ZFOURGE: Extreme 5007A˚\AA emission may be a common early-lifetime phase for star-forming galaxies at z>2.5z > 2.5

Using the \prospector\ spectral energy distribution (SED) fitting code, we analyze the properties of 19 Extreme Emission Line Galaxies (EELGs) identified in the bluest composite SED in the \zfourge\ survey at $2.5 \leq z \leq 4$. \prospector\ includes a physical model for nebular emission and returns probability distributions for stellar mass, stellar metallicity, dust attenuation, and nonparametric star formation history (SFH). The EELGs show evidence for a starburst in the most recent 50 Myr, with the median EELG having a specific star formation rate (sSFR) of 4.6 Gyr$^{-1}$ and forming 15\% of its mass in this short time. For a sample of more typical star-forming galaxies (SFGs) at the same redshifts, the median SFG has a sSFR of 1.1 Gyr$^{-1}$ and forms only $4\%$ of its mass in the last 50 Myr. We find that virtually all of our EELGs have rising SFHs, while most of our SFGs do not. From our analysis, we hypothesize that many, if not most, star-forming galaxies at $z \geq 2.5$ undergo an extreme H$\beta$+[\hbox{{\rm O}\kern 0.1em{\sc iii}}] emission line phase early in their lifetimes. In a companion paper, we obtain spectroscopic confirmation of the EELGs as part of our {\sc MOSEL} survey. In the future, explorations of uncertainties in modeling the UV slope for galaxies at $z>2$ are needed to better constrain their properties, e.g. stellar metallicities.Comment: 11 pages, 5 figures (main figure is fig 5), accepted for publication in Ap

An In Vitro System for Studying Murid Herpesvirus-4 Latency and Reactivation

The narrow species tropisms of Epstein-Barr Virus (EBV) and the Kaposi's Sarcoma -associated Herpesvirus (KSHV) have made Murid Herpesvirus-4 (MuHV-4) an important tool for understanding how gammaherpesviruses colonize their hosts. However, while MuHV-4 pathogenesis studies can assign a quantitative importance to individual genes, the complexity of in vivo infection can make the underlying mechanisms hard to discern. Furthermore, the lack of good in vitro MuHV-4 latency/reactivation systems with which to dissect mechanisms at the cellular level has made some parallels with EBV and KSHV hard to draw. Here we achieved control of the MuHV-4 lytic/latent switch in vitro by modifying the 5′ untranslated region of its major lytic transactivator gene, ORF50. We terminated normal ORF50 transcripts by inserting a polyadenylation signal and transcribed ORF50 instead from a down-stream, doxycycline-inducible promoter. In this way we could establish fibroblast clones that maintained latent MuHV-4 episomes without detectable lytic replication. Productive virus reactivation was then induced with doxycycline. We used this system to show that the MuHV-4 K3 gene plays a significant role in protecting reactivating cells against CD8+ T cell recognition

Effects of insurance status on children's access to specialty care: a systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>The current climate of rising health care costs has led many health insurance programs to limit benefits, which may be problematic for children needing specialty care. Findings from pediatric primary care may not transfer to pediatric specialty care because pediatric specialists are often located in academic medical centers where institutional rules determine accepted insurance. Furthermore, coverage for pediatric specialty care may vary more widely due to systematic differences in inclusion on preferred provider lists, lack of availability in staff model HMOs, and requirements for referral. Our objective was to review the literature on the effects of insurance status on children's access to specialty care.</p> <p>Methods</p> <p>We conducted a systematic review of original research published between January 1, 1992 and July 31, 2006. Searches were performed using Pubmed.</p> <p>Results</p> <p>Of 30 articles identified, the majority use number of specialty visits or referrals to measure access. Uninsured children have poorer access to specialty care than insured children. Children with public coverage have better access to specialty care than uninsured children, but poorer access compared to privately insured children. Findings on the effects of managed care are mixed.</p> <p>Conclusion</p> <p>Insurance coverage is clearly an important factor in children's access to specialty care. However, we cannot determine the structure of insurance that leads to the best use of appropriate, quality care by children. Research about specific characteristics of health plans and effects on health outcomes is needed to determine a structure of insurance coverage that provides optimal access to specialty care for children.</p

Combining Independent, Weighted P-Values: Achieving Computational Stability by a Systematic Expansion with Controllable Accuracy

