Pipes and Connections

This document describes the low-level Pipe and ConnectionManager objects of the Mesh- Router system. The overall MeshRouter framework provides a general scheme for interest- limited communications among a number of client processes. This generality is achieved by a carefully factorized, object-oriented software implementation. Within this framework, the Pipe and ConnectionManager (base) classes dened in this note specify the interfaces for i) ac- tual `bits on the wire' communications and ii) dynamic client insertions during overall system execution. Two specic implementations of the Pipe class are described in detail: a `Memo- ryPipe' linking objects instanced on a single processor and a more general 'rtisPipe' providing inter-processor communications built entirely from the standard RTI-s library used in current JSAF applications. Initialization procedures within the overall MeshRouter system are dis- cussed, with particular attention given to dynamic management of inter-processor connections. Prototype RTI-s router processes are discussed, and simple extensions of the standard system conguration data les are presented

Opportunities for Improving the Drug Development Process: Results from a Survey of Industry and the FDA

In the United States, the Food and Drug Administration (FDA) agency is responsible for regulating the safety and efficacy of biopharmaceutical drug products. Furthermore, the FDA is tasked with speeding new medical innovations to market. These two missions create an inherent tension within the agency and between the agency and key stakeholders. Oftentimes, communications and interactions between regulated companies and the FDA suffer. The focus of this research is on the interactions between the FDA and the biopharmaceutical companies that perform drug R&D. To assess the current issues and state of communication and interaction between the FDA and industry, we carried out a survey of industry leadership in R&D and regulatory positions as well as senior leadership at the FDA who have responsibility for drug evaluation and oversight. Based on forty-nine industry and eight FDA interviews we conducted, we found that industry seeks additional structured and informal interactions with the FDA, especially during Phase II of development. Overall, industry placed greater value on additional communication than did the FDA. Furthermore, industry interviewees indicated that they were willing to pay PDUFA-like fees during clinical development to ensure that the FDA could hire additional, well-qualified staff to assist with protocol reviews and decision-making. Based on our survey and discussions, we uncovered several thematic opportunities to improve interactions between the FDA and industry and to reduce clinical development times: 1) develop metrics and goals at the FDA for clinical development times in exchange for PDUFA like fees; 2) establish an oversight board consisting of industry, agency officials, and premier external scientists (possibly at NIH or CDC) to evaluate and audit retrospectively completed and terminated drug projects; and 3) construct a knowledge database that can simultaneously protect proprietary data while allowing sponsor companies to understand safety issues and problems of previously developed/failed drug programs. While profound scientific and medical challenges face the FDA and industry, the first step to reducing development times and associated costs and facilitating innovation is to provide an efficient regulatory process that reduces unnecessary uncertainty and delays due to lack of communication and interaction.

Risk communication and generic preparedness: from agent-based to action-based planning - a conceptual framework

Responses to recent infectious disease outbreaks, such as to Influenza Pandemic 2009 and the on-going Ebola outbreak in West Africa, reveal the need for new and strengthened approaches to risk communication and governance. The article argues for a fundamental re-conceptualisation of current approaches to risk communication, preparedness planning and response. It calls for a reframing of the way we currently identify and respond to outbreaks around a set of core behaviour-based response patterns. This new model moves away from the current risk communication focus on a plethora of agent-specific threats to five generic response patterns that are based on socially relevant response activities such as 1) controlling vectors, 2) enhancing hygiene, 3) isolation of the sick, 4) protection of the well, and 5) systemic protection of people and their environments. Emphasis is placed on gaining relevant insights into the context specific needs of different communities related to these five patterns. Governance structures are then built and evaluated based on their capacity to collect, communicate, share and prepare the public to take appropriate action related to the five different patterns before, during and after an event. Reframing risk communication and preparedness approaches around a better understanding of the determinants of these general behavioural patterns in infectious control could strengthen infection control literacy, response competence and build resilience of both individuals and health systems to address future epidemics, pandemics and other public health threats

Dynamical Backreaction in Robertson-Walker Spacetime

The treatment of a quantized field in a curved spacetime requires the study of backreaction of the field on the spacetime via the semiclassical Einstein equation. We consider a free scalar field in spatially flat Robertson-Walker space time. We require the state of the field to allow for a renormalized semiclassical stress tensor. We calculate the sigularities of the stress tensor restricted to equal times in agreement with the usual renormalization prescription for Hadamard states to perform an explicit renormalization. The dynamical system for the Robertson Walker scale parameter $a(t)$ coupled to the scalar field is finally derived for the case of conformal and also general coupling.Comment: Obtained equation of motion for non-conformal coupling, not just counter terms as in previous version. Typos fixed, renormalization term proportional to R adde

Respiration-Induced Intraorgan Deformation of the Liver: Implications for Treatment Planning in Patients Treated With Fiducial Tracking.

