Are Transplant Recipients Human Subjects When Research Is Conducted on Organ Donors?

Interventional research on deceased organ donors and donor organs prior to transplant holds the promise of reducing the number of patients who die waiting for an organ by expanding the pool of transplantable organs and improving transplant outcomes. However, one of the key challenges researchers face is an assumption that someone who receives an organ that was part of an interventional research protocol is always a human subject of that same study. The consequences of this assumption include the need for oversight by an institutional review board and for research‐level informed consent from transplant recipients, all within the complex practical realities of the organ donation and transplantation process in the United States. The current national focus on this issue provides an opportunity to think critically about the policy goals of the human subjects regulations and their application to the nascent field of deceased organ donor intervention research. We propose that for donor research where the transplant recipient does not fall under the definition of human subject, the clinical consent model—rather than the consent model used for human research subjects—best facilitates the policy objectives of balancing clinical innovation, transparency, and protection of patients in an ethically responsible and legally compliant manner.     

One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -     

Creutzfeldt-Jakob disease in Ireland: epidemiological aspects 1980-2002

Surveillance for Creutzfeldt-Jakob disease (CJD) has been carried out in the Republic of Ireland since 1980. Initial surveillance was passive and based on consented autopsy confirmation of CJD in patients in whom there was a high index of clinical suspicion. Since 1999, an active surveillance programme involving formal notification of all suspect CJD cases has been in place. The annual mortality rate has increased from 0.34 cases/million in 1980 to 1.27 cases/million in 2001. In all, 29 cases have been pathologically confirmed: 1 had variant CJD (vCJD), 1 had iatrogenic human growth hormone-induced CJD and 1 had fatal insomnia. Sporadic CJD (sCJD) accounted for the remainder. This paper details the change in incidence over 22 years as the surveillance programme in Ireland got under way; the increased incidence is attributed to better case ascertainment, as has occurred in other countries where active surveillance programmes have been established.     

Facial recognition test in the elderly: norms, reliability and premorbid estimation

The Facial Recognition Test (Benton, Hamsher, Varney, & Spreen, 1983; Benton, Sivan, Hamsher, Varney, & Spreen, 1994) was examined in an age-, education- and gender-stratified sample of 346 healthy older adults. Internal consistency reliability estimates were.72 for the Long Form (FRLF),.53 for the Short Form, and.69 for a new short form. Mean FRLF scores did not change over a 1-year interval (p >.5), and the stability estimate was.71 (n = 100). The first of the methods below yielded the highest correlation between estimated and obtained FRLF scores in cross-validation (n = 67): (1) multiple regression based on oral reading and demographics, (2) multiple regression based on age, education and gender, and (3) mean scores by age group.     

Time course study of the antigen-specific immune response to a PLGA microparticle vaccine formulation

Microparticle-based vaccine delivery systems are known to promote enhanced immune responses to protein antigens and can elicit T_H1-biased responses when used in combination with Toll-like receptor (TLR) agonists. It is important to understand the kinetics of the immune responses to microparticle-based protein vaccines in order to predict the duration of protective immunity and to optimize prime-boost vaccination regimens. We carried out a 10-week time course study to investigate the magnitude and kinetics of the antibody and cellular immune responses to poly(lactic-co-glycolic acid) (PLGA) microparticles containing 40 μg ovalbumin (OVA) protein and 16 μg CpG-ODN adjuvant (MP/OVA/CpG) in comparison to OVA-containing microparticles, soluble OVA plus CpG, or OVA formulated with Alhydrogel^® aluminum adjuvant. Mice vaccinated with MP/OVA/CpG developed the highest T_H1-associated IgG2b and IgG2c antibody titers, while also eliciting T_H2-associated IgG1 antibody titers on par with Alhydrogel^®-formulated OVA, with all IgG subtype titers peaking at day 56. The MP/OVA/CpG vaccine also induced the highest antigen-specific splenocyte IFN-γ responses, with high levels of IFN-γ responses persisting until day 42. Thus the MP/OVA/CpG formulation produced a sustained and heightened humoral and cellular immune response, with an overall T_H1 bias, while maintaining high levels of IgG1 antibody equivalent to that seen with Alhydrogel^® adjuvant. The time course kinetics study provides a useful baseline for designing vaccination regimens for microparticle-based protein vaccines.     

Understanding the influence of resilience for people with a lived experience of mental illness: A self‐determination theory perspective

Behaviors associated with resilience can be seen as tantamount to coping with stress and vulnerability. This is important for people who live with mental illness. This study aimed to determine whether key basic psychological needs influence resilience among people with a lived experience of mental illness. A total of 159 consumers with a lived experience of mental illness completed self‐report surveys measuring resilience and the basic psychological needs (autonomy, competence, and relatedness) espoused in self‐determination theory. A 2‐step analysis was conducted, including Pearson product correlations and stepwise multiple regression. Higher levels of relatedness significantly predicted resilience. Competence and autonomy did not have a significant influence on resilience. Reconnecting or establishing social relationships within ones community is important for people living with mental illness. The link between resilience and relatedness ought to be considered in treatment plans.     

In vivo efficacy of a chitosan/IL-12 adjuvant system for protein-based vaccines

Vaccines based on recombinant proteins require adjuvant systems in order to generate Th1-type immune responses. We have developed a vaccine adjuvant system using a viscous chitosan solution and interleukin (IL)-12, a Th1-inducing cytokine. The chitosan solution is designed to create a depot of antigen and IL-12 at a subcutaneous injection site. We measured the in vivo immune response of a vaccine containing 0.25, 1, or 4 μg murine IL-12 and 75 μg ovalbumin (OVA), formulated in a 1.5% chitosan glutamate solution. The chitosan/IL-12/OVA vaccine, in comparison to chitosan/OVA, IL-12/OVA, or OVA alone, elicited greater antigen-specific CD4(+) and CD8(+) T-cell responses, as determined by CD4(+) splenocyte proliferation, Th1 cytokine release, CD8(+) T-cell interferon-γ release, and MHC class I peptide pentamer staining. The combination of chitosan and IL-12 also enhanced IgG2a and IgG2b antibody responses to OVA. Co-formulation of chitosan and IL-12 thus promoted the generation of a Th1 immune response to a model protein vaccine.