Given the expanding availability of scientific data and tools to analyze them, combining different assessments of the same piece of information has become increasingly important for social, biological, and even physical sciences. This task demands, to begin with, a method-independent standard, such as the -value, that can be used to assess the reliability of a piece of information. Good's formula and Fisher's method combine independent -values with respectively unequal and equal weights. Both approaches may be regarded as limiting instances of a general case of combining -values from groups; -values within each group are weighted equally, while weight varies by group. When some of the weights become nearly degenerate, as cautioned by Good, numeric instability occurs in computation of the combined -values. We deal explicitly with this difficulty by deriving a controlled expansion, in powers of differences in inverse weights, that provides both accurate statistics and stable numerics. We illustrate the utility of this systematic approach with a few examples. In addition, we also provide here an alternative derivation for the probability distribution function of the general case and show how the analytic formula obtained reduces to both Good's and Fisher's methods as special cases. A C++ program, which computes the combined -values with equal numerical stability regardless of whether weights are (nearly) degenerate or not, is available for download at our group website http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/CoinedPValues.html

A clinical pathway for community-acquired pneumonia: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>Six hospitals instituted a voluntary, system-wide, pathway for community acquired pneumonia (CAP). We proposed this study to determine the impact of pathway antibiotics on patient survival, hospital length of stay (LOS), and total hospital cost.</p> <p>Methods</p> <p>Data were collected for adults from six U.S. hospitals with a principal CAP discharge diagnosis code, a chest infiltrate, and medical notes indicative of CAP from 2005-2007. Pathway and non-pathway cohorts were assigned according to antibiotics received within 48 hours of admission. Pathway antibiotics included levofloxacin 750 mg monotherapy or ceftriaxone 1000 mg plus azithromycin 500 mg daily. Multivariable regression models assessed 90-day mortality, hospital LOS, total hospital cost, and total pharmacy cost.</p> <p>Results</p> <p>Overall, 792 patients met study criteria. Of these, 505 (64%) received pathway antibiotics and 287 (36%) received non-pathway antibiotics. Adjusted means and p-values were derived from Least Squares regression models that included Pneumonia Severity Index risk class, patient age, heart failure, chronic obstructive pulmonary disease, and admitting hospital as covariates. After adjustment, patients who received pathway antibiotics experienced lower adjusted 90-day mortality (<it>p </it>= 0.02), shorter mean hospital LOS (3.9 vs. 5.0 days, <it>p </it>< 0.01), lower mean hospital costs ($2,485 vs.$3,281, <it>p </it>= 0.02), and similar mean pharmacy costs ($356 vs.$442, <it>p </it>= 0.11).</p> <p>Conclusions</p> <p>Pathway antibiotics were associated with improved patient survival, hospital LOS, and total hospital cost for patients admitted to the hospital with CAP.</p

Fast core rotation in red-giant stars revealed by gravity-dominated mixed modes

When the core hydrogen is exhausted during stellar evolution, the central region of a star contracts and the outer envelope expands and cools, giving rise to a red giant, in which convection occupies a large fraction of the star. Conservation of angular momentum requires that the cores of these stars rotate faster than their envelopes, and indirect evidence supports this. Information about the angular momentum distribution is inaccessible to direct observations, but it can be extracted from the effect of rotation on oscillation modes that probe the stellar interior. Here, we report the detection of non-rigid rotation in the interiors of red-giant stars by exploiting the rotational frequency splitting of recently detected mixed modes. We demonstrate an increasing rotation rate from the surface of the star to the stellar core. Comparing with theoretical stellar models, we conclude that the core must rotate at least ten times faster than the surface. This observational result confirms the theoretical prediction of a steep gradient in the rotation profile towards the deep stellar interior.Comment: to appear as a Letter to Natur

Prior immunity helps to explain wave-like behaviour of pandemic influenza in 1918-9

