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PURPOSE Clinical stage I (CSI) nonseminoma (NS) is a disease limited to the testis without metastases. One treatment strategy after orchiectomy is adjuvant chemotherapy. Little is known about the outcome of patients who experience relapse after such treatment. PATIENTS AND METHODS Data from 51 patients with CSI NS who experienced a relapse after adjuvant bleomycin, etoposide, and cisplatin (BEP) from 18 centers/11 countries were collected and retrospectively analyzed. Primary outcomes were overall and progression-free survivals calculated from day 1 of treatment at first relapse. Secondary outcomes were time to, stage at, and treatment of relapse and rate of subsequent relapses. RESULTS Median time to relapse was 13 months, with the earliest relapse 2 months after start of adjuvant treatment and the latest after 25 years. With a median follow-up of 96 months, the 5-year PFS was 67% (95% CI, 54% to 82%) and the 5-year OS was 81% (95% CI, 70% to 94%). Overall, 19 (37%) of 51 relapses occurred later than 2 years. Late relapses were associated with a significantly higher risk of death from NS (hazard ratio, 1.10 per year; P = .01). Treatment upon relapse was diverse: the majority of patients received a combination of chemotherapy and surgery. Twenty-nine percent of patients experienced a subsequent relapse. At last followup, 41 patients (80%) were alive and disease-free, eight (16%) had died of progressive disease, and one patient (2%) each had died from therapy-related or other causes. CONCLUSION Outcomes of patients with relapse after adjuvant BEP seem better compared with patients who experience relapse after treatment of metastatic disease but worse compared with those who have de-novo metastatic disease. We found a substantial rate of late and subsequent relapses. There seem to be three patterns of relapse with different outcomes: pure teratoma, early viable NS relapse (, 2 years), and late viable NS relapse (. 2 years). © 2019 by American Society of Clinical Oncology

By storing data about citizens for the purposes of service provision, private and public organizations have disempowered the people they serve, shifting the balance of power toward themselves as data holders. Through three co-production engagements involving families receiving "early help" support from their local authority and support workers involved in supplying this care, we have identified existing data usage practices, explored the impact of those practices upon the supported families, and co-designed new and improved approaches - both technological and practice-based - that are perceived to offer families fairer treatment, greater influence, and to benefit from better decision-making. Our findings show that by applying Human-Data Interaction and giving supported families direct access to see and manipulate their own data, both during and outside of the support engagement, the locus of decision-making could be shifted towards the data subject.

A newly supplied 80 × 80 chromium compensated GaAs sensor with a matrix of 80 × 80 pixels on a 250 μ m pixel pitch has been characterised utilising microbeam mapping techniques at the Diamond Light Source. The GaAs:Cr sensor was mounted to a HEXITEC DAQ system before raster scanning an X-ray beam with area 25 × 25 μ m 2 in steps of 25 μ m, providing sub-pixel resolution spectroscopic imaging. Scans were performed with incident X-ray energies ranging from 12 to 45 keV. Following processing of the data in MatLab 2019b an analysis of defects previously observed in etched GaAs wafers occurred. Findings indicate the presence of regions with reduced charge collection efficiency where up to 88% of incident events show significant charge loss, and changing charge carrier lifetimes across the sensor.

HR GaAs:Cr is a well known material, used for room-temperature X-ray detector applications. While GaAs:Cr detectors have typically shown good performance at 25oC, there may be benefits of running the detector at lower temperatures where leakage currents are lower. The aim of this study was to evaluate the energy resolution across the temperature range −10oC to 30oC which is easily achievable using compact electrical cooling solutions. Using HR GaAs:Cr detectors that were flip-chip-bonded to STFC's PIXIE ASIC, it was possible to measure the spectroscopic performance of the material as a function of temperature. Both HR GaAs:Cr sensors were of 500 μm thickness and mobility-lifetime products measured at room temperature comprised 0.5⋅10−4 and 1.7⋅10−4 cm2V−1 for sensors dated from 2016 and 2018, respectively. Using an 241Am sealed source, pulse height spectra were measured for pixel arrays with pitches of 250 and 500 μm for temperatures in the range -10oC to 30oC. By varying the operating voltage of the detectors it was also possible to study the variation in the charge transport properties of the HR GaAs:Cr over the same temperature range.

Across social care, healthcare and public policy, enabled by the "big data" revolution (which has normalized large-scale data-based decision-making), there are moves to "join up" citizen databases to provide care workers with holistic views of families they support. In this context, questions of personal data privacy, security, access, control and (dis-)empowerment are critical considerations for system designers and policy makers alike. To explore the family perspective on this landscape of what we call Family Civic Data, we carried out ethnographic interviews with four North-East families. Our design-game-based interviews were effective for engaging both adults and children to talk about the impact of this dry, technical topic on their lives. Our findings, delivered in the form of design guidelines, show support for dynamic consent: families would feel most empowered if involved in an ongoing co-operative relationship with state welfare and civic authorities through shared interaction with their data.

Bladder cancer is a disease of the elderly. Older patients might potentially be undertreated due to assumptions about benefit versus risk. Our objective was to determine outcomes in older patients receiving neoadjuvant chemotherapy for muscle-invasive bladder cancer (MIBC). We hypothesised that appropriately selected elderly patients (≥70 years) with MIBC could have similar clinical outcomes, and be safely treated, with standard neoadjuvant chemotherapy prior to definitive cystectomy or radiotherapy. We utilised a single institution case series analysis of patients with T2-4a N0 M0 transitional cell carcinoma of the bladder treated with cisplatin-based neoadjuvant chemotherapy between 2005 and 2011. Eighty-three patients were eligible. Median age was 68 (range 48-80), 33 patients (40%) were ≥70 years. Overall survival at 3 years was 65.8% (≥70) and 63.2% (70) (P = 0.653), relapse-free survival at 3 years was 61.6% and 54.8% respectively (P = 0.471). The rates going forward to definitive local therapy (87.9% ≥ 70 and 84.0%70) and the pathological complete response rate (31.3% ≥ 70 and 40%70) were similar. Disease relapse rate was also similar (63.6% ≥ 70 vs. 60%70, P = 0.906). Elderly patients with good functional status and limited comorbidities diagnosed with MIBC receiving standard neoadjuvant chemotherapy followed by cystectomy or radiotherapy can have similar clinical outcomes as their younger counterparts. Prospective studies evaluating the optimum curative management in this elderly population are warranted.

The Cloud provides impartial access to computer services on a pay-per-use basis, a fact that has encouraged many researchers to adopt the Cloud for the processing of large computational jobs and data storage. It has been used in the past for single research endeavours or as a mechanism for coping with excessive load on conventional computational resources (clusters). In this paper we investigate, through the use of simulation, the applicability of running an entire computer cluster on the Cloud. We investigate a number of policy decisions which can be applied to such a virtual cluster to reduce the running cost and the effect these policies have on the users of the cluster. We go further to compare the cost of running the same workload both on the Cloud and on an existing campus cluster of non-dedicated resources. We simulate a Cluster computer running on the Cloud.We compare this to a Cluster running on Campus.We show that the cost of running a Cloud Cluster is inversely related to the make-span of work on the cluster.We compare the cost of using Cloud vs local clusters.

Although it has long been realized that ACID (atomicity, consistency, isolation, durability) transactions by themselves are not adequate for structuring long-lived applications and much research work has been done on developing specific extended transaction models, no middleware support for building extended transactions is currently available and the situation remains that a programmer often has to develop application specific mechanisms. The CORBA Activity Service Framework described in this paper is a way out of this situation. The design of the service is based on the insight that the various extended transaction models can be supported by providing a general purpose event signalling mechanism that can be programmed to enable activities--application specific units of computations--to coordinate each other in a manner prescribed by the model under consideration. The different extended transaction models can be mapped onto specific implementations of this framework, permitting such transactions to span a network of systems connected indirectly by some distribution infrastructure. The framework described in this paper is an overview of the OMG's (Object Management Group) Additional Structuring Mechanisms for the OTS standard. Through a number of examples the paper shows that the framework has the flexibility to support a wide variety of extended transaction models. Although the framework is presented here in CORBA specific terms, the main ideas are sufficiently general, so that it should be possible to use them in conjunction with other middleware.

Building a software service requires careful analysis of the requirements given by the customer for the system. It is often difficult to understand the system requirements correctly, due to the fact that they are usually described in plain language. This difficulty could be overcome if a sufficiently precise description of system services to be provided can be produced that is easy to follow by both customers and designers. Given such a specification of a service that on the surface permits several ways of implementing it, the design team should be able to select with reasonable confidence, the most appropriate set of design options, before commencing the building of the service. Naturally, this requires the development of modelling and analysis techniques that enable the evaluation of various design options for a given service. As a first step towards achieving these goals, the paper briefly reviews current approaches to specifying system architectures and explores the suitability of the Unified Modelling Language (UML) as a specification tool.

Exploiting computational resources within an organisation for more than their primary task offers great benefits -- making better use of capital expenditure and provides a pool of computational power. This can be achieved through the deployment of a cycle stealing distributed system, where tasks execute during the idle time on computers. However, if a task has not completed when a computer returns to its primary function the task will be preempted, wasting time (and energy), and is often reallocated to a new resource in an attempt to complete. This becomes exacerbated when tasks are incapable of completing due to excessive execution time or faulty hardware / software, leading to a situation where tasks are perpetually reallocated between computers -- wasting time and energy. In this work we investigate techniques to increase the chance of `good' tasks completing whilst curtailing the execution of `bad' tasks. We demonstrate, through simulation, that we could have reduce the energy consumption of our cycle stealing system by approximately 50%.

Advances in Cloud computing are making it possible for service providers to offer computational resources such as storage and compute power (infrastructure as a service, IaaS) to sophisticated enterprise application services (software as a service SaaS) to remote clients for a fee on a highly dynamic basis. As in any business transaction, client access to a service is regulated by a legal Service Agreement (SA). A service agreement needs to be negotiated and agreed between the provider and the client before the latter can use the service. Then on, both the client and the provider will need assurances that service interactions are in accordance with the SA, and any violations are detected and their causes identified. There is thus a need for automated support for negotiation and enforcement of service agreements. This paper discusses key design issues for such a system, of which the main one is to ensure that the policies (termed also clauses) contained in an SA are logically sound and that they work in harmony with any private policies of the client and the provider. The paper presents an architecture and a proof of concept implementation.

Reduction of power consumption for any computer system is now an important issue, although this should be done in a manner that is not detrimental to the user base. We present a number of policies that can be applied to multi-use clusters where computers are shared between interactive users and high-throughput computing. We evaluate policies by trace-driven simulations in order to determine the effects on power consumed and impact on high-throughput users. We demonstrate that these policies could save ~60% more energy for the high-throughput jobs over our current cluster policies.

There is a growing tension within large organisations such as universities between the desire to perform vast amounts of computational processing and the desire to reduce power consumption by switching off computers. This situation will only worsen as computational problems get larger and the desire to save energy escalates. Through careful management of computing resources it is possible to maximise effective computer usage whilst minimising power consumption though this can be costly in terms of human effort. We present our work with the Agility Cloud Computing Platform to provide intelligent control over a University-wide Condor system, which works to reduce power consumption without adversely affecting the Condor users. This system also provides auditing of the power usage, which can be used to determine the power efficiency of the Condor system.

