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1.  Improving quality in general practice: qualitative case study of barriers faced by health authorities 
BMJ : British Medical Journal  1999;319(7203):164-167.
Objectives
To identify and assess the barriers that health authorities face as they manage quality improvements in general practice in the context of the NHS reforms.
Design
Qualitative case study.
Setting
Three UK health authorities: a rural health authority in the south west, a deprived inner city health authority in the north east, and an affluent suburban health authority in the south east.
Participants
Senior and junior managers.
Main outcome measures
Structure of strategic and organisational management, and barriers to the leadership and management of quality improvement in general practice.
Results
Seven barriers were identified: absence of an explicit strategic plan for general practice, competing priorities for attention of the health authority, sensitivity of health professionals, lack of information due to poor quality of clinical data, lack of authority to implement change, unclear roles and responsibilities of managers within the organisations, and isolation from other authorities or organisations facing similar challenges.
Conclusions
The health authorities faced significant barriers that would impede their ability to fulfil their responsibilities in the new NHS and that would reduce their capacity to contribute to quality improvements in general practice.
Key messages Health authorities fail to take a strategic approach to improving quality in general practice Doctors and health authority managers do not work sufficiently closely together to improve the quality of general practice Health authority managers seem to lack the authority and organisational structure to maximise the role in general practice expected of them in the NHS reforms
PMCID: PMC28169  PMID: 10406756
2.  Why do you think you should be the author on this manuscript? Analysis of open-ended responses of authors in a general medical journal 
Background
To assess how authors would describe their contribution to the submitted manuscript without reference to or requirement to satisfy authorship criteria of the International Committee of Medical Journal Editors (ICMJE), we analyzed responses of authors to an open-ended question “Why do you think you should be the author on this manuscript?”.
Methods
Responses of authors (n=1425) who submitted their manuscripts (n=345) to the Croatian Medical Journal, an international general medical journal, from March 2009 until July 2010 were transcribed and matched to ICMJE criteria. Statements that could not be matched were separately categorized. Responses according to the number of authors or their byline position on the manuscript were analyzed using Mann–Whitney U test and Moses test of extreme reactions.
Results
The number of authors per manuscript ranged from 1 to 26 (median=4, IQR=3-6), with the median of 2 contributions per author (IQR=2-3). Authors’ responses could be matched to the ICMJE criteria in 1116 (87.0%) cases. Among these, only 15.6% clearly declared contributions from all 3 ICMJE criteria; however, if signing of the authorship form was taken as the fulfillment of the third ICMJE criterion, overall fraction of deserving authorship was 54.2%. Non-ICMJE contributions were declared by 98 (7.6%) authors whose other contributions could be matched to ICMJE criteria, and by 116 (13.0%) authors whose contributions could not be matched to ICMJE criteria. The most frequently reported non-ICMJE contribution was literature review. Authors on manuscripts with more than 8 authors declared more contributions than those on manuscript with 8 or fewer authors: median 2, IQR 1–4, vs. median 2, IQR 1–3, respectively (Mann Whitney U test, p=0.001; Moses Test of Extreme Reactions, p<0.001). Almost a third of single authors (n=9; 31.0%) reported contributions that could not be matched to any ICMJE criterion.
Conclusions
In cases of multi-author collaborative efforts but not in manuscripts with fewer authors open-ended authorship declaration without instructions on ICMJE criteria elicited responses from authors that were similar to responses when ICMJE criteria were explicitly required. Current authorship criteria and the practice of contribution declaration should be revised in order to capture deserving authorship in biomedical research.
doi:10.1186/1471-2288-12-189
PMCID: PMC3552823  PMID: 23256648
Authorship; Guideline adherence; Contribution disclosure form; International Committee of Medical Journal Editors (ICMJE); Editorial policies; Croatia
3.  Promoting audit in primary care: roles and relationships of medical audit advisory groups and their managers. 
Quality in Health Care  1995;4(3):166-173.
