Genomic knock-out of rancRNAs in the archaeon H. volcanii

As translation is the final step in gene expression it is particularly important to understand the processes involved in translation regulation. It was shown in the last years that a class of RNA, the non-protein-coding RNAs (ncRNAs), is involved in regulation of gene expression via various mechanisms [1]. Herein included is the prominent example of gene silencing caused by micro RNAs (miRNAs) and small interfering RNAs (siRNAs). Almost all of these ncRNA discovered so far target the mRNA in order to modulate protein biosynthesis, this is rather unexpected considering the crucial role of the ribosome during gene expression. However, recent data from our laboratory showed that there is a new class of RNAs among the well-studied ncRNAs that target the ribosome itself [2,3]. These so called ribosome-associated ncRNAs (rancRNAs) have an impact on translation regulation, mainly by interfering / modulating the rate of protein biosynthesis. Recent studies show the presence of small regulatory RNAs (sRNAs) in archaea which are involved in many biological processes including stress response and metabolic regulation [4]. To date the biological function and the targets of these archaeal sRNAs are only described for a few examples. There are reports of sRNAs binding to the 5’ as well as to the 3’ of mRNAs [5,6]. In addition to these findings, a tRNA derived fragment (tRF) of Valine tRNA was found in a genomic screen of RNAs associated with the ribosome in H. volcanii in our laboratory [3]. This Valine tRF seems to be processed in a stress-dependent manner and showed in vitro binding to the ribosome and inhibited in vitro translation. These results showed that Valine tRF is capable to regulate translation in H. volcanii by targeting the ribosome. The main goal of this project is to identify and describe novel potential regulatory rancRNAs in H. volcanii with the focus on intergenic candidates. Northern blot analyses already revealed interactions with the ribosome and showed differential expression patterns in response to stress conditions. To investigate the biological relevance of some of the ribosome-associated ncRNA candidates, knock-out and phenotypic characterization studies are done. The genomic knock out of a hypothetical ORF (198nt), where one putative rancRNA candidate (46nt) named IG33 was detected in the library at the beginning of the ORF, showed interesting growth phenotype under specific stress conditions. Furthermore a strain with an introduced start to stop codon mutation in this hypothetical ORF still shows the same phenotype indicating that rather the missing protein than the missing sRNA causes this growth phenotype.

Influence of EMS-physician presence on survival after out-of-hospital cardiopulmonary resuscitation: systematic review and meta-analysis

BACKGROUND Evidence suggests that EMS-physician-guided cardiopulmonary resuscitation (CPR) in out-of-hospital cardiac arrest (OOHCA) may be associated with improved outcomes, yet randomized controlled trials are not available. The goal of this meta-analysis was to determine the association between EMS-physician- versus paramedic-guided CPR and survival after OOHCA. METHODS AND RESULTS Studies that compared EMS-physician- versus paramedic-guided CPR in OOHCA published until June 2014 were systematically searched in MEDLINE, EMBASE and Cochrane databases. All studies were required to contain survival data. Data on study characteristics, methods, and as well as survival outcomes were extracted. A random-effects model was used for the meta-analysis due to a high degree of heterogeneity among the studies (I (2)  = 44 %). Return of spontaneous circulation [ROSC], survival to hospital admission, and survival to hospital discharge were the outcome measures. Out of 3,385 potentially eligible studies, 14 met the inclusion criteria. In the pooled analysis (n = 126,829), EMS-physician-guided CPR was associated with significantly improved outcomes compared to paramedic-guided CPR: ROSC 36.2 % (95 % confidence interval [CI] 31.0 - 41.7 %) vs. 23.4 % (95 % CI 18.5 - 29.2 %) (pooled odds ratio [OR] 1.89, 95 % CI 1.36 - 2.63, p < 0.001); survival to hospital admission 30.1 % (95 % CI 24.2 - 36.7 %) vs. 19.2 % (95 % CI 12.7 - 28.1 %) (pooled OR 1.78, 95 % CI 0.97 - 3.28, p = 0.06); and survival to discharge 15.1 % (95 % CI 14.6 - 15.7 %) vs. 8.4 % (95 % CI 8.2 - 8.5 %) (pooled OR 2.03, 95 % CI 1.48 - 2.79, p < 0.001). CONCLUSIONS This systematic review suggests that EMS-physician-guided CPR in out-of-hospital cardiac arrest is associated with improved survival outcomes.

Automated Intervertebral Disc Detection from Low Resolution, Sparse MRI Images for the Planning of Scan Geometries

Robust and accurate identification of intervertebral discs from low resolution, sparse MRI scans is essential for the automated scan planning of the MRI spine scan. This paper presents a graphical model based solution for the detection of both the positions and orientations of intervertebral discs from low resolution, sparse MRI scans. Compared with the existing graphical model based methods, the proposed method does not need a training process using training data and it also has the capability to automatically determine the number of vertebrae visible in the image. Experiments on 25 low resolution, sparse spine MRI data sets verified its performance.

The Getting-Out-of-Bed (GoB) scale: a measure of motivation and life outlook in older adults with cancer

OBJECTIVE: To develop and evaluate the psychometric properties of a measure of motivation and life outlook (Getting-Out-of-Bed [GoB]). DESIGN: Secondary analysis of baseline and 6-month data from a longitudinal follow-up study of older breast cancer survivors. PARTICIPANTS: Women (N = 660) diagnosed with primary breast cancer stage I-IIIA disease, age >or=65 years, and permission to contact from an attending physician in four geographic regions in the United States (city-based Los Angeles, California; statewide in Minnesota, North Carolina, and Rhode Island). MEASUREMENT: Data were collected over 6-months of follow-up from consenting patients' medical records and telephone interviews with patients. Data collected included the 4-item GoB, health-related quality of life (HRQoL), breast cancer, sociodemographic, and health-related characteristics. RESULTS: Factor analysis produced, as hypothesized, one principal component with eigen values of 2.74(baseline) and 2.91(6-months) which explained 68.6%(baseline) and 72.7%(6-months) of total variance. In further psychometric analyses, GoB exhibited good construct validity (divergent: low nonstatistically significant correlations with unrelated constructs; convergent: moderate statistically significant correlations with related constructs; discriminant: distinguished high HRQoL groups with a high level of significance), excellent internal reliability (Cronbach's alpha 0.84(baseline), 0.87(6-months)), and produced stable measurements over 6-months. Women with GoB scores >or=50 at baseline were more likely at 6-months to have good HRQoL, good self-perceived health, and report regular exercise, indicating good predictive ability. CONCLUSION: GoB demonstrated overall good psychometric properties in this sample of older breast cancer survivors, suggestive of a promising tool for assessing motivation and life outlook in older adults. Nevertheless, because it was developed and initially evaluated in a select sample, using measures with similar but not exact content overlap further evaluation is needed before it can be recommended for widespread use.