Sample records for xpo-1 supports primary

  1. A method for quantification of exportin-1 (XPO1) occupancy by Selective Inhibitor of Nuclear Export (SINE) compounds

    PubMed Central

    Crochiere, Marsha L.; Baloglu, Erkan; Klebanov, Boris; Donovan, Scott; del Alamo, Diego; Lee, Margaret; Kauffman, Michael; Shacham, Sharon; Landesman, Yosef

    2016-01-01

    Selective Inhibitor of Nuclear Export (SINE) compounds are a family of small-molecules that inhibit nuclear export through covalent binding to cysteine 528 (Cys528) in the cargo-binding pocket of Exportin 1 (XPO1/CRM1) and promote cancer cell death. Selinexor is the lead SINE compound currently in phase I and II clinical trials for advanced solid and hematological malignancies. In an effort to understand selinexor-XPO1 interaction and to establish whether cancer cell response is a function of drug-target engagement, we developed a quantitative XPO1 occupancy assay. Biotinylated leptomycin B (b-LMB) was utilized as a tool compound to measure SINE-free XPO1. Binding to XPO1 was quantitated from SINE compound treated adherent and suspension cells in vitro, dosed ex vivo human peripheral blood mononuclear cells (PBMCs), and PBMCs from mice dosed orally with drug in vivo. Evaluation of a panel of selinexor sensitive and resistant cell lines revealed that resistance was not attributed to XPO1 occupancy by selinexor. Administration of a single dose of selinexor bound XPO1 for minimally 72 hours both in vitro and in vivo. While XPO1 inhibition directly correlates with selinexor pharmacokinetics, the biological outcome of this inhibition depends on modulation of pathways downstream of XPO1, which ultimately determines cancer cell responsiveness. PMID:26654943

  2. Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women.

    PubMed

    Rah, HyungChul; Jeon, Young Joo; Lee, Bo Eun; Kim, Jung O; Shim, Sung Han; Lee, Woo Sik; Choi, Dong Hee; Kim, Ji Hyang; Kim, Nam Keun

    2013-10-01

    The aim of our study was to investigate whether polymorphisms in microRNA machinery genes are associated with the risk of primary ovarian insufficiency (POI). We genotyped 136 POI patients and 236 controls among Korean women for nine single nucleotide polymorphisms (SNPs; DROSHA rs6877842 and rs10719; DICER1 rs13078 and rs3742330; RAN rs14035; and XPO5 rs34324334, rs2257082, rs11544382, and rs11077) by polymerase chain reaction-restriction fragment length polymorphism analysis. Differences in genotype frequencies between patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as measures of the strength of the association between genotype and POI. Of the nine SNPs, XPO5 rs34324334 and rs11544382 were monomorphic and were not analyzed further. The XPO5 rs2257082 CT and CT + TT variant genotypes were more frequent in patients (OR, 2.097; 95% CI, 1.207-3.645) than in controls (OR, 2.030; 95% CI, 1.196-3.445). The combined frequencies of XPO5 rs2257082 CT + TT and rs11077 AC + CC genotypes were higher in patients than in controls (OR, 2.526; 95% CI, 1.088-5.865). An association of POI risk with other polymorphisms was not found. A haplotype-based analysis of seven polymorphisms of the microRNA machinery genes for gene-gene interactions suggests that ***ACTA, ***GCCA, ***G*C*, *T*ATTA, and ***ACT* haplotypes (asterisk indicates SNP locus not included; DROSHA rs6877842 and rs10719, DICER1 rs13078 and rs3742330, RAN rs14035, and XPO5 rs2257082 and rs11077 polymorphisms) are associated with higher POI prevalence, and that ***GCTA, ***ACCA, *C*ATTA, and *C*ATT* haplotypes are associated with lower POI prevalence. Our data demonstrate that the XPO5 rs2257082 T variant allele occurs more frequently in POI patients than in controls, suggesting that this allele may be associated with increased POI risk.

  3. Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia

    PubMed Central

    Lapalombella, Rosa; Sun, Qingxiang; Williams, Katie; Tangeman, Larissa; Jha, Shruti; Zhong, Yiming; Goettl, Virginia; Mahoney, Emilia; Berglund, Caroline; Gupta, Sneha; Farmer, Alicia; Mani, Rajeswaran; Johnson, Amy J.; Lucas, David; Mo, Xiaokui; Daelemans, Dirk; Sandanayaka, Vincent; Shechter, Sharon; McCauley, Dilara; Shacham, Sharon; Kauffman, Michael

    2012-01-01

    The nuclear export protein XPO1 is overexpressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby inhibiting nuclear export of cargo proteins. The clinical relevance of SINEs was explored in chronic lymphocytic leukemia (CLL), a disease associated with recurrent XPO1 mutations. Evidence is presented that SINEs can restore normal regulation to the majority of the dysregulated pathways in CLL both in vitro and in vivo and induce apoptosis of CLL cells with a favorable therapeutic index, with enhanced killing of genomically high-risk CLL cells that are typically unresponsive to traditional therapies. More importantly, SINE slows disease progression, and improves overall survival in the Eμ-TCL1-SCID mouse model of CLL with minimal weight loss or other toxicities. Together, these findings demonstrate that XPO1 is a valid target in CLL with minimal effects on normal cells and provide a basis for the development of SINEs in CLL and related hematologic malignancies. PMID:23034282

  4. Inhibition of the Nuclear Export Receptor XPO1 as a Therapeutic Target for Platinum-Resistant Ovarian Cancer.

    PubMed

    Chen, Ying; Camacho, Sandra Catalina; Silvers, Thomas R; Razak, Albiruni R A; Gabrail, Nashat Y; Gerecitano, John F; Kalir, Eva; Pereira, Elena; Evans, Brad R; Ramus, Susan J; Huang, Fei; Priedigkeit, Nolan; Rodriguez, Estefania; Donovan, Michael; Khan, Faisal; Kalir, Tamara; Sebra, Robert; Uzilov, Andrew; Chen, Rong; Sinha, Rileen; Halpert, Richard; Billaud, Jean-Noel; Shacham, Sharon; McCauley, Dilara; Landesman, Yosef; Rashal, Tami; Kauffman, Michael; Mirza, Mansoor R; Mau-Sørensen, Morten; Dottino, Peter; Martignetti, John A

    2017-03-15

    Purpose: The high fatality-to-case ratio of ovarian cancer is directly related to platinum resistance. Exportin-1 (XPO1) is a nuclear exporter that mediates nuclear export of multiple tumor suppressors. We investigated possible clinicopathologic correlations of XPO1 expression levels and evaluated the efficacy of XPO1 inhibition as a therapeutic strategy in platinum-sensitive and -resistant ovarian cancer. Experimental Design: XPO1 expression levels were analyzed to define clinicopathologic correlates using both TCGA/GEO datasets and tissue microarrays (TMA). The effect of XPO1 inhibition, using the small-molecule inhibitors KPT-185 and KPT-330 (selinexor) alone or in combination with a platinum agent on cell viability, apoptosis, and the transcriptome was tested in immortalized and patient-derived ovarian cancer cell lines (PDCL) and platinum-resistant mice (PDX). Seven patients with late-stage, recurrent, and heavily pretreated ovarian cancer were treated with an oral XPO1 inhibitor. Results: XPO1 RNA overexpression and protein nuclear localization were correlated with decreased survival and platinum resistance in ovarian cancer. Targeted XPO1 inhibition decreased cell viability and synergistically restored platinum sensitivity in both immortalized ovarian cancer cells and PDCL. The XPO1 inhibitor-mediated apoptosis occurred through both p53-dependent and p53-independent signaling pathways. Selinexor treatment, alone and in combination with platinum, markedly decreased tumor growth and prolonged survival in platinum-resistant PDX and mice. In selinexor-treated patients, tumor growth was halted in 3 of 5 patients, including one with a partial response, and was safely tolerated by all. Conclusions: Taken together, these results provide evidence that XPO1 inhibition represents a new therapeutic strategy for overcoming platinum resistance in women with ovarian cancer. Clin Cancer Res; 23(6); 1552-63. ©2016 AACR . ©2016 American Association for Cancer Research.

  5. Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph+ leukemias

    PubMed Central

    Walker, Christopher J.; Oaks, Joshua J.; Santhanam, Ramasamy; Neviani, Paolo; Harb, Jason G.; Ferenchak, Gregory; Ellis, Justin J.; Landesman, Yosef; Eisfeld, Ann-Kathrin; Gabrail, Nash Y.; Smith, Carrie L.; Caligiuri, Michael A.; Hokland, Peter; Roy, Denis Claude; Reid, Alistair; Milojkovic, Dragana; Goldman, John M.; Apperley, Jane; Garzon, Ramiro; Marcucci, Guido; Shacham, Sharon; Kauffman, Michael G.

    2013-01-01

    As tyrosine kinase inhibitors (TKIs) fail to induce long-term response in blast crisis chronic myelogenous leukemia (CML-BC) and Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL), novel therapies targeting leukemia-dysregulated pathways are necessary. Exportin-1 (XPO1), also known as chromosome maintenance protein 1, regulates cell growth and differentiation by controlling the nucleocytoplasmic trafficking of proteins and RNAs, some of which are aberrantly modulated in BCR-ABL1+ leukemias. Using CD34+ progenitors from CML, B-ALL, and healthy individuals, we found that XPO1 expression was markedly increased, mostly in a TKI-sensitive manner, in CML-BC and Ph+ B-ALL. Notably, XPO1 was also elevated in Ph− B-ALL. Moreover, the clinically relevant XPO1 inhibitor KPT-330 strongly triggered apoptosis and impaired the clonogenic potential of leukemic, but not normal, CD34+ progenitors, and increased survival of BCR-ABL1+ mice, 50% of which remained alive and, mostly, became BCR-ABL1 negative. Moreover, KPT-330 compassionate use in a patient with TKI-resistant CML undergoing disease progression significantly reduced white blood cell count, blast cells, splenomegaly, lactate dehydrogenase levels, and bone pain. Mechanistically, KPT-330 altered the subcellular localization of leukemia-regulated factors including RNA-binding heterogeneous nuclear ribonucleoprotein A1 and the oncogene SET, thereby inducing reactivation of protein phosphatase 2A tumor suppressor and inhibition of BCR-ABL1 in CML-BC cells. Because XPO1 is important for leukemic cell survival, KPT-330 may represent an alternative therapy for TKI-refractory Ph+ leukemias. PMID:23970380

  6. XPO1-dependent nuclear export is a druggable vulnerability in KRAS-mutant lung cancer

    PubMed Central

    Kim, Jimi; McMillan, Elizabeth; Kim, Hyun Seok; Venkateswaran, Niranjan; Makkar, Gurbani; Rodriguez-Canales, Jaime; Villalobos, Pamela; Neggers, Jasper Edgar; Mendiratta, Saurabh; Wei, Shuguang; Landesman, Yosef; Senapedis, William; Baloglu, Erkan; Chow, Chi-Wan B.; Frink, Robin E.; Gao, Boning; Roth, Michael; Minna, John D.; Daelemans, Dirk; Wistuba, Ignacio I.; Posner, Bruce A.; Scaglioni, PierPaolo; White, Michael A.

    2016-01-01

    The common participation of oncogenic KRAS proteins in many of the most lethal human cancers, together with the ease of detecting somatic KRAS mutant alleles in patient samples, has spurred persistent and intensive efforts to develop drugs that inhibit KRAS activity1. However, advances have been hindered by the pervasive inter- and intra-lineage diversity in the targetable mechanisms that underlie KRAS-driven cancers, limited pharmacological accessibility of many candidate synthetic-lethal interactions and the swift emergence of unanticipated resistance mechanisms to otherwise effective targeted therapies. Here we demonstrate the acute and specific cell-autonomous addiction of KRAS-mutant non-small-cell lung cancer cells to receptor-dependent nuclear export. A multi-genomic, data-driven approach, utilizing 106 human non-small-cell lung cancer cell lines, was used to interrogate 4,725 biological processes with 39,760 short interfering RNA pools for those selectively required for the survival of KRAS-mutant cells that harbour a broad spectrum of phenotypic variation. Nuclear transport machinery was the sole process-level discriminator of statistical significance. Chemical perturbation of the nuclear export receptor XPO1 (also known as CRM1), with a clinically available drug, revealed a robust synthetic-lethal interaction with native or engineered oncogenic KRAS both in vitro and in vivo. The primary mechanism underpinning XPO1 inhibitor sensitivity was intolerance to the accumulation of nuclear IκBα (also known as NFKBIA), with consequent inhibition of NFκB transcription factor activity. Intrinsic resistance associated with concurrent FSTL5 mutations was detected and determined to be a consequence of YAP1 activation via a previously unappreciated FSTL5–Hippo pathway regulatory axis. This occurs in approximately 17% of KRAS-mutant lung cancers, and can be overcome with the co-administration of a YAP1–TEAD inhibitor. These findings indicate that clinically

  7. Xpo7 is a broad-spectrum exportin and a nuclear import receptor.

    PubMed

    Aksu, Metin; Pleiner, Tino; Karaca, Samir; Kappert, Christin; Dehne, Heinz-Jürgen; Seibel, Katharina; Urlaub, Henning; Bohnsack, Markus T; Görlich, Dirk

    2018-05-10

    Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future. © 2018 Aksu et al.

  8. Crystal structure of the Xpo1p nuclear export complex bound to the SxFG/PxFG repeats of the nucleoporin Nup42p.

    PubMed

    Koyama, Masako; Hirano, Hidemi; Shirai, Natsuki; Matsuura, Yoshiyuki

    2017-10-01

    Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif. The crystal structure of Xpo1p-PKI-Nup42p-Gsp1p-GTP complex identified three binding sites for the SxFG/PxFG repeats on HEAT repeats 14-20 of Xpo1p. Mutational analyses of Nup42p showed that the conserved serines and prolines in the SxFG/PxFG repeats contribute to Xpo1p-Nup42p binding. Our structural and biochemical data suggest that SxFG/PxFG-Nups such as Nup42p and Nup159p at the cytoplasmic face of NPCs provide high-affinity docking sites for the Xpo1p nuclear export complex in the terminal stage of NPC passage and that subsequent disassembly of the nuclear export complex facilitates recycling of free Xpo1p back to the nucleus. © 2017 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  9. Efficient UV-emitting X-ray phosphors: octahedral Zr(PO 4) 6 luminescence centers in potassium hafnium-zirconium phosphates K 2Hf 1- xZr x(PO 4) 2 and KHf 2(1- x) Zr 2 x(PO 4) 3

    NASA Astrophysics Data System (ADS)

    Torardi, C. C.; Miao, C. R.; Li, J.

    2003-02-01

    Potassium hafnium-zirconium phosphates, K 2Hf 1- xZr x(PO 4) 2 and KHf 2(1- x) Zr 2 x(PO 4) 3, are broad-band UV-emitting phosphors. At room temperature, they have emission peak maxima at approximately 322 and 305 nm, respectively, under 30 kV peak molybdenum X-ray excitation. Both phosphors demonstrate luminescence efficiencies that make them up to ˜60% as bright as commercially available CaWO 4 Hi-Plus. The solid-state and flux synthesis conditions, and X-ray excited UV luminescence of these two phosphors are discussed. Even though the two compounds have different atomic structures, they contain zirconium in the same active luminescence environment as that found in highly efficient UV-emitting BaHf 1- xZr x(PO 4) 2. All the three materials have hafnium and zirconium in octahedral coordination via oxygen-atom corner sharing with six separate PO 4 tetrahedra. This octahedral Zr(PO 4) 6 moiety appears to be an important structural element for efficient X-ray excited luminescence, as are the edge-sharing octahedral TaO 6 chains for tantalate emission.

  10. STAT6 is a cargo of exportin 1: Biological relevance in primary mediastinal B-cell lymphoma.

    PubMed

    Miloudi, Hadjer; Leroy, Karen; Jardin, Fabrice; Sola, Brigitte

    2018-06-01

    Primary mediastinal B-cell lymphoma (PMBL) is a distinct B-cell lymphoma subtype with unique clinicopathological and molecular features. PMBL cells are characterised by several genetic abnormalities that conduct to the constitutive activation of the Janus kinase 2/signal transducer and activator of transcription 6 (JAK2/STAT6) signalling pathway. Among recurrent genetic changes in PMBL, we previously reported that the XPO1 gene encoding exportin 1 that controls the nuclear export of cargo proteins and RNAs, is mutated (p.E571K) in about 25% of PMBL cases. We therefore hypothesized that STAT6 could be a cargo of XPO1 and that STAT6 cytoplasm/nucleus shuttle could be altered in a subset of PMBL cells. Using immunocytochemistry techniques as well as the proximity ligation assay, we showed that STAT6 bound XPO1 in PBML cell lines and in HEK-293 cells genetically engineered to produce STAT6. Moreover, XPO1-mediated export of STAT6 occurs in cells expressing either a wild-type or the E571K mutated XPO1 protein. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. Anti-tumor activity of selective inhibitors of XPO1/CRM1-mediated nuclear export in diffuse malignant peritoneal mesothelioma: the role of survivin

    PubMed Central

    Doldi, Valentina; Lopergolo, Alessia; Deraco, Marcello; Gandellini, Paolo; Friedlander, Sharon; Landesman, Yosef; Kauffman, Michael G.; Shacham, Sharon

    2015-01-01

    Survivin, which is highly expressed and promotes cell survival in diffuse malignant peritoneal mesothelioma (DMPM), exclusively relies on exportin 1 (XPO1/CRM1) to be shuttled into the cytoplasm and perform its anti-apoptotic function. Here, we explored the efficacy of Selective Inhibitors of Nuclear Export (SINE), KPT-251, KPT-276 and the orally available, clinical stage KPT-330 (selinexor), in DMPM preclinical models. Exposure to SINE induced dose-dependent inhibition of cell growth, cell cycle arrest at G1-phase and caspase-dependent apoptosis, which were consequent to a decrease of XPO1/CRM1 protein levels and the concomitant nuclear accumulation of its cargo proteins p53 and CDKN1a. Cell exposure to SINE led to a time-dependent reduction of cytoplasmic survivin levels. In addition, after an initial accumulation, the nuclear protein abundance progressively decreased, as a consequence of an enhanced ubiquitination and proteasome-dependent degradation. SINE and the survivin inhibitor YM155 synergistically cooperated in reducing DMPM cell proliferation. Most importantly, orally administered SINE caused a significant anti-tumor effect in subcutaneous and orthotopic DMPM xenografts without appreciable toxicity. Overall, we have demonstrated a marked efficacy of SINE in DMPM preclinical models that may relay on the interference with survivin intracellular distribution and function. Our study suggests SINE-mediated XPO1/CRM1 inhibition as a novel therapeutic option for DMPM. PMID:25948791

  12. Yeast Ran-Binding Protein 1 (Yrb1) Shuttles between the Nucleus and Cytoplasm and Is Exported from the Nucleus via a CRM1 (XPO1)-Dependent Pathway

    PubMed Central

    Künzler, Markus; Gerstberger, Thomas; Stutz, Françoise; Bischoff, F. Ralf; Hurt, Ed

    2000-01-01

    The RanGTP-binding protein RanBP1, which is located in the cytoplasm, has been implicated in release of nuclear export complexes from the cytoplasmic side of the nuclear pore complex. Here we show that Yrb1 (the yeast homolog of RanBP1) shuttles between the nucleus and the cytoplasm. Nuclear import of Yrb1 is a facilitated process that requires a short basic sequence within the Ran-binding domain (RBD). By contrast, nuclear export of Yrb1 requires an intact RBD, which forms a ternary complex with the Xpo1 (Crm1) NES receptor in the presence of RanGTP. Nuclear export of Yrb1, however, is insensitive towards leptomycin B, suggesting a novel type of substrate recognition between Yrb1 and Xpo1. Taken together, these data suggest that ongoing nuclear import and export is an important feature of Yrb1 function in vivo. PMID:10825193

  13. Structure of the exportin Xpo4 in complex with RanGTP and the hypusine-containing translation factor eIF5A

    PubMed Central

    Aksu, Metin; Trakhanov, Sergei; Görlich, Dirk

    2016-01-01

    Xpo4 is a bidirectional nuclear transport receptor that mediates nuclear export of eIF5A and Smad3 as well as import of Sox2 and SRY. How Xpo4 recognizes such a variety of cargoes is as yet unknown. Here we present the crystal structure of the RanGTP·Xpo4·eIF5A export complex at 3.2 Å resolution. Xpo4 has a similar structure as CRM1, but the NES-binding site is occluded, and a new interaction site evolved that recognizes both globular domains of eIF5A. eIF5A contains hypusine, a unique amino acid with two positive charges, which is essential for cell viability and eIF5A function in translation. The hypusine docks into a deep, acidic pocket of Xpo4 and is thus a critical element of eIF5A's complex export signature. This further suggests that Xpo4 recognizes other cargoes differently, and illustrates how Xpo4 suppresses – in a chaperone-like manner – undesired interactions of eIF5A inside nuclei. PMID:27306458

  14. Durability of the Li 1+xTi 2–xAl x(PO 4) 3 Solid Electrolyte in Lithium–Sulfur Batteries

    DOE PAGES

    Wang, Shaofei; Ding, Yu; Zhou, Guangmin; ...

    2016-10-31

    Adoption of cells with a solid-state electrolyte is a promising solution for eliminating the polysulfide shuttle problem in Li-S batteries. Among the various known lithium-ion conducting solid electrolytes, the sodium superionic conductor (NASICON)-type Li 1+xTi 2-xAl x(PO 4) 3 offers the advantage of good stability under ambient conditions and in contact with air. Accordingly, we present here a comprehensive assessment of the durability of Li 1+xTi 2-xAl x(PO 4) 3 in contact with polysulfide solution and in Li-S cells. Because of its high reduction potential (2.5 V vs Li/Li +), Li 1+xTi 2-xAl x(PO 4) 3 gets lithiated in contactmore » with lithium polysulfide solution and Li 2CO 3 is formed on the particle surface, blocking the interfacial lithium-ion transport between the liquid and solid-state electrolytes. After the lithium insertion into the NASICON framework, the crystal expands in an anisotropic way, weakening the crystal bonds, causing fissures and resultant cracks in the ceramic, corroding the grain boundaries by polysulfide solution, and leaving unfavorable pores. The assembly of pores creates a gateway for polysulfide diffusion from the cathode side to the anode side, causing an abrupt decline in cell performance. Therefore, the solid-state electrolytes need to have good chemical compatibility with both the electrode and electrolyte, long-term stability under harsh chemical environment, and highly stable grain boundaries.« less

  15. The XPO1 inhibitor Selinexor inhibits translation and enhances the radiosensitivity of glioblastoma cells grown in vitro and in vivo.

    PubMed

    Wahba, Amy; Rath, Barbara H; O'Neill, John W; Camphausen, Kevin; Tofilon, Philip J

    2018-06-04

    Analysis of the radiation-induced translatome of glioblastoma stem-like cells (GSCs) identified an interacting network in which XPO1 serves as a major hub protein. To determine whether this nuclear export protein provides a target for radiosensitization, we defined the effects of the clinically relevant XPO1 inhibitor Selinexor on the radiosensitivity of glioblastoma cells. As determined by clonogenic survival analysis, Selinexor enhanced the radiosensitivity of GSCs but not normal fibroblast cell lines. Based on γH2AX foci and neutral comet analyses, Selinexor inhibited the repair of radiation-induced DNA double strand breaks in GSCs suggesting that the Selinexor-induced radiosensitization is mediated by an inhibition of DNA repair. Consistent with a role for XPO1 in the nuclear to cytoplasm export of rRNA, Selinexor reduced 5S and 18S rRNA nuclear export in GSCs, which was accompanied by a decrease in gene translation efficiency, as determined from polysome profiles, as well as in protein synthesis. In contrast, rRNA nuclear export and protein synthesis were not reduced in normal cells treated with Selinexor. Orthotopic xenografts initiated from a GSC line were then used to define the in vivo response to Selinexor and radiation. Treatment of mice bearing orthotopic xenografts with Selinexor decreased tumor translational efficiency as determined from polysome profiles. Although Selinexor treatment alone had no effect on the survival of mice with brain tumors, it significantly enhanced the radiation-induced prolongation of survival. These results indicate that Selinexor enhances the radiosensitivity of glioblastoma cells and suggest that this effect involves a global inhibition of gene translation. Copyright ©2018, American Association for Cancer Research.

  16. Tuning Li-Ion Diffusion in α-LiMn 1–xFe xPO 4 Nanocrystals by Antisite Defects and Embedded β-Phase for Advanced Li-Ion Batteries

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hu, Jiangtao; Xiao, Yinguo; Tang, Hanting

    Olivine-structured LiMn 1–xFe xPO 4 has become a promising candidate for cathode materials owing to its higher working voltage of 4.1 V and thus larger energy density than that of LiFePO 4, which has been used for electric vehicles batteries with the advantage of high safety but disadvantage of low energy density due to its lower working voltage of 3.4 V. One drawback of LiMn 1–xFe xPO 4 electrode is its relatively low electronic and Li-ionic conductivity with Li-ion one-dimensional diffusion. In this paper, olivine-structured α-LiMn 0.5Fe 0.5PO 4 nanocrystals were synthesized with optimized Li-ion diffusion channels in LiMn 1–xFemore » xPO 4 nanocrystals by inducing high concentrations of Fe 2+–Li + antisite defects, which showed impressive capacity improvements of approaching 162, 127, 73, and 55 mAh g –1 at 0.1, 10, 50, and 100 C, respectively, and a long-term cycling stability of maintaining about 74% capacity after 1000 cycles at 10 C. By using high-resolution transmission electron microscopy imaging and joint refinement of hard X-ray and neutron powder diffraction patterns, we revealed that the extraordinary high-rate performance could be achieved by suppressing the formation of electrochemically inactive phase (β-LiMn 1–xFe xPO 4, which is first reported in this work) embedded in α-LiMn 0.5Fe 0.5PO 4. Because of the coherent orientation relationship between β- and α-phases, the β-phase embedded would impede the Li + diffusion along the [100] and/or [001] directions that was activated by the high density of Fe 2+–Li + antisite (4.24%) in α-phase. Thus, by optimizing concentrations of Fe 2+–Li + antisite defects and suppressing β-phase-embedded olivine structure, Li-ion diffusion properties in LiMn 1–xFe xPO 4 nanocrystals can be tuned by generating new Li + tunneling. Finally, these findings may provide insights into the design and generation of other advanced electrode materials with improved rate performance.« less

  17. Tuning Li-Ion Diffusion in α-LiMn 1–xFe xPO 4 Nanocrystals by Antisite Defects and Embedded β-Phase for Advanced Li-Ion Batteries

    DOE PAGES

    Hu, Jiangtao; Xiao, Yinguo; Tang, Hanting; ...

    2017-07-13

    Olivine-structured LiMn 1–xFe xPO 4 has become a promising candidate for cathode materials owing to its higher working voltage of 4.1 V and thus larger energy density than that of LiFePO 4, which has been used for electric vehicles batteries with the advantage of high safety but disadvantage of low energy density due to its lower working voltage of 3.4 V. One drawback of LiMn 1–xFe xPO 4 electrode is its relatively low electronic and Li-ionic conductivity with Li-ion one-dimensional diffusion. In this paper, olivine-structured α-LiMn 0.5Fe 0.5PO 4 nanocrystals were synthesized with optimized Li-ion diffusion channels in LiMn 1–xFemore » xPO 4 nanocrystals by inducing high concentrations of Fe 2+–Li + antisite defects, which showed impressive capacity improvements of approaching 162, 127, 73, and 55 mAh g –1 at 0.1, 10, 50, and 100 C, respectively, and a long-term cycling stability of maintaining about 74% capacity after 1000 cycles at 10 C. By using high-resolution transmission electron microscopy imaging and joint refinement of hard X-ray and neutron powder diffraction patterns, we revealed that the extraordinary high-rate performance could be achieved by suppressing the formation of electrochemically inactive phase (β-LiMn 1–xFe xPO 4, which is first reported in this work) embedded in α-LiMn 0.5Fe 0.5PO 4. Because of the coherent orientation relationship between β- and α-phases, the β-phase embedded would impede the Li + diffusion along the [100] and/or [001] directions that was activated by the high density of Fe 2+–Li + antisite (4.24%) in α-phase. Thus, by optimizing concentrations of Fe 2+–Li + antisite defects and suppressing β-phase-embedded olivine structure, Li-ion diffusion properties in LiMn 1–xFe xPO 4 nanocrystals can be tuned by generating new Li + tunneling. Finally, these findings may provide insights into the design and generation of other advanced electrode materials with improved rate performance.« less

  18. Leukemia-Associated Nup214 Fusion Proteins Disturb the XPO1-Mediated Nuclear-Cytoplasmic Transport Pathway and Thereby the NF-κB Signaling Pathway.

    PubMed

    Saito, Shoko; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2016-07-01

    Nuclear-cytoplasmic transport through nuclear pore complexes is mediated by nuclear transport receptors. Previous reports have suggested that aberrant nuclear-cytoplasmic transport due to mutations or overexpression of nuclear pore complexes and nuclear transport receptors is closely linked to diseases. Nup214, a component of nuclear pore complexes, has been found as chimeric fusion proteins in leukemia. Among various Nup214 fusion proteins, SET-Nup214 and DEK-Nup214 have been shown to be engaged in tumorigenesis, but their oncogenic mechanisms remain unclear. In this study, we examined the functions of the Nup214 fusion proteins by focusing on their effects on nuclear-cytoplasmic transport. We found that SET-Nup214 and DEK-Nup214 interact with exportin-1 (XPO1)/CRM1 and nuclear RNA export factor 1 (NXF1)/TAP, which mediate leucine-rich nuclear export signal (NES)-dependent protein export and mRNA export, respectively. SET-Nup214 and DEK-Nup214 decreased the XPO1-mediated nuclear export of NES proteins such as cyclin B and proteins involved in the NF-κB signaling pathway by tethering XPO1 onto nuclear dots where Nup214 fusion proteins are localized. We also demonstrated that SET-Nup214 and DEK-Nup214 expression inhibited NF-κB-mediated transcription by abnormal tethering of the complex containing p65 and its inhibitor, IκB, in the nucleus. These results suggest that SET-Nup214 and DEK-Nup214 perturb the regulation of gene expression through alteration of the nuclear-cytoplasmic transport system. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Photoluminescence Properties of Red-Emitting Ca3Sr3-x(PO4)4:xEu3+ Phosphors for White Light-Emitting Diodes.

    PubMed

    Hakeem, D A; Park, K

    2015-07-01

    The photoluminescent properties of the Eu(3+)-activated Ca3Sr3(PO4)4 phosphors prepared by a solution combustion method were investigated. The excitation spectra of Ca3Sr3-x(PO4)4:xEu3+ (0.05 ≤ x ≤ 0.6) phosphors under 614 nm wavelength showed a broad band centered at 266 nm along with other peaks at 320, 362, 381, 394, 414, 464, and 534 nm. The emission spectra observed in the range of 450 to 750 nm under excitation at 394 nm were ascribed to the 5D0-7F1-4 transitions of Eu3+ ions. The Ca3Sr3-x(PO4)4:xEu3+ phosphors showed the strongest red emission at 614 nm due to the electric dipole 5DO -->7F2 transition of Eu3+. The strongest emission intensity was obtained for the Eu3+ ions of x = 0.5. The prepared Ca3Sr3-x(PO4)4:xEu3+ can be used as an efficient red phosphor for UV-based white LEDs.

  20. Targeting Pin1 by inhibitor API-1 regulates microRNA biogenesis and suppresses hepatocellular carcinoma development.

    PubMed

    Pu, Wenchen; Li, Jiao; Zheng, Yuanyuan; Shen, Xianyan; Fan, Xin; Zhou, Jian-Kang; He, Juan; Deng, Yulan; Liu, Xuesha; Wang, Chun; Yang, Shengyong; Chen, Qiang; Liu, Lunxu; Zhang, Guolin; Wei, Yu-Quan; Peng, Yong

    2018-01-30

    Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide, but there are few effective treatments. Aberrant microRNA (miRNA) biogenesis is correlated with HCC development. We previously demonstrated that peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (Pin1) participates in miRNA biogenesis and is a potential HCC treatment target. However, how Pin1 modulates miRNA biogenesis remains obscure. Here, we present in vivo evidence that Pin1 overexpression is directly linked to the development of HCC. Administration with the Pin1 inhibitor (API-1), a specific small molecule targeting Pin1 peptidyl-prolyl isomerase domain and inhibiting Pin1 cis-trans isomerizing activity, suppresses in vitro cell proliferation and migration of HCC cells. But API-1-induced Pin1 inhibition is insensitive to HCC cells with low Pin1 expression and/or low exportin-5 (XPO5) phosphorylation. Mechanistically, Pin1 recognizes and isomerizes the phosphorylated serine-proline motif of phosphorylated XPO5 and passivates phosphorylated XPO5. Pin1 inhibition by API-1 maintains the active conformation of phosphorylated XPO5 and restores XPO5-driven precursor miRNA nuclear-to-cytoplasm export, activating anticancer miRNA biogenesis and leading to both in vitro HCC suppression and HCC suppression in xenograft mice. Experimental evidence suggests that Pin1 inhibition by API-1 up-regulates miRNA biogenesis by retaining active XPO5 conformation and suppresses HCC development, revealing the mechanism of Pin1-mediated miRNA biogenesis and unequivocally supporting API-1 as a drug candidate for HCC therapy, especially for Pin1-overexpressing, extracellular signal-regulated kinase-activated HCC. (Hepatology 2018). © 2018 by the American Association for the Study of Liver Diseases.

  1. Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma.

    PubMed

    Camus, Vincent; Stamatoullas, Aspasia; Mareschal, Sylvain; Viailly, Pierre-Julien; Sarafan-Vasseur, Nasrin; Bohers, Elodie; Dubois, Sydney; Picquenot, Jean Michel; Ruminy, Philippe; Maingonnat, Catherine; Bertrand, Philippe; Cornic, Marie; Tallon-Simon, Valérie; Becker, Stéphanie; Veresezan, Liana; Frebourg, Thierry; Vera, Pierre; Bastard, Christian; Tilly, Hervé; Jardin, Fabrice

    2016-09-01

    Classical Hodgkin lymphoma is one of the most common lymphomas and shares clinical and genetic features with primary mediastinal B-cell lymphoma. In this retrospective study, we analyzed the recurrent hotspot mutation of the exportin 1 (XPO1, p.E571K) gene, previously identified in primary mediastinal B-cell lymphoma, in biopsies and plasma circulating cell-free DNA from patients with classical Hodgkin lymphoma using a highly sensitive digital PCR technique. A total of 94 patients were included in the present study. This widely expressed XPO1 E571K mutation is present in one quarter of classical Hodgkin lymphoma patients (24.2%). Mutated and wild-type classical Hodgkin lymphomas were similar regarding the main clinical features. Patients with a detectable XPO1 mutation at the end of treatment displayed a tendency toward shorter progression-free survival, as compared to patients with undetectable mutation in plasma cell-free DNA (2-year progression-free survival: 57.1%, 95% confidence interval: 30.1-100% versus 2-year progression-free survival: 90.5%, 95% confidence interval: 78.8-100%, respectively, P=0.0601). To conclude, the detection of the XPO1 E571K mutation in biopsy and plasma cell-free DNA by digital PCR may be used as a novel biomarker in classical Hodgkin lymphoma for both diagnosis and minimal residual disease, and pinpoints a crucial role of XPO1 in classical Hodgkin lymphoma pathogenesis. The detection of somatic mutation in the plasma cell-free DNA of patients represents a major technological advance in the context of liquid biopsies and noninvasive management of classical Hodgkin lymphoma. Copyright© Ferrata Storti Foundation.

  2. XPO1 Inhibition Using Selinexor Synergizes With Chemotherapy in Acute Myeloid Leukemia (AML) by Targeting DNA Repair and Restoring Topoisomerase IIα to the Nucleus

    PubMed Central

    Ranganathan, Parvathi; Kashyap, Trinayan; Yu, Xueyan; Meng, Xiaomei; Lai, Tzung-Huei; McNeil, Betina; Bhatnagar, Bhavana; Shacham, Sharon; Kauffman, Michael; Dorrance, Adrienne M.; Blum, William; Sampath, Deepa; Landesman, Yosef; Garzon, Ramiro

    2016-01-01

    Purpose Selinexor, a selective inhibitor of XPO1, is currently being tested as single agent in clinical trials in acute myeloid leukemia (AML). However, considering the molecular complexity of AML, it is unlikely that AML can be cured with monotherapy. Therefore we asked whether adding already established effective drugs such as Topoisomerase (Topo) II inhibitors to selinexor will enhance its anti-leukemic effects in AML. Experimental Design The efficacy of combinatorial drug treatment using Topo II inhibitors (idarubicin, daunorubicin, mitoxantrone, etoposide) and selinexor was evaluated in established cellular and animal models of AML. Results Concomitant treatment with selinexor and Topo II inhibitors resulted in therapeutic synergy in AML cell lines and patient samples. Using a xenograft MV4-11 AML mouse model, we show that treatment with selinexor and idarubicin significantly prolongs survival of leukemic mice compared to each single therapy. Conclusions Aberrant nuclear export and cytoplasmic localization of Topo IIα has been identified as one of the mechanisms leading to drug resistance in cancer. Here, we show that in a subset of AML patients that express cytoplasmic Topo IIα, selinexor treatment results in nuclear retention of Topo IIα protein, resulting in increased sensitivity to idarubicin. Selinexor treatment of AML cells resulted in a c-MYC dependent reduction of DNA damage repair genes (Rad51 and Chk1) mRNA and protein expression, and subsequent inhibition of homologous recombination repair and increased sensitivity to Topo II inhibitors. The preclinical data reported here support further clinical studies using selinexor and Topo II inhibitors in combination to treat AML. PMID:27358488

  3. Luminescence and scintillation properties of XPO4:Nd3+ (X = Y, Lu, Sc, La) crystals

    NASA Astrophysics Data System (ADS)

    Makowski, Michał; Witkowski, Marcin E.; Drozdowski, Winicjusz; Wojtowicz, Andrzej J.; Wisniewski, Krzysztof; Boatner, Lynn A.

    2018-05-01

    Due to their very fast short-wavelength emission, neodymium-doped materials are a subject of current interest as potential scintillators. Although the initial reports regarding neodymium-doped orthophosphates (in crystalline form) and their scintillation properties appeared almost twenty years ago, they remain an interesting class of materials since there is no in-depth understanding of their fundamental scintillation mechanism. In the present research, we focus on the crystalline systems: XPO4:Nd3+, where X = Y, Lu, La, Sc. The pulse height, optical absorption, radioluminescence and photoluminescence spectra were investigated and are reported here for various temperatures from 10 to 350 K. Additionally, results of both low and high temperature thermoluminescence measurements are reported in this communication.

  4. KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia.

    PubMed

    Etchin, Julia; Sanda, Takaomi; Mansour, Marc R; Kentsis, Alex; Montero, Joan; Le, Bonnie T; Christie, Amanda L; McCauley, Dilara; Rodig, Scott J; Kauffman, Michael; Shacham, Sharon; Stone, Richard; Letai, Anthony; Kung, Andrew L; Thomas Look, A

    2013-04-01

    This study explored the anti-leukaemic efficacy of novel irreversible inhibitors of the major nuclear export receptor, chromosome region maintenance 1 (CRM1, also termed XPO1). We found that these novel CRM1 antagonists, termed SINE (Selective Inhibitors of Nuclear Export), induced rapid apoptosis at low nanomolar concentrations in a panel of 14 human T-cell acute lymphoblastic leukaemia (T-ALL) cell lines representing different molecular subtypes of the disease. To assess in vivo anti-leukaemia cell activity, we engrafted immunodeficient mice intravenously with the human T-ALL MOLT-4 cells, which harbour activating mutations of NOTCH1 and NRAS as well as loss of function of the CDKN2A, PTEN and TP53 tumour suppressors and express a high level of oncogenic transcription factor TAL1. Importantly, we examined the in vivo anti-leukaemic efficacy of the clinical SINE compound KPT-330 against T-ALL and acute myeloid leukaemia (AML) cells. These studies demonstrated striking in vivo activity of KPT-330 against T-ALL and AML cells, with little toxicity to normal murine haematopoietic cells. Taken together, our results show that SINE CRM1 antagonists represent promising 'first-in-class' drugs with a novel mechanism of action and wide therapeutic index, and imply that drugs of this class show promise for the targeted therapy of T-ALL and AML. © 2013 Blackwell Publishing Ltd.

  5. Luminescence and scintillation properties of XPO 4:Nd 3+ (X = Y, Lu, Sc, La) crystals

    DOE PAGES

    Makowski, Michal; Witkowski, Marcin E.; Drozdowski, Winicjusz; ...

    2018-04-12

    Due to their very fast short-wavelength emission, neodymium-doped materials are a subject of current interest as potential scintillators. Although the initial reports regarding neodymium-doped orthophosphates (in crystalline form) and their scintillation properties appeared almost twenty years ago, they remain an interesting class of materials since there is no in-depth understanding of their fundamental scintillation mechanism. In the present research, we focus on the crystalline systems: XPO 4:Nd 3+, where X = Y, Lu, La, Sc. The pulse height, optical absorption, radioluminescence and photoluminescence spectra were investigated and are reported here for various temperatures from 10 to 350 K. Here, resultsmore » of both low and high temperature thermoluminescence measurements are reported in this communication.« less

  6. Luminescence and scintillation properties of XPO 4:Nd 3+ (X = Y, Lu, Sc, La) crystals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Makowski, Michal; Witkowski, Marcin E.; Drozdowski, Winicjusz

    Due to their very fast short-wavelength emission, neodymium-doped materials are a subject of current interest as potential scintillators. Although the initial reports regarding neodymium-doped orthophosphates (in crystalline form) and their scintillation properties appeared almost twenty years ago, they remain an interesting class of materials since there is no in-depth understanding of their fundamental scintillation mechanism. In the present research, we focus on the crystalline systems: XPO 4:Nd 3+, where X = Y, Lu, La, Sc. The pulse height, optical absorption, radioluminescence and photoluminescence spectra were investigated and are reported here for various temperatures from 10 to 350 K. Here, resultsmore » of both low and high temperature thermoluminescence measurements are reported in this communication.« less

  7. HIV-1 Vif's Capacity To Manipulate the Cell Cycle Is Species Specific.

    PubMed

    Evans, Edward L; Becker, Jordan T; Fricke, Stephanie L; Patel, Kishan; Sherer, Nathan M

    2018-04-01

    Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1 NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3.CX cells). 3T3.CX cells supported both Rev-independent and Rev-dependent viral gene expression and produced relatively robust levels of virus particles, confirming that CCNT1 and XPO1 represent the predominant blocks to these stages. Unexpectedly, however, 3T3.CX cells were remarkably resistant to virus-induced cytopathic effects observed in human cell lines, which we mapped to the viral protein Vif and its apparent species-specific capacity to induce G 2 /M cell cycle arrest. Vif was able to mediate rapid degradation of human APOBEC3G and the PPP2R5D regulatory B56 subunit of the PP2A phosphatase holoenzyme in mouse cells, thus demonstrating that Vif NL4-3 's modulation of the cell cycle can be functionally uncoupled from some of its other defined roles in CUL5-dependent protein degradation. Vif was also unable to induce G 2 /M cell cycle arrest in other nonhuman cell types, including cells derived from nonhuman primates, leading us to propose that one or more human-specific cofactors underpin Vif's ability to modulate the cell cycle. IMPORTANCE Cells derived from mice and other rodents exhibit profound blocks to HIV-1 replication, thus hindering the development of a low-cost small-animal model for studying HIV/AIDS. Here, we engineered otherwise-nonpermissive mouse cells to express HIV-1-compatible versions of two species-specific host dependency factors, cyclin T1 (CCNT1) and exportin-1 (XPO1) (3T3.CX cells). We show that 3T3.CX cells rescue HIV-1

  8. Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p.

    PubMed

    Cherkasova, Vera; Maury, Luis Lopez; Bacikova, Dagmar; Pridham, Kevin; Bähler, Jürg; Maraia, Richard J

    2012-02-01

    Deletion of the sla1(+) gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1(+) have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1-like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1(+) (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1(+) regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae.

  9. Altered nuclear tRNA metabolism in La-deleted Schizosaccharomyces pombe is accompanied by a nutritional stress response involving Atf1p and Pcr1p that is suppressible by Xpo-t/Los1p

    PubMed Central

    Cherkasova, Vera; Lopez Maury, Luis; Bacikova, Dagmar; Pridham, Kevin; Bähler, Jürg; Maraia, Richard J.

    2012-01-01

    Deletion of the sla1+ gene, which encodes a homologue of the human RNA-binding protein La in Schizosaccharomyces pombe, causes irregularities in tRNA processing, with altered distribution of pre-tRNA intermediates. We show, using mRNA profiling, that cells lacking sla1+ have increased mRNAs from amino acid metabolism (AAM) genes and, furthermore, exhibit slow growth in Edinburgh minimal medium. A subset of these AAM genes is under control of the AP-1–like, stress-responsive transcription factors Atf1p and Pcr1p. Although S. pombe growth is resistant to rapamycin, sla1-Δ cells are sensitive, consistent with deficiency of leucine uptake, hypersensitivity to NH4, and genetic links to the target of rapamycin (TOR) pathway. Considering that perturbed intranuclear pre-tRNA metabolism and apparent deficiency in tRNA nuclear export in sla1-Δ cells may trigger the AAM response, we show that modest overexpression of S. pombe los1+ (also known as Xpo-t), encoding the nuclear exportin for tRNA, suppresses the reduction in pre-tRNA levels, AAM gene up-regulation, and slow growth of sla1-Δ cells. The conclusion that emerges is that sla1+ regulates AAM mRNA production in S. pombe through its effects on nuclear tRNA processing and probably nuclear export. Finally, the results are discussed in the context of stress response programs in Saccharomyces cerevisiae. PMID:22160596

  10. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia

    PubMed Central

    Puente, Xose S.; Pinyol, Magda; Quesada, Víctor; Conde, Laura; Ordóñez, Gonzalo R.; Villamor, Neus; Escaramis, Georgia; Jares, Pedro; Beà, Sílvia; González-Díaz, Marcos; Bassaganyas, Laia; Baumann, Tycho; Juan, Manel; López-Guerra, Mónica; Colomer, Dolors; Tubío, José M. C.; López, Cristina; Navarro, Alba; Tornador, Cristian; Aymerich, Marta; Rozman, María; Hernández, Jesús M.; Puente, Diana A.; Freije, José M. P.; Velasco, Gloria; Gutiérrez-Fernández, Ana; Costa, Dolors; Carrió, Anna; Guijarro, Sara; Enjuanes, Anna; Hernández, Lluís; Yagüe, Jordi; Nicolás, Pilar; Romeo-Casabona, Carlos M.; Himmelbauer, Heinz; Castillo, Ester; Dohm, Juliane C.; de Sanjosé, Silvia; Piris, Miguel A.; de Alava, Enrique; Miguel, Jesús San; Royo, Romina; Gelpí, Josep L.; Torrents, David; Orozco, Modesto; Pisano, David G.; Valencia, Alfonso; Guigó, Roderic; Bayés, Mónica; Heath, Simon; Gut, Marta; Klatt, Peter; Marshall, John; Raine, Keiran; Stebbings, Lucy A.; Futreal, P. Andrew; Stratton, Michael R.; Campbell, Peter J.; Gut, Ivo; López-Guillermo, Armando; Estivill, Xavier; Montserrat, Emili; López-Otín, Carlos; Campo, Elías

    2012-01-01

    Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer. PMID:21642962

  11. Institutional and matrix support and its relationship with primary healthcare

    PubMed Central

    dos Santos, Alaneir de Fátima; Machado, Antônio Thomaz Gonzaga da Matta; dos Reis, Clarice Magalhães Rodrigues; Abreu, Daisy Maria Xavier; de Araújo, Lucas Henrique Lobato; Rodrigues, Simone Cristina; de Lima, Ângela Maria de Lourdes Dayrell; Jorge, Alzira de Oliveira; Fonseca, Délcio

    2015-01-01

    OBJECTIVE To analyze whether the level of institutional and matrix support is associated with better certification of primary healthcare teams. METHODS In this cross-sectional study, we evaluated two kinds of primary healthcare support – 14,489 teams received institutional support and 14,306 teams received matrix support. Logistic regression models were applied. In the institutional support model, the independent variable was “level of support” (as calculated by the sum of supporting activities for both modalities). In the matrix support model, in turn, the independent variables were the supporting activities. The multivariate analysis has considered variables with p < 0.20. The model was adjusted by the Hosmer-Lemeshow test. RESULTS The teams had institutional and matrix supporting activities (84.0% and 85.0%), respectively, with 55.0% of them performing between six and eight activities. For the institutional support, we have observed 1.96 and 3.77 chances for teams who had medium and high levels of support to have very good or good certification, respectively. For the matrix support, the chances of their having very good or good certification were 1.79 and 3.29, respectively. Regarding to the association between institutional support activities and the certification, the very good or good certification was positively associated with self-assessment (OR = 1.95), permanent education (OR = 1.43), shared evaluation (OR = 1.40), and supervision and evaluation of indicators (OR = 1.37). In regards to the matrix support, the very good or good certification was positively associated with permanent education (OR = 1.50), interventions in the territory (OR = 1.30), and discussion in the work processes (OR = 1.23). CONCLUSIONS In Brazil, supporting activities are being incorporated in primary healthcare, and there is an association between the level of support, both matrix and institutional, and the certification result. PMID:26274872

  12. Nuclear Export Inhibition Enhances HLH-30/TFEB Activity, Autophagy, and Lifespan.

    PubMed

    Silvestrini, Melissa J; Johnson, Joseph R; Kumar, Anita V; Thakurta, Tara G; Blais, Karine; Neill, Zachary A; Marion, Sarah W; St Amand, Victoria; Reenan, Robert A; Lapierre, Louis R

    2018-05-15

    Transcriptional modulation of the process of autophagy involves the transcription factor HLH-30/TFEB. In order to systematically determine the regulatory network of HLH-30/TFEB, we performed a genome-wide RNAi screen in C. elegans and found that silencing the nuclear export protein XPO-1/XPO1 enhances autophagy by significantly enriching HLH-30 in the nucleus, which is accompanied by proteostatic benefits and improved longevity. Lifespan extension via xpo-1 silencing requires HLH-30 and autophagy, overlapping mechanistically with several established longevity models. Selective XPO1 inhibitors recapitulated the effect on autophagy and lifespan observed by silencing xpo-1 and protected ALS-afflicted flies from neurodegeneration. XPO1 inhibition in HeLa cells enhanced TFEB nuclear localization, autophagy, and lysosome biogenesis without affecting mTOR activity, revealing a conserved regulatory mechanism for HLH-30/TFEB. Altogether, our study demonstrates that altering the nuclear export of HLH-30/TFEB can regulate autophagy and establishes the rationale of targeting XPO1 to stimulate autophagy in order to prevent neurodegeneration. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Identifying candidate genes for 2p15p16.1 microdeletion syndrome using clinical, genomic, and functional analysis

    PubMed Central

    Bagheri, Hani; Badduke, Chansonette; Qiao, Ying; Colnaghi, Rita; Abramowicz, Iga; Alcantara, Diana; Dunham, Christopher; Wen, Jiadi; Wildin, Robert S.; Nowaczyk, Malgorzata J.M.; Eichmeyer, Jennifer; Lehman, Anna; Maranda, Bruno; Martell, Sally; Shan, Xianghong; Lewis, Suzanne M.E.; O’Driscoll, Mark; Gregory-Evans, Cheryl Y.

    2016-01-01

    The 2p15p16.1 microdeletion syndrome has a core phenotype consisting of intellectual disability, microcephaly, hypotonia, delayed growth, common craniofacial features, and digital anomalies. So far, more than 20 cases of 2p15p16.1 microdeletion syndrome have been reported in the literature; however, the size of the deletions and their breakpoints vary, making it difficult to identify the candidate genes. Recent reports pointed to 4 genes (XPO1, USP34, BCL11A, and REL) that were included, alone or in combination, in the smallest deletions causing the syndrome. Here, we describe 8 new patients with the 2p15p16.1 deletion and review all published cases to date. We demonstrate functional deficits for the above 4 candidate genes using patients’ lymphoblast cell lines (LCLs) and knockdown of their orthologs in zebrafish. All genes were dosage sensitive on the basis of reduced protein expression in LCLs. In addition, deletion of XPO1, a nuclear exporter, cosegregated with nuclear accumulation of one of its cargo molecules (rpS5) in patients’ LCLs. Other pathways associated with these genes (e.g., NF-κB and Wnt signaling as well as the DNA damage response) were not impaired in patients’ LCLs. Knockdown of xpo1a, rel, bcl11aa, and bcl11ab resulted in abnormal zebrafish embryonic development including microcephaly, dysmorphic body, hindered growth, and small fins as well as structural brain abnormalities. Our multifaceted analysis strongly implicates XPO1, REL, and BCL11A as candidate genes for 2p15p16.1 microdeletion syndrome. PMID:27699255

  14. Lightweight structure design for supporting plate of primary mirror

    NASA Astrophysics Data System (ADS)

    Wang, Xiao; Wang, Wei; Liu, Bei; Qu, Yan Jun; Li, Xu Peng

    2017-10-01

    A topological optimization design for the lightweight technology of supporting plate of the primary mirror is presented in this paper. The supporting plate of the primary mirror is topologically optimized under the condition of determined shape, loads and environment. And the optimal structure is obtained. The diameter of the primary mirror in this paper is 450mm, and the material is SiC1 . It is better to select SiC/Al as the supporting material. Six points of axial relative displacement can be used as constraints in optimization2 . Establishing the supporting plate model and setting up the model parameters. After analyzing the force of the main mirror on the supporting plate, the model is applied with force and constraints. Modal analysis and static analysis of supporting plates are calculated. The continuum structure topological optimization mathematical model is created with the variable-density method. The maximum deformation of the surface of supporting plate under the gravity of the mirror and the first model frequency are assigned to response variable, and the entire volume of supporting structure is converted to object function. The structures before and after optimization are analyzed using the finite element method. Results show that the optimized fundamental frequency increases 29.85Hz and has a less displacement compared with the traditional structure.

  15. Dicer cleaves 5'-extended microRNA precursors originating from RNA polymerase II transcription start sites.

    PubMed

    Sheng, Peike; Fields, Christopher; Aadland, Kelsey; Wei, Tianqi; Kolaczkowski, Oralia; Gu, Tongjun; Kolaczkowski, Bryan; Xie, Mingyi

    2018-05-09

    MicroRNAs (miRNAs) are approximately 22 nucleotide (nt) long and play important roles in post-transcriptional regulation in both plants and animals. In animals, precursor (pre-) miRNAs are ∼70 nt hairpins produced by Drosha cleavage of long primary (pri-) miRNAs in the nucleus. Exportin-5 (XPO5) transports pre-miRNAs into the cytoplasm for Dicer processing. Alternatively, pre-miRNAs containing a 5' 7-methylguanine (m7G-) cap can be generated independently of Drosha and XPO5. Here we identify a class of m7G-capped pre-miRNAs with 5' extensions up to 39 nt long. The 5'-extended pre-miRNAs are transported by Exportin-1 (XPO1). Unexpectedly, a long 5' extension does not block Dicer processing. Rather, Dicer directly cleaves 5'-extended pre-miRNAs by recognizing its 3' end to produce mature 3p miRNA and extended 5p miRNA both in vivo and in vitro. The recognition of 5'-extended pre-miRNAs by the Dicer Platform-PAZ-Connector (PPC) domain can be traced back to ancestral animal Dicers, suggesting that this previously unrecognized Dicer reaction mode is evolutionarily conserved. Our work reveals additional genetic sources for small regulatory RNAs and substantiates Dicer's essential role in RNAi-based gene regulation.

  16. Twelve evidence-based principles for implementing self-management support in primary care.

    PubMed

    Battersby, Malcolm; Von Korff, Michael; Schaefer, Judith; Davis, Connie; Ludman, Evette; Greene, Sarah M; Parkerton, Melissa; Wagner, Edward H

    2010-12-01

    Recommendations to improve self-management support and health outcomes for people with chronic conditions in primary care settings are provided on the basis of expert opinion supported by evidence for practices and processes. Practices and processes that could improve self-management support in primary care were identified through a nominal group process. In a targeted search strategy, reviews and meta-analyses were then identifed using terms from a wide range of chronic conditions and behavioral risk factors in combination with Self-Care, Self-Management, and Primary Care. On the basis of these reviews, evidence-based principles for self-management support were developed. The evidence is organized within the framework of the Chronic Care Model. Evidence-based principles in 12 areas were associated with improved patient self-management and/or health outcomes: (1) brief targeted assessment, (2) evidence-based information to guide shared decision-making, (3) use of a nonjudgmental approach, (4) collaborative priority and goal setting, (5) collaborative problem solving, (6) self-management support by diverse providers, (7) self-management interventions delivered by diverse formats, (8) patient self-efficacy, (9) active followup, (10) guideline-based case management for selected patients, (11) linkages to evidence-based community programs, and (12) multifaceted interventions. A framework is provided for implementing these principles in three phases of the primary care visit: enhanced previsit assessment, a focused clinical encounter, and expanded postvisit options. There is a growing evidence base for how self-management support for chronic conditions can be integrated into routine health care.

  17. EXPORTIN1 Genes are Essential for Development and Function of the Gametophytes in Arabidopsis thaliana

    USDA-ARS?s Scientific Manuscript database

    Gametes are produced in plants through mitotic divisions in the haploid gametophytes. We investigated the role of EXPORTIN1 (XPO1) genes during the development of both female and male gametophytes of Arabidopsis. Exportins exclude target proteins from the nucleus and are also part of a complex recru...

  18. Section 4 User Guide – Primary Support

    EPA Pesticide Factsheets

    This document presents the user guide for the Office of Pollution Prevention and Toxics (OPPT) Section 4 application submission process. This document is the user guide for the Primary Support user of the Section 4 tool.

  19. 2016 eCDRweb User Guide–Primary Support

    EPA Pesticide Factsheets

    This document presents the user guide for the Office of Pollution Prevention and Toxics’ (OPPT) 2016 e-CDR web tool. This document is the user guide for the Primary Support user of the 2016 e-CDRweb tool.

  20. eCDRweb User Guide–Primary Support

    EPA Pesticide Factsheets

    This document presents the user guide for the Office of Pollution Prevention and Toxics’ (OPPT) e-CDR web tool. E-CDRweb is the electronic, web-based tool provided by the Environmental Protection Agency (EPA) for the submission of Chemical Data Reporting (CDR) information. This document is the user guide for the Primary Support user of the e-CDRweb tool.

  1. [Social support versus chosen health status indicators in primary care patients].

    PubMed

    Kurpas, Donata; Piotrowski, Patryk; Marciniak, Doininik; Kasprzak, Maja; MroczekS, Bożena; Nitsch-Osuchi, Aneta; Kasssolik, Krzysztof; Karakiewicz, Beata; Bielska, Dorota; Kiejna, Andrzej

    2014-01-01

    The purposes of our study were to determine the level of total social support, informational support, instrumental support, appraisal support and emotional support received by patients of primary care as well as factors related to this level with reference to health status and sociodemographic variables. The sample for current analysis included 516 patients of primary care clinics in Poland cooperating with medical universities. Questionnaires: STAI (State-Trait Anxiety Inventory), SCL-90 (Symptom Checklist-90), EPQ-R (Eysenck Personality Questionnaire-Revised), GHQ (General Health Questionnaire)and SSS (Social Support Scale)were used in the study. Results from last two questionnaires are presented in the paper. The highest mean levels were obtained for instrumental support, while the lowest levels were observed for emotional support. The highest means were indicated in the GHQ-28-social dysfunction, the lowest-GHQ-severe depression. Statistically significant relation was found between the level of social support and gender. Less subjectively evaluated total social support as well as instrumental and appraisal support were obtained by women. The highest Spearman score was found in the case of total GHQ-28 score, somatic symptoms, anxiety and insomnia, severe depression and total support. Taking into account the ANOVA findings, it was observed that an increasing GHQ score was associated with intensively increasing emotional support, informative support, appraisal support and the most- instrumental support. The results display the underestimated role of emotional, informational and appraisal support and the overestimated role of instrumental support in primary care. The consequence may be a more frequent using health care accompanied by low level of patients' satisfaction, severity of social dysfunction disorders, particularly in patients with chronic diseases, who constitute an increasingly large group of primary health care.

  2. Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.

    Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cellsmore » (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision

  3. Function of Nup98 subtypes and their fusion proteins, Nup98-TopIIβ and Nup98-SETBP1 in nuclear-cytoplasmic transport.

    PubMed

    Saito, Shoko; Yokokawa, Takafumi; Iizuka, Gemmei; Cigdem, Sadik; Okuwaki, Mitsuru; Nagata, Kyosuke

    2017-05-20

    Nup98 is a component of the nuclear pore complex. The nup98-fusion genes derived by chromosome translocations are involved in hematopoietic malignancies. Here, we investigated the functions of Nup98 isoforms and two unexamined Nup98-fusion proteins, Nup98-TopIIβ and Nup98-SETBP1. We first demonstrated that two Nup98 isoforms are expressed in various mouse tissues and similarly localized in the nucleus and the nuclear envelope. We also showed that Nup98-TopIIβ and Nup98-SETBP1 are localized in the nucleus and partially co-localized with full-length Nup98 and a nuclear export receptor XPO1. We demonstrated that Nup98-TopIIβ and Nup98-SETBP1 negatively regulate the XPO1-mediated protein export. Our results will contribute to the understanding of the molecular mechanism by which the Nup98-fusion proteins induce tumorigenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Unraveling the Complex Delithiation Mechanisms of Olivine-Type Cathode Materials, LiFe x Co 1–x PO 4

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Strobridge, Fiona C.; Liu, Hao; Leskes, Michal

    2016-06-14

    The delithiation mechanisms occurring within the olivine-type class of cathode materials for Li-ion batteries have received considerable attention owing to the good capacity retention at high rates for LiFePO4. A comprehensive mechanistic study of the (de)lithiation reactions that occur when the substituted olivine-type cathode materials LiFexCo1-xPO4 (x = 0, 0.05, 0.125, 0.25, 0.5, 0.75, 0.875, 0.95 and 1) are electrochemically cycled is reported here, using in situ X-ray diffraction (XRD) data. On the first charge, two intermediate phases are observed and identified: Li1-x(Fe3+)x(Co2+)1- xPO4 for 0 < x < 1 (i.e. after oxidation of Fe2+ => Fe3+) and Li2/3FexCo1-xPO4 formore » 0 ≤ x ≤ 0.5 (i.e. the Co-majority materials). For the Fe-rich materials, we study how nonequilibrium, single-phase mechanisms that occur discretely in single particles, as observed for LiFePO4 at high rates, is affected by Co substitution. In the Co-majority materials, a two-phase mechanism with a coherent interface is observed, as was seen in LiCoPO4, and we discuss how it is manifested in the XRD patterns. We then compare the nonequilibrium, single-phase mechanism with the bulk single-phase and the coherent interface two-phase mechanisms. Despite the apparent differences between these mechanisms, we discuss how they are related and interconverted as a function of Fe/Co substitution and the potential implications for the electrochemistry of this system.« less

  5. Synthesis and crystal structure of the solid solution Co3(SeO3)3-x(PO3OH)x(H2O) involving crystallographic split positions of Se4+ and P5+.

    PubMed

    Zimmermann, Iwan; Johnsson, Mats

    2013-10-21

    Three new cobalt selenite hydroxo-phosphates laying in the solid solution Co3(SeO3)3-x(PO3OH)x(H2O), with x = 0.8, x = 1.0, and x = 1.2 are reported. Single crystals were obtained by hydrothermal synthesis and the crystal structure was determined by single crystal X-ray diffraction. The structure can be described as a 3D framework having selenite and hydroxo-phosphate groups protruding into channels in the crystal structure. Se(4+) and P(5+) share a split position in the structure so that either SeO3 groups having a stereochemically active lone pair or tetrahedrally coordinated PO3OH groups are present. The OH-group is thus only present when the split position is occupied by P(5+). The crystal water is coordinated to a cobalt atom and TG and IR measurements show that the water and hydroxyl groups leave the structure at unusually high temperatures (>450 °C). Magnetic susceptibility measurements show antiferromagnetic coupling below 16 K and a magnetic moment of 4.02(3) μB per Co atom was observed.

  6. Argonaute proteins are key determinants of RNAi efficacy, toxicity, and persistence in the adult mouse liver.

    PubMed

    Grimm, Dirk; Wang, Lora; Lee, Joyce S; Schürmann, Nina; Gu, Shuo; Börner, Kathleen; Storm, Theresa A; Kay, Mark A

    2010-09-01

    shRNA overexpression from viral gene therapy vectors can trigger cytotoxicity leading to organ failure and lethality in mice and rats. This process likely involves saturation of endogenous cellular RNAi factors including exportin-5 (Xpo-5). Here, we have shown that Xpo-5 overexpression enhanced shRNA efficiency in the liver of adult mice but increased hepatotoxicity. We identified the 4 members of the human Argonaute (Ago) protein family as downstream factors involved in saturation of endogenous cellular RNAi, all of which were able to interact with shRNAs in cells and mice. In Ago/shRNA coexpression studies, Ago-2 (Slicer) was the primary rate-limiting determinant of both in vitro and in vivo RNAi efficacy, toxicity, and persistence. In adult mice, vector-based Ago-2/Xpo-5 coexpression enhanced U6-driven shRNA silencing of exogenous and endogenous hepatic targets, reduced hepatotoxicity, and extended RNAi stability by more than 3 months. Use of weaker RNA polymerase III promoters to minimize shRNA expression likewise alleviated in vivo toxicity and permitted greater than 95% persistent knockdown of hepatitis B virus and other transgenes in mouse liver for more than 1 year. Our studies substantiate that abundant small RNAs can overload the endogenous RNAi pathway and reveal possible strategies for reducing hepatotoxicity of short- and long-term clinical gene silencing in humans.

  7. User-centered design to improve clinical decision support in primary care.

    PubMed

    Brunner, Julian; Chuang, Emmeline; Goldzweig, Caroline; Cain, Cindy L; Sugar, Catherine; Yano, Elizabeth M

    2017-08-01

    A growing literature has demonstrated the ability of user-centered design to make clinical decision support systems more effective and easier to use. However, studies of user-centered design have rarely examined more than a handful of sites at a time, and have frequently neglected the implementation climate and organizational resources that influence clinical decision support. The inclusion of such factors was identified by a systematic review as "the most important improvement that can be made in health IT evaluations." (1) Identify the prevalence of four user-centered design practices at United States Veterans Affairs (VA) primary care clinics and assess the perceived utility of clinical decision support at those clinics; (2) Evaluate the association between those user-centered design practices and the perceived utility of clinical decision support. We analyzed clinic-level survey data collected in 2006-2007 from 170 VA primary care clinics. We examined four user-centered design practices: 1) pilot testing, 2) provider satisfaction assessment, 3) formal usability assessment, and 4) analysis of impact on performance improvement. We used a regression model to evaluate the association between user-centered design practices and the perceived utility of clinical decision support, while accounting for other important factors at those clinics, including implementation climate, available resources, and structural characteristics. We also examined associations separately at community-based clinics and at hospital-based clinics. User-centered design practices for clinical decision support varied across clinics: 74% conducted pilot testing, 62% conducted provider satisfaction assessment, 36% conducted a formal usability assessment, and 79% conducted an analysis of impact on performance improvement. Overall perceived utility of clinical decision support was high, with a mean rating of 4.17 (±.67) out of 5 on a composite measure. "Analysis of impact on performance

  8. Factors associated with integrating self-management support into primary care.

    PubMed

    Crespo, Richard; Shrewsberry, Molly

    2007-06-01

    The purpose of this article is to expand the understanding of self-management support by describing factors that contribute to implementing a comprehensive self-management program in primary care. Four rural health centers in medically underserved areas participated in a study to document the implementation of a self-management program. This program consisted of a social marketing plan and decision-making tools to guide patients in making self-management behavior changes. The stages of change constructs of the transtheoretical model were used to design the social marketing plan. Key informant interviews were conducted at 6-month and 9-month intervals to document the implementation process. A standardized set of questions was used in the interviews. The data from the interviews were analyzed using content analysis techniques. One of the principle findings is that self-management support requires putting a system in place, not just adding a new component to primary care. The health centers that fully implemented the self-management program made an organizational commitment to keep self-management on the agenda in management meetings, clinical staff set the example by adopting self-management behaviors, and patient self-management support was implemented in multiple patient care venues. Primary care centers with limited financial resources are able to integrate self-management support into their system of chronic illness care.

  9. For Your Information (FYI) User Guide – Primary Support

    EPA Pesticide Factsheets

    This document is the user guide for the Primary Support user of the FYI tool which is part of the Office of Pollution Prevention and Toxics (OPPT) ‘For Your Information (FYI)’ application submission process.

  10. Section 8(e) Notice User Guide – Primary Support

    EPA Pesticide Factsheets

    This document is the user guide for the Primary Support user of the Section 8(e) Notice tool which is part of the Office of Pollution Prevention and Toxics (OPPT) ‘Section 8(e) Notice’ application submission process.

  11. Supporting nurse practitioners' practice in primary healthcare settings: a three-level qualitative model.

    PubMed

    Chouinard, Véronique; Contandriopoulos, Damien; Perroux, Mélanie; Larouche, Catherine

    2017-06-26

    While greater reliance on nurse practitioners in primary healthcare settings can improve service efficiency and accessibility, their integration is not straightforward, challenging existing role definitions of both registered nurses and physicians. Developing adequate support practices is therefore essential in primary healthcare nurse practitioners' integration. This study's main objective is to examine different structures and mechanisms put in place to support the development of primary healthcare nurse practitioner's practice in different healthcare settings, and develop a practical model for identifying and planning adequate support practices. This study is part of a larger multicentre study on primary healthcare nurse practitioners in the province of Quebec, Canada. It focuses on three healthcare settings into which one or more primary healthcare nurse practitioners have been integrated. Case studies have been selected to cover a maximum of variations in terms of location, organizational setting, and stages of primary healthcare nurse practitioner integration. Findings are based on the analysis of available documentation in each primary healthcare setting and on semi-structured interviews with key actors in each clinical team. Data were analyzed following thematic and cross-sectional analysis approaches. This article identifies three types of support practices: clinical, team, and systemic. This three-level analysis demonstrates that, on the ground, primary healthcare nurse practitioner integration is essentially a team-based, multilevel endeavour. Despite the existence of a provincial implementation plan, the three settings adopted very different implementation structures and practices, and different actors were involved at each of the three levels. The results also indicated that nursing departments played a decisive role at all three levels. Based on these findings, we suggest that support practices should be adapted to each organization's environment and

  12. Electronic health records and support for primary care teamwork.

    PubMed

    O'Malley, Ann S; Draper, Kevin; Gourevitch, Rebecca; Cross, Dori A; Scholle, Sarah Hudson

    2015-03-01

    Consensus that enhanced teamwork is necessary for efficient and effective primary care delivery is growing. We sought to identify how electronic health records (EHRs) facilitate and pose challenges to primary care teams as well as how practices are overcoming these challenges. Practices in this qualitative study were selected from those recognized as patient-centered medical homes via the National Committee for Quality Assurance 2011 tool, which included a section on practice teamwork. We interviewed 63 respondents, ranging from physicians to front-desk staff, from 27 primary care practices ranging in size, type, geography, and population size. EHRs were found to facilitate communication and task delegation in primary care teams through instant messaging, task management software, and the ability to create evidence-based templates for symptom-specific data collection from patients by medical assistants and nurses (which can offload work from physicians). Areas where respondents felt that electronic medical record EHR functionalities were weakest and posed challenges to teamwork included the lack of integrated care manager software and care plans in EHRs, poor practice registry functionality and interoperability, and inadequate ease of tracking patient data in the EHR over time. Practices developed solutions for some of the challenges they faced when attempting to use EHRs to support teamwork but wanted more permanent vendor and policy solutions for other challenges. EHR vendors in the United States need to work alongside practicing primary care teams to create more clinically useful EHRs that support dynamic care plans, integrated care management software, more functional and interoperable practice registries, and greater ease of data tracking over time. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association.

  13. Who can provide diabetes self-management support in primary care? Findings from a randomized controlled trial.

    PubMed

    Siminerio, Linda; Ruppert, Kristine M; Gabbay, Robert A

    2013-01-01

    The purpose of this comparative effectiveness study is to compare diabetes self-management support (DSMS) approaches and determine who can be most effective in helping patients maintain/improve clinical outcomes, self-care behaviors, distress, and satisfaction following diabetes self-management education (DSME) delivered in primary care. After receiving DSME, 141 participants were randomized to receive DSMS delivered by a trained supporter: educator, peer, practice staff, or usual education during a 6-month follow-up period. DSMS groups were compared to determine which supporter helped participants to maintain/improve A1C, blood pressure, lipids, weight, self-care, and distress. DSMS satisfaction was also examined. There was a significant improvement in A1C, empowerment, aspects of self-care, and distress following DSME at 6 weeks. Those in the educator DSMS group best sustained improved A1C while those in the other DSMS groups maintained glycemic improvements but began to show trends toward worsening. No significant differences or clear trends were seen in other clinical, behavioral, or psychosocial outcomes. The Program Reinforcement Impacts Self-Management (PRISM) study demonstrates that following DSME, participants maintained improved glycemia, lipid, weight, and self-care behaviors and reductions in distress throughout the delivery of DSMS interventions regardless of DSMS supporter. All of the participants reported satisfaction with DSMS. These findings reaffirm the critical role of educators but suggest that others may serve as DSMS supporters. Results suggest that DSME delivered in primary care is effective and multiple DSMS agents are reasonable. As patient-centered self-management approaches are being explored in primary care, delivery of DSME and DSMS becomes paramount.

  14. Using an internet intervention to support self-management of low back pain in primary care: findings from a randomised controlled feasibility trial (SupportBack)

    PubMed Central

    Geraghty, Adam W A; Stanford, Rosie; Stuart, Beth; Little, Paul; Roberts, Lisa C; Foster, Nadine E; Hill, Jonathan C; Hay, Elaine M; Turner, David; Malakan, Wansida; Leigh, Linda; Yardley, Lucy

    2018-01-01

    Objective To determine the feasibility of a randomised controlled trial of an internet intervention for low back pain (LBP) using three arms: (1) usual care, (2) usual care plus an internet intervention or (3) usual care plus an internet intervention with additional physiotherapist telephone support. Design and setting A three-armed randomised controlled feasibility trial conducted in 12 general practices in England. Participants Primary care patients aged over 18 years, with current LBP, access to the internet and without indicators of serious spinal pathology or systemic illness. Interventions The ‘SupportBack’ internet intervention delivers a 6-week, tailored programme, focused on graded goal setting, self-monitoring and provision of tailored feedback to encourage physical activity. Additional physiotherapist telephone support consisted of three brief telephone calls over a 4-week period, to address any concerns and provide reassurance. Outcomes The primary outcomes were the feasibility of the trial design including recruitment, adherence and retention at follow-up. Secondary descriptive and exploratory analyses were conducted on clinical outcomes including LBP-related disability at 3 months follow-up. Results Primary outcomes: 87 patients with LBP were recruited (target 60–90) over 6 months, and there were 3 withdrawals. Adherence to the intervention was higher in the physiotherapist-supported arm, compared with the stand-alone internet intervention. Trial physiotherapists adhered to the support protocol. Overall follow-up rate on key clinical outcomes at 3 months follow-up was 84%. Conclusions This study demonstrated the feasibility of a future definitive randomised controlled trial to determine the clinical and cost-effectiveness of the SupportBack intervention in primary care patients with LBP. Trial registration number ISRCTN31034004; Results. PMID:29525768

  15. Women's experiences of social support during the first year following primary breast cancer surgery.

    PubMed

    Drageset, Sigrunn; Lindstrøm, Torill Christine; Giske, Tove; Underlid, Kjell

    2016-06-01

    The aim of this qualitative follow-up study was to describe women's individual experiences of social support during their first year after primary breast cancer surgery. Individual semi-structured interviews with 10 women 1 year after surgery analysed by Kvales' meaning condensation method. Sharing experiences, being understood as an individual, continuity, and information and explanations were themes identified. Sharing mutual experiences increased the women's knowledge regarding cancer, increased experience of support and minimised rumination. After 1 year, the women felt that the network around them had 'normalised' and was less supportive. Being seen as a person, not as 'a diagnosis being treated', and continuity of professional support were important, giving feelings of security and trust. The women felt uncertainty after loss of professional support post-treatment. Information and explanations regarding treatment and treatment-related problems were essential. Mutual sharing of experiences is an important part of social support. Continuity, availability, information and respect were essential aspects of experienced professional support. © 2015 Nordic College of Caring Science.

  16. Technical support and delegation to practice staff - status quo and (possible) future perspectives for primary health care in Germany.

    PubMed

    Urban, Elisabeth; Ose, Dominik; Joos, Stefanie; Szecsenyi, Joachim; Miksch, Antje

    2012-08-01

    Primary health care in industrialized countries faces major challenges due to demographic changes, an increasing prevalence of chronic diseases and a shortage of primary care physicians. One approach to counteract these developments might be to reduce primary care physicians' workload supported by the use of health information technology (HIT) and non-physician practice staff. In 2009, the U.S. Commonwealth Fund (CWF) conducted an international survey of primary care physicians which the present secondary descriptive analysis is based on. The aim of this analysis was twofold: First, to explore to what extend German primary care physicians already get support by HIT and non-physician practice staff, and second, to show possible future perspectives. The CWF questionnaire was sent to a representative random sample of 1,500 primary care physicians all over Germany. The data was descriptively analyzed. Group comparisons regarding differences in gender and age groups were made by means of Chi Square Tests for categorical variables. An alpha-level of p < 0.05 was used for statistical significance. Altogether 715 primary care physicians answered the questionnaire (response rate 49%). Seventy percent of the physicians use electronic medical records. Technical features such as electronic ordering and access to laboratory parameters are mainly used. However, the majority does not routinely use technical functions for drug prescribing, reminder-systems for guideline-based interventions or recall of patients. Six percent of surveyed physicians are able to transfer prescriptions electronically to a pharmacy, 1% use email communication with patients regularly. Seventy-two percent of primary care physicians get support by non-physician practice staff in patient care, mostly in administrative tasks or routine preventive services. One fourth of physicians is supported in telephone calls to the patient or in patient education and counseling. Within this sample the majority of primary

  17. Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostrate Cancer Development and Metastasis

    DTIC Science & Technology

    2010-09-01

    of KLF6 and KLF6-SV1 it will be important to define the functionality of the putative NLS, the 5BR, as well as the role of nucleo-cytoplasmic...presence of basic residues, Lys and Arg. In many cases 18 these signals are located near or within other important domains that regulate protein...transporter protein Crm1/Xpo1, first discovered in yeast (33-36). Subcellular localization and protein turnover are two related events that are tightly

  18. Serum heme oxygenase-1 levels in patients with primary dysmenorrhea.

    PubMed

    Aksoy, Ayse Nur; Laloglu, Esra; Ozkaya, Alev Lazoglu; Yilmaz, Emsal Pınar Topdagi

    2017-04-01

    Primary dysmenorrhea effects the life-quality of women negatively. The aim of this study was to evaluate heme oxygenase-1 (HO1) activity together with malondialdehyde (MDA) and nitric oxide (NO) levels in patients with primary dysmenorrhea. A total of 28 nulliparous women with the diagnosis of primary dysmenorrhea and 26 healthy controls were included in this study. On the first day of menstruation, all patients underwent ultrasound examination to exclude pelvic pathology and the visual analogue scale was applied to patients. Patient's visual analogue scale (VAS) scores, age, body mass index (BMI), menstrual cycle length (day), length of bleeding (day) were recorded. In the same day, fasting blood samples were taken from each patient for biochemical analysis. Serum MDA, NO and HO1 levels were found to be higher in women with primary dysmenorrhea compared to healthy controls (p = 0.012, p = 0.009, p < 0.001, respectively). There were no correlation among serum levels of HO1, NO and MDA, age, BMI, cycle length, pain score and menses duration in both groups. In Pearson's correlation analysis, positive correlation was found between HO1 levels with the NO levels (r = 0.316, p < 0.05) and VAS scores (r = 0.520, p < 0.01). Also, positive correlation was found between MDA levels and VAS scores (r = 0.327, p < 0.05). Serum HO1, NO and MDA levels increase in patients with primary dysmenorrhea. Antioxidant support might be helpful to reduce pain severity in primary dysmenorrhea.

  19. Use of support services in a sample of patients with high-risk primary melanomas in urban, regional and rural Queensland.

    PubMed

    von Schuckmann, Lena A; Smithers, Bernhard M; Khosrotehrani, Kiarash; Beesley, Vanessa L; van der Pols, Jolieke C; Hughes, Maria B; Green, Adele C

    2017-06-01

    To characterise use of support services in patients diagnosed with high-risk primary melanoma by their location of residence. In a cross-sectional study of 787 patients with histologically-confirmed clinical stage 1B-2 melanoma, we estimated odds ratios (ORs) using regression models to assess the association of support service use with residence in rural, regional or urban areas. We also evaluated demographic and clinical correlates of support service use. Among 113 rural patients, 33 (29%) used support services around time of diagnosis compared to 88 (39%) of 224 regional participants and 164 of 448 (37%) urban participants. Regional participants more commonly used support services compared to rural participants (OR 1.84; CI 1.09-3.10), but there was no association with urban versus rural residence (OR 1.32; CI 0.82-2.13). As well, females (OR 1.58; CI 1.15-2.18), those <65 years (OR 1.96; CI 1.42-2.71), or with higher education (OR 2.30; CI 1.53-3.44), or those with T-stage 4B (OR 2.69; CI 1.36-5.32) were more likely to use support services than other patients. Use of support services is lower among rural patients and other sub-groups of primary melanoma patients who have poorer prognoses than others. Implications for public health: Appropriate triage to support services is required for rural and other vulnerable patient groups to ensure optimal patient care. © 2017 The Authors.

  20. The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology.

    PubMed

    Xia, Li; Wang, Minjie; Li, Hongying; Tang, Xiangjing; Chen, Fei; Cui, Jinquan

    2018-05-24

    The therapeutic challenge of advanced, recurrent, and refractory cervical cancer (CC) needs to develop new molecularly targeted drugs. Rad21 is an important regulatory gene that maintains the correct dissociation of sister chromatids during cell mitosis. The aim of this study was to investigate the effect of Rad21 on CC. Rad21 expression in CC and cervical intraepithelial neoplasia III was significantly increased. Women with the rs2289937 C genotype (CC+CT) of rs4570 and rs4579555 genotypes and haplotype 1 (TTTCAGGCGC) were significantly associated with CC risk, while women with low frequencies of haplotype 6 (TTTTAGGCGC) also increased the risk of CC.Rad21-specific shRNA decreased cancerous cell proliferation, migration, and invasion and increased the proportion of cells in G2/M phase as well as sensitivity to radiation. The Rad21 influenced the expression of XPO1, CyclinB1, CDK1, P21, P27, and P53 through up-and downregulating the Rad21 expression. The TCGA database of CC also showed that Rad21 expression was associated with poor disease survival and XPO1 expression. Moreover, the KEGG pathway indicated that Rad21 is broadly involved in the cell cycle and RNA transportation via XPO1. This suggests that Rad21 involves the development of cervical cancer possibly by participating in the regulation of cell cycle and the nuclear output of the tumor suppressor gene via XPO1. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  1. A Self-Study Guide for Managers and Staff of Primary Support Programs for Young People.

    ERIC Educational Resources Information Center

    Costello, Joan; Barker, Gary; Pickens, Lisa Marie; Cassaniga, Neide; Merry, Sheila; Falcon, Adrienne

    Identifying the voluntary activities, programs, and services that children and families use during students' out-of-school time as primary supports, this self-study guide provides a framework for developing primary support programs that allow school-aged children and adolescents to develop physical, cognitive, social, and emotional skills. The…

  2. Primary iris claw IOL retrofixation with intravitreal triamcinolone acetonide in cases of inadequate capsular support.

    PubMed

    Kelkar, Aditya; Shah, Rachana; Vasavda, Viraj; Kelkar, Jai; Kelkar, Shreekant

    2018-02-01

    To assess the outcomes and analyze complication rates following primary iris claw IOL retrofixation with intravitreal triamcinolone acetonide. This is a retrospective interventional case series. Patients with poor capsular support-diagnosed preoperatively or owing to intraoperative complications-were treated with iris claw IOL retrofixation with intravitreal triamcinolone acetonide. The data were retrospectively analyzed. 104 eyes of 102 patients with poor capsular support who underwent the procedure between 2010 and 2013 were analyzed. The minimum follow-up period was 12 months (ranging from 12 to 36 months). Iris claw IOL was implanted in-traumatic subluxated cataracts-24 cases (23.07%), non-traumatic subluxated cataracts in 16 cases (15.38%), or as a complication of cataract surgery-intraoperative posterior capsular rent in 48 cases (46.15%) and intraoperative nucleus drop in 16 cases (15.38%). The final mean best-corrected logMAR visual acuity improved from 1.36 ± 0.64 preoperatively to 0.36 ± 0.32 at 1-year follow-up. Complications included pupil ovalization in 11 cases (10.57%), transient elevation in intraocular pressure in 7 eyes (6.73%), postoperative hypotony in 5 eyes (4.80%), cystoid macular edema in 2 eyes (1.92%), retinal detachment in 1 eye (0.96%), vitreous hemorrhage in 1 eye (0.96%), and hyphema in 1 eye (0.96%). Primary iris claw IOL retrofixation provided excellent alternative in patients with inadequate capsular support. The visual outcomes were good along with favorable rates of complications. The addition of triamcinolone acetonide helps in reducing the chances of cystoid macular edema.

  3. Promoting Mental Health in Unaccompanied Refugee Minors: Recommendations for Primary Support Programs

    PubMed Central

    El-Awad, Usama; Petermann, Franz; Reinelt, Tilman

    2017-01-01

    During the last years, the number of refugees around the world increased to about 22.5 million. The mental health of refugees, especially of unaccompanied minors (70% between the ages of 16 and 18 years) who have been exposed to traumatic events (e.g., war), is generally impaired with symptoms of post-traumatic stress disorder, depression, and anxiety. Several studies revealed (1) a huge variation among the prevalence rates of these mental problems, and (2) that post-migration stressors (e.g., language barriers, cultural differences) might be at least as detrimental to mental health as the traumatic events in pre- and peri-flight. As psychotherapy is a limited resource that should be reserved for severe cases and as language trainings are often publicly offered for refugees, we recommend focusing on intercultural competence, emotion regulation, and goal setting and goal striving in primary support programs: Intercultural competence fosters adaptation by giving knowledge about cultural differences in values and norms. Emotion regulation regarding empathy, positive reappraisal, and cultural differences in emotion expression fosters both adaptation and mental health. Finally, supporting unaccompanied refugee minors in their goal setting and goal striving is necessary, as they carry many unrealistic wishes and unattainable goals, which can be threatening to their mental health. Building on these three psychological processes, we provide recommendations for primary support programs for unaccompanied refugee minors that are aged 16 to 18 years. PMID:29104237

  4. Verdinexor Targeting of CRM1 is a Promising Therapeutic Approach against RSV and Influenza Viruses

    PubMed Central

    Pickens, Jennifer A.

    2018-01-01

    Two primary causes of respiratory tract infections are respiratory syncytial virus (RSV) and influenza viruses, both of which remain major public health concerns. There are a limited number of antiviral drugs available for the treatment of RSV and influenza, each having limited effectiveness and each driving selective pressure for the emergence of drug-resistant viruses. Novel broad-spectrum antivirals are needed to circumvent problems with current disease intervention strategies, while improving the cytokine-induced immunopathology associated with RSV and influenza infections. In this review, we examine the use of Verdinexor (KPT-335, a novel orally bioavailable drug that functions as a selective inhibitor of nuclear export, SINE), as an antiviral with multifaceted therapeutic potential. KPT-335 works to (1) block CRM1 (i.e., Chromosome Region Maintenance 1; exportin 1 or XPO1) mediated export of viral proteins critical for RSV and influenza pathogenesis; and (2) repress nuclear factor κB (NF-κB) activation, thus reducing cytokine production and eliminating virus-associated immunopathology. The repurposing of SINE compounds as antivirals shows promise not only against RSV and influenza virus but also against other viruses that exploit the nucleus as part of their viral life cycle. PMID:29361733

  5. Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6.

    PubMed

    Fiore, Ana Paula Zen Petisco; Spencer, Virginia A; Mori, Hidetoshi; Carvalho, Hernandes F; Bissell, Mina J; Bruni-Cardoso, Alexandre

    2017-06-06

    Nuclear actin (N-actin) is known to participate in the regulation of gene expression. We showed previously that N-actin levels mediate the growth and quiescence of mouse epithelial cells in response to laminin-111 (LN1), a component of the mammary basement membrane (BM). We know that BM is defective in malignant cells, and we show here that it is the LN1/N-actin pathway that is aberrant in human breast cancer cells, leading to continuous growth. Photobleaching assays revealed that N-actin exit in nonmalignant cells begins as early as 30 min after LN1 treatment. LN1 attenuates the PI3K pathway leading to upregulation of exportin-6 (XPO6) activity and shuttles actin out of the nucleus. Silencing XPO6 prevents quiescence. Malignant cells are impervious to LN1 signaling. These results shed light on the crucial role of LN1 in quiescence and differentiation and how defects in the LN1/PI3K/XPO6/N-actin axis explain the loss of tissue homeostasis and growth control that contributes to malignant progression. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Mechanism of N[superscript 10]-formyltetrahydrofolate synthetase derived from complexes with intermediates and inhibitors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Celeste, Lesa R.; Chai, Geqing; Bielak, Magdalena

    N{sup 10}-formyltetrahydrofolate synthetase (FTHFS) is a folate enzyme that catalyzes the formylation of tetrahydrofolate (THF) in an ATP dependent manner. Structures of FTHFS from the thermophilic homoacetogen, Moorella thermoacetica, complexed with (1) a catalytic intermediate-formylphosphate (XPO) and product-ADP; (2) with an inhibitory substrate analog-folate; (3) with XPO and an inhibitory THF analog, ZD9331, were used to analyze the enzyme mechanism. Nucleophilic attack of the formate ion on the gamma phosphate of ATP leads to the formation of XPO and the first product ADP. A channel that leads to the putative formate binding pocket allows for the binding of ATP andmore » formate in random order. Formate binding is due to interactions with the gamma-phosphate moiety of ATP and additionally to two hydrogen bonds from the backbone nitrogen of Ala276 and the side chain of Arg97. Upon ADP dissociation, XPO reorients and moves to the position previously occupied by the beta-phosphate of ATP. Conformational changes that occur due to the XPO presence apparently allow for the recruitment of the third substrate, THF, with its pterin moiety positioned between Phe384 and Trp412. This position overlaps with that of the bound nucleoside, which is consistent with a catalytic mechanism hypothesis that FTHFS works via a sequential ping-pong mechanism. More specifically, a random bi uni uni bi ping-pong ter ter mechanism is proposed. Additionally, the native structure originally reported at a 2.5 {angstrom} resolution was redetermined at a 2.2 {angstrom} resolution.« less

  7. 41 CFR 128-1.5005-1 - Primary delegations.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 41 Public Contracts and Property Management 3 2013-07-01 2013-07-01 false Primary delegations. 128... Personal Property Management § 128-1.5005-1 Primary delegations. The following authorities are redelegated... individual as PMO and PC providing that the functions and responsibilities are compatible and are within the...

  8. 41 CFR 128-1.5005-1 - Primary delegations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false Primary delegations. 128... Personal Property Management § 128-1.5005-1 Primary delegations. The following authorities are redelegated... individual as PMO and PC providing that the functions and responsibilities are compatible and are within the...

  9. 41 CFR 128-1.5005-1 - Primary delegations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 41 Public Contracts and Property Management 3 2014-01-01 2014-01-01 false Primary delegations. 128... Personal Property Management § 128-1.5005-1 Primary delegations. The following authorities are redelegated... individual as PMO and PC providing that the functions and responsibilities are compatible and are within the...

  10. 41 CFR 128-1.5005-1 - Primary delegations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Primary delegations. 128... Personal Property Management § 128-1.5005-1 Primary delegations. The following authorities are redelegated... individual as PMO and PC providing that the functions and responsibilities are compatible and are within the...

  11. 41 CFR 128-1.5005-1 - Primary delegations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 41 Public Contracts and Property Management 3 2012-01-01 2012-01-01 false Primary delegations. 128... Personal Property Management § 128-1.5005-1 Primary delegations. The following authorities are redelegated... individual as PMO and PC providing that the functions and responsibilities are compatible and are within the...

  12. A Nuclear Attack on Traumatic Brain Injury: Sequestration of Cell Death in the Nucleus.

    PubMed

    Tajiri, Naoki; De La Peña, Ike; Acosta, Sandra A; Kaneko, Yuji; Tamir, Sharon; Landesman, Yosef; Carlson, Robert; Shacham, Sharon; Borlongan, Cesar V

    2016-04-01

    Exportin 1 (XPO1/CRM1) plays prominent roles in the regulation of nuclear protein export. Selective inhibitors of nuclear export (SINE) are small orally bioavailable molecules that serve as drug-like inhibitors of XPO1, with potent anti-cancer properties. Traumatic brain injury (TBI) presents with a secondary cell death characterized by neuroinflammation that is putatively regulated by nuclear receptors. Here, we report that the SINE compounds (KPT-350 or KPT-335) sequestered TBI-induced neuroinflammation-related proteins (NF-(k)B, AKT, FOXP1) within the nucleus of cultured primary rat cortical neurons, which coincided with protection against TNF-α (20 ng/mL)-induced neurotoxicity as shown by at least 50% and 100% increments in preservation of cell viability and cellular enzymatic activity, respectively, compared to non-treated neuronal cells (P's < 0.05). In parallel, using an in vivo controlled cortical impact (CCI) model of TBI, we demonstrate that adult Sprague-Dawley rats treated post-injury with SINE compounds exhibited significant reductions in TBI-induced behavioral and histological deficits. Animals that received KPT-350 orally starting at 2 h post-TBI and once a day thereafter over the next 4 days exhibited significantly better motor coordination, and balance in the rotorod test and motor asymmetry test by 100-200% improvements, as early as 4 h after initial SINE compound injection that was sustained during subsequent KPT-350 dosing, and throughout the 18-day post-TBI study period compared to vehicle treatment (P's < 0.05). Moreover, KPT-350 reduced cortical core impact area and peri-impact cell death compared to vehicle treatment (P's < 0.05). Both in vitro and in vivo experiments revealed that KPT-350 increased XPO1, AKT, and FOXP1 nuclear expression and relegated NF-(k)B expression within the neuronal nuclei. Altogether, these findings advance the utility of SINE compounds to stop trafficking of cell death proteins within the nucleus as an efficacious

  13. Interventions to support recovery after domestic and sexual violence in primary care.

    PubMed

    Hegarty, Kelsey; Tarzia, Laura; Hooker, Leesa; Taft, Angela

    2016-10-01

    Experiences of domestic and sexual violence are common in patients attending primary care. Most often they are not identified due to barriers to asking by health practitioners and disclosure by patients. Women are more likely than men to experience such violence and present with mental and physical health symptoms to health practitioners. If identified through screening or case finding as experiencing violence they need to be supported to recover from these traumas. This paper draws on systematic reviews published in 2013-2015 and a further literature search undertaken to identify recent intervention studies relevant to recovery from domestic and sexual violence in primary care. There is limited evidence as to what interventions in primary care assist with recovery from domestic violence; however, they can be categorized into the following areas: first line response and referral, psychological treatments, safety planning and advocacy, including through home visitation and peer support programmes, and parenting and mother-child interventions. Sexual violence interventions usually include trauma informed care and models to support recovery. The most promising results have been from nurse home visiting advocacy programmes, mother-child psychotherapeutic interventions, and specific psychological treatments (Cognitive Behaviour Therapy, Trauma informed Cognitive Behaviour Therapy and, for sexual assault, Exposure and Eye Movement Desensitization and Reprocessing Interventions). Holistic healing models have not been formally tested by randomized controlled trials, but show some promise. Further research into what supports women and their children on their trajectory of recovery from domestic and sexual violence is urgently needed.

  14. Space shuttle EVA/IVA support equipment requirements study. Volume 1: Final summary report

    NASA Technical Reports Server (NTRS)

    1973-01-01

    A study was conducted to determine the support equipment requirements for space shuttle intravehicular and extravehicular activities. The subjects investigated are; (1) EVA/IVA task identification and analysis,. (2) primary life support system, (3) emergency life support system, (4) pressure suit assembly, (5) restraints, (6) work site provision, (7) emergency internal vehicular emergencies, and (8) vehicular interfaces.

  15. Spacelab Operations Support Room Space Engineering Support Team in the SL POCC During the IML-1

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The primary payload for Space Shuttle Mission STS-42, launched January 22, 1992, was the International Microgravity Laboratory-1 (IML-1), a pressurized manned Spacelab module. The goal of IML-1 was to explore in depth the complex effects of weightlessness of living organisms and materials processing. Around-the-clock research was performed on the human nervous system's adaptation to low gravity and effects of microgravity on other life forms such as shrimp eggs, lentil seedlings, fruit fly eggs, and bacteria. Materials processing experiments were also conducted, including crystal growth from a variety of substances such as enzymes, mercury iodide, and a virus. The Huntsville Operations Support Center (HOSC) Spacelab Payload Operations Control Center (SL POCC) at the Marshall Space Flight Center (MSFC) was the air/ground communication channel used between the astronauts and ground control teams during the Spacelab missions. Featured is the Spacelab Operations Support Room Space Engineering Support team in the SL POCC during STS-42, IML-1 mission.

  16. [Telephone support for breastfeeding by primary care: a randomised multicentre trial].

    PubMed

    Balaguer Martínez, Josep Vicent; Valcarce Pérez, Inmaculada; Esquivel Ojeda, Jessica Noelia; Hernández Gil, Alicia; Martín Jiménez, María Del Pilar; Bernad Albareda, Mercè

    2018-03-22

    To evaluate a telephone support programme for mothers who breastfeed for the first 6 months. A randomised unmasked clinical trial was conducted in 5 urban Primary Care centres that included mothers with healthy newborns who were breastfeeding exclusively (EBF) or partially (PBF). The control group received the usual care. The intervention group also received telephone support for breastfeeding on a weekly basis for the first 2months and then every 2weeks until the sixth month. The type of breastfeeding was recorded in the usual check-up visit (1, 2, 4 and 6 months). The study included 193 patients in the intervention group, and 187 in a control group. The greatest increase in the percentage of EBF was observed at 6 months: 21.4% in the control group compared to 30.1% in the intervention group. However, in the adjusted odds ratios analysis, confidence intervals did not show statistical significance. The odds ratio at 1 month, 2 months, 4 months, and 6 months for EBF were 1.45 (0.91-2.31), 1.35 (0.87-2.08), 1.21 (0.80-1.81), and 1.58 (0.99-2.53), respectively. The odds ratio in the same age groups for any type of breastfeeding (EBF + PBF) were 1.65 (0.39-7.00), 2.08 (0.94-4.61), 1.37 (0.79-2.38), and 1.60 (0.98-2.61), respectively. Telephone intervention was not effective enough to generalise it. Copyright © 2018. Publicado por Elsevier España, S.L.U.

  17. Development of Trace Contaminant Control Prototypes for the Primary Life Support System (PLSS)

    NASA Technical Reports Server (NTRS)

    Wojtowicz, Marek; Cosgrove, Joseph E.; Serio, Michael E.; Nalette, Tim; Guerrero, Sandra V.; Papale, William; Wilburn, Monique S.

    2017-01-01

    Results are presented on the development of Trace Contaminant Control (TCC) Prototypes for use in Extravehicular Activities (EVAs), and more specifically in the Primary Life Support System (PLSS). The current TC-control technology involves the use of a packed bed of acid-impregnated granular charcoal, which is non-regenerable, and the carbon-based sorbent under development in this project can be regenerated by exposure to vacuum at room temperature. Data on sorption and desorption of ammonia and formaldehyde, which are major TCs of concern, as well as pressure-drop calculations were used to design and test 1/6-scale and full-scale trace contaminant control system (TCCS) prototypes. Carbon sorbents were fabricated in both the granular and foam-supported forms. Sorbent performance was tested for ammonia sorption and vacuum regeneration in 1/6-scale, and pressure-drop characteristics were measured at flow rates relevant to the PLSS application.

  18. Effects of Support on the Attitude of the Primary Caregiver of a Child with Down Syndrome.

    ERIC Educational Resources Information Center

    Heritage, Jeannette G.; And Others

    Parents of children with mental or physical handicaps often experience overwhelming feelings of stress and anxiety. Research indicates that support for the primary caregiver can help alleviate some stressors involved in raising a child with a handicap. This study examined how level of support affects feelings of satisfaction the primary caregiver…

  19. The localization of nuclear exporters of the importin-beta family is regulated by Snf1 kinase, nutrient supply and stress.

    PubMed

    Quan, XinXin; Yu, Jennifer; Bussey, Howard; Stochaj, Ursula

    2007-07-01

    In the budding yeast Saccharomyces cerevisiae, four members of the importin-beta family of nuclear carriers, Xpo1p/Crm1p, Cse1p, Msn5p and Los1p, function as exporters of protein and tRNA. Under normal growth conditions GFP-tagged exporters are predominantly associated with nuclei. The presence of Snf1 kinase, a key regulator of cell growth and a metabolic sensor, controls the localization of GFP-exporters. Additional glucose-dependent, but Snf1-independent, mechanisms regulate carrier distribution and a switch from fermentable to non-fermentable carbon sources relocates all of the carriers, suggesting a link to the nutritional status of the cell. Moreover, stress controls the proper localization of GFP-exporters, which mislocalize upon exposure to heat, ethanol and starvation. Stress may activate the MAPK cell integrity cascade, and we tested the role of this pathway in exporter localization. Under non-stress conditions, the proper distribution of GFP-Cse1p and Xpo1p/Crm1p-GFP requires kinases of the cell integrity cascade. By contrast, Msn5p-GFP and Los1p-GFP rely on the MAPK module to relocate to the cytoplasm when cells are stressed with ethanol. Our results indicate that the association of nuclear exporters with nuclei is controlled by multiple mechanisms that are organized in a hierarchical fashion and linked to the physiological state of the cell.

  20. Research on large-aperture primary mirror supporting way of vehicle-mounted laser communication system

    NASA Astrophysics Data System (ADS)

    Meng, Lixin; Meng, Lingchen; Zhang, Yiqun; Zhang, Lizhong; Liu, Ming; Li, Xiaoming

    2018-01-01

    In the satellite to earth laser communication link, large-aperture ground laser communication terminals usually are used in order to realize the requirement of high rate and long distance communication and restrain the power fluctuation by atmospheric scintillation. With the increasing of the laser communication terminal caliber, the primary mirror weight should also be increased, and selfweight, thermal deformation and environment will affect the surface accuracy of the primary mirror surface. A high precision vehicular laser communication telescope unit with an effective aperture of 600mm was considered in this paper. The primary mirror is positioned with center hole, which back is supported by 9 floats and the side is supported by a mercury band. The secondary mirror adopts a spherical adjusting mechanism. Through simulation analysis, the system wave difference is better than λ/20 when the primary mirror is in different dip angle, which meets the requirements of laser communication.

  1. Social support is a primary influence on home fruit, 100% juice, and vegetable availability.

    PubMed

    Baranowski, Tom; Watson, Kathy; Missaghian, Mariam; Broadfoot, Alison; Cullen, Karen; Nicklas, Theresa; Fisher, Jennifer; Baranowski, Janice; O'Donnell, Sharon

    2008-07-01

    Children tend to eat more fruit and vegetables when more are available in the home. We proposed and tested a model that predicts the availability at home (hereinafter termed "home availability") of fruit, 100% juice, and vegetables, using new measures of frequency of food shopping, purchase, and comparative purchase outcome expectancies (ie, the perceived benefits and costs of purchasing fruit and vegetables), home food pantry management practices, family social support for purchasing fruit and vegetables, food shopping practices, and body mass index (BMI). Participants (N=98) were recruited in 2004 in front of grocery stores and completed two telephone interviews. Cross-sectional hierarchical regression was employed with backward deletion of nonsignificant variables. Despite many statistically significant bivariate correlations between the new variables and home fruit, 100% juice, and vegetable availability, social support was the primary predictor of home fruit availability in multivariate regression. BMI and home 100% juice pantry management were the primary predictors of home 100% juice availability. Social support, BMI, and shopping practices were the primary predictors of home vegetable availability. Social support for purchasing fruit, 100% juice, and vegetables was an important, consistent predictor of home availability. These findings need to be replicated in larger samples.

  2. Perceived social support mediates anxiety and depressive symptom changes following primary care intervention.

    PubMed

    Dour, Halina J; Wiley, Joshua F; Roy-Byrne, Peter; Stein, Murray B; Sullivan, Greer; Sherbourne, Cathy D; Bystritsky, Alexander; Rose, Raphael D; Craske, Michelle G

    2014-05-01

    The current study tested whether perceived social support serves as a mediator of anxiety and depressive symptom change following evidence-based anxiety treatment in the primary care setting. Gender, age, and race were tested as moderators. Data were obtained from 1004 adult patients (age M = 43, SD = 13; 71% female; 56% White, 20% Hispanic, 12% Black) who participated in a randomized effectiveness trial (coordinated anxiety learning and management [CALM] study) comparing evidence-based intervention (cognitive-behavioral therapy and/or psychopharmacology) to usual care in the primary care setting. Patients were assessed with a battery of questionnaires at baseline, as well as at 6, 12, and 18 months following baseline. Measures utilized in the mediation analyses included the Abbreviated Medical Outcomes (MOS) Social Support Survey, the Brief Symptom Index (BSI)-Somatic and Anxiety subscales, and the Patient Health Questionnaire (PHQ-9). There was a mediating effect over time of perceived social support on symptom change following treatment, with stronger effects for 18-month depression than anxiety. None of the mediating pathways were moderated by gender, age, or race. Perceived social support may be central to anxiety and depressive symptom changes over time with evidence-based intervention in the primary care setting. These findings possibly have important implications for development of anxiety interventions. © 2013 Wiley Periodicals, Inc.

  3. Supporting Primary Care Practices in Building Capacity to Use Health Information Data

    PubMed Central

    Fernald, Douglas; Wearner, Robyn; Dickinson, W. Perry

    2014-01-01

    Introduction: Our objective was to describe essential support resources and strategies in order to advance the pace and scope of the use of health information technology (HIT) data. Background and Context: Primary data were collected between January 2011 and October 2012. The primary study population comprised 51 primary care practices enrolled in the Colorado Beacon Consortium in western Colorado. Methods: We used qualitative methods embedded in a mixed-method evaluation: monthly narrative reports from practices; interviews with providers and staff; and focused, group discussions with quality improvement (QI) advisors and staff from the Health Information Technology Regional Extension Center. Findings: Practices valued effective support strategies to assist with using HIT, including the following: translating rules and regulations into individual practice settings; facilitating peer-to-peer connections; providing processes and tools for practice improvement; maintaining accountability and momentum; and providing local electronic health record (EHR) technical expertise. Benefits of support included improved quality measures, operational improvements, increased provider and staff engagement, and deeper understanding of EHR data. Discussion: The findings affirm the utility of practice facilitation for HIT-focused aims with personalized attention and cross-fertilization among practices for improvements. Facilitation to sustain ongoing improvements and prepare for future HIT-intensive improvement activities was highly valued. In addition to the general practice facilitator, an EHR technical expert was critical to improving practice capacity to use electronic clinical data. Collaborative learning expands the pool of mentors and teachers, who can further translate their own lessons into practical advice for their peers, yielding the emergence of a stronger sense of community among the practices. Conclusions: Using HIT more effectively in primary care will require

  4. Section 8(d) Health Safety Data Reporting User Guide – Primary Support

    EPA Pesticide Factsheets

    This document presents the user guide for the Office of Pollution Prevention and Toxics (OPPT) Section 8(d) Health & Safety Data Reporting application. This document is the user guide for the Primary Support user.

  5. Helping Families Improve: An Evaluation of Two Primary Care Approaches to Parenting Support in the Netherlands

    ERIC Educational Resources Information Center

    de Graaf, Ireen; Onrust, Simone; Haverman, Merel; Janssens, Jan

    2009-01-01

    The present study evaluated two primary care parenting interventions. First, we evaluated the most widely used Dutch practices for primary care parenting support. Second, we assessed the applicability of the Primary Care Triple P approach, which is now being utilized in a wide variety of primary care settings. Both interventions target parents of…

  6. Primary care support for tackling obesity: a qualitative study of the perceptions of obese patients.

    PubMed

    Brown, Ian; Thompson, Joanne; Tod, Angela; Jones, Georgina

    2006-09-01

    Obesity has become a major public health issue and there is concern about the response of health services to patients who are obese. The perceptions of obese patients using primary care services have not been studied in depth. To explore obese patients' experiences and perceptions of support in primary care. Qualitative study with semi-structured interviews conducted in participants' homes. Five general practices contrasting in socioeconomic populations in Sheffield. Purposive sampling and semi-structured interviewing of 28 patients with a diverse range of ages, backgrounds, levels of obesity and experiences of primary care services. Participants typically felt reluctance when presenting with concerns about weight and ambivalence about the services received. They also perceived there to be ambivalence and a lack of resources on the part of the health services. Participants showed a strong sense of personal responsibility about their condition and stigma-related cognitions were common. These contributed to their ambivalence about using services and their sensitivity to its features. Good relationships with primary care professionals and more intensive support partly ameliorated these effects. The challenges of improving access to and quality of primary care support in tackling obesity are made more complex by patients' ambivalence and other effects of the stigma associated with obesity.

  7. Social support, marital adjustment, and psychological distress among women with primary infertility in Pakistan.

    PubMed

    Qadir, Farah; Khalid, Amna; Medhin, Girmay

    2015-01-01

    This study aimed to identify prevalence rates of psychological distress among Pakistani women seeking help for primary infertility. The associations of social support, marital adjustment, and sociodemographic factors with psychological distress were also examined. A total of 177 women with primary infertility were interviewed from one hospital in Islamabad using a Self-Reporting Questionnaire, the Multidimensional Scale of Perceived Social Support, and the Locke-Wallace Marital Adjustment Test. The data were collected between November 2012 and March 2013. The prevalence of psychological distress was 37.3 percent. The results of the logistic regression suggested that marital adjustment and social support were significantly negatively associated with psychological distress in this sample. These associations were not confounded by any of the demographic variables controlled in the multivariable regression models. The role of perceived social support and adjustment in marriage among women experiencing primary infertility are important factors in understanding their psychological distress. The results of this small-scale effort highlight the need for social and familial awareness to help tackle the psychological distress related to infertility. Future research needs to focus on the way the experience of infertility is conditioned by social structural realities. New ways need to be developed to better take into account the process and nature of the infertility experience.

  8. Policy Levers Key for Primary Health Care Organizations to Support Primary Care Practices in Meeting Medical Home Expectations: Comparing Leading States to the Australian Experience

    PubMed Central

    2016-01-01

    Abstract Several countries with highly ranked delivery systems have implemented locally-based, publicly-funded primary health care organizations (PHCOs) as vehicles to strengthen their primary care foundations. In the United States, state governments have started down a similar pathway with models that share similarities with international PHCOs. The objective of this study was to determine if these kinds of organizations were working with primary care practices to improve their ability to provide comprehensive, coordinated, and accessible patient-centered care that met quality, safety, and efficiency outcomes—all core attributes of a medical home. This qualitative study looked at 4 different PHCO models—3 from the United States and 1 from Australia—with similar objectives and scope. Primary and secondary data included semi-structured interviews with 26 PHCOs and a review of government documents. The study found that the 4 PHCO models were engaging practices to meet a number of medical home expectations, but the US PHCOs were more uniform in efforts to work with practices and focused on arranging services to meet the needs of complex patients. There was significant variation in level of effort between the Australian PHCOs. These differences can be explained through the state governments' selection of payment models and use of data frameworks to support collaboration and incentivize performance of both PHCOs and practices. These findings offer policy lessons to inform health reform efforts under way to better capitalize on the potential of PHCOs to support a high-functioning primary health foundation as an essential component to a reformed health system. PMID:26636485

  9. Policy Levers Key for Primary Health Care Organizations to Support Primary Care Practices in Meeting Medical Home Expectations: Comparing Leading States to the Australian Experience.

    PubMed

    Takach, Mary

    2016-10-01

    Several countries with highly ranked delivery systems have implemented locally-based, publicly-funded primary health care organizations (PHCOs) as vehicles to strengthen their primary care foundations. In the United States, state governments have started down a similar pathway with models that share similarities with international PHCOs. The objective of this study was to determine if these kinds of organizations were working with primary care practices to improve their ability to provide comprehensive, coordinated, and accessible patient-centered care that met quality, safety, and efficiency outcomes-all core attributes of a medical home. This qualitative study looked at 4 different PHCO models-3 from the United States and 1 from Australia-with similar objectives and scope. Primary and secondary data included semi-structured interviews with 26 PHCOs and a review of government documents. The study found that the 4 PHCO models were engaging practices to meet a number of medical home expectations, but the US PHCOs were more uniform in efforts to work with practices and focused on arranging services to meet the needs of complex patients. There was significant variation in level of effort between the Australian PHCOs. These differences can be explained through the state governments' selection of payment models and use of data frameworks to support collaboration and incentivize performance of both PHCOs and practices. These findings offer policy lessons to inform health reform efforts under way to better capitalize on the potential of PHCOs to support a high-functioning primary health foundation as an essential component to a reformed health system.

  10. Design and manufacture of 8.4 m primary mirror segments and supports for the GMT

    NASA Astrophysics Data System (ADS)

    Martin, H. M.; Angel, J. R. P.; Burge, J. H.; Cuerden, B.; Davison, W. B.; Johns, M.; Kingsley, J. S.; Kot, L. B.; Lutz, R. D.; Miller, S. M.; Shectman, S. A.; Strittmatter, P. A.; Zhao, C.

    2006-06-01

    The design, manufacture and support of the primary mirror segments for the GMT build on the successful primary mirror systems of the MMT, Magellan and Large Binocular telescopes. The mirror segment and its support system are based on a proven design, and the experience gained in the existing telescopes has led to significant refinements that will provide even better performance in the GMT. The first 8.4 m segment has been cast at the Steward Observatory Mirror Lab, and optical processing is underway. Measurement of the off-axis surface is the greatest challenge in the manufacture of the segments. A set of tests that meets the requirements has been defined and the concepts have been developed in some detail. The most critical parts of the tests have been demonstrated in the measurement of a 1.7 m off-axis prototype. The principal optical test is a full-aperture, high-resolution null test in which a hybrid reflective-diffractive null corrector compensates for the 14 mm aspheric departure of the off-axis segment. The mirror support uses the same synthetic floatation principle as the MMT, Magellan, and LBT mirrors. Refinements for GMT include 3-axis actuators to accommodate the varying orientations of segments in the telescope.

  11. Associations Between Secondary Caregivers' Supportive Behavior and Psychological Distress of Primary Spousal Caregivers of Cognitively Intact and Impaired Elders.

    PubMed

    Lou, Vivian W Q; Kwan, Chi Wai; Chong, Ming Lin Alice; Chi, Iris

    2015-08-01

    This study examined associations between the availability and types of supportive behavior provided by secondary caregivers and the psychological distress of primary spousal caregivers of cognitively intact and impaired elders. A sample of 8,087 assessments using the validated Chinese version of the Minimum Data Set-Home Care of individuals applying for government-subsidized long-term care services from 2006 to 2009 in Hong Kong were selected based on inclusion criteria. More than 70% of primary caregivers had secondary caregivers; the rate was slightly lower for those caring for moderately or severely cognitively impaired spouses. More than half of the primary spousal caregivers had secondary caregivers who provided both emotional and instrumental support. Emotional support provided by secondary caregivers had a negative association with primary caregivers' psychological distress when their care recipients were cognitively intact. When secondary caregivers provided both instrumental and emotional support, primary caregivers had a higher likelihood of psychological distress when care recipients had greater negative mood symptoms as compared to those who had less negative mood symptoms. This is the first study that examined the association between availability and types of supportive behavior provided by secondary caregivers and the psychological distress of primary spousal caregivers of cognitively intact and impaired elders. The findings suggest a need to provide services that enhance the provision of emotional support from both secondary and primary caregivers to cognitively intact elders and support primary spousal caregivers to seek appropriate help according to the mood of care recipients. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Collateral Benefits of the Family Check-Up in Early Childhood: Primary Caregivers’ Social Support and Relationship Satisfaction

    PubMed Central

    McEachern, Amber D.; Dishion, Thomas J.; Wilson, Melvin N.; Fosco, Gregory M.; Shaw, Daniel S.; Gardner, Frances

    2013-01-01

    This research investigated potential collateral benefits of the Family Check-Up (FCU) intervention, namely, primary caregivers’ perceived social support and couple relationship satisfaction. A subsample of 435 low-income families with a 2-year-old child was recruited to participate in a randomized controlled trial assessing preventative effects of the FCU. Longitudinal growth models were used to evaluate intention-to-treat effects of the FCU on increases in primary caregivers’ ratings of social support satisfaction with perceived social support and significant-other relationships, and indirect effects on primary caregivers through improvements in children's behavior problems. Support was found for a model in which reductions in child problem behavior from ages 2 to 4 predicted positive change in caregiver-rated social support and relationship satisfaction over a 3-year period. This indirect effects model is discussed with respect to implications for early childhood prevention research focused on improving family functioning. PMID:23458695

  13. Targeted Analysis of KLF6/KLF6-SV1 Regulating Pathways in Prostate Cancer Development and Metastasis

    DTIC Science & Technology

    2011-09-01

    and KLF6-SV1 it will be important to define the functionality of the putative NLS, the 5BR, as well as the role of nucleo-cytoplasmic shuttling in...aa EGFP -56 aa -16 aa KLF6 KLF6-SV1 5BR ZF,ZF~F3 ZF, ZF2 ZF3 l29KLF6 57KLF6 17KLF6 located near or within other important domains that...the transporter protein Crm1/Xpo1, first discovered in yeast [33–36]. Subcellular localization and protein turnover are two related events that are

  14. TRAC-PF1/MOD1 support calculations for the MIST/OTIS program

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fujita, R.K.; Knight, T.D.

    1984-01-01

    We are using the Transient Reactor Analysis Code (TRAC), specifically version TRAC-PF1/MOD1, to perform analyses in support of the MultiLoop Integral-System Test (MIST) and the Once-Through Integral-System (OTIS) experiment program. We have analyzed Geradrohr Dampferzeuger Anlage (GERDA) Test 1605AA to benchmark the TRAC-PF1/MOD1 code against phenomena expected to occur in a raised-loop B and W plant during a small-break loss-of-coolant accident (SBLOCA). These results show that the code can calculate both single- and two-phase natural circulation, flow interruption, boiler-condenser-mode (BCM) heat transfer, and primary-system refill in a B and W-type geometry with low-elevation auxiliary feedwater. 19 figures, 7 tables.

  15. Collateral benefits of the family check-up in early childhood: primary caregivers' social support and relationship satisfaction.

    PubMed

    McEachern, Amber D; Fosco, Gregory M; Dishion, Thomas J; Shaw, Daniel S; Wilson, Melvin N; Gardner, Frances

    2013-04-01

    This research investigated potential collateral benefits of the Family Check-Up (FCU) intervention, namely, primary caregivers' perceived social support and couple relationship satisfaction. A subsample of 435 low-income families with a 2-year-old child was recruited to participate in a randomized controlled trial assessing preventative effects of the FCU. Longitudinal growth models were used to evaluate intention-to-treat effects of the FCU on increases in primary caregivers' ratings of social support satisfaction with perceived social support and significant-other relationships, and indirect effects on primary caregivers through improvements in children's behavior problems. Support was found for a model in which reductions in child problem behavior from ages 2 to 4 predicted positive change in caregiver-rated social support and relationship satisfaction over a 3-year period. This indirect effects model is discussed with respect to implications for early childhood prevention research focused on improving family functioning. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  16. Planning Guidelines for Primary Schools, Issue 1.

    ERIC Educational Resources Information Center

    Department of Education and Science, Tullamore (Ireland). Planning and Building Unit.

