High-Throughput and Cost-Effective Characterization of Induced Pluripotent Stem Cells.

Reprogramming somatic cells to induced pluripotent stem cells (iPSCs) offers the possibility of studying the molecular mechanisms underlying human diseases in cell types difficult to extract from living patients, such as neurons and cardiomyocytes. To date, studies have been published that use small panels of iPSC-derived cell lines to study monogenic diseases. However, to study complex diseases, where the genetic variation underlying the disorder is unknown, a sizable number of patient-specific iPSC lines and controls need to be generated. Currently the methods for deriving and characterizing iPSCs are time consuming, expensive, and, in some cases, descriptive but not quantitative. Here we set out to develop a set of simple methods that reduce cost and increase throughput in the characterization of iPSC lines. Specifically, we outline methods for high-throughput quantification of surface markers, gene expression analysis of in vitro differentiation potential, and evaluation of karyotype with markedly reduced cost

Weight discordance and perinatal mortality in twin pregnancy: systematic review and meta‐analysis

Objectives The primary aim of this systematic review was to explore the strength of association between birth‐weight (BW) discordance and perinatal mortality in twin pregnancy. The secondary aim was to ascertain the contribution of gestational age and growth restriction in predicting mortality in growth‐discordant twins. Methods MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched. Only studies reporting on the risk of mortality in twin pregnancies affected compared with those not affected by BW discordance were included. The primary outcomes explored were incidence of intrauterine death (IUD), neonatal death (NND) and perinatal death. Outcome was assessed separately for monochorionic (MC) and dichorionic (DC) twin pregnancies. Analyses were stratified according to BW discordance cut‐off (≥ 15%, ≥ 20%, ≥ 25% and ≥ 30%) and selected gestational characteristics, including incidence of IUD or NND before and after 34 weeks' gestation, presence of at least one small‐for‐gestational age (SGA) fetus in the twin pair and both twins being appropriate‐for‐gestational age. Risk of mortality in the larger vs smaller twin was also assessed. Meta‐analyses using individual data random‐effects logistic regression and meta‐analyses of proportion were used to analyze the data. Results Twenty‐two studies (10 877 twin pregnancies) were included in the analysis. In DC pregnancies, a higher risk of IUD, but not of NND, was observed in twins with BW discordance ≥ 15% (odds ratio (OR) 9.8, 95% CI, 3.9–29.4), ≥ 20% (OR 7.0, 95% CI, 4.15–11.8), ≥ 25% (OR 17.4, 95% CI, 8.3–36.7) and ≥ 30% (OR 22.9, 95% CI, 10.2–51.6) compared with those without weight discordance. For each cut‐off of BW discordance explored in DC pregnancies, the smaller twin was at higher risk of mortality compared with the larger one. In MC twin pregnancies, excluding cases affected by twin–twin transfusion syndrome, twins with BW discordance ≥ 20% (OR 2.8, 95% CI, 1.3–5.8) or ≥ 25% (OR 3.2, 95% CI, 1.5–6.7) were at higher risk of IUD, compared with controls. MC pregnancies with ≥ 25% weight discordance were also at increased risk of NND (OR 4.66, 95% CI, 1.8–12.4) compared with those with concordant weight. The risk of IUD was higher when considering discordant pregnancies involving at least one SGA fetus. The overall risk of mortality in MC pregnancies was similar between the smaller and larger twin, except in those with BW discordance ≥ 20%. Conclusion DC and MC twin pregnancies discordant for fetal growth are at higher risk of IUD but not of NND compared with pregnancies with concordant BW. The risk of IUD in BW‐discordant DC and MC twins is higher when at least one fetus is SGA

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines

Initial operation of the International Gravitational Event Collaboration

The International Gravitational Event Collaboration, IGEC, is a coordinated effort by research groups operating gravitational wave detectors working towards the detection of millisecond bursts of gravitational waves. Here we report on the current IGEC resonant bar observatory, its data analysis procedures, the main properties of the first exchanged data set. Even though the available data set is not complete, in the years 1997 and 1998 up to four detectors were operating simultaneously. Preliminary results are mentioned.Comment: 8 pages, 2 figures, 3 tables; Proceeding of the GWDAW'99. Submitted to the International Journal of Modern Physic

Risk factors for abnormally invasive placenta: a systematic review and meta-analysis.

