Ethical Issues Associated With Routine Screening and Prophylaxis for Group B Streptococcus in Pregnancy

An increased awareness of the impact of group B streptococcus (GBS) infection on neonatal outcome has prompted several seemingly discordant committee recommendations. Intrapartum antibiotics are effective in reducing the risk of neonatal morbidity when administered to a colonized woman who has a clinical condition that places her neonate at high risk for early-onset sepsis. However, less is known about the efficacy of prophylactic antibiotics in the colonized woman who does not have obvious risk factors. Some authorities have suggested that providers refrain from administering intrapartum antibiotics to colonized women who do not have any of these risk factors, primarily due to concerns about potential adverse reactions, selection of resistant pathogens, and cost-effectiveness. These recommendations may conflict with the desires of an informed woman who weighs the real, albeit low, risk for serious neonatal disease against the lower perceived risk of adverse maternal sequelae from allergic reactions to the antimicrobial agents. Selective prophylaxis for GBS disease that is limited to the colonized parturient with risk factors has the potential for creating conflict because maternal beneficence-based obligations of the physician may be at odds with maternal autonomy-based obligations. We believe that, given all currently available information, providers have a moral obligation to discuss GBS screening and treatment issues with patients. The potential for conflict between patient and physician at the time of delivery can be minimized through the use of preventive ethics, allowing patients to develop advance directives regarding intrapartum management within the confines of reasonable and cost-effective care. Until a consensus is reached among experts, the most prudent approach would be to address such issues proactively and individualize care based upon the overall estimation and anticipation of risk as well as the patient's specific desires

Observations of Giant Pulses from Pulsar PSR B0950+08 using LWA1

We report the detection of giant pulse emission from PSR B0950+08 in 24 hours of observations made at 39.4 MHz, with a bandwidth of 16 MHz, using the first station of the Long Wavelength Array, LWA1. We detected 119 giant pulses from PSR B0950+08 (at its dispersion measure), which we define as having SNRs at least 10 times larger than for the mean pulse in our data set. These 119 pulses are 0.035% of the total number of pulse periods in the 24 hours of observations. The rate of giant pulses is about 5.0 per hour. The cumulative distribution of pulse strength $S$ is a steep power law, $N(>S)\propto S^{-4.7}$, but much less steep than would be expected if we were observing the tail of a Gaussian distribution of normal pulses. We detected no other transient pulses in a dispersion measure range from 1 to 90 pc cm$^{-3}$, in the beam tracking PSR B0950+08. The giant pulses have a narrower temporal width than the mean pulse (17.8 ms, on average, vs. 30.5 ms). The pulse widths are consistent with a previously observed weak dependence on observing frequency, which may be indicative of a deviation from a Kolmogorov spectrum of electron density irregularities along the line of sight. The rate and strength of these giant pulses is less than has been observed at $\sim$100 MHz. Additionally, the mean (normal) pulse flux density we observed is less than at $\sim$100 MHz. These results suggest this pulsar is weaker and produces less frequent giant pulses at 39 MHz than at 100 MHz.Comment: 27 pages, 12 figures, typos correcte

Influenza Outbreaks during World Youth Day 2008 Mass Gathering

Novel viruses were introduced and seasonal viruses were amplified

Observations of Giant Pulses from Pulsar B0950+08 Using LWA1

We report the detection of giant pulse (GP) emission from PSR B0950+08 in 24 hours of observations made at 39.4 MHz, with a bandwidth of 16 MHz, using the first station of the Long Wavelength Array. We detected 119 GPs from PSR B0950+08 (at its dispersion measure (DM)), which we define as having a signal-to-noise ratio at least 10 times larger than for the mean pulse in our data set. These 119 pulses are 0.035% of the total number of pulse periods in the 24 hours of observations. The rate of GPs is about 5.0 per hour. The cumulative distribution of pulse strength S is a steep power law, _N(>S) ∝ S^(-4.7), but much less steep than would be expected if we were observing the tail of a Gaussian distribution of normal pulses. We detected no other transient pulses in a DM range from 1 to 90 pc cm^(−3), in the beam tracking PSR B0950+08. The GPs have a narrower temporal width than the mean pulse (17.8 ms, on average, versus 30.5 ms). The pulse widths are consistent with a previously observed weak dependence on observing frequency, which may be indicative of a deviation from a Kolmogorov spectrum of electron density irregularities along the line of sight. The rate and strength of these GPs is less than has been observed at ~100 MHz. Additionally, the mean (normal) pulse flux density we observed is less than at ~100 MHz. These results suggest this pulsar is weaker and produces less frequent GPs at 39 MHz than at 100 MHz

