Utilitarian Cops: Jeremy Bentham and The Rise of Modern Policing

It is widely accepted that modern policing first came into existence with a bill passed in 1829, establishing the Metropolitan London Police under British Home Secretary Sir Robert Peel. It is Peel after all, who has been labeled the founder of modern policing, an English institution that inspired North American police. I argue that it was Jeremy Bentham who developed an early model of modern policing and whose work on applying his utilitarian philosophy to institutional reform directly influenced Peel’s innovation. I intend to show how Bentham and reformer Patrick Colquhoun established the first modern police department when they collaborated in drafting the Thames River Police Bill adopted by Parliament in 1800, almost thirty years before Peel’s legislation. It is the Thames River Police created by Bentham and Colquhoun that is the world’s oldest, not the Metropolitan London Police introduced by Peel. John Stuart Mill once wrote that Bentham was a great subversive. And as the great subversive whose years of work on improving police was often done in secret and whose efforts were largely ignored, it is Bentham not Peel, who should be considered the single most important figure in the development of modern policing

Improving the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration using microRNAs

Comment on: A microRNA-based test improves endoscopic ultrasound-guided cytologic diagnosis of pancreatic cancer

Targeting EZH2-mediated methylation of H3K27 inhibits proliferation and migration of Synovial Sarcoma in vitro.

Synovial sarcoma is an aggressive soft tissue sarcoma genetically defined by the fusion oncogene SS18-SSX. It is hypothesized that either SS18-SSX disrupts SWI/SNF complex inhibition of the polycomb complex 2 (PRC2) methyltransferase Enhancer of Zeste Homologue 2 (EZH2), or that SS18-SSX is able to directly recruit PRC2 to aberrantly silence target genes. This is of potential therapeutic value as several EZH2 small molecule inhibitors are entering early phase clinical trials. In this study, we first confirmed EZH2 expression in the 76% of human synovial sarcoma samples. We subsequently investigated EZH2 as a therapeutic target in synovial sarcoma in vitro. Knockdown of EZH2 by shRNA or siRNA resulted in inhibition of cell growth and migration across a series of synovial sarcoma cell lines. The EZH2 selective small-molecule inhibitor EPZ005687 similarly suppressed cell proliferation and migration. These data support the hypothesis that targeting EZH2 may be a promising therapeutic strategy in the treatment of synovial sarcoma; clinical trials are initiating enrollment currently

Obscure Overt Gastrointestinal Bleeding Due To Isolated Small Bowel Angiomatosis

Isolated small bowel angiomatosis is a rare entity with a distinctive endoscopic appearance. A multidisciplinary approach is often required to diagnose and treat these complex lesions. We present 2 cases of isolated small bowel angiomatosis, and illustrate the endoscopic findings that may guide similar diagnoses

Multimodality local ablative therapy of 23 lung metastases with surgical resection and percutaneous cryoablation in a patient with Li-Fraumeni Syndrome: A case report

Patients with Li-Fraumeni syndrome (LFS) are prone to develop a variety of malignancies due to insufficient activity of the encoded tumor suppressor protein P53, including adrenocortical carcinoma, breast cancer, lung cancer, pancreatic cancer, and sarcoma. In the setting of LFS, local treatment options for lung metastases are limited to surgery and thermal ablation since radiotherapy and some systemic therapies predispose patients to additional future malignancies. We present the case of a 45-year-old woman with LFS with leiomyosarcoma metastases to both lungs who underwent bilateral wedge resections to treat a total of eight lung metastases followed by six percutaneous cryoablation sessions to treat 15 additional lung metastases over a period of 24 months. Our case demonstrates the option of multimodal local ablative therapies for lung metastases in patients with LFS, including percutaneous cryoablation

Synergistic effects of targeted PI3K signaling inhibition and chemotherapy in liposarcoma.

While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%). No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma

Prognostic Factors in Dedifferentiated Chondrosarcoma: A Retrospective Analysis of a Large Series Treated at a Single Institution.

Background:Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. Methods:In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors. Results:Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis. Conclusions:The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients