114 research outputs found

    Suffix Trees Considered Harmful

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    The implications of adaptive theory have been far-reaching and pervasive. In this paper, au- thors demonstrate the evaluation of journaling file systems, which embodies the intuitive principles of programming languages. We prove that despite the fact that Scheme and Markov models are often incompatible, 802.11 mesh networks and Web services can agree to answer this grand challenge

    Reexamination of a putative diploid hybrid Taxon using genetic evidence: The distinctiveness of Phlox pilosa subsp. deamii (Polemoniaceae)

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    Premise of research. A number of recent studies have shown that hybridization plays a key role in the evolution of plants and can lead to the development of genetic and taxonomic novelty, even without a change in ploidy level. Documenting patterns of population genetic diversity for taxa of proposed homoploid hybrid origin and their putative parents leads to an improved understanding of the role of hybridization in the generation of plant diversity. Methodology. Phlox pilosa subsp. deamii is hypothesized to have arisen from diploid hybridization between P. pilosa subsp. pilosa and Phlox amoena. Here we analyzed 18 populations representing all three taxa using a population genetic approach, including microsatellite and chloroplast DNA sequence data. We addressed questions concerning genetic diversity and structure, hybrid origin, and ongoing evolutionary processes. Pivotal results. Several different analyses revealed that genetic variation in P. pilosa subsp. deamii was a mixture of (or was intermediate to) the genetic variation found in P. pilosa subsp. pilosa and P. amoena. However, populations of P. pilosa subsp. deamii were also notably distinct genetically and maintained high levels of genetic diversity. Comparisons between nuclear and chloroplast genetic data provided some evidence for ongoing gene exchange within this system. Conclusions. Phlox pilosa subsp. deamii is distinctive in its genetics, as well as its morphology and ecology. Combined with data from previous studies, population genetic data support a diploid hybrid origin for P. pilosa subsp. deamii, although with sufficient time since its origin for establishment of unique genetic variation. Furthermore, its formation may have come about through complex interactions among the closely related parental taxa, potentially with multiple hybrid generations, backcrossing, and introgression. Such a complex scenario of formation for this subspecific taxon raises questions with respect to the current distinction we make between homoploid hybrid origin of taxa, which is viewed as rare, and introgression, which is undoubtedly prevalent in plants

    Recommendations for change in infection prevention programs and practice

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    Fifty years of evolution in infection prevention and control programs have involved significant accomplishments related to clinical practices, methodologies, and technology. However, regulatory mandates, and resource and research limitations, coupled with emerging infection threats such as the COVID-19 pandemic, present considerable challenges for infection preventionists. This article provides guidance and recommendations in 14 key areas. These interventions should be considered for implementation by United States health care facilities in the near future

    HCV genome-wide genetic analyses in context of disease progression and hepatocellular carcinoma

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    <div><p>Hepatitis C virus (HCV) is a major cause of hepatitis and hepatocellular carcinoma (HCC) world-wide. Most HCV patients have relatively stable disease, but approximately 25% have progressive disease that often terminates in liver failure or HCC. HCV is highly variable genetically, with seven genotypes and multiple subtypes per genotype. This variation affects HCV’s sensitivity to antiviral therapy and has been implicated to contribute to differences in disease. We sequenced the complete viral coding capacity for 107 HCV genotype 1 isolates to determine whether genetic variation between independent HCV isolates is associated with the rate of disease progression or development of HCC. Consensus sequences were determined by sequencing RT-PCR products from serum or plasma. Positions of amino acid conservation, amino acid diversity patterns, selection pressures, and genome-wide patterns of amino acid covariance were assessed in context of the clinical phenotypes. A few positions were found where the amino acid distributions or degree of positive selection differed between in the HCC and cirrhotic sequences. All other assessments of viral genetic variation and HCC failed to yield significant associations. Sequences from patients with slow disease progression were under a greater degree of positive selection than sequences from rapid progressors, but all other analyses comparing HCV from rapid and slow disease progressors were statistically insignificant. The failure to observe distinct sequence differences associated with disease progression or HCC employing methods that previously revealed strong associations with the outcome of interferon α-based therapy implies that variable ability of HCV to modulate interferon responses is not a dominant cause for differential pathology among HCV patients. This lack of significant associations also implies that host and/or environmental factors are the major causes of differential disease presentation in HCV patients.</p></div

    Choline transporter gene variation is associated with attention-deficit hyperactivity disorder

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    The neurotransmitter acetylcholine (ACh) plays a critical role in brain circuits mediating motor control, attention, learning and memory. Cholinergic dysfunction is associated with multiple brain disorders including Alzheimer’s Disease, addiction, schizophrenia and Attention-Deficit Hyperactivity Disorder (ADHD). The presynaptic choline transporter (CHT, SLC5A7) is the major, rate-limiting determinant of ACh production in the brain and periphery and is consequently upregulated during tasks that require sustained attention. Given the contribution of central cholinergic circuits to the control of movement and attention, we hypothesized that functional CHT gene variants might impact risk for ADHD. We performed a case-control study, followed by family-based association tests on a separate cohort, of two purportedly functional CHT polymorphisms (coding variant Ile89Val (rs1013940) and a genomic SNP 3’ of the CHT gene (rs333229), affording both a replication sample and opportunities to reduce potential population stratification biases. Initial genotyping of pediatric ADHD subjects for two purportedly functional CHT alleles revealed a 2–3 fold elevation of the Val89 allele (n = 100; P = 0.02) relative to healthy controls, as well as a significant decrease of the 3’SNP minor allele in Caucasian male subjects (n = 60; P = 0.004). In family based association tests, we found significant overtransmission of the Val89 variant to children with a Combined subtype diagnosis (OR = 3.16; P = 0.01), with an increased Odds Ratio for a haplotype comprising both minor alleles. These studies show evidence of cholinergic deficits in ADHD, particularly for subjects with the Combined subtype, and, if replicated, may encourage further consideration of cholinergic agonist therapy in the disorder

    American Thoracic Society and National Heart, Lung, and Blood Institute Implementation Research Workshop Report

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    To advance implementation research (IR) in respiratory, sleep, and critical care medicine, the American Thoracic Society and the Division of Lung Diseases from the NHLBI cosponsored an Implementation Research Workshop on May 17, 2014. The goals of IR are to understand the barriers and facilitators of integrating new evidence into healthcare practices and to develop and test strategies that systematically target these factors to accelerate the adoption of evidence-based care. Throughout the workshop, presenters provided examples of IR that focused on the rate of adoption of evidence-based practices, the feasibility and acceptability of interventions to patients and other stakeholders who make healthcare decisions, the fidelity with which practitioners use specific interventions, the effects of specific barriers on the sustainability of an intervention, and the implications of their research to inform policies to improve patients’ access to high-quality care. During the discussions that ensued, investigators’ experience led to recommendations underscoring the importance of identifying and involving key stakeholders throughout the research process, ensuring that those who serve as reviewers understand the tenets of IR, managing staff motivation and turnover, and tackling the challenges of scaling up interventions across multiple settings

    A randomized, open-label, multicentre, phase 2/3 study to evaluate the safety and efficacy of lumiliximab in combination with fludarabine, cyclophosphamide and rituximab versus fludarabine, cyclophosphamide and rituximab alone in subjects with relapsed chronic lymphocytic leukaemia

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    Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

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    Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction
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