OBJECTIVES--To investigate perceptions of family health service authorities and medical audit advisory groups of advisory groups' involvement in clinical audit and wider quality issues; communication with the authorities; and manager satisfaction. DESIGN--National postal questionnaire survey in 1994. SETTING--All family health services authority districts in England and Wales. SUBJECTS--Chief executives or other responsible authority officers and advisory group chairpersons in each district. MAIN MEASURES--Priorities of advisory group and authority for audit; involvement of advisory group in wider quality issues; communication of information to, and contacts with, the authority and its involvement in planning the future work of the advisory group; and authorities' satisfaction. RESULTS--Both groups' views about audit were similar and broadly consistent with current policy. Advisory group involvement in wider quality issues was extensive, and the majority of both groups thought this appropriate. Much of the information about their activities collected by advisory groups was not passed on to the authority. The most frequent contact between the two groups was the advisory group's annual report, but formal personal contact was the most valued. Most authority respondents thought their views had been recognised in the advisory group's planning of future work; only a small minority were not satisfied with their advisory groups. Dissatisfied respondents received less information from their advisory groups, had less contact with them, and thought they had less input into their plans. There was some evidence that advisory groups in the "dissatisfied districts" were less involved in clinical audit and with their authorities in wider quality issues. CONCLUSIONS--Most advisory groups are developing their activities in clinical audit and have expanded their scope of work. The quality and availability of information about progress with audit is a cause for concern to both groups.
PMCID: PMC1055311  PMID: 10161268
4.  The Optic Nerve Head as a Robust Biomechanical System 
Purpose.
Understanding the effects of IOP on the optic nerve head (ONH) is important in understanding glaucoma and ONH structure and function. The authors tested the hypothesis that the ONH is a robust biomechanical structure wherein various factors combine to produce a relatively stable response to IOP.
Methods.
The authors generated two populations of 100,000 ONH numerical models each with randomly selected values, but controlled distributions, either uniform or Gaussian, of ONH geometry and mechanical properties. The authors predicted the lamina cribrosa displacement (LCD), scleral canal expansion (SCE), and the stresses (forces) and deformations (strains) produced by a 10 mm Hg increase in IOP. The authors analyzed the distributions of the responses.
Results.
The responses were distributed nonuniformly, with the majority of the models having a response within a small region, often less than 30% of the size of the overall response region. This concentration of responses was more marked in the Gaussian population than in the uniform population. All the responses were positively skewed. Whether a particular case was typical or not depended on the response used for classification and on whether the decision was made using one-dimensional or two-dimensional criteria.
Conclusions.
Despite wide variations in ONH characteristics and responses to IOP, some responses were much more common than others. This supports conceiving of the eye as a robust structure, particularly for LCD and SCE, which is tolerant to variations in tissue geometry and mechanical properties. The authors also provide the first estimates of the typical mechanical response of the ONH to variations in IOP over a large population of ONHs.
The authors evaluated a large population of models and found that despite wide variations in ONH characteristics and responses to IOP some mechanical effects of IOP were more common than others. This supports conceiving of the eye as a robust biomechanical system which is tolerant to variations in tissue geometry and properties.
doi:10.1167/iovs.11-9303
PMCID: PMC3357115  PMID: 22427598
5.  Where should health services go: local authorities versus the NHS? 
BMJ : British Medical Journal  1995;310(6994):1580-1584.
The Association of Metropolitan Authorities has recently proposed that responsibility for the NHS should pass from health authorities to local authorities. One of the fiercest debates at the outset of the NHS was whether the hospitals should be run by local authorities. In the end the minister for health, Aneurin Bevan, decided against local democracy and in favour of a national health service. His arguments included the fact that equality of treatment could not be guaranteed if facilities varied with local finances and that even the largest authorities were not big enough to pool risks and expertise. All these arguments still apply today, and the recent changes in community care provide an insight into how a market model of local authority control might work. The changes have been accompanied by a shift from public to private sector provision and the introduction of charges for services that the NHS once provided free. As important, the willingness and ability of local authorities to raise extra revenue from local taxes and charges affect the service they can provide, so leading to inequalities of provision. Local authorities have yet to make the case that they can preserve the fundamental principles and benefits of the NHS, including its reliance on central taxation and unified funding formulas.
PMCID: PMC2549948  PMID: 7787651
6.  Screening children from overseas for infections: is it justified? 
BMJ : British Medical Journal  1990;301(6755):800-802.
