From Molecular Cores to Planet-forming Disks with SIRTF

The SIRTF mission and the Legacy programs will provide coherent data bases for extra-galactic and Galactic science that will rapidly become available to researchers through a public archive. The capabilities of SIRTF and the six legacy programs are described briefly. Then the cores to disks (c2d) program is described in more detail. The c2d program will use all three SIRTF instruments (IRAC, MIPS, and IRS) to observe sources from molecular cores to protoplanetary disks, with a wide range of cloud masses, stellar masses, and star-forming environments. The SIRTF data will stimulate many follow-up studies, both with SIRTF and with other instruments.Comment: 6 pages, from Fourth Cologne-Bonn-Zermatt-Symposium, The Dense Interstellar Matter in Galaxie

Diffusion tensor image segmentation of the cerebrum provides a single measure of cerebral small vessel disease severity related to cognitive change.

Cerebral small vessel disease (SVD) is the primary cause of vascular cognitive impairment and is associated with decline in executive function (EF) and information processing speed (IPS). Imaging biomarkers are needed that can monitor and identify individuals at risk of severe cognitive decline. Recently there has been interest in combining several magnetic resonance imaging (MRI) markers of SVD into a unitary score to describe disease severity. Here we apply a diffusion tensor image (DTI) segmentation technique (DSEG) to describe SVD related changes in a single unitary score across the whole cerebrum, to investigate its relationship with cognitive change over a three-year period. 98 patients (aged 43-89) with SVD underwent annual MRI scanning and cognitive testing for up to three years. DSEG provides a vector of 16 discrete segments describing brain microstructure of healthy and/or damaged tissue. By calculating the scalar product of each DSEG vector in reference to that of a healthy ageing control we generate an angular measure (DSEG θ) describing the patients' brain tissue microstructural similarity to a disease free model of a healthy ageing brain. Conventional MRI markers of SVD brain change were also assessed including white matter hyperintensities, cerebral atrophy, incident lacunes, cerebral-microbleeds, and white matter microstructural damage measured by DTI histogram parameters. The impact of brain change on cognition was explored using linear mixed-effects models. Post-hoc sample size analysis was used to assess the viability of DSEG θ as a tool for clinical trials. Changes in brain structure described by DSEG θ were related to change in EF and IPS (p < 0.001) and remained significant in multivariate models including other MRI markers of SVD as well as age, gender and premorbid IQ. Of the conventional markers, presence of new lacunes was the only marker to remain a significant predictor of change in EF and IPS in the multivariate models (p = 0.002). Change in DSEG θ was also related to change in all other MRI markers (p < 0.017), suggesting it may be used as a surrogate marker of SVD damage across the cerebrum. Sample size estimates indicated that fewer patients would be required to detect treatment effects using DSEG θ compared to conventional MRI and DTI markers of SVD severity. DSEG θ is a powerful tool for characterising subtle brain change in SVD that has a negative impact on cognition and remains a significant predictor of cognitive change when other MRI markers of brain change are accounted for. DSEG provides an automatic segmentation of the whole cerebrum that is sensitive to a range of SVD related structural changes and successfully predicts cognitive change. Power analysis shows DSEG θ has potential as a monitoring tool in clinical trials. As such it may provide a marker of SVD severity from a single imaging modality (i.e. DTIs)

Concentrations of procalcitonin and C-reactive protein, white blood cell count, and the immature-to-total neutrophil ratio in the blood of neonates with nosocomial infections: Gram-negative bacilli vs coagulase-negative staphylococci

This study was undertaken to determine whether concentrations of procalcitonin in the blood of neonates with nosocomial infections depend on the type of pathogen. Qualification for the study group was based on the clinical signs of infection. We found that infections with Gram-positive (chiefly coagulase-negative staphylococci) and Gram-negative bacteria are accompanied by elevated concentrations of procalcitonin. In the case of Gram-positive bacteria, other laboratory signs of infection studied by us (concentration of C-reactive protein, white blood cell count, immature-to-total neutrophil ratio) were not discriminatory, confirming the diagnostic usefulness of procalcitonin measurements in nosocomial infections of the neonate with Gram-negative or Gram-positive bacteria

A Bayesian method for evaluating and discovering disease loci associations

Background: A genome-wide association study (GWAS) typically involves examining representative SNPs in individuals from some population. A GWAS data set can concern a million SNPs and may soon concern billions. Researchers investigate the association of each SNP individually with a disease, and it is becoming increasingly commonplace to also analyze multi-SNP associations. Techniques for handling so many hypotheses include the Bonferroni correction and recently developed Bayesian methods. These methods can encounter problems. Most importantly, they are not applicable to a complex multi-locus hypothesis which has several competing hypotheses rather than only a null hypothesis. A method that computes the posterior probability of complex hypotheses is a pressing need. Methodology/Findings: We introduce the Bayesian network posterior probability (BNPP) method which addresses the difficulties. The method represents the relationship between a disease and SNPs using a directed acyclic graph (DAG) model, and computes the likelihood of such models using a Bayesian network scoring criterion. The posterior probability of a hypothesis is computed based on the likelihoods of all competing hypotheses. The BNPP can not only be used to evaluate a hypothesis that has previously been discovered or suspected, but also to discover new disease loci associations. The results of experiments using simulated and real data sets are presented. Our results concerning simulated data sets indicate that the BNPP exhibits both better evaluation and discovery performance than does a p-value based method. For the real data sets, previous findings in the literature are confirmed and additional findings are found. Conclusions/Significance: We conclude that the BNPP resolves a pressing problem by providing a way to compute the posterior probability of complex multi-locus hypotheses. A researcher can use the BNPP to determine the expected utility of investigating a hypothesis further. Furthermore, we conclude that the BNPP is a promising method for discovering disease loci associations. © 2011 Jiang et al

