Graded Exercise Therapy Guided Self-Help Trial for Patients with Chronic Fatigue Syndrome (GETSET): Protocol for a Randomized Controlled Trial and Interview Study

Background: Chronic fatigue syndrome, also known as myalgic encephalomyelitis (CFS/ME), is characterized by chronic disabling fatigue and other symptoms, which are not explained by an alternative diagnosis. Previous trials have suggested that graded exercise therapy (GET) is an effective and safe treatment. GET itself is therapist-intensive with limited availability. Objective: While guided self-help based on cognitive behavior therapy appears helpful to patients, Guided graded Exercise Self-help (GES) is yet to be tested. Methods: This pragmatic randomized controlled trial is set within 2 specialist CFS/ME services in the South of England. Adults attending secondary care clinics with National Institute for Health and Clinical Excellence (NICE)-defined CFS/ME (N=218) will be randomly allocated to specialist medical care (SMC) or SMC plus GES while on a waiting list for therapist-delivered rehabilitation. GES will consist of a structured booklet describing a 6-step graded exercise program, supported by up to 4 face-to-face/telephone/Skype™ consultations with a GES-trained physiotherapist (no more than 90 minutes in total) over 8 weeks. The primary outcomes at 12-weeks after randomization will be physical function (SF-36 physical functioning subscale) and fatigue (Chalder Fatigue Questionnaire). Secondary outcomes will include healthcare costs, adverse outcomes, and self-rated global impression change scores. We will follow up all participants until 1 year after randomization. We will also undertake qualitative interviews of a sample of participants who received GES, looking at perceptions and experiences of those who improved and worsened. Results: The project was funded in 2011 and enrolment was completed in December 2014, with follow-up completed in March 2016. Data analysis is currently underway and the first results are expected to be submitted soon. Conclusions: This study will indicate whether adding GES to SMC will benefit patients who often spend many months waiting for rehabilitative therapy with little or no improvement being made during that time. The study will indicate whether this type of guided self-management is cost-effective and safe. If this trial shows GES to be acceptable, safe, and comparatively effective, the GES booklet could be made available on the Internet as a practitioner and therapist resource for clinics to recommend, with the caveat that patients also be supported with guidance from a trained physiotherapist. The pragmatic approach in this trial means that GES findings will be generalizable to usual National Health Service (NHS) practice.

Effectiveness and Cost-effectiveness of Outpatient Physiotherapy After Knee Replacement for Osteoarthritis: Study Protocol for a Randomised Controlled Trial

Background: Primary total knee replacement is a common operation that is performed to provide pain relief and restore functional ability. Inpatient physiotherapy is routinely provided after surgery to enhance recovery prior to hospital discharge. However, international variation exists in the provision of outpatient physiotherapy after hospital discharge. While evidence indicates that outpatient physiotherapy can improve short-term function, the longer term benefits are unknown. The aim of this randomised controlled trial is to evaluate the long-term clinical effectiveness and cost-effectiveness of a 6-week group-based outpatient physiotherapy intervention following knee replacement. Methods/design: Two hundred and fifty-six patients waiting for knee replacement because of osteoarthritis will be recruited from two orthopaedic centres. Participants randomised to the usual-care group (n = 128) will be given a booklet about exercise and referred for physiotherapy if deemed appropriate by the clinical care team. The intervention group (n = 128) will receive the same usual care and additionally be invited to attend a group-based outpatient physiotherapy class starting 6 weeks after surgery. The 1-hour class will be run on a weekly basis over 6 weeks and will involve task-orientated and individualised exercises. The primary outcome will be the Lower Extremity Functional Scale at 12 months post-operative. Secondary outcomes include: quality of life, knee pain and function, depression, anxiety and satisfaction. Data collection will be by questionnaire prior to surgery and 3, 6 and 12 months after surgery and will include a resource-use questionnaire to enable a trial-based economic evaluation. Trial participation and satisfaction with the classes will be evaluated through structured telephone interviews. The primary statistical and economic analyses will be conducted on an intention-to-treat basis with and without imputation of missing data. The primary economic result will estimate the incremental cost per quality-adjusted life year gained from this intervention from a National Health Services (NHS) and personal social services perspective. Discussion: This research aims to benefit patients and the NHS by providing evidence on the long-term effectiveness and cost-effectiveness of outpatient physiotherapy after knee replacement. If the intervention is found to be effective and cost-effective, implementation into clinical practice could lead to improvement in patients’ outcomes and improved health care resource efficiency.

