An Admixture Approach to Trihybrid Ancestry Variation in the Philippines with Implications for Forensic Anthropology

In this study, we investigate, for the first time from a forensic anthropological perspective, the question of mixed ancestry estimation for modern Filipinos with geographic origins in the Philippines. We derive estimates of continental ancestry using craniometrics from four sources: a new documented collection of current forensic significance from the Manila North Cemetery; the Howells cranial series representing a sample of unclaimed individuals from Manila but said largely to originate from more remote areas, with dates of death before 1940; the Hanihara sample aggregated from various locations and time periods across the Philippines; and the Hanihara series capturing various local indigenous, ethnic groups that are together identified as Philippine Negrito. Parental craniometrics are selected from the Howells dataset and more recently collected samples from Europe and Asia. Using unsupervised clustering, we investigate the algorithmically defined three-cluster, or trihybrid admixture, model to infer continental ancestry for each individual, reporting their relative proportions of Asian, European, and African admixture. We employ similar clustering procedures to identify more complex models, with a larger number of clusters, to explore patterns of affinity between our four Philippine samples and the recently acquired samples from Vietnam, Thailand, China (Hong Kong), Japan, and Korea. These analyses give insight into the relationships between both macro and micro geographic regions, such that, at the country level, we reveal how different population dynamics – whether geo-political, -economic, -historical and/or -social – structure the ancestral makeup of Asian peoples, especially in the degree of European and African admixture. From these ancestry estimates, we find that population of origin explains 38-51% of the variation in each ancestry component and we detect significant differences among the Asian samples in their quantities of ancestry. Filipinos appear considerably admixed, as they appear to carry almost 20% less Asian ancestry than the average quantity (90%) estimated for the other Asian groups. We also reveal substructure within our representation of modern Filipinos, such that differences in the patterns of three-way admixture exist between each of the four Philippine samples, finding that the Manila cemetery sample has the highest level of Asian ancestry and, as we might expect, that the Negrito sample has the greatest quantity of African ancestry. We perform additional analyses that introduce craniometrics from the Howells Australo-Melanesian series in order to more fully investigate their relationship to the Asian samples and to better understand the African contributions common to the Philippine Negritos especially, as well as the other Southeast Asians and the Spanish and Portuguese groups. By mapping the cluster patterns on a global scale, these analyses reveal, with craniometrics just as with genetic loci, patterns of affinity that are informative of the complex history of Southeast Asia, as they are suggestive of the vestiges of migration, trade, and colonialism, as well as more recent periods of isolation, marginalization, and occupation

Development of Generalized Correlation for Electrical Conductivity Prediction of Pure Ionic Liquid

Ionic liquids are salts in liquid form that are composed of short-lived ion pairs. They are the new trend of solvent because of their very low vapor pressure, good chemical and thermal stability, and melting temperatures lower than 100°C. Pure ionic liquids contain ions that can conduct electricity or serve as electrolytes. But experimentation using ionic liquids would be expensive. This study aims to develop a generalized correlation for the electrical conductivity prediction of pure ionic liquids. The researchers gathered data of pure ionic liquids that involved the electrical conductivity property from the ThermoIL Database. The collected data were then trimmed based on a developed scheme and classifications. After trimming the data, the researchers evaluated the data using MATLAB software. The residual value was calculated, and a parity plot was constructed to test the models’ accuracy. The researchers gathered 2,425 data points from 310 references and were trimmed to 220 data points from 21 references. The parity plot and graph of the residuals plotted against pressure showed that the experimental and calculated values were close. Results showed that the electrical conductivity of pure ionic liquids could be predicted using a model patterned to Pitzer correlation with reduced temperature and reduced pressure as variables. Data with two or more references and low uncertainty made a good result on the models to create a generalized correlation via curve fitting

Co-Evaluation of Pattern Matching Algorithms on IoT Devices with Embedded GPUs

Pattern matching is an important building block for many security applications, including Network Intrusion Detection Systems (NIDS). As NIDS grow in functionality and complexity, the time overhead and energy consumption of pattern matching become a significant consideration that limits the deployability of such systems, especially on resource-constrained devices.\ua0On the other hand, the emergence of new computing platforms, such as embedded devices with integrated, general-purpose Graphics Processing Units (GPUs), brings new, interesting challenges and opportunities for algorithm design in this setting: how to make use of new architectural features and how to evaluate their effect on algorithm performance. Up to now, work that focuses on pattern matching for such platforms has been limited to specific algorithms in isolation.In this work, we present a systematic and comprehensive benchmark that allows us to co-evaluate both existing and new pattern matching algorithms on heterogeneous devices equipped with embedded GPUs, suitable for medium- to high-level IoT deployments. We evaluate the algorithms on such a heterogeneous device, in close connection with the architectural features of the platform and provide insights on how these features affect the algorithms\u27 behavior. We find that, in our target embedded platform, GPU-based pattern matching algorithms have competitive performance compared to the CPU and consume half as much energy as the CPU-based variants.\ua0Based on these insights, we also propose HYBRID, a new pattern matching approach that efficiently combines techniques from existing approaches and outperforms them by 1.4x, across a range of realistic and synthetic data sets. Our benchmark details the effect of various optimizations, thus providing a path forward to make existing security mechanisms such as NIDS deployable on IoT devices