    This planning guide, reflecting recent changes in the educational system in Ireland, offers guidelines for designing primary schools that need to provide additional space for the growing range of teaching and support services. It addresses increased sizes of general purpose rooms, extra floor area provision for classroom storage, administration,…

  17. Development of a computerised decisions support system for renal risk drugs targeting primary healthcare

    PubMed Central

    Helldén, Anders; Al-Aieshy, Fadiea; Bastholm-Rahmner, Pia; Bergman, Ulf; Gustafsson, Lars L; Höök, Hans; Sjöviker, Susanne; Söderström, Anders; Odar-Cederlöf, Ingegerd

    2015-01-01

    Objectives To assess general practitioners (GPs) experience from the implementation and use of a renal computerised decision support system (CDSS) for drug dosing, developed for primary healthcare, integrated into the patient’s electronic health record (EHR), and building on estimation of the patient's creatinine clearance (ClCG). Design Qualitative research design by a questionnaire and a focus group discussion. Setting and participants Eight GPs at two primary healthcare centres (PHCs). Interventions The GP at PHC 1, and the project group, developed and tested the technical solution of the CDSS. Proof-of-concept was tested by seven GPs at PHC 2. They also participated in a group discussion and answered a questionnaire. A web window in the EHR gave drug and dosage in relation to ClCG. Each advice was according to three principles: If? Why? Because. Outcome measures (1) The GPs’ experience of ‘easiness to use’ and ‘perceived usefulness’ at PHC 2, based on loggings of use, answers from a questionnaire using a 5-point Likert scale, and answers from a focus group discussion. (2) The number of patients aged 65 years and older with an estimation of ClCG before and after the implementation of the CDSS. Results The GPs found the CDSS fast, simple and easy to use. They appreciated the automatic presentation of the CICG status on opening the medication list, and the ability to actively look up specific drug recommendations in two steps. The CDSS scored high on the Likert scale. All GPs wanted to continue the use of the CDSS and to recommend it to others. The number of patients with an estimated ClCG increased 1.6-fold. Conclusions Acceptance of the simple graphical interface of this push and pull renal CDSS was high among the primary care physicians evaluating this proof of concept. The graphical model should be useful for further development of renal decision support systems. PMID:26150141

  18. Support optimization of the ring primary mirror of a 2m solar telescope

    NASA Astrophysics Data System (ADS)

    Yang, Dehua; Jin, Zhenyu; Liu, Zhong

    2016-08-01

    A special 2-m Ring Solar Telescope (2-m RST) is to be built by YNAO-Yunnan Astronomical Observatory, Kunming, China. Its distinct primary mirror is distinctively shaped in a ring with an outer diameter of 2.02 m and a ring width of 0.35 m. Careful calculation and optimization of the mirror support pattern have been carried out first of all to define optimum blank parameters in view of performance balance of support design, fabrication and cost. This paper is to review the special consideration and optimization of the support design for the unique ring mirror. Schott zerodur is the prevailing candidate for the primary mirror blank. Diverse support patterns with various blank thicknesses have been discussed by extensive calculation of axial support pattern of the mirror. We reached an optimum design of 36 axial supports for a blank thickness of 0.15 m with surface error of 5 nm RMS. Afterwards, lateral support scheme was figured out for the mirror with settled parameters. A classical push-and-pull scheme was used. Seeing the relative flexibility of the ring mirror, special consideration was taken to unusually set the acting direction of the support forces not in the mirror gravity plane, but along the gravity of the local virtual slices of the mirror blank. Nine couples of the lateral push-pull force are considered. When pointing to horizon, the mirror surface exhibits RMS error of 5 nm with three additional small force couples used to compensate for the predominant astigmatism introduced by lateral supports. Finally, error estimation has been performed to evaluate the surface degradation with introduced errors in support force and support position, respectively, for both axial and lateral supports. Monte Carlo approach was applied using unit seeds for amplitude and position of support forces. The comprehensive optimization and calculation suggests the support systems design meet the technic requirements of the ring mirror of the 2-m RST.

  19. Learning Support Policy for Mathematics in Irish Primary Schools: Equal Access but Unequal Needs

    ERIC Educational Resources Information Center

    Travers, Joseph

    2010-01-01

    This paper critiques learning-support policy for mathematics in Irish primary schools. The key policy question addressed is how equitable the development of the learning-support service has been in addressing low achievement in mathematics in designated schools compared to non-designated schools. The core argument developed is that there is a link…

  20. Technical assessment of Mir-1 life support hardware for the international space station

    NASA Technical Reports Server (NTRS)

    Mitchell, K. L.; Bagdigian, R. M.; Carrasquillo, R. L.; Carter, D. L.; Franks, G. D.; Holder, D. W., Jr.; Hutchens, C. F.; Ogle, K. Y.; Perry, J. L.; Ray, C. D.

    1994-01-01

    NASA has been progressively learning the design and performance of the Russian life support systems utilized in their Mir space station. In 1992, a plan was implemented to assess the benefits of the Mir-1 life support systems to the Freedom program. Three primary tasks focused on: evaluating the operational Mir-1 support technologies and understanding if specific Russian systems could be directly utilized on the American space station and if Russian technology design information could prove useful in improving the current design of the planned American life support equipment; evaluating the ongoing Russian life support technology development activities to determine areas of potential long-term application to the U.S. space station; and utilizing the expertise of their space station life support systems to evaluate the benefits to the current U.S. space station program which included the integration of the Russian Mir-1 designs with the U.S. designs to support a crew of six.

  1. Women with spontaneous 46,XX primary ovarian insufficiency (hypergonadotropic hypogonadism) have lower perceived social support than control women

    PubMed Central

    Orshan, Susan A.; Ventura, June L.; Covington, Sharon N.; Vanderhoof, Vien H.; Troendle, James F.; Nelson, Lawrence M.

    2009-01-01

    Objective To test the hypothesis that women with spontaneous primary ovarian insufficiency differ from control women with regard to perceived social support and to investigate the relationship between perceived social support and self-esteem. Design Cross-sectional Setting Mark O. Hatfield Clinical Research Center, National Institutes of Health. Patient(s) Women diagnosed with spontaneous primary ovarian insufficiency (N=154) at a mean age of 27 years and healthy control women (N=63). Intervention(s) Administration of validated self-reporting instruments. Main Outcome Measure(s) Personal Resource Questionnaire-85 (PRQ85), Rosenberg Self-Esteem Scale Result(s) Women with primary ovarian insufficiency had significantly lower scores than controls on the perceived social support scale and the self-esteem scale. The findings remained significant after modeling with multivariate regression for differences in age, marital status, and having children. In patients there was a significant positive correlation between self-esteem scores and perceived social support. We found no significant differences in perceived social support or self-esteem related to marital status, whether or not they had children, or time since diagnosis. Conclusion(s) This evidence supports the need for prospective controlled studies. Strategies to improve social support and self-esteem might provide a therapeutic approach to reduce the emotional suffering that accompanies the life-altering diagnosis of spontaneous primary ovarian insufficiency. PMID:18829005

  2. Common variants in ZMIZ1 and near NGF confer risk for primary dysmenorrhoea

    PubMed Central

    Li, Zhiqiang; Chen, Jianhua; Zhao, Ying; Wang, Yujiong; Xu, Jinrui; Ji, Jue; Shen, Jingyi; Zhang, Weiping; Chen, Zuosong; Sun, Qilin; Mao, Lijuan; Cheng, Shulin; Yang, Bo; Zhang, Dongtao; Xu, Yufeng; Zhao, Yingying; Liu, Danping; Shen, Yinhuan; Zhang, Weijie; Li, Changgui; Shen, Jiawei; Shi, Yongyong

    2017-01-01

    Primary dysmenorrhoea, defined as painful menstrual cramps in the absence of pelvic pathology, is a common problem in women of reproductive age. Its aetiology and pathophysiology remain largely unknown. Here we performed a two-stage genome-wide association study and subsequent replication study to identify genetic factors associated with primary dysmenorrhoea in a total of 6,770 Chinese individuals. Our analysis provided evidence of a significant (P<5 × 10−8) association at rs76518691 in the gene ZMIZ1 and at rs7523831 near NGF. ZMIZ1 has previously been associated with several autoimmune diseases, and NGF plays a key role in the generation of pain and hyperalgesia and has been associated with migraine. These findings provide future directions for research on susceptibility mechanisms for primary dysmenorrhoea. Furthermore, our genetic architecture analysis provides molecular support for the heritability and polygenic nature of this condition. PMID:28447608

  3. Supporting Medical Home Transformation Through Evaluation of Patient Experience in a Large Culturally Diverse Primary Care Safety Net.

    PubMed

    Cook, Nicole; Hollar, T Lucas; Zunker, Christie; Peterson, Michael; Phillips, Teina; De Lucca, Michael

    2016-01-01

    The prevalence of chronic disease in the United States is rapidly increasing, with a disproportionate number of underserved, vulnerable patients sharing the burden. The Patient-Centered Medical Home (PCMH) is a care delivery model that has shown promise to improve primary care and address the burden of chronic illness. The purpose of this study was to (1) understand patient characteristics that might influence perceived patient experience in a large primary care safety net undergoing PCMH transformation; (2) identify community-level quality improvement opportunities to support ongoing transformation activities; and (3) establish a baseline of patient experience across the primary care safety net that could be used in repeated evaluations over the course of transformation. A cross-sectional study design was used to conduct this research. A total of 351 racially and ethnically diverse patients of 4 primary care safety net organizations in Broward County, Florida, were surveyed regarding their experience with access to care and coordination of care. Reported access to care and coordination of care. Patients with chronic disease who reported having visited the clinic 3 or more times in the past 12 months reported a better coordination of care experience than patients who had fewer than 3 visits in the past 12 months (odds ratio = 3.57; 95% confidence interval, 1.76-7.24). Patients without chronic disease who had been receiving care at the clinic for 2 or more years of care reported worse experience with access to care than patients with less than 2 years of care (odds ratio = 0.26; 95% confidence interval, 0.11-0.60.) Race, ethnicity, language, and education were not significant predictors of patient experience. Findings support ongoing efforts to improve patient engagement among all patients and to enhance resources to manage chronic disease, including community-based self-management programs, in primary care safety nets undergoing PCMH transformation.

  4. Long-term persistence of primary genotypic resistance after HIV-1 seroconversion.

    PubMed

    Pao, David; Andrady, Ushan; Clarke, Janette; Dean, Gillian; Drake, Susan; Fisher, Martin; Green, Tanya; Kumar, Siva; Murphy, Maurice; Tang, Alan; Taylor, Stephen; White, David; Underhill, Gillian; Pillay, Deenan; Cane, Patricia

    2004-12-15

    Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.

  5. 76 FR 21034 - Dex One, et al.; Amended Certification Regarding Eligibility To Apply for Worker Adjustment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    ... firm acquiring from a foreign country services like or directly competitive with the services supplied..., Including On-Site Leased Workers of Advantage XPO, Fort Myers, Maitland, and Ocala, FL TA-W-75,172A Dex One... Advantage XPO, Arlington Heights, Chicago, Lombard, Springfield, and Tinley Park, IL TA-W-75,172B Dex One...

  6. The impact of a multidisciplinary information technology-supported program on blood pressure control in primary care.

    PubMed

    Rinfret, Stéphane; Lussier, Marie-Thérèse; Peirce, Anthony; Duhamel, Fabie; Cossette, Sylvie; Lalonde, Lyne; Tremblay, Chantal; Guertin, Marie-Claude; LeLorier, Jacques; Turgeon, Jacques; Hamet, Pavel

    2009-05-01

    Hypertension is a leading mortality risk factor yet inadequately controlled in most affected subjects. Effective programs to address this problem are lacking. We hypothesized that an information technology-supported management program could help improve blood pressure (BP) control. This randomized controlled trial included 223 primary care hypertensive subjects with mean 24-hour BP >130/80 and daytime BP >135/85 mm Hg measured with ambulatory monitoring (ABPM). Intervention subjects received a BP monitor and access to an information technology-supported adherence and BP monitoring system providing nurses, pharmacists, and physicians with monthly reports. Control subjects received usual care. The mean (+/-SD) follow-up was 348 (+/-78) and 349 (+/-84) days in the intervention and control group, respectively. The primary end point of the change in the mean 24-hour ambulatory BP was consistently greater in intervention subjects for both systolic (-11.9 versus -7.1 mm Hg; P<0.001) and diastolic BP (-6.6 versus -4.5 mm Hg; P=0.007). The proportion of subjects that achieved Canadian Guideline target BP (46.0% versus 28.6%) was also greater in the intervention group (P=0.006). We observed similar BP declines for ABPM and self-recorded home BP suggesting the latter could be an alternative for confirming BP control. The intervention was associated with more physician-driven antihypertensive dose adjustments or changes in agents (P=0.03), more antihypertensive classes at study end (P=0.007), and a trend toward improved adherence measured by prescription refills (P=0.07). This multidisciplinary information technology-supported program that provided feedback to patients and healthcare providers significantly improved blood pressure levels in a primary care setting.

  7. Primary brain tumor patients' supportive care needs and multidisciplinary rehabilitation, community and psychosocial support services: awareness, referral and utilization.

    PubMed

    Langbecker, Danette; Yates, Patsy

    2016-03-01

    Primary brain tumors are associated with significant physical, cognitive and psychosocial changes. Although treatment guidelines recommend offering multidisciplinary rehabilitation and support services to address patients' residual deficits, the extent to which patients access such services is unclear. This study aimed to assess patients' supportive care needs early after diagnosis, and quantify service awareness, referral and utilization. A population-based sample of 40 adults recently diagnosed with primary brain tumors was recruited through the Queensland Cancer Registry, representing 18.9 % of the eligible population of 203 patients. Patients or carer proxies completed surveys of supportive care needs at baseline (approximately 3 months after diagnosis) and 3 months later. Descriptive statistics summarized needs and service utilization, and linear regression identified predictors of service use. Unmet supportive care needs were highest at baseline for all domains, and highest for the physical and psychological needs domains at each time point. At follow-up, participants reported awareness of, referral to, and use of 32 informational, support, health professional or practical services. All or almost all participants were aware of at least one informational (100 %), health professional (100 %), support (97 %) or practical service (94 %). Participants were most commonly aware of speech therapists (97 %), physiotherapists (94 %) and diagnostic information from the internet (88 %). Clinician referrals were most commonly made to physiotherapists (53 %), speech therapists (50 %) and diagnostic information booklets (44 %), and accordingly, participants most commonly used physiotherapists (56 %), diagnostic information booklets (47 %), diagnostic information from the internet (47 %), and speech therapists (43 %). Comparatively low referral to and use of psychosocial services may limit patients' abilities to cope with their condition and the changes they

  8. Brief encounters: what do primary care professionals contribute to peoples' self-care support network for long-term conditions? A mixed methods study.

    PubMed

    Rogers, Anne; Vassilev, Ivaylo; Brooks, Helen; Kennedy, Anne; Blickem, Christian

    2016-02-17

    Primary care professionals are presumed to play a central role in delivering long-term condition management. However the value of their contribution relative to other sources of support in the life worlds of patients has been less acknowledged. Here we explore the value of primary care professionals in people's personal communities of support for long-term condition management. A mixed methods survey with nested qualitative study designed to identify relationships and social network member's (SNM) contributions to the support work of managing a long-term condition conducted in 2010 in the North West of England. Through engagement with a concentric circles diagram three hundred participants identified 2544 network members who contributed to illness management. The results demonstrated how primary care professionals are involved relative to others in ongoing self-care management. Primary care professionals constituted 15.5 % of overall network members involved in chronic illness work. Their contribution was identified as being related to illness specific work providing less in terms of emotional work than close family members or pets and little to everyday work. The qualitative accounts suggested that primary care professionals are valued mainly for access to medication and nurses for informational and monitoring activities. Overall primary care is perceived as providing less input in terms of extended self-management support than the current literature on policy and practice suggests. Thus primary care professionals can be described as providing 'minimally provided support'. This sense of a 'minimally' provided input reinforces limited expectations and value about what primary care professionals can provide in terms of support for long-term condition management. Primary care was perceived as having an essential but limited role in making a contribution to support work for long-term conditions. This coalesces with evidence of a restricted capacity of primary care to

  9. Supporting the Consistent Implementation of Self-Evaluation in Irish Post-Primary Schools

    ERIC Educational Resources Information Center

    O'Brien, Shivaun; McNamara, Gerry; O'Hara, Joe

    2015-01-01

    This paper explores approaches to support the consistent implementation of school self-evaluation. The first part of the paper outlines the changing nature of self-evaluation in Irish post-primary schools and how a new approach introduced by the Department of Education and Skills in 2012 demonstrates real intentionality in terms of implementation.…

  10. A pilot trial of a stress management intervention for primary caregivers of children newly diagnosed with cancer: preliminary evidence that perceived social support moderates the psychosocial benefit of intervention.

    PubMed

    Marsland, Anna L; Long, Kristin A; Howe, Chelsea; Thompson, Amanda L; Tersak, Jean; Ewing, Linda J

    2013-05-01

    (1) To examine the acceptability and feasibility of a stress management intervention for caregivers of children recently diagnosed with cancer. (2) To explore whether caregivers with lower baseline perceived social support derive greater benefit from the intervention than those with higher perceived support. 45 primary caregivers were randomly assigned to intervention or standard care. Of these, 37 completed measures of social support, depression, anxiety, and perceived stress at both pre-intervention (T1; mean = 24 days post-diagnosis) and post-intervention time points (T2; mean = 165 days post-diagnosis). Enrollment, retention, and satisfaction data support feasibility and acceptability of the intervention. There was no overall significant impact of participation in the intervention on levels of distress at T2. However, T1 social support moderated intervention response, with caregivers who perceived lower T1 support showing greater psychological benefit from the intervention. Primary caregivers with lower levels of perceived social support may benefit from preemptive stress management intervention.

  11. Patient-specific computer-based decision support in primary healthcare--a randomized trial.

    PubMed

    Kortteisto, Tiina; Raitanen, Jani; Komulainen, Jorma; Kunnamo, Ilkka; Mäkelä, Marjukka; Rissanen, Pekka; Kaila, Minna

    2014-01-20

    Computer-based decision support systems are a promising method for incorporating research evidence into clinical practice. However, evidence is still scant on how such information technology solutions work in primary healthcare when support is provided across many health problems. In Finland, we designed a trial where a set of evidence-based, patient-specific reminders was introduced into the local Electronic Patient Record (EPR) system. The aim was to measure the effects of such reminders on patient care. The hypothesis was that the total number of triggered reminders would decrease in the intervention group compared with the control group, indicating an improvement in patient care. From July 2009 to October 2010 all the patients of one health center were randomized to an intervention or a control group. The intervention consisted of patient-specific reminders concerning 59 different health conditions triggered when the healthcare professional (HCP) opened and used the EPR. In the intervention group, the triggered reminders were shown to the HCP; in the control group, the triggered reminders were not shown. The primary outcome measure was the change in the number of reminders triggered over 12 months. We developed a unique data gathering method, the Repeated Study Virtual Health Check (RSVHC), and used Generalized Estimation Equations (GEE) for analysing the incidence rate ratio, which is a measure of the relative difference in percentage change in the numbers of reminders triggered in the intervention group and the control group. In total, 13,588 participants were randomized and included. Contrary to our expectation, the total number of reminders triggered increased in both the intervention and the control groups. The primary outcome measure did not show a significant difference between the groups. However, with the inclusion of patients followed up over only six months, the total number of reminders increased significantly less in the intervention group than in

  12. An archaeal origin of eukaryotes supports only two primary domains of life.

    PubMed

    Williams, Tom A; Foster, Peter G; Cox, Cymon J; Embley, T Martin

    2013-12-12

    The discovery of the Archaea and the proposal of the three-domains 'universal' tree, based on ribosomal RNA and core genes mainly involved in protein translation, catalysed new ideas for cellular evolution and eukaryotic origins. However, accumulating evidence suggests that the three-domains tree may be incorrect: evolutionary trees made using newer methods place eukaryotic core genes within the Archaea, supporting hypotheses in which an archaeon participated in eukaryotic origins by founding the host lineage for the mitochondrial endosymbiont. These results provide support for only two primary domains of life--Archaea and Bacteria--because eukaryotes arose through partnership between them.

  13. An innovative model of diabetes care and delivery: the St. Joseph's Primary Care Diabetes Support Program (SJHC PCDSP).

    PubMed

    Reichert, Sonja M; Harris, Stewart; Harvey, Betty

    2014-06-01

    The majority of diabetes care in Canada is provided within the primary healthcare setting. It is delivered in a variety of models ranging from the physician working in a solo fee-for-service practice to an interprofessional team setting with specialist collaboration. To augment diabetes-related health services, the Ontario government has provided substantial funding to support community diabetes education programs. These models and initiatives are improving diabetes outcomes, and continued evolution of these programs can provide even greater outcomes. The St. Joseph's Primary Care Diabetes Support Program (SJHC PCDSP) is an innovative model that incorporates multidisciplinary allied health professionals together with physician support to provide care for more than 3000 patients in London, Ontario, Canada. It embodies the Canadian Diabetes Association (CDA)'s Organizations of Care recommendations to combine patient education and self-management with active medical support at each clinic encounter, all while embodying the tenets of primary care. A brief review of primary healthcare reform is provided to explain how the SJHC PCDSP combines features of current models in a unique format so as to deliver exceptional patient care. By providing a detailed description of the services delivered at the SJHC PCDSP, it is hoped that both specialists and primary care providers consider using and adapting approaches to diabetes management based on this innovative model to optimize their practices. Copyright © 2014 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  14. Is change in environmental supportiveness between primary and secondary school associated with a decline in children׳s physical activity levels?

    PubMed

    Coombes, Emma; Jones, Andy; Page, Angie; Cooper, Ashley R

    2014-09-01

    Using a sample of English schoolchildren, we evaluate whether a change in school local area environmental supportiveness between primary and secondary school is associated with changes in active travel behaviours and physical activity levels. Participant׳s activity levels and travel behaviours were recorded for a week during their primary school final year and secondary school first year. Environmental supportiveness was evaluated using a Geographical Information System. Children attending both a primary and secondary school with a more supportive local environment were more likely to maintain active travel behaviours than those with less supportive environments. However, no trends were apparent with change in school supportiveness and change in physical activity. Policies that focus on the maintenance and uptake of active travel behaviours may help maintain children׳s physical activity levels into adolescence. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Strategies to Support the Integration of Behavioral Health and Primary Care: What Have We Learned Thus Far?

