The mRNA landscape at yeast translation initiation sites.

SUMMARY: Although translation initiation has been well studied, many questions remain in elucidating its mechanisms. An ongoing challenge is to understand how ribosomes choose a translation initiation site (TIS). To gain new insights, we analyzed large sets of TISs with the aim of identifying common characteristics that are potentially of functional importance. Nucleotide sequence context has previously been demonstrated to play an important role in the ribosome's selection of a TIS, and mRNA secondary structure is also emerging as a contributing factor. Here, we analyze mRNA secondary structure using the folding predictions of the RNAfold algorithm. We present a method for analyzing these results using a rank-ordering approach to assess the overall degree of predicted secondary structure in a given region of mRNA. In addition, we used a modified version of the algorithm that makes use of only a subset of the standard version's output to incorporate base-pairing polarity constraints suggested by the ribosome scanning process. These methods were employed to study the TISs of 1735 genes in Saccharomyces cerevisiae. Trends in base composition and base-pairing probabilities suggest that efficient translation initiation and high protein expression are aided by reduced secondary structure upstream and downstream of the TIS. However, the downstream reduction is not observed for sets of TISs with nucleotide sequence contexts unfavorable for translation initiation, consistent with previous suggestions that secondary structure downstream of the ribosome can facilitate TIS recognition.

Pediatric cardiac surgical ECMO: multivariate analysis of risk factors for hospital death.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has emerged as an effective technique for the mechanical support of many pediatric postcardiotomy patients with medically refractory cardiac failure. METHODS: We retrospectively reviewed the records of 73 pediatric patients with congenital heart disease who were placed on ECMO support between August 1984 and February 1994. The patients were divided into groups defined by the timing of ECMO cannulation relative to the time of operation. Group 1 patients (n = 7, 9.6%) were placed on ECMO preoperatively. Group 2 patients (n = 66, 90.4%) were a heterogeneous population placed on ECMO at any interval after cardiac repair. Subgroup 2A consisted of patients (n = 17, 25.8%) who could not be weaned from cardiopulmonary bypass and were converted directly to ECMO support immediately after repair. Subgroup 2B patients (n = 49, 74.2%) were cannulated postoperatively after an initial period of clinical stability. RESULTS: Hospital survival for all study patients (42/73) and for group 2 patients (38/66) was 58%. Only 4 group 2A patients (23.5%) survived their hospitalization compared with 34 group 2B patients (69.4%) (p = 0.001). Multivariate analysis identified elevated right atrial pressure after ECMO decannulation (p = 0.049) and, possibly, membership in group 2A (p = 0.061) as independent risk factors for hospital death. CONCLUSIONS: Extracorporeal membrane oxygenation is most effective in salvaging pediatric cardiac surgical patients who demonstrate medically refractory hemodynamic deterioration at some interval after being successfully weaned from cardiopulmonary bypass. The right atrial pressure after extracorporeal membrane oxygenation decannulation is an independent predictor of hospital death.

Locating community health care centres in rural Saskatchewan: the case of the Living Sky Health District.

Using the Living Sky Health District in rural Saskatchewan as a sample case, this paper illustrates and discusses the use of location theory modelling tools as an aid to achieving high levels of efficiency coupled with administrator-determined levels of access. The paper begins by examining access issues as they affect location decisions. One of the empirical pillars of the paper is the well-documented idea that people will travel great distances in situations of acute circumstances, but are unwilling to travel far for important preventive care and monitoring of some chronic conditions. The study continues by presenting a non-technical overview of location theory which demonstrates the applicability of location modelling to the present problem; several possible location scenarios for Living Sky Health District are calculated, the most appropriate of which will depend on the goals and priorities of the district board. Finally, the study's results and more general conclusions are presented and discussed.