Colorectal Cancers from Distinct Ancestral Populations Show Variations in BRAF Mutation Frequency

It has been demonstrated for some cancers that the frequency of somatic oncogenic mutations may vary in ancestral populations. To determine whether key driver alterations might occur at different frequencies in colorectal cancer, we applied a high-throughput genotyping platform (OncoMap) to query 385 mutations across 33 known cancer genes in colorectal cancer DNA from 83 Asian, 149 Black and 195 White patients. We found that Asian patients had fewer canonical oncogenic mutations in the genes tested (60% vs Black 79% (P = 0.011) and White 77% (P = 0.015)), and that BRAF mutations occurred at a higher frequency in White patients (17% vs Asian 4% (P = 0.004) and Black 7% (P = 0.014)). These results suggest that the use of genomic approaches to elucidate the different ancestral determinants harbored by patient populations may help to more precisely and effectively treat colorectal cancer

Towards HCP-Style macaque connectomes: 24-Channel 3T multi-array coil, MRI sequences and preprocessing

© 2020 The Author(s) Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the smaller macaque brain, high spatial, temporal, and angular resolutions combined with high signal-to-noise ratio are required to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enables adaptation of the Human Connectome Project (HCP) image acquisition protocols to the in-vivo macaque brain. In addition, we adapted HCP preprocessing methods to the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provides the necessary high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold accelerations for dMRI and fMRI. Automated FreeSurfer segmentation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI all performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. Analyses of functional connectivity in fMRI revealed high sensitivity as compared with those from publicly shared datasets. Tractography-based connectivity estimates correlated with tracer connectivity similarly to that achieved using ex-vivo dMRI. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available in studies of the human brain

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Pharmacological Inhibition of O-GlcNAcase Enhances Autophagy in Brain through an mTOR-Independent Pathway

The glycosylation of nucleocytoplasmic proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) is conserved among metazoans and is particularly abundant within brain. O-GlcNAc is involved in diverse cellular processes ranging from the regulation of gene expression to stress response. Moreover, O-GlcNAc is implicated in various diseases including cancers, diabetes, cardiac dysfunction, and neurodegenerative diseases. Pharmacological inhibition of O-GlcNAcase (OGA), the sole enzyme that removes O-GlcNAc, reproducibly slows neurodegeneration in various Alzheimer’s disease (AD) mouse models manifesting either tau or amyloid pathology. These data have stimulated interest in the possibility of using OGA-selective inhibitors as pharmaceuticals to alter the progression of AD. The mechanisms mediating the neuroprotective effects of OGA inhibitors, however, remain poorly understood. Here we show, using a range of methods in neuroblastoma N2a cells, in primary rat neurons, and in mouse brain, that selective OGA inhibitors stimulate autophagy through an mTOR-independent pathway without obvious toxicity. Additionally, OGA inhibition significantly decreased the levels of toxic protein species associated with AD pathogenesis in the JNPL3 tauopathy mouse model as well as the 3×Tg-AD mouse model. These results strongly suggest that OGA inhibitors act within brain through a mechanism involving enhancement of autophagy, which aids the brain in combatting the accumulation of toxic protein species. Our study supports OGA inhibition being a feasible therapeutic strategy for hindering the progression of AD and other neurodegenerative diseases. Moreover, these data suggest more targeted strategies to stimulate autophagy in an mTOR-independent manner may be found within the O-GlcNAc pathway. These findings should aid the advancement of OGA inhibitors within the clinic

Prostate cancer disparities in Black men of African descent: a comparative literature review of prostate cancer burden among Black men in the United States, Caribbean, United Kingdom, and West Africa

<p>Abstract</p> <p>Background</p> <p>African American men have the highest prostate cancer morbidity and mortality rates than any other racial or ethnic group in the US. Although the overall incidence of and mortality from prostate cancer has been declining in White men since 1991, the decline in African American men lags behind White men. Of particular concern is the growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry in the Caribbean Islands, United Kingdom and West Africa. This higher incidence of prostate cancer observed in populations of African descent may be attributed to the fact that these populations share ancestral genetic factors. To better understand the burden of prostate cancer among men of West African Ancestry, we conducted a review of the literature on prostate cancer incidence, prevalence, and mortality in the countries connected by the Transatlantic Slave Trade.</p> <p>Results</p> <p>Several published studies indicate high prostate cancer burden in Nigeria and Ghana. There was no published literature for the countries Benin, Gambia and Senegal that met our review criteria. Prostate cancer morbidity and/or mortality data from the Caribbean Islands and the United Kingdom also provided comparable or worse prostate cancer burden to that of US Blacks.</p> <p>Conclusion</p> <p>The growing literature on the disproportionate burden of prostate cancer among other Black men of West African ancestry follows the path of the Transatlantic Slave Trade. To better understand and address the global prostate cancer disparities seen in Black men of West African ancestry, future studies should explore the genetic and environmental risk factors for prostate cancer among this group.</p