Drug discovery in advanced prostate cancer: translating biology into therapy.

Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs

613 cases of splenic rupture without risk factors or previously diagnosed disease: a systematic review

Background Rupture of the spleen in the absence of trauma or previously diagnosed disease is largely ignored in the emergency literature and is often not documented as such in journals from other fields. We have conducted a systematic review of the literature to highlight the surprisingly frequent occurrence of this phenomenon and to document the diversity of diseases that can present in this fashion. Methods Systematic review of English and French language publications catalogued in Pubmed, Embase and CINAHL between 1950 and 2011. Results We found 613 cases of splenic rupture meeting the criteria above, 327 of which occurred as the presenting complaint of an underlying disease and 112 of which occurred following a medical procedure. Rupture appeared to occur spontaneously in histologically normal (but not necessarily normal size) spleens in 35 cases and after minor trauma in 23 cases. Medications were implicated in 47 cases, a splenic or adjacent anatomical abnormality in 31 cases and pregnancy or its complications in 38 cases. The most common associated diseases were infectious (n = 143), haematologic (n = 84) and non-haematologic neoplasms (n = 48). Amyloidosis (n = 24), internal trauma such as cough or vomiting (n = 17) and rheumatologic diseases (n = 10) are less frequently reported. Colonoscopy (n = 87) was the procedure reported most frequently as a cause of rupture. The anatomic abnormalities associated with rupture include splenic cysts (n = 6), infarction (n = 6) and hamartomata (n = 5). Medications associated with rupture include anticoagulants (n = 21), thrombolytics (n = 13) and recombinant G-CSF (n = 10). Other causes or associations reported very infrequently include other endoscopy, pulmonary, cardiac or abdominal surgery, hysterectomy, peliosis, empyema, remote pancreato-renal transplant, thrombosed splenic vein, hemangiomata, pancreatic pseudocysts, splenic artery aneurysm, cholesterol embolism, splenic granuloma, congenital diaphragmatic hernia, rib exostosis, pancreatitis, Gaucher's disease, Wilson's disease, pheochromocytoma, afibrinogenemia and ruptured ectopic pregnancy. Conclusions Emergency physicians should be attuned to the fact that rupture of the spleen can occur in the absence of major trauma or previously diagnosed splenic disease. The occurrence of such a rupture is likely to be the manifesting complaint of an underlying disease. Furthermore, colonoscopy should be more widely documented as a cause of splenic rupture

The anatomy of digital trade infrastructures

In global supply chains information about transactions resides in fragmented pockets within business and government systems. The lack of reliable, accurate and complete information makes it hard to detect risks (such as safety, security, compliance, commercial) and at the same time makes international trade inefficient. The introduction of digital infrastructures that transcend organizational and systems domains is driven by the prospect of reducing information fragmentation, thereby enabling improved security and efficiency in trade process. The potential of such digital trade infrastructures has been showcased in demonstrator settings, but in practice adoption and growth has been slow. In order to understand the problem at hand and build cumulative knowledge about its resolution, we need a way to conceptualize the different infrastructure initiatives. This paper therefore develops the Digital Trade Infrastructure Framework that aims to identify the structural components (anatomy) of the digital infrastructures in the trade area. The framework is developed through an empirically grounded analysis of four digital infrastructures in the trade domain within the conceptual lens of digital infrastructure. The framework can be used to position digital trade infrastructure initiatives to allow for cumulative knowledge building about its challenges as well as to articulate forward-looking agendas covering to development of instruments to oversee its resolution.Information and Communication Technolog

The anatomy of digital trade infrastructures

In global supply chains information about transactions resides in fragmented pockets within business and government systems. The introduction of digital trade infrastructures (DTI) that transcend organizational and systems domains is driven by the prospect of reducing this information fragmentation, thereby enabling improved security and efficiency in trade process. To understand the problem at hand and build cumulative knowledge about its resolution a way to conceptualize the different digital trade infrastructure initiatives is needed. This paper develops the Digital Trade Infrastructure Framework that identifies its structural components.Information and Communication Technolog