The primordial Helium-4 abundance determination: systematic effects

By extrapolating to O/H = N/H = 0 the empirical correlations Y-O/H and Y-N/H defined by a relatively large sample of ~ 45 Blue Compact Dwarfs (BCDs), we have obtained a primordial 4Helium mass fraction Yp= 0.2443+/-0.0015 with dY/dZ = 2.4+/-1.0. This result is in excellent agreement with the average Yp= 0.2452+/-0.0015 determined in the two most metal-deficient BCDs known, I Zw 18 (Zsun/50) and SBS 0335-052 (Zsun/41), where the correction for He production is smallest. The quoted error (1sigma) of < 1% is statistical and does not include systematic effects. We examine various systematic effects including collisional excitation of Hydrogen lines, ionization structure and temperature fluctuation effects, and underlying stellar HeI absorption, and conclude that combining all systematic effects, our Yp may be underestimated by ~ 2-4%. Taken at face value, our Yp implies a baryon-to-photon number ratio eta = 4.7x10^-10 and a baryon mass fraction Omega_b h^2_{100} = 0.017+/-0.005 (2sigma), consistent with the values obtained from deuterium and Cosmic Microwave Background measurements. Correcting Yp upward by 2-4% would make the agreement even better.Comment: 12 pages, 5 PS figures, to appear in "Matter in the Universe", ed P. Jetzer, K. Pretzl and R. von Steiger, Kluwer, Dordrecht (2002

Molecular basis of FIR-mediated c-myc transcriptional control

The far upstream element (FUSE) regulatory system promotes a peak in the concentration of c-Myc during cell cycle. First, the FBP transcriptional activator binds to the FUSE DNA element upstream of the c-myc promoter. Then, FBP recruits its specific repressor (FIR), which acts as an on/off transcriptional switch. Here we describe the molecular basis of FIR recruitment, showing that the tandem RNA recognition motifs of FIR provide a platform for independent FUSE DNA and FBP protein binding and explaining the structural basis of the reversibility of the FBP-FIR interaction. We also show that the physical coupling between FBP and FIR is modulated by a flexible linker positioned sequentially to the recruiting element. Our data explain how the FUSE system precisely regulates c-myc transcription and suggest that a small change in FBP-FIR affinity leads to a substantial effect on c-Myc concentration.MRC Grant-in-aid U11757455

Altered growth characteristics of skin fibroblasts from wild-derived mice, and genetic loci regulating fibroblast clone size

Mouse fibroblast senescence in vitro is an important model for the study of aging at cellular level. However, common laboratory mouse strains may have lost some important allele variations related to aging processes. In this study, growth in vitro of tail skin fibroblasts (TSFs) derived from a wild-derived stock, Pohnpei (Pohn) mice, differed from growth of control C57BL/6 J (B6) TSFs. Pohn TSFs exhibited higher proliferative ability, fewer apoptotic cells, decreased expression of Cip1 , smaller surface areas, fewer cells positive for senescence associated-β-galactosidase (SA-β-gal) and greater resistance to H 2 O 2 -induced SA-β-gal staining and Cip1 expression. These data suggest that TSFs from Pohn mice resist cellular senescence-like changes. Using large clone ratio (LCR) as the phenotype, a quantitative trait locus (QTL) analysis in a Pohn/B6 backcross population found four QTLs for LCR: Fcs1 on Chr 3 at 55 cm; Fcs2 on Chr X at 50 cm; Fcs3 on Chr 4 at 51 cm and Fcs4 on Chr 10 at 25 cm. Together, these four QTLs explain 26.1% of the variations in LCRs in the N2 population. These are the first QTLs reported that regulate fibroblast growth. Glutathione S transferase mu ( GST-mu ) genes are overrepresented in the 95% confidence interval of Fcs1 , and Pohn TSFs have higher H 2 O 2 -induced GST-mu 4 , 5 and 7 mRNA levels than B6 TSFs. These enzymes may protect Pohn TSFs from oxidation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71416/1/j.1474-9726.2006.00208.x.pd

Effectiveness of interventions for diagnosis and treatment of tuberculosis in hard-to-reach populations in countries of low and medium tuberculosis incidence: a systematic review

Tuberculosis is over-represented in hard-to-reach (underserved) populations in high-income countries of low tuberculosis incidence. The mainstay of tuberculosis care is early detection of active tuberculosis (case finding), contact tracing, and treatment completion. We did a systematic review with a scoping component of relevant studies published between 1990 and 2015 to update and extend previous National Institute for Health and Care Excellence (NICE) reviews on the effectiveness of interventions for identifying and managing tuberculosis in hard-to-reach populations. The analyses showed that tuberculosis screening by (mobile) chest radiography improved screening coverage and tuberculosis identification, reduced diagnostic delay, and was cost-effective among several hard-to-reach populations. Sputum culture for pre-migration screening and active referral to a tuberculosis clinic improved identification. Furthermore, monetary incentives improved tuberculosis identification and management among drug users and homeless people. Enhanced case management, good cooperation between services, and directly observed therapy improved treatment outcome and compliance. Strong conclusions cannot be drawn because of the heterogeneity of evidence with regard to study population, methodology, and quality