OBJECTIVES--To investigate current practice of screening children from abroad for infections after coming to the United Kingdom, and to make recommendations for future practice. DESIGN--A review of literature and a questionnaire sent to all health authorities and boards in the United Kingdom. SETTING--All health authorities and boards in the United Kingdom. SUBJECTS--167 Health authorities or boards that completed questionnaires (response rate 80%), 59 of which used a screening programme. MAIN OUTCOME MEASURE--Response to questionnaire on policies for screening children for infections on their return from overseas. RESULTS--12 Of the 59 authorities screened all children and one screened only those from the West Indian subcontinent. 13 Authorities excluded children from school while awaiting results; 58 screened for tuberculosis and four for diphtheria. CONCLUSIONS--There is a wide variation in screening policies around the country with no national consensus. Screening for diphtheria, typhoid, and salmonellosis is hard to justify and is probably not effective. Screening for tuberculosis, however, is supported by many authorities, is widely practised, and probably is effective. There is a strong case for rationalisation of screening.
PMCID: PMC1663906  PMID: 2224270
7.  Converting systematic reviews to Cochrane format: a cross-sectional survey of Australian authors of systematic reviews 
Background
Despite the growing reputation and subject coverage of the Cochrane Database of Systematic Reviews, many systematic reviews continue to be published solely in paper-based health care journals. This study was designed to determine why authors choose to publish their systematic reviews outside of the Cochrane Collaboration and if they might be interested in converting their reviews to Cochrane format for publication in the Cochrane Database of Systematic Reviews.
Methods
Cross-sectional survey of Australian primary authors of systematic reviews not published on the Cochrane Database of Systematic Reviews identified from the Database of Abstracts of Reviews of Effectiveness.
Results
We identified 88 systematic reviews from the Database of Abstracts of Reviews of Effectiveness with an Australian as the primary author. We surveyed 52 authors for whom valid contact information was available. The response rate was 88 per cent (46/52). Ten authors replied without completing the survey, leaving 36 valid surveys for analysis. The most frequently cited reasons for not undertaking a Cochrane review were: lack of time (78%), the need to undergo specific Cochrane training (46%), unwillingness to update reviews (36%), difficulties with the Cochrane process (26%) and the review topic already registered with the Cochrane Collaboration (21%). (Percentages based on completed responses to individual questions.) Nearly half the respondents would consider converting their review to Cochrane format. Dedicated time emerged as the most important factor in facilitating the potential conversion process. Other factors included navigating the Cochrane system, assistance with updating and financial support. Eighty-six per cent were willing to have their review converted to Cochrane format by another author.
Conclusion
Time required to complete a Cochrane review and the need for specific training are the primary reasons why some authors publish systematic reviews outside of the Cochrane Collaboration. Encouragingly, almost half of the authors would consider converting their review to Cochrane format. Based on the current number of reviews in the Database of Abstracts of Reviews of Effectiveness, this could result in more than 700 additional Cochrane reviews. Ways of supporting these authors and how to provide dedicated time to convert systematic reviews needs further consideration.
doi:10.1186/1472-6963-3-2
PMCID: PMC149345  PMID: 12533194
8.  Authors' perceptions of electronic publishing: two cross sectional surveys 
BMJ : British Medical Journal  2004;328(7452):1350-1353.
Objectives To evaluate how acceptable authors find the BMJ's current practice of publishing short versions of research articles in the paper journal and a longer version on the web and to determine authors' attitudes towards publishing only abstracts in the paper journal and publishing unedited versions on bmj.com once papers have been accepted for publication.
Design Two cross sectional surveys.
Setting General medical journal.
Participants Survey 1: corresponding authors of a consecutive sample of published BMJ research articles that had undergone the ELPS (electronic long, paper short) process. Survey 2: corresponding authors of consecutive research articles submitted to BMJ.
Results Response rates were 90% (104/115) in survey 1 and 75% (213/283) in survey 2. ELPS is largely acceptable to BMJ authors, but there is some concern that electronic information is not permanent and uncertainty about how versions are referenced. While authors who had experienced ELPS reported some problems with editors shortening papers, most were able to rectify these. Overall, 70% thought that the BMJ should continue to use ELPS; 49% thought that publishing just the abstract in the printed journal with the full version only on bmj.com was unacceptable; and 23% thought it unacceptable to post unedited versions on bmj.com once a paper had been accepted for publication.