Downregulation of FIP200 Induces Apoptosis of Glioblastoma Cells and Microvascular Endothelial Cells by Enhancing Pyk2 Activity

The expression of focal adhesion kinase family interacting protein of 200-kDa (FIP200) in normal brain is limited to some neurons and glial cells. On immunohistochemical analysis of biopsies of glioblastoma tumors, we detected FIP200 in the tumor cells, tumor-associated endothelial cells, and occasional glial cells. Human glioblastoma tumor cell lines and immortalized human astrocytes cultured in complete media also expressed FIP200 as did primary human brain microvessel endothelial cells (MvEC), which proliferate in culture and resemble reactive endothelial cells. Downregulation of endogenous expression of FIP200 using small interfering RNA resulted in induction of apoptosis in the human glioblastoma tumor cells, immortalized human astrocytes, and primary human brain MvEC. It has been shown by other investigators using cells from other tissues that FIP200 can interact directly with, and inhibit, proline-rich tyrosine kinase 2 (Pyk2) and focal adhesion kinase (FAK). In the human glioblastoma tumor cells, immortalized human astrocytes, and primary human brain MvEC, we found that downregulation of FIP200 increased the activity of Pyk2 without increasing its expression, but did not affect the activity or expression of FAK. Coimmunoprecipitation and colocalization studies indicated that the endogenous FIP200 was largely associated with Pyk2, rather than FAK, in the glioblastoma tumor cells and brain MvEC. Moreover, the pro-apoptotic effect of FIP200 downregulation was inhibited significantly by a TAT-Pyk2-fusion protein containing the Pyk2 autophosphorylation site in these cells. In summary, downregulation of endogenous FIP200 protein in glioblastoma tumor cells, astrocytes, and brain MvECs promotes apoptosis, most likely due to the removal of a direct interaction of FIP200 with Pyk2 that inhibits Pyk2 activation, suggesting that FIP200 expression may be required for the survival of all three cell types found in glioblastoma tumors

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor

© 2019 Elsevier Inc. Embryonal tumors with multilayered rosettes (ETMRs) are highly lethal infant brain cancers with characteristic amplification of Chr19q13.41 miRNA cluster (C19MC) and enrichment of pluripotency factor LIN28A. Here we investigated C19MC oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. Our data show that this powerful oncogenic circuit, which entraps an early neural lineage network, is potently abrogated by bromodomain inhibitor JQ1, leading to ETMR cell death. Sin-Chan et al. uncover a C19MC-LIN28A-MYCN super-enhancer-dependent oncogenic circuit in embryonal tumors with multilayered rosettes (ETMRs). The circuit entraps an early neural lineage network to sustain embryonic epigenetic programming and is vulnerable to bromodomain inhibition, which promotes ETMR cell death

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses.

Background: Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods: We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results: The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. Conclusions: GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts

Identification and mitigation of narrow spectral artifacts that degrade searches for persistent gravitational waves in the first two observing runs of Advanced LIGO

Searches are under way in Advanced LIGO and Virgo data for persistent gravitational waves from continuous sources, e.g. rapidly rotating galactic neutron stars, and stochastic sources, e.g. relic gravitational waves from the Big Bang or superposition of distant astrophysical events such as mergers of black holes or neutron stars. These searches can be degraded by the presence of narrow spectral artifacts (lines) due to instrumental or environmental disturbances. We describe a variety of methods used for finding, identifying and mitigating these artifacts, illustrated with particular examples. Results are provided in the form of lists of line artifacts that can safely be treated as non-astrophysical. Such lists are used to improve the efficiencies and sensitivities of continuous and stochastic gravitational wave searches by allowing vetoes of false outliers and permitting data cleaning