Purpose of the article. To explore the strength of association between different maternal and pregnancy characteristics and the occurrence of abnormally invasive placenta (AIP). MATERIALS AND METHODS: Pubmed, Embase, CINAHL databases were searched. The risk factors for AIP explored were: obesity, age > 35 years, smoking before or during pregnancy, placenta previa, prior cesarean section (CS), placenta previa and prior CS, prior uterine surgery, abortion and uterine curettage, in vitro fertilization (IVF) pregnancy and interval between a previous CS and a subsequent pregnancy. Random-effect head-to-head meta-analyses were used to analyze the data. RESULTS: Forty-six were included in the systematic review. Maternal obesity (Odd ratio, OR: 1.4, 95% CI 1.0-1.8), advanced maternal age (OR: 3.1, 95% CI 1.4-7.0) and parity (OR: 2.5, 95% CI 1.7-3.6), but not smoking were associated with a higher risk of AIP. The presence of placenta previa in women with at least a prior CS was associated with a higher risk of AIP compared to controls, with an OR of 12.0, 95% CI 1.6-88.0. Furthermore, the risk of AIP increased with the number of prior CS (OR of 2.6, 95% CI 1.6-4.4 and 5.4, 95% CI 1.7-17.4 for two and three prior CS respectively). Finally, IVF pregnancies were associated with a high risk of AIP, with an OR of 2.8 (95% CI 1.2-6.8). CONCLUSION: A prior CS and placenta previa are among the strongest risk factors for the occurrence of AIP

Searching for prompt signatures of nearby core-collapse supernovae by a joint analysis of neutrino and gravitational-wave data

We discuss the science motivations and prospects for a joint analysis of gravitational-wave (GW) and low-energy neutrino data to search for prompt signals from nearby supernovae (SNe). Both gravitational-wave and low-energy neutrinos are expected to be produced in the innermost region of a core-collapse supernova, and a search for coincident signals would probe the processes which power a supernova explosion. It is estimated that the current generation of neutrino and gravitational-wave detectors would be sensitive to Galactic core-collapse supernovae, and would also be able to detect electromagnetically dark SNe. A joint GW-neutrino search would enable improvements to searches by way of lower detection thresholds, larger distance range, better live-time coverage by a network of GW and neutrino detectors, and increased significance of candidate detections. A close collaboration between the GW and neutrino communities for such a search will thus go far toward realizing a much sought-after astrophysics goal of detecting the next nearby supernova.Comment: 10 pages, 3 figures. To appear in Class. Quantum Gra

Global change, global trade, and the next wave of plant invasions

Copyright © 2012 Ecological Society of AmericaMany non-native plants in the US have become problematic invaders of native and managed ecosystems, but a new generation of invasive species may be at our doorstep. Here, we review trends in the horticultural trade and invasion patterns of previously introduced species and show that novel species introductions from emerging horticultural trade partners are likely to rapidly increase invasion risk. At the same time, climate change and water restrictions are increasing demand for new types of species adapted to warm and dry environments. This confluence of forces could expose the US to a range of new invasive species, including many from tropical and semiarid Africa as well as the Middle East. Risk assessment strategies have proven successful elsewhere at identifying and preventing invasions, although some modifications are needed to address emerging threats. Now is the time to implement horticulture import screening measures to prevent this new wave of plant invasions.National Science Foundatio

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Astrophysically Triggered Searches for Gravitational Waves: Status and Prospects

In gravitational-wave detection, special emphasis is put onto searches that focus on cosmic events detected by other types of astrophysical observatories. The astrophysical triggers, e.g. from gamma-ray and X-ray satellites, optical telescopes and neutrino observatories, provide a trigger time for analyzing gravitational wave data coincident with the event. In certain cases the expected frequency range, source energetics, directional and progenitor information is also available. Beyond allowing the recognition of gravitational waveforms with amplitudes closer to the noise floor of the detector, these triggered searches should also lead to rich science results even before the onset of Advanced LIGO. In this paper we provide a broad review of LIGO's astrophysically triggered searches and the sources they target