Conclusions It is acceptable to authors to publish short versions of research articles in the printed version of a general medical journal with longer versions on the website. Authors dislike the idea of publishing only abstracts in the printed journal but are in favour of posting accepted articles on the website ahead of the printed version.
doi:10.1136/bmj.38117.624259.55
PMCID: PMC420287  PMID: 15151965
9.  Health authority commissioning for quality in contraception services 
Quality in Health Care : QHC  1998;7(3):142-148.
OBJECTIVE: To compare the commissioning of contraception services by London health authorities with accepted models of good practice. DESIGN: Combined interview and postal surveys of all health authorities and National Health Service (NHS) trusts responsible for running family planning clinics in the Greater London area. MAIN OUTCOME MEASURES: Health authority commissioning was assessed on the presence of four key elements of good practice--strategies, coordination, service specifications, and quality standards in contracts--by monitoring activity and quality. RESULTS: Less than half the health authorities surveyed had written strategies or service specifications for contraception services. Arrangements for coordination of services were limited and monitoring was underdeveloped. CONCLUSION: The process of commissioning services for contraception seems to be relatively underdeveloped despite the importance of health problems associated with unplanned pregnancy in London. These findings raise questions about the capacity of health authorities to improve the quality of these services through the commissioning process.
PMCID: PMC2483602  PMID: 10185140
10.  Authors' opinions on publication in relation to annual performance assessment 
BMC Medical Education  2010;10:21.
Background
In the past 50 years there has been a substantial increase in the volume of published research and in the number of authors per scientific publication. There is also significant pressure exerted on researchers to produce publications. Thus, the purpose of this study was to survey corresponding authors in published medical journals to determine their opinion on publication impact in relation to performance review and promotion.
Methods
Cross-sectional survey of corresponding authors of original research articles published in June 2007 among 72 medical journals. Measurement outcomes included the number of publications, number of authors, authorship order and journal impact factor in relation to performance review and promotion.
Results
Of 687 surveys, 478 were analyzed (response rate 69.6%). Corresponding authors self-reported that number of publications (78.7%), journal impact factor (67.8%) and being the first author (75.9%) were most influential for their annual performance review and assessment. Only 17.6% of authors reported that the number of authors on a manuscript was important criteria for performance review and assessment. A higher percentage of Asian authors reported that the number of authors was key to performance review and promotion (41.4% versus 7.8 to 22.2%). compared to authors from other countries.
Conclusions
The number of publications, authorship order and journal impact factor were important factors for performance reviews and promotion at academic and non-academic institutes. The number of authors was not identified as important criteria. These factors may be contributing to the increase in the number of authors per publication.
doi:10.1186/1472-6920-10-21
PMCID: PMC2842280  PMID: 20214826
11.  What are health authorities doing about the health problems caused by unemployment? 
Unemployment is over three million in Britain, and unemployment is known to be associated with poor health. It has been suggested that health authorities should produce a comprehensive response to the health problems caused by unemployment, and a survey was undertaken to find how many had done so. All the regional and district health authorities in England, the health boards of Wales, Scotland, and Northern Ireland, and the family practitioner committees of England and Wales were asked by letter what they were doing to respond to the health problems of unemployment. A list of suggestions of what they might be doing was enclosed. The overall response rate was 77% (255/331), and 50% (127/255) of the respondents were doing something--33.3% (3/9) of the regional health authorities, 64% (101/158) of the district health authorities and health boards, and 26% (23/88) of the family practitioner committees. The paper describes what they were doing. A relation was sought between the level of unemployment in an area and the extent of the response, and a significant association was found. Half of Britain's health authorities are now responding in some way to the health problems associated with unemployment.
Images
PMCID: PMC1246228  PMID: 3580820
12.  Empirical Study of Data Sharing by Authors Publishing in PLoS Journals 
PLoS ONE  2009;4(9):e7078.
Background
Many journals now require authors share their data with other investigators, either by depositing the data in a public repository or making it freely available upon request. These policies are explicit, but remain largely untested. We sought to determine how well authors comply with such policies by requesting data from authors who had published in one of two journals with clear data sharing policies.
Methods and Findings
We requested data from ten investigators who had published in either PLoS Medicine or PLoS Clinical Trials. All responses were carefully documented. In the event that we were refused data, we reminded authors of the journal's data sharing guidelines. If we did not receive a response to our initial request, a second request was made. Following the ten requests for raw data, three investigators did not respond, four authors responded and refused to share their data, two email addresses were no longer valid, and one author requested further details. A reminder of PLoS's explicit requirement that authors share data did not change the reply from the four authors who initially refused. Only one author sent an original data set.