Service providers are looking to computer vendors to provide low-cost, scalable faulttolerant solutions. The prime requirement is to minimise reliance on specialist equipment and techniques for delivering core services. Indeed, an ideal solution would make use of ‘standard’' middleware services (e.g., CORBA services for persistence, transactions etc.). Research results on distributed objects and software implemented fault-tolerance techniques hold the promise of providing such solutions. However, the task of constructing such solutions using general-purpose, low cost components, such as commodity UNIX servers, middleware services etc. is extremely challenging. The central problem is that any software implemented distributed fault-tolerance technique consumes resources (a combination of network bandwidth, processing power and disk storage) that otherwise would be available for normal use. Thus software implemented distributed fault-tolerance techniques must be applied with care. In this tutorial, we will cover basic principles of software implemented fault-tolerance techniques and discuss their application in the construction of reliable distributed applications. Emphasis will be placed on applications in the Internet/Web domain. Mark Little is a Distinguished Engineer/Architect, within HP Arjuna Labs., Newcastle upon Tyne,England, where he leads the Total-e-Transactions team. He joined HP via a series of company acquisitions: Bluestone Software, Arjuna Solutions, of which he was one of the founders. Before joining Arjuna Solutions he was for over 10 years a member of the Arjuna team within the University of Newcastle upon Tyne (where he continues to have a Visiting Fellowship). His research within the Arjuna team included replication and transactions support, which include the construction of an OTS/JTS compliant transaction processing system. Santosh Shrivastava was appointed a Professor of Computing Science, University of Newcastle upon Tyne in 1986; he leads the Distributed Systems Research Group. He received his Ph.D. in computing science from Cambridge in 1975. His research interests are in the areas of distributed systems, real-time systems, fault tolerance and application of transaction and workflow technologies to e-commerce. His group is well known as the developers of an innovative distributed transaction system, called Arjuna and a CORBA based dependable workflow system for the Internet. Together with his colleagues he set Proceedings of the Third International Symposium on Distributed-Objects and Applications (DOA’01) 0-7695-1300-X/01 $10.00 © 2001 IEEE up Arjuna Solutions Ltd in 1998 in Newcastle to productise Arjuna transaction and workflow technologies. The company is now part of Hewlett-Packard. Stuart Wheater is a Distinguished Engineer/Architect, within HP Arjuna Labs., Newcastle upon Tyne, England. He joined HP via a series of company acquisitions: Bluestone Software, Arjuna Solutions, of which he was one of the founders. Before joining Arjuna Solutions he was for over 10 years a member of the Arjuna team within the University of Newcastle upon Tyne (where he continues to have a Visiting Fellowship). His research within the Arjuna team included transactions and long-lived process support, which includes the construction of a CORBA based transactional workflow system. Proceedings of the Third International Symposium on Distributed-Objects and Applications (DOA’01) 0-7695-1300-X/01 $10.00 © 2001 IEEE

Organisations increasingly use the Internet to offer their own services and to utilise the services of others. This naturally leads to information sharing across organisational boundaries. However, despite the requirement to share information, the autonomy and privacy requirements of organisations must not be compromised. This demands the strict policing of inter-organisational interactions. Thus there is a requirement for dependable mechanisms for information sharing between organisations that do not necessarily trust each other. The paper describes the design of a novel distributed object middleware that guarantees both safety and liveness in this context. The safety property ensures that local policies are not compromised despite failures and/or misbehaviour by other parties. The liveness property ensures that, if no party misbehaves, agreed interactions will take place despite a bounded number of temporary network and computer related failures. The paper describes a prototype implementation with example applications.