Stereotactic body radiation therapy is a well-tolerated modality for the treatment of primary and metastatic liver lesions, and fiducials are often used as surrogates for tumor tracking during treatment. We evaluated respiratory-induced liver deformation by measuring the rigidity of the fiducial configuration during the breathing cycle. Seventeen patients, with 18 distinct treatment courses, were treated with stereotactic body radiosurgery using multiple fiducials. Liver deformation was empirically quantified by measuring the intrafiducial distances at different phases of respiration. Data points were collected at the 0%, 50%, and 100% inspiration points, and the distance between each pair of fiducials was measured at the 3 phases. The rigid body error was calculated as the maximum difference in the intrafiducial distances. Liver disease was calculated with Child-Pugh score using laboratory values within 3 months of initiation of treatment. A peripheral fiducial was defined as within 1.5 cm of the liver edge, and all other fiducials were classified as central. For 5 patients with only peripheral fiducials, the fiducial configuration had more deformation (average maximum rigid body error 7.11 mm, range: 1.89-11.35 mm) when compared to patients with both central and peripheral and central fiducials only (average maximum rigid body error 3.36 mm, range: 0.5-9.09 mm, P = .037). The largest rigid body errors (11.3 and 10.6 mm) were in 2 patients with Child-Pugh class A liver disease and multiple peripheral fiducials. The liver experiences internal deformation, and the fiducial configuration should not be assumed to act as a static structure. We observed greater deformation at the periphery than at the center of the liver. In our small data set, we were not able to identify cirrhosis, which is associated with greater rigidity of the liver, as predictive for deformation. Treatment planning based only on fiducial localization must take potential intraorgan deformation into account

Investigating the clinical advantages of a robotic linac equipped with a multileaf collimator in the treatment of brain and prostate cancer patients.

The purpose of this study was to evaluate the performance of a commercially available CyberKnife system with a multileaf collimator (CK-MLC) for stereotactic body radiotherapy (SBRT) and standard fractionated intensity-modulated radiotherapy (IMRT) applications. Ten prostate and ten intracranial cases were planned for the CK-MLC. Half of these cases were compared with clinically approved SBRT plans generated for the CyberKnife with circular collimators, and the other half were compared with clinically approved standard fractionated IMRT plans generated for conventional linacs. The plans were compared on target coverage, conformity, homogeneity, dose to organs at risk (OAR), low dose to the surrounding tissue, total monitor units (MU), and treatment time. CK-MLC plans generated for the SBRT cases achieved more homogeneous dose to the target than the CK plans with the circular collimators, for equivalent coverage, conformity, and dose to OARs. Total monitor units were reduced by 40% to 70% and treatment time was reduced by half. The CK-MLC plans generated for the standard fractionated cases achieved prescription isodose lines between 86% and 93%, which was 2%-3% below the plans generated for conventional linacs. Compared to standard IMRT plans, the total MU were up to three times greater for the prostate (whole pelvis) plans and up to 1.4 times greater for the intracranial plans. Average treatment time was 25 min for the whole pelvis plans and 19 min for the intracranial cases. The CK-MLC system provides significant improvements in treatment time and target homogeneity compared to the CK system with circular collimators, while maintaining high conformity and dose sparing to critical organs. Standard fractionated plans for large target volumes (>100 cm3) were generated that achieved high prescription isodose levels. The CK-MLC system provides more efficient SRS and SBRT treatments and, in select clinical cases, might be a potential alternative for standard fractionated treatments. PACS numbers: 87.56.nk, 87.56.bd

Cohousing for older people: Housing innovation in the Netherlands and Denmark

Objective: The aim of this paper is to elucidate cohousing for older people. Method: The research is based on a literature review and interviews (in English) with residents of seven schemes in the Netherlands and Denmark, a social housing organisation and several researchers in the field (in 1995 and 2002). Results and Conclusions: Cohousing for older people is now well established in its countries of origin - Denmark and the Netherlands - as a way for older people to live in their own house or unit, with a self-chosen group of other older people as neighbours, with shared space and facilities they collectively determine or control. As more such housing is built and occupied it has become easier to choose and assess this option. It remains to be seen how widespread its appeal will be, but cohousing for older people is now a valued housing niche