Conclusions
We received only one of ten raw data sets requested. This suggests that journal policies requiring data sharing do not lead to authors making their data sets available to independent investigators.
doi:10.1371/journal.pone.0007078
PMCID: PMC2739314  PMID: 19763261
13.  White Students Reflecting on Whiteness: Understanding Emotional Responses 
In the present investigation, the authors explored potential predictors of White students’ general emotional responses after they reflected on their Whiteness in a semi-structured interview (n = 88) or written reflection (n = 187). Specifically, the authors examined how color-blindness (i.e., awareness of White privilege) and racial affect (i.e., White empathy, White guilt, and White fear), assessed before the interview or written reflection, may predict positive and negative emotional responses, assessed immediately following the interview or written reflection. Furthermore, the authors considered whether affective costs of racism to Whites moderated the association between racial color-blindness and general positive and negative emotional responses of White students. Findings indicated that affective costs of racism moderated associations between racial color-blindness and general emotional responses. Specifically, White fear moderated associations for the written reflection group whereas White empathy moderated an association in the interview. White guilt did not moderate, but instead directly predicted a negative emotional response in the written reflection group. Findings suggest that the interaction between racial color-blindness and racial affect is important when predicting students’ emotional responses to reflecting on their Whiteness. Implications for educators and administrators are discussed.
doi:10.1037/a0019299
PMCID: PMC2907903  PMID: 20657811
14.  Is the money following the clients with learning disabilities? 
BMJ : British Medical Journal  1993;306(6883):987-990.
For the past decade patients with learning disabilities living in long stay mental handicap hospitals have been resettled in the community. Local authorities have also taken on the care of new patients who would once have been long stay residents. The imperfect data that are available suggest that in England about half the residents in mental handicap hospitals in 1981 are now the responsibility of local authorities; the figures for Wales and Northern Ireland are 38% and 33%. Data on revenue suggest that the savings to the health service are much less--perhaps 9% in Northern Ireland and 3.6% in England, although there have also been capital gains through the sale of hospitals. Existing methods of transferring money from health to local authorities--joint finance and "dowries" for individual patients--do not seem adequately to have compensated local authorities. Moreover, as patients still to be transferred are more severely disabled local authorities will require larger sums--about 26 000 pounds per patient per year plus 39 200 pounds in capital. If the government chooses not to transfer these resources from health authorities it will be switching funds away from learning disabled people to other care groups.
Images
PMCID: PMC1677466  PMID: 8490482
15.  Health impact assessment of housing improvements: incorporating research evidence 
Methods, results, and conclusions: A recent systematic review of housing intervention studies found a lack of research. The authors recommended that a broader evidence base would be needed to support HIA. In response to consultation with policymakers and HIA practitioners this paper presents a way in which research can be used to inform HIA. Based on the systematic review, the authors have developed a table of synthesised findings indicating the expected health effects of specific housing improvements. The authors also reviewed observational data of housing associated health risks to highlight the key impacts to consider when doing a housing HIA. The findings are presented and the authors discuss how they should be used to inform evidence based housing HIA. In addition to considering the existing research, HIA must consider the local relevance of research. Consultation with local stakeholders also needs to be incorporated to the final assessment. The lack of data and the difficulties in gathering and reviewing data mean that not all HIAs will be able to be informed by research evidence. Well conducted prospective validation of HIAs would contribute to the development of healthy housing investment by informing future housing HIA.
doi:10.1136/jech.57.1.11
PMCID: PMC1732281  PMID: 12490642
16.  A comparison of authors publishing in two groups of U.S. medical journals. 
This study compared the editorial peer review experiences of authors who published in two groups of indexed U.S. medical journals. The study tested the hypothesis that after one journal rejects a manuscript an author selects a less well-known journal for submission. Group One journals were defined as those indexed in 1992 MEDLINE that satisfied several additional qualitative measures; Group Two journals were indexed in the 1992 MEDLINE only. Surveys were sent to the first authors of 616 randomly selected articles, and 479 surveys were returned, for a response rate of 78.1%. A total of 20.8% of Group One and 15.7% of Group Two articles previously had been rejected. Group One authors were more likely to select a journal for its prestige and article quality, while Group Two authors were more likely to have been invited to submit the manuscript. More than 60% of both groups felt the peer review had offered constructive suggestions, but that it had changed article conclusions less than 3% of the time. Both groups thought the review process only marginally improved content, organization, or statistical analysis, or clarified conclusions. Between 3% and 15% of all authors received considerable conflicting advice from different reviewers. Authors from both groups differed as to their reasons for journal selection, their connections with the publishing journal, and patterns of resubmission after rejection.
