Comparison of Electronic Physician Prompts versus Waitroom Case-Finding on Clinical Trial Enrollment

BACKGROUND: Recruiting patients into clinical research protocols is challenging. Electronic medical record (EMR) systems capable of prompting clinicians may facilitate enrollment. OBJECTIVE: To compare an EMR-based clinician prompt versus a wait-room-based case-finding strategy at enrolling patients into a clinical trial. DESIGN: Cross-sectional comparison of recruitment data from two trials to treat anxiety disorders in primary care. Both studies utilized similar enrollment criteria, intervention strategies, and the same four practice sites and EMR system. PARTICIPANTS: Patients referred by their (primary care physicians) PCPs in response to an EMR prompt (recruited 1/2005–10/2006), and patients enrolled by research assistants stationed in practice waiting rooms (7/2000–4/2002). MEASUREMENTS: Referral counts, patients’ baseline sociodemographic and clinical characteristics. RESULTS: Over a 22-month period, EMR-prompted PCPs referred 794 patients and 176 (22%) met study inclusion criteria and enrolled, compared to 8,095 patients approached by wait room-based recruiters of whom 193 (2.4%) enrolled. Subjects enrolled by EMR-prompted PCPs were more likely to be non-white (23% vs 5%; P < 0.001), male (28% vs 18%; P = 0.03), and have higher anxiety levels than those recruited by wait-room recruiters (P < 0.0001). CONCLUSIONS: EMR systems prompting clinicians to refer patients with specific characteristics are an efficient recruitment tool with critical implications for increasing minority participation in clinical research

My care manager, my computer therapy and me: the relationship triangle in computerized cognitive behavioural therapy

Previous research has reported mixed findings regarding the relationship between therapeutic alliance, engagement and outcomes in e-mental health. This study aims to overcome some of the methodological limitations of previous research and extend our understanding of alliance-outcome relationships in e-mental health by exploring the nature of the relationship triangle between the patient, their care manager and their computerized cognitive behavioural therapy (CCBT) program, accessed with or without an Internet Support Group (ISG). Positive patient-rated alliance with both their care manager and the CCBT program itself was found and these were significantly associated with measures of engagement and clinical outcome. The magnitude of this association was moderate, and within the range of that reported for traditional face-to-face psychotherapies in recent meta-analyses. Limitations of the study, including the reliance on completer data and a cross-sectional design, and directions for future research are presented. Our findings suggest that both the training and supervision of support staff and the optimization of CCBT interventions themselves to enhance alliance and experience may lead to improved engagement and outcomes

Technology requirements of exploration beyond Neptune by solar sail propulsion

This paper provides a set of requirements for the technology development of a solar sail propelled Interstellar Heliopause Probe mission. The mission is placed in the context of other outer solar systems missions, ranging from a Kuiper Belt mission through to an Oort cloud mission. Mission requirements are defined and a detailed parametric trajectory analysis and launch date scan performed. Through analysis of the complete mission trade space a set of critical technology development requirements are identified which include an advanced lightweight composite High-Gain Antenna, a high-efficiency Ka-band travelling-wave tube amplifier and a radioisotope thermoelectric generator with power density of approximately 12 W/kg. It is also shown that the Interstellar Heliopause Probe mission necessitates the use of a spinning sail, limiting the direct application of current hardware development activities. A Kuiper Belt mission is then considered as a pre-curser to the Interstellar Heliopause Probe, while it is also shown through study of an Oort cloud mission that the Interstellar Heliopause Probe mission is the likely end-goal of any future solar sail technology development program. As such, the technology requirements identified to enable the Interstellar Heliopause Probe must be enabled through all prior missions, with each mission acting as an enabling facilitator towards the next

P21^WAF1/CIP1 RNA expression in highly HIV-1 exposed, uninfected individuals

Some individuals remain HIV-1 antibody and PCR negative after repeated exposures to the virus, and are referred to as HIV-exposed seronegatives (HESN). However, the causes of resistance to HIV-1 infection in cases other than those with a homozygous CCR5Δ32 deletion are unclear. We hypothesized that human p21WAF1/CIP1 (a cyclin-dependent kinase inhibitor) could play a role in resistance to HIV-1 infection in HESN, as p21 expression has been associated with suppression of HIV-1 in elite controllers and reported to block HIV-1 integration in cell culture. We measured p21 RNA expression in PBMC from 40 HESN and 40 low exposure HIV-1 seroconverters (LESC) prior to their infection using a real-time PCR assay. Comparing the 20 HESN with the highest exposure risk (median = 111 partners/2.5 years prior to the 20 LESC with the lowest exposure risk (median = 1 partner/2.5 years prior), p21 expression trended higher in HESN in only one of two experiments (P = 0.11 vs. P = 0.80). Additionally, comparison of p21 expression in the top 40 HESN (median = 73 partners/year) and lowest 40 LESC (median = 2 partners/year) showed no difference between the groups (P = 0.84). There was a weak linear trend between risk of infection after exposure and increasing p21 gene expression (R2 = 0.02, P = 0.12), but again only in one experiment. Hence, if p21 expression contributes to the resistance to viral infection in HESN, it likely plays a minor role evident only in those with extremely high levels of exposure to HIV-1

On selection of foxes for enhanced aggressiveness and its correlated implications

The results of a 35-year selection of foxes for aggressive response to humans are reported. Averaged estimates of the phenotypic manifestation of aggressiveness in all selection generations are presented. The dynamics of these estimates shows that the phenotypic response to the selection was obvious only in the first 12 generations. Subsequent selection did not alter the mean aggressiveness score. Analysis of variance was performed for the intergroup variability (among descendants of different mothers) and intragroup variability (among the offspring within a family). The intragroup variability was constantly low. Most likely, the trait is stabilized by maternal prenatal and early neonatal factors. The general tendency in the dynamics of intergroup variability is that it does not decrease over time during selection, no matter how long the population has been under it. It follows from the statistical indices of the phenotypic similarity between parents and offspring that additive interactions are insufficient for the explanation of the persisting variability. The contribution of epistatic interactions is not ruled out, though. Emphasis is laid on the correlated consequences of the selection for aggressiveness and their coordination with the consequences of the selection in the opposite direction, for elimination of aggressive response to humans, or for tameness. The parallelism of correlated changes in the selection in contrasting directions is illustrated by the examples of some physiological and morphological traits. The phenomenon is discussed in the light of classical notions of the resource of cryptic genetic variation and the role of selection in its phenotypic manifestation. Its interpretation also invokes molecular data pointing that some genetic pathways may regulate parameters of both aggression and tameness and that the selection processes in both directions may have some genetic targets in common