Street lighting mesh network protocol

The digital revolution of the 21st century contributed to stem the Internet of Things (IoT). Trillions of embedded devices using the Internet Protocol (IP), also called smart objects, will be an integral part of the Internet. In order to support such an extremely large address space, a new Internet Protocol, called Internet Protocol Version 6 (IPv6) is being adopted. The IPv6 over Low Power Wireless Personal Area Networks (6LoWPAN) has accelerated the integration of WSNs into the Internet. At the same time, the Constrained Application Protocol (CoAP) has made it possible to provide resource constrained devices with RESTful Web services functionalities. This work builds upon previous experience in street lighting networks, for which a proprietary protocol, devised by the Lighting Living Lab, was implemented and used for several years. The proprietary protocol runs on a broad range of lighting control boards. In order to support heterogeneous applications with more demanding communication requirements and to improve the application development process, it was decided to port the Contiki OS to the four channel LED driver (4LD) board from Globaltronic. This thesis describes the work done to adapt the Contiki OS to support the Microchip TM PIC24FJ128GA308 microprocessor and presents an IP based solution to integrate sensors and actuators in smart lighting applications. Besides detailing the system’s architecture and implementation, this thesis presents multiple results showing that the performance of CoAP based resource retrievals in constrained nodes is adequate for supporting networking services in street lighting networks.

Selecting candidate predictor variables for the modelling of post-discharge mortality from sepsis: a protocol development project.

Background: Post-discharge mortality is a frequent but poorly recognized contributor to child mortality in resource limited countries. The identification of children at high risk for post-discharge mortality is a critically important first step in addressing this problem. Objectives: The objective of this project was to determine the variables most likely to be associated with post-discharge mortality which are to be included in a prediction modelling study. Methods: A two-round modified Delphi process was completed for the review of a priori selected variables and selection of new variables. Variables were evaluated on relevance according to (1) prediction (2) availability (3) cost and (4) time required for measurement. Participants included experts in a variety of relevant fields. Results: During the first round of the modified Delphi process, 23 experts evaluated 17 variables. Forty further variables were suggested and were reviewed during the second round by 12 experts. During the second round 16 additional variables were evaluated. Thirty unique variables were compiled for use in the prediction modelling study. Conclusion: A systematic approach was utilized to generate an optimal list of candidate predictor variables for the incorporation into a study on prediction of pediatric post-discharge mortality in a resource poor setting.

Interoperable Resource Brokering with Policy-based Provisioning and Job Allocation

The increasing needs for computational power in areas such as weather simulation, genomics or Internet applications have led to sharing of geographically distributed and heterogeneous resources from commercial data centers and scientific institutions. Research in the areas of utility, grid and cloud computing, together with improvements in network and hardware virtualization has resulted in methods to locate and use resources to rapidly provision virtual environments in a flexible manner, while lowering costs for consumers and providers. However, there is still a lack of methodologies to enable efficient and seamless sharing of resources among institutions. In this work, we concentrate in the problem of executing parallel scientific applications across distributed resources belonging to separate organizations. Our approach can be divided in three main points. First, we define and implement an interoperable grid protocol to distribute job workloads among partners with different middleware and execution resources. Second, we research and implement different policies for virtual resource provisioning and job-to-resource allocation, taking advantage of their cooperation to improve execution cost and performance. Third, we explore the consequences of on-demand provisioning and allocation in the problem of site-selection for the execution of parallel workloads, and propose new strategies to reduce job slowdown and overall cost.

WIPO and the Reinforcement of the Nagoya Protocol: Towards Effective Implementation of an Access and Benefit Sharing Regime for the Protection of Traditional Knowledge Associated with Genetic Resources

Traditional knowledge associated with genetic resources (TKaGRs) is acknowledged as a valuable resource. Its value draws from economic, social, cultural, and innovative uses. This value places TK at the heart of competing interests as between indigenous peoples who hold it and depend on it for their survival, and profitable industries which seek to exploit it in the global market space. The latter group seek, inter alia, to advance and maintain their global competitiveness by exploiting TKaGRs leads in their research and development activities connected with modern innovation. Biopiracy remains an issue of central concern to the developing world and has emerged in this context as a label for the inequity arising from the misappropriation of TKaGRs located in the South by commercial interests usually located in the North. Significant attention and resources are being channeled at global efforts to design and implement effective protection mechanisms for TKaGRs against the incidence of biopiracy. The emergence and recent entry into force of the Nagoya Protocol offers the latest example of a concluded multilateral effort in this regard. The Nagoya Protocol, adopted on the platform of the Convention on Biological Diversity (CBD), establishes an open-ended international access and benefit sharing (ABS) regime which is comprised of the Protocol as well as several complementary instruments. By focusing on the trans-regime nature of biopiracy, this thesis argues that the intellectual property (IP) system forms a central part of the problem of biopiracy, and so too to the very efforts to implement solutions, including through the Nagoya Protocol. The ongoing related work within the World Intellectual Property Organization (WIPO), aimed at developing an international instrument (or a series of instruments) to address the effective protection of TK, constitutes an essential complementary process to the Nagoya Protocol, and, as such, forms a fundamental element within the Nagoya Protocol’s evolving ABS regime-complex. By adopting a third world approach to international law, this thesis draws central significance from its reconceptualization of biopiracy as a trans-regime concept. By construing the instrument(s) being negotiated within WIPO as forming a central component part of the Nagoya Protocol, this dissertation’s analysis highlights the importance of third world efforts to secure an IP-based reinforcement to the Protocol for the effective eradication of biopiracy.