PMCID: PMC226156  PMID: 8883984
17.  A Graphics Workstation for the Authoring of Computer-Based Medical Education Programs 
Creation of software for computer-based medical education (CBME) is a time-intensive, tedious task. Authoring tools of varying levels of sophistication have been developed in order to insulate the content author from programing responsibility, and to expedite the creation of teaching programs. To date, most of these authoring tools provide only primitive graphics capabilities and simple functions to manipulate hardware extensions such as a videodisc player.
Recent advances in microcomputer technology have encouraged us to design an authoring workstation which will provide a medical content specialist with the ability to: 1) access and manipulate high-resolution graphics images, 2) directly access videodisc images through keyword searching and 3) easily incorporate these images into interactive CBME programs.
This paper discusses the workstation's hardware and software capabilities and our development of a graphics image library for incorporation into a visual learning environment for undergraduate medical students.
PMCID: PMC2245279
18.  Adequacy of authors’ replies to criticism raised in electronic letters to the editor: cohort study 
Objective To investigate whether substantive criticism in electronic letters to the editor, defined as a problem that could invalidate the research or reduce its reliability, is adequately addressed by the authors.
Design Cohort study.
Setting BMJ between October 2005 and September 2007.
Inclusion criteria Research papers generating substantive criticism in the rapid responses section on bmj.com.
Main outcome measures Severity of criticism (minor, moderate, or major) as judged by two editors and extent to which the criticism was addressed by authors (fully, partly, or not) as judged by two editors and the critics.
Results A substantive criticism was raised against 105 of 350 (30%, 95% confidence interval 25% to 35%) included research papers, and of these the authors had responded to 47 (45%, 35% to 54%). The severity of the criticism was the same in those papers as in the 58 without author replies (mean score 2.2 in both groups, P=0.72). For the 47 criticisms with replies, there was no relation between the severity of the criticism and the adequacy of the reply, neither as judged by the editors (P=0.88 and P=0.95, respectively) nor by the critics (P=0.83; response rate 85%). However, the critics were much more critical of the replies than the editors (average score 2.3 v 1.4, P<0.001).
Conclusions Authors are reluctant to respond to criticisms of their work, although they are not less likely to respond when criticisms are severe. Editors should ensure that authors take relevant criticism seriously and respond adequately to it.
doi:10.1136/bmj.c3926
PMCID: PMC2919680  PMID: 20699306
19.  Describing and Modeling Workflow and Information Flow in Chronic Disease Care 
Objectives
The goal of the study was to develop an in-depth understanding of work practices, workflow, and information flow in chronic disease care, to facilitate development of context-appropriate informatics tools.
Design
The study was conducted over a 10-month period in three ambulatory clinics providing chronic disease care. The authors iteratively collected data using direct observation and semi-structured interviews.
Measurements
The authors observed all aspects of care in three different chronic disease clinics for over 150 hours, including 157 patient-provider interactions. Observation focused on interactions among people, processes, and technology. Observation data were analyzed through an open coding approach. The authors then developed models of workflow and information flow using Hierarchical Task Analysis and Soft Systems Methodology. The authors also conducted nine semi-structured interviews to confirm and refine the models.
Results
The study had three primary outcomes: models of workflow for each clinic, models of information flow for each clinic, and an in-depth description of work practices and the role of health information technology (HIT) in the clinics. The authors identified gaps between the existing HIT functionality and the needs of chronic disease providers.
Conclusions
In response to the analysis of workflow and information flow, the authors developed ten guidelines for design of HIT to support chronic disease care, including recommendations to pursue modular approaches to design that would support disease-specific needs. The study demonstrates the importance of evaluating workflow and information flow in HIT design and implementation.
doi:10.1197/jamia.M3000
PMCID: PMC3002133  PMID: 19717802
20.  Macrophage IL-12p70 Signaling Prevents HSV-1–Induced CNS Autoimmunity Triggered by Autoaggressive CD4+ Tregs 
The authors demonstrate that CD4+CD25+FoxP3+ Tregs have an autoaggressive function that is inhibited by macrophage IL-12p70 signaling, resulting in the prevention of HSV-1–induced CNS injury.
