Results of a reevaluation of cardiovascular outcomes in the RECORD trial

Background The US Food and Drug Administration (FDA) required a reevaluation of cardiovascular (CV) outcomes in the RECORD trial. This provided an opportunity to assess the implications of event adjudication by 2 groups and quantify the differences as well as to use new FDA end point definitions in development.<p></p> Methods Original data were used to systematically identify all potential deaths, myocardial infarctions (MIs), and strokes. Site investigators were approached for additional source documents and information about participants lost to follow-up. Suspected events were adjudicated using standard procedures, and the results were compared with the original trial outcomes.<p></p> Results Follow-up for mortality was 25,833 person-years, including an additional 328 person-years identified during the reevaluation effort. A total of 184 CV or unknown-cause deaths (88 rosiglitazone, 96 metformin/sulfonylurea), 128 participants with an MI (68 rosiglitazone, 60 metformin/sulfonylurea), and 113 participants with a stroke (50 rosiglitazone, 63 metformin/sulfonylurea) were included. The hazard ratio (HR) for rosiglitazone versus metformin/sulfonylurea for the end point of CV (or unknown cause) death, MI, or stroke was 0.95 (95% CI 0.78-1.17) compared with 0.93 (95% CI 0.74-1.15) for the original RECORD results. Treatment comparisons for MI (HR 1.13, 95% CI 0.80-1.59) and mortality (HR 0.86, 95% CI 0.68-1.08) were also the same compared with the original RECORD results. Sensitivity analyses were also consistent with the original RECORD results. Analyses using the FDA definitions showed similar results.<p></p> Conclusions Only a modest number of additional person-years of follow-up were ascertained from this reevaluation of CV end points in RECORD. Observed HRs and CIs from these analyses using the original RECORD or new FDA end point definitions showed similar treatment effects of rosiglitazone compared with the original RECORD results.<p></p&gt

Beyond Blackboards: Engaging Underserved Middle School Students in Engineering

Beyond Blackboards is an inquiry-centered, after-school program designed to enhance middle school students’ engagement with engineering through design-based experiences focused on the 21st Century Engineering Challenges. Set within a predominantly lowincome, majority-minority community, our study aims to investigate the impact of Beyond Blackboards on students’ interest in and understanding of engineering, as well as their ability to align their educational and career plans. We compare participants’ and nonparticipants’ questionnaire responses before the implementation and at the end of the program’s first academic year. Statistically significant findings indicate a school-wide increase in students’ interest in engineering careers, supporting a shift in school culture. However, only program participants showed increased enjoyment of design-based strategies, understanding of what engineers do, and awareness of the steps for preparing for an engineering career. These quantitative findings are supported by qualitative evidence from participant focus groups highlighting the importance of mentors in shaping students’ awareness of opportunities within engineering

Bacterial analysis by MALDI-TOF mass spectrometry: An inter-laboratory comparison

Bacterial analysis by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has been demonstrated in numerous laboratories, and a few attempts have been made to compare results from different laboratories on the same organism. It has been difficult to understand the causes behind the observed differences between laboratories when different instruments, matrices, solvents, etc. are used. In order to establish this technique as a useful tool for bacterial identification, additional efforts in standardizing the methods by which MALDI mass spectra are obtained and comparisons of spectra from different instruments with different operators are needed. Presented here is an extension of our previous single-laboratory reproducibility study with three different laboratories in a controlled experiment with aliquots of the same bacterial culture, matrix stock solution, and calibrant standards. Using automated spectral collection of whole-cell bacteria and automated data processing and analysis algorithms, fingerprints from three different laboratories were constructed and compared. Nine of the ions appeared reproducibly within all three laboratories, with additional unique ions observed within each of the laboratories. An initial evaluation of the ability to use a fingerprint generated within one laboratory for bacterial identification of a sample from another laboratory is presented, and strategies for improving identification rates between laboratories is discussed

