SYSTEM AND METHOD FOR GLOBAL TRAINING

A technique is proposed to translate slide-based documents, for example, into videos with or without captions or subtitles. The presentation intake component extracts a script or speaker notes from the content inputted by the user, and creates a text file corresponding to each slide or image. The translation component then translates the script into multiple target languages. The synthesizing component uses a text-to-speech conversion to create an audio file for each slide or image. The video creator component creates a silent video for each image for the duration of the audio file corresponding to each still image, with or without captions or subtitles created using the translated text. The video creator component merges the silent video files with the audio files in order to produce a final video translation. Along each step of the way, the technique saves each file as intermediate artifacts, which may be downloaded, altered and/or uploaded by the user during the production process

Medicare Expenditures and Healthcare Utilization in a Multi-ethnic Community-based Population with Dementia from Incidence to Death

Introduction: While individuals live with dementia for many years, utilization and expenditures from disease onset through the end-of-life period have not been examined in ethnically diverse samples. Methods: We used a multiethnic, population-based, prospective study of cognitive aging (Washington Heights-Inwood Columbia Aging Project) linked to Medicare claims to examine total Medicare expenditures and health care utilization among individuals with clinically diagnosed incident dementia from disease onset to death. Results: High-intensity treatment (hospitalizations, life-sustaining procedures) was common and mean Medicare expenditures per year after diagnosis was $69,000. Non-Hispanic blacks exhibited higher spending relative to Hispanics and non-Hispanic whites 1 year after diagnosis. Non-Hispanic blacks had higher total (mean=$205,000) Medicare expenditures from diagnosis to death compared with non-Hispanic whites (mean=$118,000). Hispanics’ total expenditures and utilization after diagnosis was similar to non-Hispanic whites despite living longer with dementia. Discussion: Health care spending for patients with dementia after diagnosis through the end-of-life is high and varies by ethnicity

Family history and risk of bladder cancer:an analysis accounting for first- and second-degree relatives

Although evidence suggests that a positive family history of bladder cancer in first-degree relatives is an important risk factor for bladder cancer occurrence, results remain unclear. The influence of family history of non-bladder cancers and more distant relatives on bladder cancer risk is inconsistent. This research therefore, aims to increase the understanding of the association between family history and bladder cancer risk based on worldwide case-control studies. In total 4,327 cases and 8,948 non-cases were included. Pooled odds ratios (ORs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel logistic regression models, adjusted by age, sex, ethnicity, smoking status, and smoking pack-years. The results show bladder cancer risk increased by having a first- or second-degree relative affected with bladder cancer (OR 2.72, 95%CI 1.55-4.77 and OR 1.71, 95%CI 1.22-2.40, respectively), and non-urologic cancers (OR 1.61, 95%CI 1.19-2.18). Moreover, bladder cancer risk increased by number of cancers affected first-degree relatives (for 1 and >1 first-degree relatives: OR 1.42, 95% CI 1.02-2.04; OR 2.67, 95% CI 1.84-3.86, respectively). Our findings highlight an increased bladder cancer risk for a positive bladder cancer family history in first- and second-degree relatives, and indicate a possible greater effect for an increment of numbers of affected relatives

The selection landscape and genetic legacy of ancient Eurasians

The Holocene (beginning around 12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using a dataset of more than 1,600 imputed ancient genomes, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify key selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in over 400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, whereas risk alleles for diabetes and Alzheimer’s disease are enriched for Western hunter-gatherer ancestry. Our results indicate that ancient selection and migration were large contributors to the distribution of phenotypic diversity in present-day Europeans

The genomic basis of adaptive evolution in threespine sticklebacks

Marine stickleback fish have colonized and adapted to thousands of streams and lakes formed since the last ice age, providing an exceptional opportunity to characterize genomic mechanisms underlying repeated ecological adaptation in nature. Here we develop a high-quality reference genome assembly for threespine sticklebacks. By sequencing the genomes of twenty additional individuals from a global set of marine and freshwater populations, we identify a genome-wide set of loci that are consistently associated with marine–freshwater divergence. Our results indicate that reuse of globally shared standing genetic variation, including chromosomal inversions, has an important role in repeated evolution of distinct marine and freshwater sticklebacks, and in the maintenance of divergent ecotypes during early stages of reproductive isolation. Both coding and regulatory changes occur in the set of loci underlying marine–freshwater evolution, but regulatory changes appear to predominate in this well known example of repeated adaptive evolution in nature.National Human Genome Research Institute (U.S.)National Human Genome Research Institute (U.S.) (NHGRI CEGS Grant P50-HG002568

Kita Driven Expression of Oncogenic HRAS Leads to Early Onset and Highly Penetrant Melanoma in Zebrafish

Melanoma is the most aggressive and lethal form of skin cancer. Because of the increasing incidence and high lethality of melanoma, animal models for continuously observing melanoma formation and progression as well as for testing pharmacological agents are needed.Using the combinatorial Gal4-UAS system, we have developed a zebrafish transgenic line that expresses oncogenic HRAS under the kita promoter. Already at 3 days transgenic kita-GFP-RAS larvae show a hyper-pigmentation phenotype as earliest evidence of abnormal melanocyte growth. By 2-4 weeks, masses of transformed melanocytes form in the tail stalk of the majority of kita-GFP-RAS transgenic fish. The adult tumors evident between 1-3 months of age faithfully reproduce the immunological, histological and molecular phenotypes of human melanoma, but on a condensed time-line. Furthermore, they show transplantability, dependence on mitfa expression and do not require additional mutations in tumor suppressors. In contrast to kita expressing melanocyte progenitors that efficiently develop melanoma, mitfa expressing progenitors in a second Gal4-driver line were 4 times less efficient in developing melanoma during the three months observation period.This indicates that zebrafish kita promoter is a powerful tool for driving oncogene expression in the right cells and at the right level to induce early onset melanoma in the presence of tumor suppressors. Thus our zebrafish model provides a link between kita expressing melanocyte progenitors and melanoma and offers the advantage of a larval phenotype suitable for large scale drug and genetic modifier screens

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation

Understanding the circumgalactic medium is critical for understanding galaxy evolution

Galaxies evolve under the influence of gas flows between their interstellar medium and their surrounding gaseous halos known as the circumgalactic medium (CGM). The CGM is a major reservoir of galactic baryons and metals, and plays a key role in the long cycles of accretion, feedback, and recycling of gas that drive star formation. In order to fully understand the physical processes at work within galaxies, it is therefore essential to have a firm understanding of the composition, structure, kinematics, thermodynamics, and evolution of the CGM. In this white paper we outline connections between the CGM and galactic star formation histories, internal kinematics, chemical evolution, quenching, satellite evolution, dark matter halo occupation, and the reionization of the larger-scale intergalactic medium in light of the advances that will be made on these topics in the 2020s. We argue that, in the next decade, fundamental progress on all of these major issues depends critically on improved empirical characterization and theoretical understanding of the CGM. In particular, we discuss how future advances in spatially-resolved CGM observations at high spectral resolution, broader characterization of the CGM across galaxy mass and redshift, and expected breakthroughs in cosmological hydrodynamic simulations will help resolve these major problems in galaxy evolution.Comment: Astro2020 Decadal Science White Pape