An efficient method to identify,date, and describe admixture events using haplotype information

We present fastGLOBETROTTER, an efficient new haplotype-based technique to identify, date, and describe admixture events using genome-wide autosomal data. With simulations, we show how fastGLOBETROTTER reduces computation time by an order of magnitude relative to the related technique GLOBETROTTER without suffering loss of accuracy. We apply fastGLOBETROTTER to a cohort of more than 6000 Europeans from 10 countries, revealing previously unreported admixture signals. In particular, we infer multiple periods of admixture related to East Asian or Siberian-like sources, starting >2000 yr ago, in people living in countries north of the Baltic Sea. In contrast, we infer admixture related to West Asian, North African, and/or Southern European sources in populations south of the Baltic Sea, including admixture dated to ∼300–700 CE, overlapping the fall of the Roman Empire, in people from Belgium, France, and parts of Germany. Our new approach scales to analyzing hundreds to thousands of individuals from a putatively admixed population and, hence, is applicable to emerging large-scale cohorts of genetically homogeneous populations.

In recent years, numerous techniques have emerged that exploit expected patterns of linkage disequilibrium (LD) among single-nucleotide-polymorphisms (SNPs) in admixed populations that descend from the intermixing of multiple ancestral sources in order to identify, describe, and date these admixture events. Many of these techniques assume a pulse(s) of instantaneous admixture between two or more sources, followed by random mating in the admixed population (Falush et al. 2003). Under this model, the probability of inheriting two DNA segments from the same ancestral source along the genome of an admixed individual decays exponentially, with a rate proportional to the date of admixture (in generations ago) and genetic distance between the segments (Hellenthal et al. 2014). This relationship is exploited by software, including ROLLOFF (Moorjani et al. 2011; Patterson et al. 2012), ALDER (Loh et al. 2013), MALDER (Pickrell et al. 2014), GLOBETROTTER (Hellenthal et al. 2014), and MOSAIC (Salter-Townshend and Myers 2019). These approaches can date such admixture events, as well as estimate the proportions of DNA contributed by each admixing source. In contrast to other admixture inference techniques (e.g., Pool and Nielsen 2009), an additional advantage is that they do not require accurately assigning each local segment of an admixed person''s genome to one of the admixing sources, which can be challenging in cases in which admixing sources are genetically similar. These techniques and others have shown admixture occurring in the past ∼4000 yr to be ubiquitous among modern human populations (Loh et al. 2013; Hellenthal et al. 2014).To infer admixture, each technique uses a set of sampled reference populations that act as surrogates to the admixing sources. Although ROLLOFF and ALDER identify a single best surrogate for each admixing source by finding the best model fit out of pairings of available surrogates, GLOBETROTTER and MOSAIC infer the genetic make-up of each source as a mixture of DNA from all surrogate groups, that is, without requiring one prespecified surrogate per source, giving these approaches more flexibility. Furthermore, although ROLLOFF, ALDER, and MALDER do not model fine-scale haplotype information, GLOBETROTTER and MOSAIC leverage this information when inferring the probabilities of descending from each admixing source for segments along an admixed individual''s genome. Using such haplotype information can be more powerful for characterizing admixture signals when using densely genotyped or sequenced individuals (Hellenthal et al. 2014; Wangkumhang and Hellenthal 2018). Also, although MALDER, MOSAIC, and GLOBETROTTER can each infer multiple dates of admixture, presently among these, only GLOBETROTTER can infer multiple pulses of admixture involving the same surrogate groups.However, a key drawback of GLOBETROTTER is its computational complexity. In particular, inferring and dating admixture in a target population of more than 100 individuals might take GLOBETROTTER over a month on a single computing node. Here, we present fastGLOBETROTTER, a new method that increases the speed of inferring admixture events, for example, performing the same analysis in less than a day, without sacrificing accuracy relative to GLOBETROTTER. We compare both methods using simulations of admixture events with a wide range of dates, admixture proportions, and varying degrees of genetic similarity among the admixing sources. We also assess fastGLOBETROTTER''s sensitivity to demographic effects like strong bottlenecks. Finally, we apply fastGLOBETROTTER to a cohort of 6209 Europeans from 10 countries genotyped at 477,417 SNPs (Sawcer et al. 2011), inferring previously unreported admixture signals spanning Europe.     