<p>Abstract</p> <p>Background</p> <p>The ecology of influenza may be more complex than is usually assumed. For example, despite multiple waves in the influenza pandemic of 1918-19, many people in urban locations were apparently unaffected. Were they unexposed, or protected by pre-existing cross-immunity in the first wave, by acquired immunity in later waves, or were their infections asymptomatic?</p> <p>Methods</p> <p>We modelled all these possibilities to estimate parameters to best explain patterns of repeat attacks in 24,706 individuals potentially exposed to summer, autumn and winter waves in 12 English populations during the 1918-9 pandemic.</p> <p>Results</p> <p>Before the summer wave, we estimated that only 52% of persons (95% credibility estimates 41-66%) were susceptible, with the remainder protected by prior immunity. Most people were exposed, as virus transmissibility was high with R₀credibility estimates of 3.10-6.74. Because of prior immunity, estimates of effective R at the start of the summer wave were lower at 1.57-3.96. Only 25-66% of exposed and susceptible persons reported symptoms. After each wave, 33-65% of protected persons became susceptible again before the next wave through waning immunity or antigenic drift. Estimated rates of prior immunity were less in younger populations (19-59%) than in adult populations (38-66%), and tended to lapse more frequently in the young (49-92%) than in adults (34-76%).</p> <p>Conclusions</p> <p>Our model for pandemic influenza in 1918-9 suggests that pre-existing immune protection, presumably induced by prior exposure to seasonal influenza, may have limited the pandemic attack-rate in urban populations, while the waning of that protection likely contributed to recurrence of pandemic waves in exposed cities. In contrast, in isolated populations, pandemic attack rates in 1918-9 were much higher than in cities, presumably because prior immunity was less in populations with infrequent prior exposure to seasonal influenza. Although these conclusions cannot be verified by direct measurements of historical immune mechanisms, our modelling inferences from 1918-9 suggest that the spread of the influenza A (H1N1) 2009 pandemic has also been limited by immunity from prior exposure to seasonal influenza. Components of that immunity, which are measurable, may be short-lived, and not necessarily correlated with levels of HI antibody.</p

Disparities in preventive procedures: comparisons of self-report and Medicare claims data

BACKGROUND: Racial/ethnic disparities are assessed using either self-report or claims data. We compared these two data sources and examined contributors to discrepancies in estimates of disparities. METHODS: We analyzed self-report and matching claims data from Medicare Beneficiaries 65 and older who participated in the Medicare Current Beneficiary Survey, 1999–2002. Six preventive procedures were included: PSA testing, influenza vaccination, Pap smear testing, cholesterol testing, mammography, and colorectal cancer testing. We examined predictors of self-reports in the absence of claims and claims in the absence of self-reports. RESULTS: With the exception of PSA testing, racial/ethnic disparities in preventive procedures are generally larger when using Medicare claims than when using patients' self-report. Analyses adjusting for age, gender, income, educational level, health status, proxy response and supplemental insurance showed that minorities were more likely to self-report preventive procedures in the absence of claims. Adjusted odds ratios ranged from 1.07 (95% CI: 0.88 – 1.30) for PSA testing to 1.83 (95% CI: 1.46 – 2.30) for Pap smear testing. Rates of claims in the absence of self-report were low. Minorities were more likely to have PSA test claims in the absence of self-reports (1.55 95% CI: 1.17 – 2.06), but were less likely to have influenza vaccination claims in the absence of self-reports (0.69 95% CI: 0.51 – 0.93). CONCLUSION: These findings are consistent with either racial/ethnic reporting biases in receipt of preventive procedures or less efficient Medicare billing among providers with large minority practices

The role of bioreductive activation of doxorubicin in cytotoxic activity against leukaemia HL60-sensitive cell line and its multidrug-resistant sublines

Clinical usefulness of doxorubicin (DOX) is limited by the occurrence of multidrug resistance (MDR) associated with the presence of membrane transporters (e.g. P-glycoprotein, MRP1) responsible for the active efflux of drugs out of resistant cells. Doxorubicin is a well-known bioreductive antitumour drug. Its ability to undergo a one-electron reduction by cellular oxidoreductases is related to the formation of an unstable semiquionone radical and followed by the production of reactive oxygen species. There is an increasing body of evidence that the activation of bioreductive drugs could result in the alkylation or crosslinking binding of DNA and lead to the significant increase in the cytotoxic activity against tumour cells. The aim of this study was to examine the role of reductive activation of DOX by the human liver NADPH cytochrome P450 reductase (CPR) in increasing its cytotoxic activity especially in regard to MDR tumour cells. It has been evidenced that, upon CPR catalysis, DOX underwent only the redox cycling (at low NADPH concentration) or a multistage chemical transformation (at high NADPH concentration). It was also found, using superoxide dismutase (SOD), that the first stage undergoing reductive activation according to the mechanism of the redox cycling had the key importance for the metabolic conversion of DOX. In the second part of this work, the ability of DOX to inhibit the growth of human promyelocytic-sensitive leukaemia HL60 cell line as well as its MDR sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX) was studied in the presence of exogenously added CPR. Our assays showed that the presence of CPR catalysing only the redox cycling of DOX had no effect in increasing its cytotoxicity against sensitive and MDR tumour cells. In contrast, an important increase in cytotoxic activity of DOX after its reductive conversion by CPR was observed against HL60 as well as HL60/VINC and HL60/DOX cells