real life triplet fir fox chemotherapy in first line metastatic pancreatic ductal adenocarcinoma recommended schedule for expected activity and safety and phase ii study

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Bag-and-Dump: Design and Evaluation of a User Interface for manipulating items across multiple contexts.

The copy-and-paste paradigm is a fundamental operation in graphical user interfaces. However, existing copy-and-paste techniques have limitations, in particular in terms of efficiency and robustness against interruptions. This thesis is focusing on improving the user interface used to copy-and-paste objects across different contexts, such as a series folders. To improve this fundamental operation, a new copy-and-paste technique, called Bag-and-Dump, is proposed, implemented and evaluated. Bag-and-Dump aims to substantially reduce mouse movement by allowing the user to gather up (‘bag’) source data across different folders before ‘dumping’ the whole load at the destination. Additionally, Bag-and-Dump provides constant visual feedback in the form of a bag-like semantic cursor to increase robustness against interruptions. Bag-and-Dump was eval- uated against two standard copy-and-paste techniques (Keyboard Shortcuts and Drag-and-Drop) under a different number of contexts (folders) and with and without inter- ruptions. Results from the experiment not only showed that Bag-and-Dump indeed significantly reduces mouse movement, it also confirmed that Bag-and-Dump was 9% faster than Keyboard Shortcuts, one of the most popular copy-paste techniques among “expert users”

Acute Surgical Pulmonary Embolectomy: A 9-Year Retrospective Analysis

Acute pulmonary embolism is a substantial cause of morbidity and death. Although the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines recommend surgical pulmonary embolectomy in patients with acute pulmonary embolism associated with hypotension, there are few reports of 30-day mortality rates. We performed a retrospective review of acute pulmonary embolectomy procedures performed in 96 consecutive patients who had severe, globally hypokinetic right ventricular dysfunction as determined by transthoracic echocardiography. Data on patients who were treated from January 2003 through December 2011 were derived from health system databases of the New York State Cardiac Surgery Reporting System and the Society of Thoracic Surgeons. The data represent procedures performed at 3 tertiary care facilities within a large health system operating in the New York City metropolitan area. The overall 30-day mortality rate was 4.2%. Most patients (68 [73.9%]) were discharged home or to rehabilitation facilities (23 [25%]). Hemodynamically stable patients with severe, globally hypokinetic right ventricular dysfunction had a 30-day mortality rate of 1.4%, with a postoperative mean length of stay of 9.1 days. Comparable findings for hemodynamically unstable patients were 12.5% and 13.4 days, respectively. Acute pulmonary embolectomy can be a viable procedure for patients with severe, globally hypokinetic right ventricular dysfunction, with or without hemodynamic compromise; however, caution is warranted. Our outcomes might be dependent upon institutional capability, experience, surgical ability, and careful patient selection

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. Methods: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. Findings: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4–7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80–1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86–1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). Interpretation: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. Funding: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London

Community-based distributive medical education: Advantaging society

This paper presents a narrative summary of an increasingly important trend in medical education by addressing the merits of community-based distributive medical education (CBDME). This is a relatively new and compelling model for teaching and training physicians in a manner that may better meet societal needs and expectations. Issues and trends regarding the growing shortage and imbalanced distribution of physicians in the USA are addressed, including the role of international medical graduates. A historical overview of costs and funding sources for medical education is presented, as well as initiatives to increase the training and placement of physicians cost-effectively through new and expanded medical schools, two- and four-year regional or branch campuses and CBDME. Our research confirms that although medical schools have responded to Association of American Medical Colleges calls for higher student enrollment and societal concerns about the distribution and placement of physicians, significant opportunities for improvement remain. Finally, the authors recommend further research be conducted to guide policy on incentives for physicians to locate in underserved communities, and determine the cost-effectiveness of the CBDME model in both the near and long terms

Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer

Hypoxia-inducible genes have been linked to the aggressive phenotype of cancer. However, nearly all work on hypoxia-regulated genes has been conducted in vitro on cell lines. We investigated the hypoxia transcriptome in primary human bladder cancer using cDNA microarrays to compare genes induced by hypoxia in vitro in bladder cancer cell line EJ28 with genes upregulated in 39 bladder tumour specimens (27 superficial and 12 invasive). We correlated array mRNA fold changes with carbonic anhydrase 9 (CA IX) staining of tumours as a surrogate marker of hypoxia. Of 6000 genes, 32 were hypoxia inducible in vitro more than two-fold, five of which were novel, including lactate transporter SLC16A3 and RNAse 4. Eight of 32 hypoxia-inducible genes in vitro were also upregulated on the vivo array. Vascular endothelial growth factor mRNA was upregulated two-fold by hypoxia and 2–18-fold in 31 out of 39 tumours. Glucose transporter 1 was also upregulated on both arrays mRNA, and fold changes on the in vivo array significantly correlated with CA IX staining of tumours (P=0.008). However, insulin-like growth factor binding protein 3 mRNA was the most strongly differentially expressed gene in both arrays and this confirmed its upregulation in urine of bladder cancer patients (n=157, P<0.01). This study defines genes suitable for an in vivo hypoxia ‘profile', shows the heterogeneity of the hypoxia response and describes new hypoxia-regulated genes