Conduit integrity is compromised during acute lymph node expansion

Lymph nodes (LNs) work as filtering organs, constantly sampling peripheral cues. This is facilitated by the conduit network, a parenchymal tubular-like structure formed of bundles of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 5-fold expansion with every adaptive immune response and yet these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering functions are affected during cycles of LN expansion and resolution is not known. Here we show that the conduit structure is disrupted during acute LN expansion but FRC-FRC contacts remain intact. In homeostasis, polarised FRCs adhere to the underlying substrate to deposit ECM ba-solaterally. ECM production by FRCs is regulated by the C-type lectin CLEC-2, expressed by dendritic cells (DCs), at transcriptional and secretory levels. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, which allows soluble antigens to reach more antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism that enables LNs to prevent inflammation-induced fibrosis

Recycling Aluminum

Students will investigate and compare the energy cost to produce aluminum products from aluminum ore and recycled aluminum. Students will perform an electrolysis activity to reinforce the idea that recycling metal requires less energy than mining and refining metals from their original source in the earth

The Ages, Metallicities and Alpha Element Enhancements of Globular Clusters in the Elliptical NGC 5128: A Homogeneous Spectroscopic Study with Gemini/GMOS

We present new integrated light spectroscopy of globular clusters (GCs) in NGC 5128 in order to measure radial velocities and derive ages, metallicities, and alpha-element abundance ratios. Using Gemini-S 8-m/GMOS, we obtained spectroscopy in the range of ~3400-5700 AA for 72 GCs with S/N > 30 /AA and we have also discovered 35 new GCs within NGC 5128 from our radial velocity measurements. We measured and compared the Lick indices from HdeltaA through Fe5406 with the single stellar population (SSP) models of Thomas et al.(2003,2004). We also measure Lick indices for 41 Milky Way GCs from Puzia et al. (2002) and Schiavon et al. (2005) with the same methodology for direct comparison. Our results show that 68% of the NGC 5128 GCs have old ages (> 8 Gyr), 14% have intermediate ages (5-8 Gyr), and 18% have young ages (< 5 Gyr). However, when we look at the metallicity of the GCs as a function of age, we find 92% of metal-poor GCs and 56% of metal-rich GCs in NGC 5128 have ages > 8 Gyr, indicating that the majority of both metallicity subpopulations of GCs formed early, with a significant population of young and metal-rich GCs forming later. Our metallicity distribution function generated directly from spectroscopic Lick indices is clearly bimodal, as is the color distribution of the same set of GCs. Thus the metallicity bimodality is real and not an artifact of the color to metallicity conversion. The [alpha/Fe] values are supersolar with a mean value of 0.14pm0.04, indicating a fast formation timescale. However, the GCs in NGC 5128 are not as [alpha/Fe] enhanced as the Milky Way GCs also examined in this study. Our results support a rapid, early formation of the GC system in NGC 5128, with subsequent major accretion and/or GC and star forming events in more recent times (abridged).Comment: Accepted to The Astrophysical Journal, 36 pages, 14 figures, 7 table

Mutation of RNA Pol III Subunit rpc2/polr3b Leads to Deficiency of Subunit Rpc11 and Disrupts Zebrafish Digestive Development

The role of RNA polymerase III (Pol III) in developing vertebrates has not been examined. Here, we identify a causative mutation of the second largest Pol III subunit, polr3b, that disrupts digestive organ development in zebrafish slim jim (slj) mutants. The slj mutation is a splice-site substitution that causes deletion of a conserved tract of 41 amino acids in the Polr3b protein. Structural considerations predict that the slj Pol3rb deletion might impair its interaction with Polr3k, the ortholog of an essential yeast Pol III subunit, Rpc11, which promotes RNA cleavage and Pol III recycling. We engineered Schizosaccharomyces pombe to carry an Rpc2 deletion comparable to the slj mutation and found that the Pol III recovered from this rpc2-Δ yeast had markedly reduced levels of Rpc11p. Remarkably, overexpression of cDNA encoding the zebrafish rpc11 ortholog, polr3k, rescued the exocrine defects in slj mutants, indicating that the slj phenotype is due to deficiency of Rpc11. These data show that functional interactions between Pol III subunits have been conserved during eukaryotic evolution and support the utility of zebrafish as a model vertebrate for analysis of Pol III function