The improvement in hole-transporting and electroluminescent properties of diketopyrrolopyrrole pigment by grafting with carbazole dendrons

Diketopyrrolopyrrole (DPP) pigments are essential and have been intensively exploited as building-blocks for the synthesis of organic semiconducting polymers and small molecules; however, DPP derivatives as emissive materials for electroluminescent (EL) devices have rarely been explored. In this work, a series of new DPP derivatives grafted with carbazole dendrons in a non-conjugated fashion using an amide linkage was designed to improve the performance of DPP in EL devices. Three DPP derivatives (G0DPP, G1DPP and G2DPP) bearing di(p-chlorophenyl)-DPP (Pigment Red 254) as the core substituted with a hexyl chain, N-hexyl carbazole and N-hexyl-N′-9,3′:6′,N′′-tercarbazole, respectively, were synthesized to afford improved hole-transporting properties without affecting the photophysical and electronic properties of the DPP core. The synthesized DPP derivatives displayed an intense yellow fluorescence emission peaked at 536 nm with an absolute photoluminescence quantum yield close to unity in solution. The hole-transporting capability of molecules was improved when carbazole dendrons were incorporated, which increased with an increase in the generation of substituent carbazole dendrons in the order of G0DPP < G1DPP < G2DPP. Significantly, the use of G2DPP, showing the highest hole mobility, in an EL device yielded a strong and stable yellow emission peaked at 556 nm (CIE x, y color coordinates of (0.45, 0.53)) with a brightness of 3060 cd m⁻², maximum luminous efficiency of 9.24 cd A⁻¹ and a maximum EQE of 3.11%.

Diketopyrrolopyrrole pigments grafted with carbazole dendrons in OLEDs exhibit strong and stable yellow emissions with brightness of 3060 cd m⁻², luminous efficiency of 9.24 cd A⁻¹ and EQE of 3.11%.     

Effects of prehospital adrenaline administration on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis

Introduction

The aim of this study was to conduct a systematic review and meta-analysis for determining the effects of prehospital adrenaline administration on return of spontaneous circulation, hospital admission, survival to discharge and discharge with cerebral performance category 1 or 2 in out-of-hospital cardiac arrest patients.

Methods

MEDLINE and Scopus databases were searched to identify studies reported to March 2014. Study selection and data extraction were independently completed by two reviewers (PA and SR). The baseline characteristics of each study and number of events were extracted. Risk ratios (RR) and 95% confidence interval (CI) were estimated. Heterogeneity and publication bias were also explored.

Results

In total 15 studies were eligible and included in the study. Of 13 adult observational studies, four to eight studies were pooled for each outcome. These yielded a total sample size that ranged from 2,381 to 421,459. A random effects model suggested that patients receiving prehospital adrenaline were 2.89 times (95% CI: 2.36, 3.54) more likely to achieve prehospital return of spontaneous circulation than those not administered adrenaline. However, there were no significant effects on overall return of spontaneous circulation (RR = 0.93, 95% CI: 0.5, 1.74), admission (RR = 1.05, 95% CI: 0.80, 1.38) and survival to discharge (RR = 0.69, 95% CI: 0.48, 1.00).

Conclusions

Prehospital adrenaline administration may increase prehospital return of spontaneous circulation, but it does not improve overall rates of return of spontaneous circulation, hospital admission and survival to discharge.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0463-7) contains supplementary material, which is available to authorized users.     

Nasal provocation test: how to maximize its clinical use?