Purpose.
CD4+CD25+FoxP3+ naturally occurring regulatory T cells (Tregs) maintain self-tolerance and function to suppress overly exuberant immune responses. However, it is unclear whether innate immune cells modulate Treg function. Here the authors examined the role of innate immunity in lymphomyeloid homeostasis.
Methods.
The involvement of B cells, dendritic cells (DCs), macrophages, natural killer (NK) cells, and T cells in central nervous system (CNS) demyelination in different strains of mice infected ocularly with herpes simplex virus type 1 (HSV-1) was investigated.
Results.
The authors found that depletion of macrophages, but not DCs, B cells, NK cells, CD4+ T cells, or CD8+ T cells, induced CNS demyelination irrespective of virus or mouse strain. As with macrophage depletion, mice deficient in interleukin (IL)-12p35 or IL-12p40 showed CNS demyelination after HSV-1 infection, whereas demyelination was undetectable in HSV-1–infected, IL-23p19–deficient, or Epstein-Barr virus–induced gene 3-deficient mice. Demyelination could be rescued in macrophage-depleted mice after the injection of IL-12p70 DNA and in IL-12p35−/− or IL-12p40−/− mice after injection with IL-12p35 or IL-12p40 DNA or with recombinant viruses expressing IL-12p35 or IL-12p40. Using FoxP3-, CD4-, CD8-, or CD25-depletion and gene-deficient mouse approaches, the authors demonstrated that HSV-1–induced demyelination was blocked in the absence of CD4, CD25, or FoxP3 in macrophage-depleted mice. Flow cytometry showed an elevation of CD4+CD25+FoxP3+ T cells in the spleens of infected macrophage-depleted mice, and adoptive transfer of CD4+CD25+ T cells to infected macrophage-depleted severe combined immunodeficient mice induced CNS demyelination.
Conclusions.
The authors demonstrated that macrophage IL-12p70 signaling plays an important role in maintaining immune homeostasis in the CNS by preventing the development of autoaggressive CD4+ Tregs.
doi:10.1167/iovs.10-6536
PMCID: PMC3080735  PMID: 21220560
21.  Homophily and Contagion Are Generically Confounded in Observational Social Network Studies 
Sociological methods & research  2011;40(2):211-239.
The authors consider processes on social networks that can potentially involve three factors: homophily, or the formation of social ties due to matching individual traits; social contagion, also known as social influence; and the causal effect of an individual’s covariates on his or her behavior or other measurable responses. The authors show that generically, all of these are confounded with each other. Distinguishing them from one another requires strong assumptions on the parametrization of the social process or on the adequacy of the covariates used (or both). In particular the authors demonstrate, with simple examples, that asymmetries in regression coefficients cannot identify causal effects and that very simple models of imitation (a form of social contagion) can produce substantial correlations between an individual’s enduring traits and his or her choices, even when there is no intrinsic affinity between them. The authors also suggest some possible constructive responses to these results.
doi:10.1177/0049124111404820
PMCID: PMC3328971  PMID: 22523436
contagion; social influence; homophily; causal inference; network confounding; neutral models
22.  Winston's "No Additives" campaign: "straight up"? "no bull"? 
Public Health Reports  1999;114(6):522-527.
OBJECTIVE: The author used data from a larger study to examine adolescents' and adults' responses to Winston cigarettes' "No Additives" advertising campaign. METHODS: The author analyzed responses from 400 adolescents ages 12-17 and 203 adults ages 30-50 who were asked what they believed the meaning of the "No Additives" slogan to be. The author also analyzed adolescents' responses to questions about four specific Winston "No Additives" ads. RESULTS: Two-thirds of adolescents and 27% of adults believed that "No Additives" meant one or more of the following: that Winston cigarettes are healthier than other cigarettes, that they are less likely to harm health, or that they are less likely to be addictive. Adolescents perceived the models in three ads to be younger than 25 years old. Among adolescent respondents, smokers were more likely than nonsmokers to like the ads and to believe the ads made smoking more appealing. CONCLUSIONS: The "No Additives" slogan was perceived by a majority of adolescents and about a quarter of adults as implying one or more health claims. The results of this analysis suggest that the Federal Trade Commission's action in requiring a disclaimer on the "No Additives" ads is well founded but the disclaimer should be strengthened.