Enterprises increasingly use the Internet to offer their own services and to utilise the services of others. An extension of this trend is Internet-based collaboration to form virtual enterprises for the delivery of goods or services. Effective formation of a virtual enterprise will require information sharing across organisational boundaries. Despite the requirement to share information, the autonomy and privacy requirements of enterprises must not be compromised. This demands strict policing of inter-enterprise interactions, including non-repudiable access to shared information. For a member of a virtual enterprise, a typical requirement is the ability to inspect/modify shared information together with private information within a single ACID transaction. At the same time, inspection/modification of the shared information should both generate non-repudiation evidence and be consistent with inter-enterprise agreements. The paper describes how information sharing middleware can be enhanced with distributed transaction support to perform regulated transactional information sharing. Design and implementation of a prototype Java middleware is presented.

Software systems are typically composed of numerous components, each of which is responsible for a different function. Different implementations of a component may be possible, with each implementation tailored for a specific set of applications or environments. Being able to reconfigure software systems to make use of these different implementations with the minimum of effect on existing users and applications is desirable. Configurable software systems are also important for a number of other reasons: additional components or modifications to those currently available, may be required. For example, new versions of software components may be necessary due to the discovery of design flaws in a component; a RPC which provider unreliable message delivery may be suitable for an application in a local area network, but if the application is to be used in a wide area network, a different RPC implementation, which guarantees message delivery, may be necessary. Therefore, software is often required to be configurable, enabling modifications to occur with minimal effect on existing users. To allow this configurability, components should only be available through interfaces that are clearly separated from their implementations, allowing users to be isolated from any implementation changes. Object-oriented programming techniques offer a good basis upon which this separation can be provided. This paper describes a model for constructing configurable software based upon this separation, and illustrates this with a software development system.

Support for dynamic reconfiguration permitting changes to the structure of an application while it is in operation is becoming more and more important for distributed applications. One use of such a reconfiguration facility would be to dynamically change the structure of an application in order to improve its performance. In this paper we describe the design and implementation of a dynamic performance improvement scheme that is based on controlling clustering of persistent objects. Our scheme provides a means of dynamically reconfiguring storage structures of application objects, from no clustering (all objects treated as independent), to maximum clustering (all objects grouped together), including any intermediate level of clustering, to suit a given pattern of usage. >

In a distributed environment, it is inevitable that long-running applications will require support for dynamic reconfiguration because, for example, machines may fail, services may be moved or withdrawn and user requirements may change. In such an environment, it is essential that the structure of running applications can be modified to reflect such changes. A complication is that such long-running applications are frequently composed our of existing applications. The resulting application can be very complex in structure, containing many temporal dependencies between constituent applications. This paper describes an approach that supports the dynamic reconfiguration of large-scale distributed applications. An application composition and execution environment has been designed and implemented as a transactional workflow system that enables sets of inter-related tasks (applications) to be carried out and supervised in a dependable manner. A task model that is expressive enough to represent temporal dependencies between constituent tasks has been developed. The workflow system maintains this structure and makes it available through transactional operations for performing changes to it. Use of transactions ensure that changes can be carried out atomically with respect to running applications. The workflow system is general purpose and open: it has been designed and implemented as a set of CORBA services to run on top of a given ORB.

This paper describes the design of a scripting language aimed at expressing task (unit of computation) composition and inter-task dependencies of distributed applications whose execution could span arbitrary large durations. This work is motivated by the observation that an increasingly large number of distributed applications are constructed by composing them out of existing applications and are executed in an heterogeneous environment. The resulting applications can be very complex in structure, containing many notification and dataflow dependencies between their constituent applications. The language enables applications to be structured with the properties of modularity, interoperability, dynamic reconfigurability and fault-tolerance.

There are many reasons why applications may require configuration, however the one which dominates Java applications is that of security restrictions. Because an application may be provided different capabilities by different users, it becomes difficult to write "build-once, run-anywhere" applications. Insisting that all security sensitive applications execute within controlled or restricted environments may limit the types of application which can be built. Therefore, we describe how we have constructed a configuration infrastructure in Java which allows applications to dynamically adapt themselves to the types of security restrictions that exist when they are executed. Because the system does not change the language it is portable across Java implementations. We also describe how we have used this system to build a toolkit for the construction of electronic commerce applications, which allow atomic transactions to span Web browsers and servers.