Small states and the promotion of their foreign policy agenda in the international scenario: Trinidad and Tobago and the Kyoto Protocol

Este estudio de caso busca identificar los elementos del portafolio de política exterior de Trinidad y Tobago que le permitieron promover exitosamente sus intereses en el Protocolo de Kioto. Al hacer esto, este texto analizará las limitaciones de Trinidad y Tobago en términos de vulnerabilidades de localización, burocracia y recursos. Posteriormente, una revisión del portafolio de política exterior de este Estado ilustrará el uso de estrategias de creación de capacidades y de organización como lo son el contacto con actores institucionales y no gubernamentales, la formación de coaliciones y estrategias argumentativas, entre otras. Finalmente, este artículo concluirá que dichas acciones permitieron la promoción de la agenda de política exterior de Trinidad y Tobago a través de la creación de hojas de ruta y la coordinación de la incertidumbre con el Protocolo de Kioto. Para hacer esto, este trabajo se concentrará en examinar conceptos como vulnerabilidad y priorización, asimismo contrastando diferentes artículos académicos en la materia junto con documentos oficiales de Trinidad y Tobago.

Unibo-BP: an innovative free software implementation of Bundle Protocol Version 7 (RFC 9171)

The BP (Bundle Protocol) version 7 has been recently standardized by IETF in RFC 9171, but it is the whole DTN (Delay-/Disruption-Tolerant Networking) architecture, of which BP is the core, that is gaining a renewed interest, thanks to its planned adoption in future space missions. This is obviously positive, but at the same time it seems to make space agencies more interested in deployment than in research, with new BP implementations that may challenge the central role played until now by the historical BP reference implementations, such as ION and DTNME. To make Unibo research on DTN independent of space agency decisions, the development of an internal BP implementation was in order. This is the goal of this thesis, which deals with the design and implementation of Unibo-BP: a novel, research-driven BP implementation, to be released as Free Software. Unibo-BP is fully compliant with RFC 9171, as demonstrated by a series of interoperability tests with ION and DTNME, and presents a few innovations, such as the ability to manage remote DTN nodes by means of the BP itself. Unibo-BP is compatible with pre-existing Unibo implementations of CGR (Contact Graph Routing) and LTP (Licklider Transmission Protocol) thanks to interfaces designed during the thesis. The thesis project also includes an implementation of TCPCLv3 (TCP Convergence Layer version 3, RFC 7242), which can be used as an alternative to LTPCL to connect with proximate nodes, especially in terrestrial networks. Summarizing, Unibo-BP is at the heart of a larger project, Unibo-DTN, which aims to implement the main components of a complete DTN stack (BP, TCPCL, LTP, CGR). Moreover, Unibo-BP is compatible with all DTNsuite applications, thanks to an extension of the Unified API library on which DTNsuite applications are based. The hope is that Unibo-BP and all the ancillary programs developed during this thesis will contribute to the growth of DTN popularity in academia and among space agencies.

An Efficient Protocol For The Generation Of Monocyte Derived Dendritic Cells Using Serum-free Media For Clinical Applications In Post Remission Aml Patients.

Protocols for the generation of dendritic cells (DCs) using serum as a supplementation of culture media leads to reactions due to animal proteins and disease transmissions. Several types of serum-free media (SFM), based on good manufacture practices (GMP), have recently been used and seem to be a viable option. The aim of this study was to evaluate the results of the differentiation, maturation, and function of DCs from Acute Myeloid Leukemia patients (AML), generated in SFM and medium supplemented with autologous serum (AS). DCs were analyzed by phenotype characteristics, viability, and functionality. The results showed the possibility of generating viable DCs in all the conditions tested. In patients, the X-VIVO 15 medium was more efficient than the other media tested in the generation of DCs producing IL-12p70 (p=0.05). Moreover, the presence of AS led to a significant increase of IL-10 by DCs as compared with CellGro (p=0.05) and X-Vivo15 (p=0.05) media, both in patients and donors. We concluded that SFM was efficient in the production of DCs for immunotherapy in AML patients. However, the use of AS appears to interfere with the functional capacity of the generated DCs.