PMCID: PMC1308535  PMID: 10670619
23.  Effects of enhanced calling efforts on response rates, estimates of health behavior, and costs in a telephone health survey using random-digit dialing. 
Public Health Reports  1993;108(3):372-379.
Public health researchers frequently rely on random-digit dialing (RDD) telephone surveys in monitoring trends in health behavior and evaluating health promotion interventions. RDD response rates have declined during the past decade, and cost-effective methods to increase response rates are needed. The authors evaluated two levels of enhanced calling efforts in an RDD survey of cancer-related health behavior in the State of Washington. The first level of enhanced calling effort was 1 month after 11 original calling attempts to a household, when the authors attempted up to 11 recalls. The second level was 6 months after the first answered call, when the authors recalled those persons who could not be interviewed. Enhanced calling efforts increased the overall survey response rate by 11 percent. Nine percentage points of the increase were attributable to call backs. There were demographic differences among the participants reached at different levels of calling effort, but no consistent associations of level of calling effort with health behavior related to alcohol use, smoking, diet, or health screening. Marginal costs for interviews completed with enhanced calling efforts were about 50 percent higher than costs for interviews reached in the first 11 calls. The authors concluded that enhanced calling efforts may be justified, because they increase confidence in the generalizability of survey results. However, the authors found very little change in survey results by including interviews from persons who were difficult to reach and to interview.
PMCID: PMC1403389  PMID: 8497576
24.  A Comparison of Sample Size and Power in Case-Only Association Studies of Gene-Environment Interaction 
American Journal of Epidemiology  2010;171(4):498-505.
Assuming continuous, normally distributed environmental and categorical genotype variables, the authors compare 6 case-only designs for tests of association in gene-environment interaction. Novel tests modeling the environmental variable as either the response or the predictor and allowing a genetic variable with multiallelic variants are included. The authors show that tests imposing the same genotypic pattern of inheritance perform similarly regardless of whether genotype is the response variable or the predictor variable. The novel tests using the genetic variable as the response variable are advantageous because they are robust to non-normally distributed environmental exposures. Dominance deviance—deviation from additivity in the main or interaction effects—is key to test performance: When it is zero or modest, tests searching for a trend with increasing risk alleles are optimal; when it is large, tests for genotypic effects are optimal. However, the authors show that dominance deviance is attenuated when it is observed at a proxy locus, which is common in genome-wide association studies, so large dominance deviance is likely to be rare. The authors conclude that the trend test is the appropriate tool for large-scale association scans where the true gene-environment interaction model is unknown. The common practice of assuming a dominant pattern of inheritance can cause serious losses of power in the presence of any recessive, or modest dominant, effects.
doi:10.1093/aje/kwp398
PMCID: PMC2816730  PMID: 20047976
dominance; genome-wide association study; interaction; linkage disequilibrium; lung neoplasms; power; research design; sample size
25.  How Attributional Ambiguity Shapes Physiological and Emotional Responses to Social Rejection and Acceptance 
The authors examined White and Black participants’ emotional, physiological, and behavioral responses to same-race or different-race evaluators, following rejecting social feedback or accepting social feedback. As expected, in ingroup interactions, the authors observed deleterious responses to social rejection and benign responses to social acceptance. Deleterious responses included cardiovascular (CV) reactivity consistent with threat states and poorer performance, whereas benign responses included CV reactivity consistent with challenge states and better performance. In intergroup interactions, however, a more complex pattern of responses emerged. Social rejection from different-race evaluators engendered more anger and activational responses, regardless of participants’ race. In contrast, social acceptance produced an asymmetrical race pattern—White participants responded more positively than did Black participants. The latter appeared vigilant and exhibited threat responses. Discussion centers on implications for attributional ambiguity theory and potential pathways from discrimination to health outcomes.
doi:10.1037/0022-3514.94.2.278
PMCID: PMC2535927  PMID: 18211177
intergroup interactions; discrimination; attributional ambiguity; emotion and stress responses; cardiovascular reactivity

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