Barriers to translational research in Windsor Ontario: a survey of clinical care providers and health researchers.

BACKGROUND: Translational research is an ideology focussed on streamlining the transition of novel research into clinical practice to ultimately benefit populations. Central to this approach is overcoming barriers to research involvement and interdisciplinary collaboration. Identifying barriers has been the subject of several studies focused on communities with large academic hospitals. The Windsor-Essex region is currently built around community hospitals which have less of an emphasis on research, employ fewer physicians holding academic appointments and generally do not provide incentivised time for research and training. In this study, we surveyed clinicians and researchers working in Windsor-Essex to gain insight into barriers to translational research important to those working in smaller sized, community-based research networks. METHODS: Using an anonymous close-ended Qualtrics survey distributed via email, we surveyed faculty members from The University of Windsor and clinical care providers from Windsor-Essex (n = 68). This included 24 physicians, 14 allied health professionals, and 30 non-clinician researchers. RESULTS: Managing competing interests, lack of time, funding, infrastructure, and networks were identified by greater than 75% of participants as barriers to research involvement. 62% of physicians identified the lack of permanent post-graduate medical trainees as a barrier. Clinicians were consistently less experienced in research skills compared to others; particularly in publishing results and applying for funding (p < 0.001). Schedule incompatibility, funding issues and identifying interested collaborators with overlapping interests were identified as barriers to interdisciplinary collaboration by 80% of participants. Moreover, 46% of those surveyed were unhappy with their research involvement and these individuals were 13% more likely to perceive research as important for their career progression (p = 0.244). CONCLUSIONS: This study identifies several important barriers to translational research in Windsor-Essex and suggests that many motivated researchers are unhappy with their current involvement. These results will inform decision making in the research community of Windsor-Essex and provides insight for communities of similar size and research capacity. Ultimately, enabling the translation of clinical research in all communities is required to ensure equitable access to cutting edge care.

High-impact practices in cancer education and research: Undergraduate students' perceptions of skills and career development.

High-impact practices (HIPs) are educational practices that foster student success. HIPs have not been widely used in cancer education and research despite the need for students to develop key transferable skills and cultivate social responsibility. Our study addresses this need by implementing four community-based learning HIPs within the context of cancer education and research. Each HIP was classified as having low, moderate, or high alignment with the traits of effective HIPs. Undergraduate science students participated in one to four HIPs as a Feedback Participant, General Volunteer, Student Leader, or Cancer Undergraduate Research and Education (CURES) Class Student. We then studied the effect of these HIPs on students' development of knowledge and skills; career interest and preparedness; and social responsibility. Results from self-reported questionnaires showed that HIPs increased students' cancer knowledge and developed their transferable and technical skills. Many students reported that these HIPs strongly impacted their career preparedness; positively influenced their interest in pursuing careers in health or biomedical sciences; and encouraged them to participate in community service activities. Thus, these findings provide new insights into the perceived benefits of HIPs in cancer education and research by undergraduate students.

Building prevention research science communication and knowledge translation capacity through multidisciplinary collaboration.

OBJECTIVE: To document the outcomes of a dedicated Science Communication Community of Practice (CoP) for increasing prevention-focused knowledge translation (KT) and evidence uptake. Type of program: Shared priorities and a united vision to communicate the value of prevention research led to the formation of a dedicated Science Communication CoP within an Australian public health prevention-focused research collaboration. Members of the CoP included science communication experts and early- and mid-career researchers (EMCRs) with KT-focused roles. METHODS: The CoP met monthly, with semi-structured meetings led by an experienced science communication professional. A priority of the CoP was to develop resources that could help members and external parties to communicate their findings, especially EMCRs and those working on low-resourced projects. Insights from CoP members were synthesised to document if, and how, the CoP increased communication and KT capacity. RESULTS: CoP members found that participatory dialogue - dialogue that involves sharing perspectives and listening to others in order to develop a shared understanding - helped promote a greater understanding of science communication techniques and led to KT being embedded within projects. The CoP itself resulted in shared narratives and communication outputs that could not have been produced by individual members, primarily due to a lack of dedicated resourcing. Members found that engaging in the CoP increased their use of a range of science communication skills, tactics, and methods (e.g., targeted messaging for policy and practice, use of media and social media, and event management to engage audiences and build trust). LESSONS LEARNT: The CoP helped build a greater working knowledge of science communication among its members, leading to increased KT activities. Within an environment of low resourcing for science communication, bringing researchers together with science communication experts can help promote the communication of synthesised evidence and unified messaging on 'what works for prevention'.

Empowering teachers to change youth practices: evaluating teacher delivery and responses to the FLHE programme in Edo State, Nigeria.

School-based programming is one of the most common approaches to HIV/AIDS prevention among youth. This paper presents the history and development of the Family Life and HIV Education (FLHE) programme in Edo State, Nigeria and results of evaluation of teacher actions and responses to training in its delivery. Results indicate that teachers benefited from the training, were aware of new and/or existing teaching resources and began to teach about HIV/AIDS. Teachers expressed that the programme facilitated open dialogue about HIV/AIDS. However, given limited human resources, FLHE was viewed as additional work to already overloaded teaching schedules. It is recommended that the Ministry of Education channel resources to enhance teachers' efforts towards combating HIV/AIDS. To facilitate learning about sexual health and family life, it is recommended that FLHE-based training be viewed as the first rather than the only step towards teacher professional development in this area.

Characterization of a Cynomolgus Macaque Model of Pneumonic Plague for Evaluation of Vaccine Efficacy.

