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

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

Ultralight Structures for Space Solar Power Satellites

The design of a deployable spacecraft, measuring 60 m × 60 m, and with an areal density 100 g m^(−2) , is described. This spacecraft can be packaged into a cylinder measuring 1.5 m in height and 1 m in diameter. It can be deployed to a flat configuration, where it acts as a stiff, lightweight support framework for multifunctional tiles that collect sunlight, generate electric power, and transmit to a ground station on Earth

Phylogenetic Studies of Transmission Dynamics in Generalized HIV Epidemics: An Essential Tool Where the Burden is Greatest?

Efficient and effective HIV prevention measures for generalized epidemics in sub-Saharan Africa have not yet been validated at the population-level. Design and impact evaluation of such measures requires fine-scale understanding of local HIV transmission dynamics. The novel tools of HIV phylogenetics and molecular epidemiology may elucidate these transmission dynamics. Such methods have been incorporated into studies of concentrated HIV epidemics to identify proximate and determinant traits associated with ongoing transmission. However, applying similar phylogenetic analyses to generalized epidemics, including the design and evaluation of prevention trials, presents additional challenges. Here we review the scope of these methods and present examples of their use in concentrated epidemics in the context of prevention. Next, we describe the current uses for phylogenetics in generalized epidemics, and discuss their promise for elucidating transmission patterns and informing prevention trials. Finally, we review logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized epidemics, and suggest potential solutions

Selection against Spurious Promoter Motifs Correlates with Translational Efficiency across Bacteria

Because binding of RNAP to misplaced sites could compromise the efficiency of transcription, natural selection for the optimization of gene expression should regulate the distribution of DNA motifs capable of RNAP-binding across the genome. Here we analyze the distribution of the −10 promoter motifs that bind the σ70 subunit of RNAP in 42 bacterial genomes. We show that selection on these motifs operates across the genome, maintaining an over-representation of −10 motifs in regulatory sequences while eliminating them from the nonfunctional and, in most cases, from the protein coding regions. In some genomes, however, −10 sites are over-represented in the coding sequences; these sites could induce pauses effecting regulatory roles throughout the length of a transcriptional unit. For nonfunctional sequences, the extent of motif under-representation varies across genomes in a manner that broadly correlates with the number of tRNA genes, a good indicator of translational speed and growth rate. This suggests that minimizing the time invested in gene transcription is an important selective pressure against spurious binding. However, selection against spurious binding is detectable in the reduced genomes of host-restricted bacteria that grow at slow rates, indicating that components of efficiency other than speed may also be important. Minimizing the number of RNAP molecules per cell required for transcription, and the corresponding energetic expense, may be most relevant in slow growers. These results indicate that genome-level properties affecting the efficiency of transcription and translation can respond in an integrated manner to optimize gene expression. The detection of selection against promoter motifs in nonfunctional regions also confirms previous results indicating that no sequence may evolve free of selective constraints, at least in the relatively small and unstructured genomes of bacteria