Workflow management systems are required to provide flexible ways of managing workflows as the business processes they represent frequently require changes over time. Provision of flexibility features in workflow management systems is very much a research issue as workflow systems in use today have been found lacking in such features. Two approaches to achieving flexibility in workflows have been identified, namely flexibility by selection and flexibility by adaptation. Flexibility by selection is achieved by ensuring that there are a number of execution paths through the workflow process, such that key decision making points are well represented. This allows the appropriate path to be selected on a per-instance basis to take account of the prevailing circumstances. Flexibility by adaptation permits dynamic changes to workflows to include one or more new execution paths. The paper describes how flexibility is supported in the OPENflow distributed workflow system. In particular, it describes high level tool support for performing dynamic changes to a workflow. In OPENflow, dynamic reconfiguration mechanisms have been provided by making use of atomic transactions to add and remove one or more tasks and to allow the addition and removal of dependencies between tasks from a running workflow. Use of transactions ensures that changes are carried out atomically with respect to normal processing. An example application is described to illustrate flexible workflow management.

Practical experience indicates that the definition of real-world workflow applications is a complex and error-prone process. Existing workflow management systems provide the means, in the best case, for very primitive syntactic verification, which is not enough to guarantee the overall correctness and robustness of workflow applications. The paper presents an approach for formal verification of workflow schemas (definitions). Workflow behaviour is modelled by means of an automata-based method, which facilitates exhaustive compositional reachability analysis. The workflow behaviour can then be analysed and checked for safety and liveness properties. The model generation and the analysis procedure are governed by well-defined rules that can be fully automated. Therefore, the approach is accessible by designers who are not experts in formal methods.

The design and implementation of a dependable system that provides a composition and execution environment for distributed applications whose executions could span arbitrarily large durations is described. The objective is to create a framework for complex service provisioning. By complex service provisioning we primarily mean the ability to compose a given service out of existing ones as well as the ability to exercise dynamic control over the execution of the service. The approach taken is centred around building middleware services based on integration of workflow and agent technologies. The platform enables these two systems to interact via CORBA services. Service behaviour and service deployment are represented as workflow processes. Individual tasks that make up the workflow would be legacy applications, specially created tasks, and agent applications. Agents are able to create workflow instances, receive results from workflow and send inputs to workflows. This enables agents to act as user agents capable of managing workflows on behalf of users.

Although it has long been realised that ACID transactions by themselves are not adequate for structuring long-lived applications and much research work has been done on developing specific extended transaction models, no middleware support for building extended transactions is currently available and the situation remains that a programmer often has to develop application specific mechanisms. The CORBA Activity Service Framework described in this paper is a way out of this situation. The design of the service is based on the insight that the various extended transaction models can be supported by providing a general purpose event signalling mechanism that can be programmed to enable activities — application specific units of computations — to coordinate each other in a manner prescribed by the model under consideration. The different extended transaction models can be mapped onto specific implementations of this framework permitting such transactions to span a network of systems connected indirectly by some distribution infrastructure. The framework described in this paper is an overview the OMG’s Additional Structuring Mechanisms for the OTS standard now reaching completion. Through a number of examples the paper shows that the Framework has the flexibility to support a wide variety of extended transaction models. Although the framework is presented here in CORBA specific terms, the main ideas are sufficiently general, so that it should be possible to use them in conjunction with other middleware.

The paper describes an application composition and execution environment implemented as a transactional workflow system that enables sets of inter-related tasks to be carried out and supervised in a dependable manner. The paper describes how the system meets the requirements of interoperability, scalability, flexible task composition, dependability and dynamic reconfiguration. The system is general purpose and open: it has been designed and implemented as a set of CORBA services. The system serves as an example of the use of middleware technologies to provide a fault-tolerant execution environment for long running distributed applications.