The efficacy of a recombinant plague vaccine (rF1V) was evaluated in cynomolgus macaques (CMs) to establish the relationship among vaccine doses, antibody titers, and survival following an aerosol challenge with a lethal dose of Yersinia pestis strain Colorado 92. CMs were vaccinated with a range of rF1V doses on a three-dose schedule (days 0, 56, and 121) to provide a range of survival outcomes. The humoral immune response following vaccination was evaluated with anti-rF1, anti-rV, and anti-rF1V bridge enzyme-linked immunosorbent assays (ELISAs). Animals were challenged via aerosol exposure on day 149. Vaccine doses and antibody responses were each significantly associated with the probability of CM survival (P < 0.0001). Vaccination also decreased signs of pneumonic plague in a dose-dependent manner. There were statistically significant correlations between the vaccine dose and the time to onset of fever (P < 0.0001), the time from onset of fever to death (P < 0.0001), the time to onset of elevated respiratory rate (P = 0.0003), and the time to onset of decreased activity (P = 0.0251) postinfection in animals exhibiting these clinical signs. Delays in the onset of these clinical signs of disease were associated with larger doses of rF1V. Immunization with ≥ 12 µg of rF1V resulted in 100% CM survival. Since both the vaccine dose and anti-rF1V antibody titers correlate with survival, rF1V bridge ELISA titers can be used as a correlate of protection.

Botulinum neurotoxin neutralizing activity of immune globulin (IG) purified from clinical volunteers vaccinated with recombinant botulinum vaccine (rBV A/B).

The basis for efficacy of the recombinant botulinum vaccine, serotypes A and B (rBV A/B) is that neutralizing antibodies induced by vaccination bind to botulinum neurotoxin complex serotype A, subtype A1 (BoNT/A1) and serotype B, subtype B1 (BoNT/B1) and prevent their actions at cholinergic neurons. The protective capacity of BoNT/A1 and BoNT/B1 neutralizing antibodies derived from the serum of clinical volunteers vaccinated with rBV A/B was evaluated in a guinea pig passive transfer model and a mouse bioassay. Guinea pigs passively immunized to achieve circulating neutralizing antibody concentration (NAC) levels representing the lowest measurable concentrations for BoNT/A1 and BoNT/B1 were protected against an intramuscular (IM) challenge more than 10 times the guinea pig IM median lethal dosage for BoNT/A1 and BoNT/B1. The passively immunized guinea pigs were asymptomatic during the 14-day post-challenge observation period. Control guinea pigs died within 48 h after challenge. Calculation of neutralizing efficiency of antibodies using results from a mouse bioassay indicated that a simple linearly proportional relationship does not exist between NAC level and the amount of BoNT neutralized. Based on this finding, estimates of level of protection must consider variability in BoNT neutralizing efficiency at different NAC levels. The protective capacity of human BoNT/A1 and BoNT/B1 neutralizing antibodies induced by rBV A/B vaccination was verified in a guinea pig passive immunization model. Additionally, estimates of the neutralizing efficiency have been established for BoNT/A1 and BoNT/B1 neutralizing antibodies obtained from clinical volunteers vaccinated with the rBV A/B.

Inhalational botulism in rhesus macaques exposed to botulinum neurotoxin complex serotypes A1 and B1.

A recombinant botulinum vaccine (rBV A/B) is being developed for protection against inhalational intoxication with botulinum neurotoxin (BoNT) complex serotype A, subtype A1 (BoNT/A1), and BoNT serotype B, subtype B1 (BoNT/B1). A critical component for evaluating rBV A/B efficacy will be the use of animal models in which the pathophysiology and dose-response relationships following aerosol exposure to well-characterized BoNT are thoroughly understood and documented. This study was designed to estimate inhaled 50% lethal doses (LD(50)) and to estimate 50% lethal exposure concentrations relative to time (LCt(50)) in rhesus macaques exposed to well-characterized BoNT/A1 and BoNT/B1. During the course of this study, clinical observations, body weights, clinical hematology results, clinical chemistry results, circulating neurotoxin levels, and telemetric parameters were documented to aid in the understanding of disease progression. The inhaled LD(50) and LCt(50) for BoNT/A1 and BoNT/B1 in rhesus macaques were determined using well-characterized challenge material. Clinical observations were consistent with the recognized pattern of botulism disease progression. A dose response was demonstrated with regard to the onset of these clinical signs for both BoNT/A1 and BoNT/B1. Dose-related changes in physiologic parameters measured by telemetry were also observed. In contrast, notable changes in body weight, hematology, and clinical chemistry parameters were not observed. Circulating levels of BoNT/B1 were detected in animals exposed to the highest levels of BoNT/B1; however, BoNT/A1 was not detected in the circulation at any aerosol exposure level. The rhesus macaque aerosol challenge model will be used for future evaluations of rBV A/B efficacy against inhalational BoNT/A1 and BoNT/B1 intoxication.

Phase I study of safety and immunogenicity of an Escherichia coli-derived recombinant protective antigen (rPA) vaccine to prevent anthrax in adults.

BACKGROUND: The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA). METHODOLOGY/PRINCIPAL FINDINGS: A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA. CONCLUSIONS/SIGNIFICANCE: The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00057525.

The sexual scripts of Kenyan young people and HIV prevention.

The scripting of sexual encounters among young people in Kenyan is described using results of 28 focus group discussions conducted with young people attending primary school standard 7, from four different ethnic groups and living in 22 different communities. Sexual encounters were described as both mundane and inevitable and followed a predetermined scripted sequence of events and interactions in which girls and boys played complementary roles. These scripts were set within discourses of force and the exchange of gifts for sex. The gendered nature of the script and its social and cultural foundations are discussed. Potential strategies for developing HIV prevention programming are discussed from the perspective of existing sexual scripts.