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The use of item libraries for patient-reported outcome (PRO) measurement in oncology allows for the customisation of PRO assessment to measure key health-related quality of life concepts of relevance to the target population and intervention. However, no high-level recommendations exist to guide users on the design and implementation of these customised PRO measures (item lists) across different PRO measurement systems. To address this issue, a working group was set up, including international stakeholders (academic, independent, industry, health technology assessment, regulatory, and patient advocacy), with the goal of creating recommendations for the use of item libraries in oncology trials. A scoping review was carried out to identify relevant publications and highlight any gaps. Stakeholders commented on the available guidance for each research question, proposed recommendations on how to address gaps in the literature, and came to an agreement using discussion-based methods. Nine primary research questions were identified that formed the scope and structure of the recommendations on how to select items and implement item lists created from item libraries. These recommendations address methods to drive item selection, plan the structure and analysis of item lists, and facilitate their use in conjunction with other measures. The findings resulted in high-level, instrument-agnostic recommendations on the use of item-library-derived item lists in oncology trials.

Attribution of adverse events (AEs) is critical to oncology drug development and the regulatory process. However, processes for determining the causality of AEs are often sub-optimal, unreliable, and inefficient. Thus, we conducted a toxicity-attribution workshop in Silver Springs MD to develop guidance for improving attribution of AEs in oncology clinical trials. Attribution stakeholder experts from regulatory agencies, sponsors and contract research organizations, clinical trial principal investigators, pre-clinical translational scientists, and research staff involved in capturing attribution information participated. We also included patients treated in oncology clinical trials and academic researchers with expertise in attribution. We identified numerous challenges with AE attribution, including the non-informative nature of and burdens associated with the 5-tier system of attribution, increased complexity of trial logistics, costs and time associated with AE attribution data collection, lack of training in attribution for early-career investigators, insufficient baseline assessments, and lack of consistency in the reporting of treatment-related and treatment-emergent AEs in publications and clinical scientific reports. We developed recommendations to improve attribution: we propose transitioning from the present 5-tier system to a 2-3 tier system for attribution, more complete baseline information on patients' clinical status at trial entry, and mechanisms for more rapid sharing of AE information during trials. Oncology societies should develop recommendations and training in attribution of toxicities. We call for further harmonization and synchronization of recommendations regarding causality safety reporting between FDA, EMA and other regulatory agencies. Finally, we suggest that journals maintain or develop standardized requirements for reporting attribution in oncology clinical trials.

The clinical development of cancer therapeutics is a global undertaking, and incorporation of the patient experience into the clinical decision-making process is of increasing interest to the international regulatory and health policy community. Disease and treatment-related symptoms and their effect on patient function and health-related quality of life are important outcomes to consider. The identification of methods to scientifically assess, analyse, interpret, and present these clinical outcomes requires sustained international collaboration by multiple stakeholders including patients, clinicians, scientists, and policy makers. Several data sources can be considered to capture the patient experience, including patient-reported outcome (PRO) measures, performance measures, wearable devices, and biosensors, as well as the careful collection and analysis of clinical events and supportive care medications. In this Policy Review, we focus on PRO measures and present the perspectives of three international regulatory scientists to identify areas of common ground regarding opportunities to incorporate rigorous PRO data into the regulatory decision-making process.

This paper examines security networks in a context where security is increasingly regarded as a problem of intelligence. Data are derived from interviews with officers in criminal intelligence units in Ontario, Canada. A conceptual framework is developed to understand the limits of security intelligence within an emerging security network paradigm, focussing on the normative dimensions governing security networking, and the mechanisms and technologies limiting information deployment among public security agencies. Despite efforts to address security through the sharing of actionable information, security intelligence maintains an exclusive value. Technologies of control promoting this exclusivity also function to prevent intelligence from becoming common knowledge. Because of its limited value, intelligence is ill-suited for export into security governance writ large.

Purpose: The purpose of this study was to characterize the radiologic changes that are seen in the first 24 to 48 hours after head injury and to correlate those changes with clinical findings, to determine which children are at greatest risk for progression of their neurologic injury. Methods: The authors identified 104 children ([le ]17 years of age) who had a second computed tomography (CT) scan of the head within 24 to 48 hours of admission. CT scans were evaluated systematically in a blinded fashion. Mechanism of injury, findings on physical examination, therapeutic measures, and changes in management were recorded from hospital medical records. The 50 children whose second CT scan showed progression of injury were compared with the 54 patients whose intracranial injuries were unchanged or improved on their second CT. Results: Twenty-six percent of patients (13 of 50) with radiographic progression of injury had an admission Glasgow coma score of 15. Progression of injury was more common, however, in patients with lower Glasgow coma scores, averaging 9 on admission and 10 at the time of the second CT. Progression of injury also was more common if the initial head CT showed 3 or more intracranial injuries, mass effect, intraventricular hemorrhage, or an epidural hematoma. Conclusions: Children with an intracranial injury identified on their initial head CT scan should undergo a second scan 24 hours after injury, especially if the initial CT shows 3 or more intracranial injuries, mass effect, intraventricular hemorrhage, or an epidural hematoma.

This study investigates the extent and nature of Use of the government documents collection at Rutgers University's main library for research in the social sciences and humanities. Because most academic libraries find that their documents collections are not fully utilized, this study investigates how to improve bibliographic access, whether to institute a more comprehensive bibliographic instruction program in government information, which sections of documents might be withdrawn or retired to storage, and which sections merit increased or decreased selection activity. A questionnaire was distributed to 575 users to explore the extent of their use of federal, state, municipal, international, and foreign documents, as well as usage of various bibliographic tools to gain access to them. After student respondents named 118 faculty members who had given assignments motivating them to use the documents collection, a sample of these professors was selected to be interviewed. It was found that bibliographic instruction in the classroom significantly affected access to documents and use of microform collections. Users expressed a need for improved bibliographic access, particularly by subject and title. Although the majority of users wanted recently issued federal documents, faculty members and graduate students tended to have more varied research needs.

Ab-initio molecular orbital theory at both the minimal and extended basis set levels have been applied to the study of internal rotation in hydroxylamine and its fluorinated derivatives. The computed energies are analyzed in terms of a Fourier-type expansion of the potential function. The total potential function V(φ)can be dissected into onefold (V1), twofold (V2) and threefold (V3) components and plots of these components together with V(φ) are given for each of the molecules studied herein. Additionally geometry optimizations have been carried out as a function of the internal rotation angle φ (φ = : NOX dihedral angle) for H2NOH and F2NOF. For H2NOH geometry optimizations are found to be less important than for F2NOF. In general the fluorinated hydroxylamines prefer a trans -conformation (φ = 180°) while hydroxylamine itself adopts the cis -conformation (φ = 0°) largely as a result of a lower dipole interaction (V1 term) in the cis -conformation.