Reply to M. Horiguchi et al

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Big Ideas paper: Policy-driven middleware for a legally-compliant Internet of Things.

Internet of Things (IoT) applications, systems and services are subject to law. We argue that for the IoT to develop lawfully, there must be technical mechanisms that allow the enforcement of speci ed policy, such that systems align with legal realities. The audit of policy enforcement must assist the apportionment of liability, demonstrate compliance with regulation, and indicate whether policy correctly captures le- gal responsibilities. As both systems and obligations evolve dynamically, this cycle must be continuously maintained. This poses a huge challenge given the global scale of the IoT vision. The IoT entails dynamically creating new ser- vices through managed and exible data exchange . Data management is complex in this dynamic environment, given the need to both control and share information, often across federated domains of administration. We see middleware playing a key role in managing the IoT. Our vision is for a middleware-enforced, uni ed policy model that applies end-to-end, throughout the IoT. This is because policy cannot be bound to things, applications, or administrative domains, since functionality is the result of composition, with dynamically formed chains of data ows. We have investigated the use of Information Flow Control (IFC) to manage and audit data ows in cloud computing; a domain where trust can be well-founded, regulations are more mature and associated responsibilities clearer. We feel that IFC has great potential in the broader IoT context. However, the sheer scale and the dynamic, federated nature of the IoT pose a number of signi cant research challenges

Big Ideas paper: Policy-driven middleware for a legally-compliant Internet of Things.

Internet of Things (IoT) applications, systems and services are subject to law. We argue that for the IoT to develop lawfully, there must be technical mechanisms that allow the enforcement of speci ed policy, such that systems align with legal realities. The audit of policy enforcement must assist the apportionment of liability, demonstrate compliance with regulation, and indicate whether policy correctly captures le- gal responsibilities. As both systems and obligations evolve dynamically, this cycle must be continuously maintained. This poses a huge challenge given the global scale of the IoT vision. The IoT entails dynamically creating new ser- vices through managed and exible data exchange . Data management is complex in this dynamic environment, given the need to both control and share information, often across federated domains of administration. We see middleware playing a key role in managing the IoT. Our vision is for a middleware-enforced, uni ed policy model that applies end-to-end, throughout the IoT. This is because policy cannot be bound to things, applications, or administrative domains, since functionality is the result of composition, with dynamically formed chains of data ows. We have investigated the use of Information Flow Control (IFC) to manage and audit data ows in cloud computing; a domain where trust can be well-founded, regulations are more mature and associated responsibilities clearer. We feel that IFC has great potential in the broader IoT context. However, the sheer scale and the dynamic, federated nature of the IoT pose a number of signi cant research challenges.Engineering and Physical Sciences Research Council (Grant ID: EP/K011510 CloudSafetyNet: End-to-End Application Security in the Cloud), Microsoft (through the Microsoft Cloud Computing Research Centre

Patient needs in advanced Renal Cell Carcinoma: What are patients’ priorities and how well are we meeting them?

Treatment options and duration of therapy for patients with metastatic renal cell carcinoma (mRCC) have increased. Many patients now spend in excess of 2 years on active therapy. These patients’ needs, and the ability of health services to respond to them, are poorly understood. Ten patients living with mRCC for more than 2 years and treated with at least one targeted agent were selected at random from three hospitals in the United Kingdom (UK). One interviewer who was not involved in their care conducted in-depth interviews. Interview transcripts were analysed using Interpretative Phenomenological Analysis (IPA) to identify issues of greatest importance to patients, and to understand how well patients felt their needs were being addressed. Perceived delay in initial diagnosis was a major theme. Being told the truth about treatment side effects upfront was important, but was often at odds with perceived delivery. ‘Dealing with side effects’, understanding dose and its effects and not letting ‘negative thoughts get in’ were highlighted as important, but were highly personal to patients and areas where patients struggled. Concordance was observed with delivery of ‘a clear next step’ for treatment, timely access to drugs and guidance on a drug ‘holiday’. Patient experience of mRCC and its treatment requires a tailored approach. This research suggests there are key opportunities for service improvement and improved communication throughout the pathway to better meet the needs of patients, including non-clinical support to build personal resilience

Randomized phase II study investigating pazopanib versus weekly paclitaxel in relapsed or progressive urothelial cancer

Purpose: Two previous single-arm trials have drawn conflicting conclusions regarding the activity of pazopanib in urothelial cancers after failure of platinum-based chemotherapy. Patients and Methods: This randomized (1:1) open-label phase II trial compared the efficacy of pazopanib 800 mg orally with paclitaxel (80 mg/m2 days 1, 8, and 15 every 28 days) in the second-line setting. The primary end point was overall survival (OS). Results: Between August 2012 and October 2014, 131 patients, out of 140 planned, were randomly assigned. The study was terminated early on the recommendation of the independent data monitoring committee because of futility. Final analysis after the preplanned number of deaths (n = 110) occurred after a median follow-up of 18 months. One hundred fifteen deaths had occurred at the final data extract presented here. Median OS was 8.0 months for paclitaxel (80% CI, 6.9 to 9.7 months) and 4.7 months for pazopanib (80% CI, 4.2 to 6.4 months). The hazard ratio (HR) adjusted for baseline stratification factors was 1.28 (80% CI, 0.99 to 1.67; one-sided P = .89). Median progression-free survival was 4.1 months for paclitaxel (80% CI, 3.0 to 5.6 months) and 3.1 months for pazopanib (80% CI, 2.7 to 4.6 months; HR, 1.09; 80% CI, 0.85 to 1.40; one-sided P = .67). Discontinuations for toxicity occurred in 7.8% and 23.1% for paclitaxel and pazopanib, respectively. Conclusion: Pazopanib did not have greater efficacy than paclitaxel in the second-line treatment of urothelial cancers. There was a trend toward superior OS for paclitaxel

Accelerated BEP : a phase I trial of dose-dense BEP for intermediate and poor prognosis metastatic germ cell tumour

Background: We used bleomycin, etoposide, cisplatin (BEP), the most effective regimen in the treatment of germ cell tumours (GCTs) and increased dose-density by using pegfilgrastim to shorten cycle length. Our aim was to assess safety and tolerability. Methods: Sixteen male patients with intermediate or poor prognosis metastatic GCT were treated with four cycles of 3-day BEP with G-CSF on a 14-day cycle for a planned relative dose-density of 1.5 compared with standard BEP. Results: Eleven intermediate and five poor prognosis patients were treated. In all, 14 of 16 patients completed the study treatment. Toxicities were comparable to previous studies using standard BEP, except for mucositis and haematological toxicity that were more severe. The overall relative dose-density for all 16 patients was mean 1.38 (range 0.72–1.5; median 1.46). Complete response was achieved after chemotherapy alone in two patients (13%) and following chemotherapy plus surgery in nine additional patients (56%). Four patients (25%) had a partial response and normalised their marker levels. At a median follow-up of 4.4 years (range 2.1–6.8) the estimated 5-year progression-free survival probability is 81% (95% CI 64–100%). Conclusion: Accelerated BEP is tolerable without major additional toxicity. A randomised controlled trial will be required to obtain comparative efficacy data