A Conversation with Dorothy Gilford

In 1946, Public Law 588 of the 79th Congress established the Office of Naval Research (ONR). Its mission was to plan, foster and encourage scientific research in support of Naval problems. The establishment of ONR predates the National Science Foundation and initiated the refocusing of scientific infrastructure in the United States following World War II. At the time, ONR was the only source for federal support of basic research in the United States. Dorothy Gilford was one of the first Heads of the Probability and Statistics program at the Office of Naval Research (1955 to 1962), and she went on to serve as Director of the Mathematical Sciences Division (1962 to 1968). During her time at ONR, Dorothy influenced many areas of statistics and mathematics and was ahead of her time in promoting interdisciplinary projects. Dorothy continued her career at the National Center for Education Statistics (1969 to 1974). She was active in starting international comparisons of education outcomes in different countries, which has influenced educational policy in the United States. Dorothy went on to serve in many capacities at the National Academy of Sciences, including Director of Human Resources Studies (1975 to 1978), Senior Statistician on the Committee on National Statistics (1978 to 1988) and Director of the Board on International Comparative Studies in Education (1988 to 1994). The following is a conversation we had with Dorothy Gilford in March of 2004. We found her to be an interesting person and a remarkable statistician. We hope you agree.Comment: Published in at http://dx.doi.org/10.1214/088342307000000023 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Task 2: ShARe/CLEF eHealth evaluation lab 2014

This paper reports on Task 2 of the 2014 ShARe/CLEF eHealth evaluation lab which extended Task 1 of the 2013 ShARe/CLEF eHealth evaluation lab by focusing on template lling of disorder attributes. The task was comprised of two subtasks: attribute normalization (task 2a) and cue identication (task 2b).We instructed participants to develop a system which either kept or updated a default attribute value for each task. Participant systems were evaluated against a blind reference standard of 133 discharge summaries using Accuracy (task 2a) and F-score (task 2b). In total, ten teams participated in task 2a, and three teams in task 2b. For task 2a and 2b, the HITACHI team systems (run 2) had the highest performances, with an overall average average accuracy of 0.868 and F1-score (strict) of 0.676, respectively

Models of Consent to Return of Incidental Findings in Genomic Research

Genomic research has the capacity to generate a wide array of findings that go beyond the goals of the study—usually referred to as “incidental findings.” The evolving consensus of researchers, participants, and expert panels is that at least some incidental results should be made available to participants. However, there are a number of challenges to discussing these issues with participants and ascertaining their preferences, including the complexity and magnitude of the relevant information. Believing that usual models of informed consent are not likely to be effective in this context, we identify four approaches that investigators and IRBs might consider: traditional consent, staged consent, mandatory return, and outsourcing. Each has advantages and disadvantages compared with the other options, and which one is selected for a given project will depend on a mix of practical and normative considerations that are described in this paper

Overview of the ShARe/CLEF eHealth evaluation lab 2013

Discharge summaries and other free-text reports in healthcare transfer information between working shifts and geographic locations. Patients are likely to have difficulties in understanding their content, because of their medical jargon, non-standard abbreviations, and ward-specific idioms. This paper reports on an evaluation lab with an aim to support the continuum of care by developing methods and resources that make clinical reports in English easier to understand for patients, and which helps them in finding information related to their condition. This ShARe/CLEFeHealth2013 lab offered student mentoring and shared tasks: identification and normalisation of disorders (1a and 1b) and normalisation of abbreviations and acronyms (2) in clinical reports with respect to terminology standards in healthcare as well as information retrieval (3) to address questions patients may have when reading clinical reports. The focus on patients' information needs as opposed to the specialised information needs of physicians and other healthcare workers was the main feature of the lab distinguishing it from previous shared tasks. De-identied clinical reports for the three tasks were from US intensive care and originated from the MIMIC II database. Other text documents for Task 3 were from the Internet and originated from the Khresmoi project. Task 1 annotations originated from the ShARe annotations. For Tasks 2 and 3, new annotations, queries, and relevance assessments were created. 64, 56, and 55 people registered their interest in Tasks 1, 2, and 3, respectively. 34 unique teams (3 members per team on average) participated with 22, 17, 5, and 9 teams in Tasks 1a, 1b, 2 and 3, respectively. The teams were from Australia, China, France, India, Ireland, Republic of Korea, Spain, UK, and USA. Some teams developed and used additional annotations, but this strategy contributed to the system performance only in Task 2. The best systems had the F1 score of 0.75 in Task 1a; Accuracies of 0.59 and 0.72 in Tasks 1b and 2; and Precision at 10 of 0.52 in Task 3. The results demonstrate the substantial community interest and capabilities of these systems in making clinical reports easier to understand for patients. The organisers have made data and tools available for future research and development

Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly α-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against Shigella flexneri and S. sonnei in the lethal pulmonary challenge. It also offered limited protection against S. dysenteriae challenge. Our results show the feasibility of generating a protective Shigella vaccine comprised of the DB fusion

Informed consent for return of incidental findings in genomic research

Purpose: Researchers face the dilemma of how to obtain consent for return of incidental findings from genomic research. We surveyed and interviewed investigators and study participants, with the goal of providing suggestions for how to shape the consent process. Methods: We performed an online survey of 254 US genetic researchers identified through the NIH RePORTER database, abstracts from the 2011 American Society of Human Genetics meeting, and qualitative semi-structured interviews with 28 genomic researchers and 20 research participants. Results: Most researchers and participants endorsed disclosure of a wide range of information about return of incidental findings, including risks, benefits, impact on family members, data security, and procedures, for return of results in the event of death or incapacity and for recontact. However, most researchers were willing to devote 30 min or less to this process and expressed concerns that disclosed information would overwhelm participants, a concern shared by many participants themselves. Conclusion: There is a disjunction between the views of investigators and participants about the amount of information that should be disclosed and the practical realities of the research setting, including the time available for consent discussions. This strongly suggests the need for innovative approaches to the informed consent process

Research Participants’ Preferences for Hypothetical Secondary Results from Genomic Research

Secondary or incidental results can be identified in genomic research that increasingly uses whole exome/genome sequencing. Understanding research participants’ preferences for secondary results and what influences these decisions is important for patient education, counseling, and consent, and for the development of policies regarding return of secondary results. Two hundred nineteen research participants enrolled in genomic studies were surveyed regarding hypothetical preferences for specific types of secondary results, and these preferences were correlated with demographic information and psychosocial data. The majority of research participants (73%) indicated a preference to learn about all results offered, with no clear pattern regarding which results were not desired by the remaining participants. Participants who reported greater interest in genetic privacy were less likely to indicate a preference to learn all results, as were individuals who self‐identified as Jewish. Although most research participants preferred to receive all secondary results offered, a significant subset preferred to exclude some results, suggesting that an all‐or‐none policy would not be ideal for all participants. The correlations between preferences to receive secondary results, religious identification, and privacy concerns demonstrate the need for culturally sensitive counseling and educational materials accessible to all education levels to allow participants to make the best choices for themselves

Sedentary time in older men and women: an international consensus statement and research priorities

Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies

Researchers’ views on return of incidental genomic research results: qualitative and quantitative findings

Purpose: Comprehensive genomic analysis including exome and genome sequencing is increasingly being utilized in research studies, leading to the generation of incidental genetic findings. It is unclear how researchers plan to deal with incidental genetic findings. Methods: We conducted a survey of the practices and attitudes of 234 members of the US genetic research community and performed qualitative semistructured interviews with 28 genomic researchers to understand their views and experiences with incidental genetic research findings. Results: We found that 12% of the researchers had returned incidental genetic findings, and an additional 28% planned to do so. A large majority of researchers (95%) believe that incidental findings for highly penetrant disorders with immediate medical implications should be offered to research participants. However, there was no consensus on returning incidental results for other conditions varying in penetrance and medical actionability. Researchers raised concerns that the return of incidental findings would impose significant burdens on research and could potentially have deleterious effects on research participants if not performed well. Researchers identified assistance needed to enable effective, accurate return of incidental findings. Conclusion: The majority of the researchers believe that research participants should have the option to receive at least some incidental genetic research results