In order to diagnose allergic rhinitis (AR), skin prick tests and serum specific IgE level are the most common used methods. But there are some conditions which the results of both methods do not correlate with the clinical presentation of AR. Nasal provocation test is the method of detecting local IgE at the shock organ. There are some variations of NPT in terms of dosage, allergen administration, evaluation and scoring system. This article summarized the usefulness of NPT, its indication and contraindication, dosage and instillation techniques for allergens and evaluation of outcome in the hope that if we can standardize the procedure and make it easier to perform, NPT will be applied more in clinical practice. In addition normal values among Asian ethnics are presented for appropriate interpretation of the test.     

Inhibitory activities of plumbagin on cell migration and invasion and inducing activity on cholangiocarcinoma cell apoptosis

Objective: To investigate the cytotoxic, apoptotic and inhibitory activities on cell migration and invasion of plumbagin in the human cholangiocarcinoma(CCA) cell line(CL-6) in comparison with human embryonic fibroblast cell line(OUMS). Methods: Cytotoxicity activity was evaluated using MTT assay. Inhibitory effect on cell migration and invasion were investigated using label-free real-time cell analysis and QCM ECMatrix cell invasion chamber, respectively. Apoptotic activity was evaluated using flow cytometry and Cell Event? Caspase 3/7 assay. Results: Based on results of the cytotoxicity test in CL-6 cells, 50% inhibitory concentration(IC_(50), Mean±SD) values of plumbagin and the standard drug 5-fluorouracil were(24.00±3.33) and(1 036.00±137.77) μmol/L, respectively. The corresponding values for OUMS cells were(57.00±5.23) and(2 147.00±209.98) μmol/L, respectively. The selectivity index was 2.28. The inhibitory activities of plumbagin on cell migration and invasion were potent and concentration-dependent with IC_(50) of 25.0 μmol/L and complete inhibition at 25.0 μmol/L. Flow cytometry analysis showed that plumbagin at 12.5 μmol/L(half IC_(50)) induced CL-6 cell apoptosis(43.24% of control) through stimulation of caspase 3/7 activities. Complete cell apoptosis was observed at 12.5 μmol/L. Conclusions: The cytotoxic activity and inhibition of migration and invasion including apoptosis induction in the human CCA cell line(CL-6) suggest that plumbagin could be a promising candidate for CCA chemotherapeutics. However, its relatively low selective cytotoxic effect on CCA cells is a major concern.     

Effects of different numbers of mini-dental implants on alveolar ridge strain distribution under mandibular implant-retained overdentures

Purpose

To investigate the strains around mini-dental implants (MDIs) and retromolar edentulous areas when using different numbers of MDIs in order to retain mandibular overdentures.

Modifying morphology and defects of low-dimensional,semi-transparent perovskite thin films via solvent type

(PEA)₂(MA)_n−1Pb_nI_n+1Br_2n perovskites are semi-transparent, color-tunable thin films with broader band gaps. They have the potential for semi-transparent solar cell and smart window applications. Solvent engineering significantly alters the morphology, absorbance, crystallinity, charge separation, and defects, thereby influencing the optoelectronic properties. Herein, we investigated the effect of the solvent type on the low dimensional, mixed halide perovskite thin films (n = 1, 3, and 5) and identified DMF : DMSO = 8 : 2 as the most suitable solvent. The mixed solvent regulated the growth rate of perovskites, which led to the smooth morphology and larger crystallite size. Through surface photovoltage spectroscopy and time resolved photoluminescence, good charge separation and low defects were linked to DD82 usage.

Low dimensional perovskites via DMF : DMSO = 8 : 2 with potential for semi-transparent solar cell led to superior surface morphology with large crystallite size and low defects.     

Ancestry-informative marker (AIM) SNP panel for the Malay population

International Journal of Legal Medicine - Ancestry-informative markers (AIMs) can be used to infer the ancestry of an individual to minimize the inaccuracy of self-reported ethnicity in biomedical...