESULTS: Eighty-five patients met eligibility criteria. Preoperative factors that correlated with improved survival were disease-free interval of greater than 12 months (por=1 cm (p CONCLUSION: When selecting patients for secondary cytoreduction, the most significant preoperative factors are disease-free interval and success of a prior cytoreductive effort. Once secondary cytoreductive surgery is attempted, the most important factor for improved survival is optimal cytoreduction. Of equal importance is counseling regarding the significant risk for bowel surgery, colostomy, and complications

Multi-model attribution of upper-ocean temperature changes using an isothermal approach

1

'Part'ly first among equals: Semantic part-based benchmarking for state-of-the-art object recognition systems

An examination of object recognition challenge leaderboards (ILSVRC, PASCAL-VOC) reveals that the top-performing classifiers typically exhibit small differences amongst themselves in terms of error rate/mAP. To better differentiate the top performers, additional criteria are required. Moreover, the (test) images, on which the performance scores are based, predominantly contain fully visible objects. Therefore, `harder' test images, mimicking the challenging conditions (e.g. occlusion) in which humans routinely recognize objects, need to be utilized for benchmarking. To address the concerns mentioned above, we make two contributions. First, we systematically vary the level of local object-part content, global detail and spatial context in images from PASCAL VOC 2010 to create a new benchmarking dataset dubbed PPSS-12. Second, we propose an object-part based benchmarking procedure which quantifies classifiers' robustness to a range of visibility and contextual settings. The benchmarking procedure relies on a semantic similarity measure that naturally addresses potential semantic granularity differences between the category labels in training and test datasets, thus eliminating manual mapping. We use our procedure on the PPSS-12 dataset to benchmark top-performing classifiers trained on the ILSVRC-2012 dataset. Our results show that the proposed benchmarking procedure enables additional differentiation among state-of-the-art object classifiers in terms of their ability to handle missing content and insufficient object detail. Given this capability for additional differentiation, our approach can potentially supplement existing benchmarking procedures used in object recognition challenge leaderboards.Comment: Extended version of our ACCV-2016 paper. Author formatting modifie