242 research outputs found

    Symptomology Associated with in Utero Exposures to Polysubstance in an Appalachian Population.

    Get PDF
    Neonatal abstinence syndrome (NAS) is seen as a very high rate at our institution in Huntington, West Virginia, and the majority of exposures are polysubstance in nature. Polysubstance can have different meaning for each region. At our institution, polysubstance is any combination of opioids, gabapentin, methamphetamine, cocaine, marijuana, benzodiazepines, nicotine or other neuroactive substances with 3-4 substances being the norm. Rapidly changing combinations of drug use and the lack of literature create a difficult situation for clinicians who are often reliant on treatment recommendations that lack references or conclusive data supporting the clinical approaches. Elucidating withdrawal symptoms consistent with in utero exposures to particular drug combinations is difficult. Many substances induce similar withdrawal symptoms in neonates and the vast majority of cases present as polysubstance exposure. Standard methodology often leads to a research approach which isolates populations and substance of exposure to determine the individual effects on the neonate. In some drug combinations, like opioid and gabapentin exposure, the substances in concert create symptoms and complications that are not observed with either drug alone. The history of responses to substance use epidemics has been to handle each drug as a separate disease process, this is no longer a viable option. The following is a review of the literature available discussing individual substance withdrawal characteristics in neonates combined with the clinical insight gained at our hospital from treating such high rates of complex polysubstance exposure

    Program transformations using temporal logic side conditions

    Get PDF
    This paper describes an approach to program optimisation based on transformations, where temporal logic is used to specify side conditions, and strategies are created which expand the repertoire of transformations and provide a suitable level of abstraction. We demonstrate the power of this approach by developing a set of optimisations using our transformation language and showing how the transformations can be converted into a form which makes it easier to apply them, while maintaining trust in the resulting optimising steps. The approach is illustrated through a transformational case study where we apply several optimisations to a small program

    Hydrogen activation by [NiFe]-hydrogenases

    Get PDF
    Hydrogenase-1 (Hyd-1) from Escherichia coli is a membrane-bound enzyme that catalyses the reversible oxidation of molecular H2 The active site contains one Fe and one Ni atom and several conserved amino acids including an arginine (Arg(509)), which interacts with two conserved aspartate residues (Asp(118) and Asp(574)) forming an outer shell canopy over the metals. There is also a highly conserved glutamate (Glu(28)) positioned on the opposite side of the active site to the canopy. The mechanism of hydrogen activation has been dissected by site-directed mutagenesis to identify the catalytic base responsible for splitting molecular hydrogen and possible proton transfer pathways to/from the active site. Previous reported attempts to mutate residues in the canopy were unsuccessful, leading to an assumption of a purely structural role. Recent discoveries, however, suggest a catalytic requirement, for example replacing the arginine with lysine (R509K) leaves the structure virtually unchanged, but catalytic activity falls by more than 100-fold. Variants containing amino acid substitutions at either or both, aspartates retain significant activity. We now propose a new mechanism: heterolytic H2 cleavage is via a mechanism akin to that of a frustrated Lewis pair (FLP), where H2 is polarized by simultaneous binding to the metal(s) (the acid) and a nitrogen from Arg(509) (the base)

    Tele-branding in TVIII: the network as brand and the programme as brand

    Get PDF
    In the era of TVIII, characterized by deregulation, multimedia conglomeration, expansion and increased competition, branding has emerged as a central industrial practice. Focusing on the case of HBO, a particularly successful brand in TVIII, this article argues that branding can be understood not simply as a feature of television networks, but also as a characteristic of television programmes. It begins by examining how the network as brand is constructed and conveyed to the consumer through the use of logos, slogans and programmes. The role of programmes in the construction of brand identity is then complicated by examining the sale of programmes abroad, where programmes can be seen to contribute to the brand identity of more than one network. The article then goes on to examine programme merchandising, an increasingly central strategy in TVIII. Through an analysis of different merchandising strategies the article argues that programmes have come to act as brands in their own right, and demonstrates that the academic study of branding not only reveals the development of new industrial practices, but also offers a way of understanding the television programme and its consumption by viewers in a period when the texts of television are increasingly extended across a range of media platforms

    Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19

    Get PDF
    SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.Fil: Sekine, Takuya. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Perez Potti, André. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Rivera Ballesteros, Olga. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Strålin, Kristoffer. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Gorin, Jean Baptiste. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Olsson, Annika. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Llewellyn Lacey, Sian. University Hospital of Wales; Reino UnidoFil: Kamal, Habiba. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Bogdanovic, Gordana. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Muschiol, Sandra. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Wullimann, David J.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Kammann, Tobias. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Emgård, Johanna. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Parrot, Tiphaine. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Folkesson, Elin. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Rooyackers, Olav. Karolinska Huddinge Hospital. Karolinska Institutet; Suecia. Karolinska University Hospital; SueciaFil: Eriksson, Lars I.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Henter, Jan Inge. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sönnerborg, Anders. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Allander, Tobias. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Albert, Jan. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Nielsen, Morten. Technical University of Denmark; Dinamarca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; ArgentinaFil: Klingstrom, Jonas. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Gredmark Russ, Sara. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Björkström, Niklas K.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Sandberg, Johan K.. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Price, David A.. Cardiff University School of Medicine; Reino UnidoFil: Ljunggren, Hans Gustaf. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Aleman, Soo. Karolinska Huddinge Hospital. Karolinska Institutet; SueciaFil: Buggert, Marcus. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

    Gold Nanostar-Coated Polystyrene Beads as Multifunctional Nanoprobes for SERS Bioimaging

    Get PDF
    Hybrid colloidal nanocomposites comprising polystyrene beads and plasmonic gold nanostars are reported as multifunctional optical nanoprobes. Such self-assembled structures are excellent Raman enhancers for bioapplications as they feature plasmon modes in the near-infrared "first biological transparency window". In this proof of concept study, we used 4-mercaptobenzoic acid as a Raman-active molecule to optimize the density of gold nanostars on polystyrene beads, improving SERS performance and thereby allowing in vitro cell culture imaging. Interestingly, intermediate gold nanostar loadings were found to yield higher SERS response, which was confirmed by electromagnetic modeling. These engineered hybrid nanostructures notably improve the possibilities of using gold nanostars as SERS tags. Additionally, when fluorescently labeled polystyrene beads are used as colloidal carriers, the composite particles can be applied as promising tools for multimodal bioimaging

    PDXNet portal: patient-derived Xenograft model, data, workflow and tool discovery.

    Get PDF
    We created the PDX Network (PDXNet) portal (https://portal.pdxnetwork.org/) to centralize access to the National Cancer Institute-funded PDXNet consortium resources, to facilitate collaboration among researchers and to make these data easily available for research. The portal includes sections for resources, analysis results, metrics for PDXNet activities, data processing protocols and training materials for processing PDX data. Currently, the portal contains PDXNet model information and data resources from 334 new models across 33 cancer types. Tissue samples of these models were deposited in the NCI\u27s Patient-Derived Model Repository (PDMR) for public access. These models have 2134 associated sequencing files from 873 samples across 308 patients, which are hosted on the Cancer Genomics Cloud powered by Seven Bridges and the NCI Cancer Data Service for long-term storage and access with dbGaP permissions. The portal includes results from freely available, robust, validated and standardized analysis workflows on PDXNet sequencing files and PDMR data (3857 samples from 629 patients across 85 disease types). The PDXNet portal is continuously updated with new data and is of significant utility to the cancer research community as it provides a centralized location for PDXNet resources, which support multi-agent treatment studies, determination of sensitivity and resistance mechanisms, and preclinical trials
    corecore