    PubMed

    Dickinson, W Perry

    2015-01-01

    The articles in this supplement contain a wealth of practical information regarding the integration of behavioral health and primary care. This type of integration effort is complex and greatly benefits from support from outside organizations, as well as collaboration with other practices attempting similar work. This editorial extracts from these articles some of the key lessons learned regarding the integration of behavioral health and primary care for practices and for organizations that support practice transformation. © Copyright 2015 by the American Board of Family Medicine.

  16. A computerized decision support system for depression in primary care.

    PubMed

    Kurian, Benji T; Trivedi, Madhukar H; Grannemann, Bruce D; Claassen, Cynthia A; Daly, Ella J; Sunderajan, Prabha

    2009-01-01

    In 2004, results from The Texas Medication Algorithm Project (TMAP) showed better clinical outcomes for patients whose physicians adhered to a paper-and-pencil algorithm compared to patients who received standard clinical treatment for major depressive disorder (MDD). However, implementation of and fidelity to the treatment algorithm among various providers was observed to be inadequate. A computerized decision support system (CDSS) for the implementation of the TMAP algorithm for depression has since been developed to improve fidelity and adherence to the algorithm. This was a 2-group, parallel design, clinical trial (one patient group receiving MDD treatment from physicians using the CDSS and the other patient group receiving usual care) conducted at 2 separate primary care clinics in Texas from March 2005 through June 2006. Fifty-five patients with MDD (DSM-IV criteria) with no significant difference in disease characteristics were enrolled, 32 of whom were treated by physicians using CDSS and 23 were treated by physicians using usual care. The study's objective was to evaluate the feasibility and efficacy of implementing a CDSS to assist physicians acutely treating patients with MDD compared to usual care in primary care. Primary efficacy outcomes for depression symptom severity were based on the 17-item Hamilton Depression Rating Scale (HDRS(17)) evaluated by an independent rater. Patients treated by physicians employing CDSS had significantly greater symptom reduction, based on the HDRS(17), than patients treated with usual care (P < .001). The CDSS algorithm, utilizing measurement-based care, was superior to usual care for patients with MDD in primary care settings. Larger randomized controlled trials are needed to confirm these findings. clinicaltrials.gov Identifier: NCT00551083.

  17. Randomised controlled feasibility trial of a web-based weight management intervention with nurse support for obese patients in primary care

    PubMed Central

    2014-01-01

    Background There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity. Automated web-based interventions might provide a solution, but evidence suggests that they may be ineffective without additional human support. The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care, comparing different levels of nurse support, to determine the optimal combination of web-based and personal support to be tested in a full trial. Methods This was an individually randomised four arm parallel non-blinded trial, recruiting obese patients in primary care. Following online registration, patients were randomly allocated by the automated intervention to either usual care, the web-based intervention only, or the web-based intervention with either basic nurse support (3 sessions in 3 months) or regular nurse support (7 sessions in 6 months). The main outcome measure (intended as the primary outcome for the main trial) was weight loss in kg at 12 months. As this was a feasibility trial no statistical analyses were carried out, but we present means, confidence intervals and effect sizes for weight loss in each group, uptake and retention, and completion of intervention components and outcome measures. Results All randomised patients were included in the weight loss analyses (using Last Observation Carried Forward). At 12 months mean weight loss was: usual care group (n = 43) 2.44 kg; web-based only group (n = 45) 2.30 kg; basic nurse support group (n = 44) 4.31 kg; regular nurse support group (n = 47) 2.50 kg. Intervention effect sizes compared with usual care were: d = 0.01 web-based; d = 0.34 basic nurse support; d = 0.02 regular nurse support. Two practices deviated from protocol by providing considerable weight management support to their usual care patients. Conclusions This study demonstrated the

  18. Primary Subcutaneous Synovial Sarcoma: First Reported Subcutaneous Case Showing TLE1 Immunoreactivity.

    PubMed

    Alegría-Landa, Victoria; Nájera, Laura; Massa, Dolores Suárez; Roustan, Gastón; Río, María Del; Kutzner, Heinz; Requena, Luis

    2018-05-08

    Synovial sarcoma (SS) accounts for 5%-10% of all soft tissue sarcomas. It is a well-defined soft tissue neoplasm with biphasic and monophasic histologic subtypes and unknown histogenesis. It usually occurs in the extremities, especially the thigh-knee region of young adults. Recurrences are frequent and distant metastasis developed in approximately half of the patients. SSs are characterized by a recurrent nonrandom chromosomal translocation, t(X; 18) (p11; q11), which is considered the primary genetic event in more than 90% of cases. Only 4 cases of cutaneous and subcutaneous SSs have been published in the literature so far. We report a case of primary subcutaneous SS in the forearm of a young woman and discuss the histopathologic differential diagnosis with other similar neoplasms. This is the first reported case of primary cutaneous SS showing immunoreactivity for TLE1 in the nuclei of neoplastic cells, supporting the use of this marker for diagnosis of this rare cutaneous neoplasm.

  19. Using old technology to implement modern computer-aided decision support for primary diabetes care.

    PubMed Central

    Hunt, D. L.; Haynes, R. B.; Morgan, D.

    2001-01-01

    BACKGROUND: Implementation rates of interventions known to be beneficial for people with diabetes mellitus are often suboptimal. Computer-aided decision support systems (CDSSs) can improve these rates. The complexity of establishing a fully integrated electronic medical record that provides decision support, however, often prevents their use. OBJECTIVE: To develop a CDSS for diabetes care that can be easily introduced into primary care settings and diabetes clinics. THE SYSTEM: The CDSS uses fax-machine-based optical character recognition software for acquiring patient information. Simple, 1-page paper forms, completed by patients or health practitioners, are faxed to a central location. The information is interpreted and recorded in a database. This initiates a routine that matches the information against a knowledge base so that patient-specific recommendations can be generated. These are formatted and faxed back within 4-5 minutes. IMPLEMENTATION: The system is being introduced into 2 diabetes clinics. We are collecting information on frequency of use of the system, as well as satisfaction with the information provided. CONCLUSION: Computer-aided decision support can be provided in any setting with a fax machine, without the need for integrated electronic medical records or computerized data-collection devices. PMID:11825194

  20. Using old technology to implement modern computer-aided decision support for primary diabetes care.

    PubMed

    Hunt, D L; Haynes, R B; Morgan, D

    2001-01-01

    Implementation rates of interventions known to be beneficial for people with diabetes mellitus are often suboptimal. Computer-aided decision support systems (CDSSs) can improve these rates. The complexity of establishing a fully integrated electronic medical record that provides decision support, however, often prevents their use. To develop a CDSS for diabetes care that can be easily introduced into primary care settings and diabetes clinics. THE SYSTEM: The CDSS uses fax-machine-based optical character recognition software for acquiring patient information. Simple, 1-page paper forms, completed by patients or health practitioners, are faxed to a central location. The information is interpreted and recorded in a database. This initiates a routine that matches the information against a knowledge base so that patient-specific recommendations can be generated. These are formatted and faxed back within 4-5 minutes. The system is being introduced into 2 diabetes clinics. We are collecting information on frequency of use of the system, as well as satisfaction with the information provided. Computer-aided decision support can be provided in any setting with a fax machine, without the need for integrated electronic medical records or computerized data-collection devices.

  1. The novel support structure design of high stability for space borne primary reflector

    NASA Astrophysics Data System (ADS)

    Yu, Fei; Ding, Lin; Tan, Ting; Pei, Jing-yang.; Zhao, Xue-min; Bai, Shao-jun

    2018-01-01

    The novel support structure design of high stability for space borne primary mirror is presented. The structure is supported by a ball head support rod, for statically determinate support of reflector. The ball head assembly includes the supporting rod, nesting, bushing and other important parts. The liner bushing of the resistant material is used to fit for ball head approximated with the reflector material, and then the bad impact of thermal mismatch could be minimized to minimum. In order to ensure that the structure of the support will not be damaged, the glue spots for limitation is added around the reflector, for position stability of reflector. Through analysis and calculation, it can be seen that the novel support structure would not transfer the external stresses to the reflector, and the external stresses usually result from thermal mismatch and assembly misalignment. The novel method is useful for solving the problem of the bad influence form thermal stress and assembly force. In this paper, the supporting structure is introduced and analyzed in detail. The simulation results show that the ball head support reflector works more stably.

  2. Using Primary Language Support via Computer to Improve Reading Comprehension Skills of First-Grade English Language Learners

    ERIC Educational Resources Information Center

    Rodriguez, Cathi Draper; Filler, John; Higgins, Kyle

    2012-01-01

    Through this exploratory study the authors investigated the effects of primary language support delivered via computer on the English reading comprehension skills of English language learners. Participants were 28 First-grade students identified as Limited English Proficient. The primary language of all participants was Spanish. Students were…

  3. INRstar: computerised decision support software for anticoagulation management in primary care.

    PubMed

    Jones, Robert Treharne; Sullivan, Mark; Barrett, David

    2005-01-01

    Computerised decision support software (CDSS) for anticoagulation management has become established practice in the UK, offering significant advantages for patients and clinicians over traditional methods of dose calculation. The New GMS Contract has been partly responsible for this shift of management from secondary to primary care, in which INRstar has been the market leader for many years. In September 2004, INRstar received the John Perry Prize, awarded by the PHCSG for excellence and innovation in medical applications of information technology.

  4. Using program evaluation to support knowledge translation in an interprofessional primary care team: a case study.

    PubMed

    Donnelly, Catherine; Shulha, Lyn; Klinger, Don; Letts, Lori

    2016-10-06

    Evaluation is a fundamental component in building quality primary care and is ideally situated to support individual, team and organizational learning by offering an accessible form of participatory inquiry. The evaluation literature has begun to recognize the unique features of KT evaluations and has described attributes to consider when evaluating KT activities. While both disciplines have focused on the evaluation of KT activities neither has explored the role of evaluation in KT. The purpose of the paper is to examine how participation in program evaluation can support KT in a primary care setting. A mixed methods case study design was used, where evaluation was conceptualized as a change process and intervention. A Memory Clinic at an interprofessional primary care clinic was the setting in which the study was conducted. An evaluation framework, Pathways of Influence provided the theoretical foundation to understand how program evaluation can facilitate the translation of knowledge at the level of the individual, inter-personal (Memory Clinic team) and the organization. Data collection included questionnaires, interviews, evaluation log and document analysis. Questionnaires and interviews were administered both before and after the evaluation: Pattern matching was used to analyze the data based on predetermined propositions. Individuals gained program knowledge that resulted in changes to both individual and program practices. One of the key themes was the importance clinicians placed on local, program based knowledge. The evaluation had less influence on the broader health organization. Program evaluation facilitated individual, team and organizational learning. The use of evaluation to support KT is ideally suited to a primary care setting by offering relevant and applicable knowledge to primary care team members while being sensitive to local context.

  5. A Computerized Decision Support System for Depression in Primary Care

    PubMed Central

    Kurian, Benji T.; Trivedi, Madhukar H.; Grannemann, Bruce D.; Claassen, Cynthia A.; Daly, Ella J.; Sunderajan, Prabha

    2009-01-01

    Objective: In 2004, results from The Texas Medication Algorithm Project (TMAP) showed better clinical outcomes for patients whose physicians adhered to a paper-and-pencil algorithm compared to patients who received standard clinical treatment for major depressive disorder (MDD). However, implementation of and fidelity to the treatment algorithm among various providers was observed to be inadequate. A computerized decision support system (CDSS) for the implementation of the TMAP algorithm for depression has since been developed to improve fidelity and adherence to the algorithm. Method: This was a 2-group, parallel design, clinical trial (one patient group receiving MDD treatment from physicians using the CDSS and the other patient group receiving usual care) conducted at 2 separate primary care clinics in Texas from March 2005 through June 2006. Fifty-five patients with MDD (DSM-IV criteria) with no significant difference in disease characteristics were enrolled, 32 of whom were treated by physicians using CDSS and 23 were treated by physicians using usual care. The study's objective was to evaluate the feasibility and efficacy of implementing a CDSS to assist physicians acutely treating patients with MDD compared to usual care in primary care. Primary efficacy outcomes for depression symptom severity were based on the 17-item Hamilton Depression Rating Scale (HDRS17) evaluated by an independent rater. Results: Patients treated by physicians employing CDSS had significantly greater symptom reduction, based on the HDRS17, than patients treated with usual care (P < .001). Conclusions: The CDSS algorithm, utilizing measurement-based care, was superior to usual care for patients with MDD in primary care settings. Larger randomized controlled trials are needed to confirm these findings. Trial Registration: clinicaltrials.gov Identifier: NCT00551083 PMID:19750065

  6. Kinetic analysis of beer primary fermentation using yeast cells immobilized by ceramic support adsorption and alginate gel entrapment.

    PubMed

    Zhang, Yongming; Kennedy, John F; Knill, Charles J; Panesar, Parmjit S

    2006-01-01

    Yeast cells were immobilized by absorption onto porous ceramic support and evaluated for continuous beer primary fermentation using a bioreactor in comparison to yeast cells immobilized by entrapment in calcium alginate gel. The effects of temperature and flow rate as a function of reaction/fermentation time on fermentation rate were investigated. The fermentation reaction (in terms of loss of total soluble solids in the beer wort as a function of time) was first-order with half-lifes in the range of approximately 9-11 hours at approximately 10-12 degrees C at beer wort linear flow rates of approximately 0.8-1.6 cm/minute for ceramic support, compared with approximately 16 hours for Ca-alginate gel, the former support matrix being more efficient and demonstrating greater potential for future commercial application.

  7. Paraprofessionals in Cyprus and England: Perceptions of Their Role in Supporting Primary School Mathematics

    ERIC Educational Resources Information Center

    Kyriakides, Andreas O.; Houssart, Jenny

    2016-01-01

    Paraprofessionals increasingly work alongside teachers in many countries, with research suggesting they undertake pedagogic roles for which they are not formally prepared. We investigate this from the perspective of paraprofessionals supporting individual children with special needs in primary schools in Cyprus and England and develop a typology…

  8. Impact of decision support in electronic medical records on lipid management in primary care.

    PubMed

    Gill, James M; Chen, Ying Xia; Glutting, Joseph J; Diamond, James J; Lieberman, Michael I

    2009-10-01

    Electronic decision-support tools may help to improve management of hyperlipidemia and other chronic diseases. This study examined the impact of lipid management tools integrated into an electronic medical record (EMR) in primary care practices. This randomized controlled trial was conducted in a national network of physicians who use an outpatient EMR. Adult primary care physicians were randomized by office to receive an electronic form that was embedded in the EMR. The form contained prompts regarding suboptimal care based on Adult Treatment Panel-III (ATP-III) guidelines, as well as reporting tools to identify patients outside of office visits whose lipid management was suboptimal. All active patients, ages 20-79 years, whose physicians participated in the study, were categorized as high, moderate, or low cardiovascular risk, and the proportion who were tested for hyperlipidemia, at lipid goal, and on lipid-lowering medications if not at goal were measured according to ATP-III guidelines. A total of 105 physicians from 25 offices and 64,150 patients were included in the study. Outcomes improved for most measures from before to 1 year after the intervention (November 1, 2005 to October 31, 2006). However, after controlling for confounding variables and for clustering in multilevel modeling, only up-to-date lipid testing for high-risk patients was statistically better in the intervention group as compared to the control group (adjusted odds ratio 15.0, P < 0.05). This study showed few differences in quality of lipid management after implementing an EMR-based disease management intervention in primary care settings. Future studies may need to examine more comprehensive interventions that include office staff in a team approach to care.

  9. Internal versus external motivation in referral of primary care patients with depression to an internet support group: randomized controlled trial.

    PubMed

    Van Voorhees, Benjamin W; Hsiung, Robert C; Marko-Holguin, Monika; Houston, Thomas K; Fogel, Joshua; Lee, Royce; Ford, Daniel E

    2013-03-12

    Depressive disorders and symptoms affect more than one-third of primary care patients, many of whom do not receive or do not complete treatment. Internet-based social support from peers could sustain depression treatment engagement and adherence. We do not know whether primary care patients will accept referral to such websites nor do we know which methods of referral would be most effective. We conducted a randomized clinical trial to determine whether (1) a simple generic referral card (control), (2) a patient-oriented brochure that provided examples of online postings and experience (internal motivation), or (3) a physician letter of recommendation (external motivation) would generate the greatest participation in a primary care Internet depression treatment support portal focused around an Internet support group (ISG). We used 3 offline methods to identify potential participants who had not used an ISG in the past 6 months. Eligibility was determined in part by a brief structured psychiatric interview based on the Patient Health Questionnaire-9 (PHQ-9). After consent and enrollment, participants were randomly assigned to 1 of 3 groups (control, internal motivation, or external motivation). We constructed a portal to connect primary care patients to both fact-based information and an established ISG (Psycho-Babble). The ISG allowed participants to view messages and then decide if they actually wished to register there. Participation in the portal and the ISG was assessed via automated activity tracking. Fifty participants were assigned to the 3 groups: a motivation-neutral control group (n=18), an internal motivation group (n=19), and an external motivation group (n=13). Of these participants, 31 (62%) visited the portal; 27 (54%) visited the ISG itself. The internal motivation group showed significantly greater participation than the control group on several measures. The external motivation group spent significantly less time logged onto the portal than the

  10. Pharmacological treatment with inhibitors of nuclear export enhances the antitumor activity of docetaxel in human prostate cancer

    PubMed Central

    Gravina, Giovanni Luca; Mancini, Andrea; Colapietro, Alessandro; Marampon, Francesco; Sferra, Roberta; Pompili, Simona; Biordi, Leda Assunta; Iorio, Roberto; Flati, Vincenzo; Argueta, Christian; Landesman, Yosef; Kauffman, Michael; Shacham, Sharon; Festuccia, Claudio

    2017-01-01

    Background and aims Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their. DTX resistant derivatives. Results and conclusions We show that DTX resistance may involve overexpression of β-III tubulin (TUBB3) and P-glycoprotein as well as increased cytoplasmic accumulation of Foxo3a. Increased levels of XPO-1 were also observed in DTX resistant cells suggesting that SINE compounds may modulate DTX effectiveness in sensitive cells as well as restore the sensitivity to DTX in resistant ones. Pretreatment with SINE compounds, indeed, sensitized to DTX through increased tumor shrinkage and apoptosis by preventing DTX-induced cell cycle arrest. Basally SINE compounds induce FOXO3a activation and nuclear accumulation increasing the expression of FOXO-responsive genes including p21, p27 and Bim causing cell cycle arrest. SINE compounds-catenin and survivin supporting apoptosis. βdown-regulated Cyclin D1, c-myc, Nuclear sequestration of p-Foxo3a was able to reduce ABCB1 and TUBB3 H2AX levels, prolonged γ expression. Selinexor treatment increased DTX-mediated double strand breaks (DSB), and reduced the levels of DNA repairing proteins including DNA PKc and Topo2A. Our results provide supportive evidence for the therapeutic use of SINE compounds in combination with DTX suggesting their clinical use in mCRPC patients. PMID:29340049

  11. Targeting of colony-stimulating factor 1 receptor (CSF1R) in the CLL microenvironment yields antineoplastic activity in primary patient samples.

    PubMed

    Edwards V, David K; Sweeney, David Tyler; Ho, Hibery; Eide, Christopher A; Rofelty, Angela; Agarwal, Anupriya; Liu, Selina Qiuying; Danilov, Alexey V; Lee, Patrice; Chantry, David; McWeeney, Shannon K; Druker, Brian J; Tyner, Jeffrey W; Spurgeon, Stephen E; Loriaux, Marc M

    2018-05-15

    In many malignancies, the tumor microenvironment includes CSF1R-expressing supportive monocyte/macrophages that promote tumor cell survival. For chronic lymphocytic leukemia (CLL), these supportive monocyte/macrophages are known as nurse-like cells (NLCs), although the potential effectiveness of selective small-molecule inhibitors of CSF1R against CLL is understudied. Here, we demonstrate the preclinical activity of two inhibitors of CSF1R, GW-2580 and ARRY-382, in primary CLL patient samples. We observed at least 25% of CLL samples showed sub-micromolar sensitivity to CSF1R inhibitors. This sensitivity was observed in samples with varying genetic and clinical backgrounds, although higher white cell count and monocyte cell percentage was associated with increased sensitivity. Depleting CD14-expressing monocytes preferentially decreased viability in samples sensitive to CSF1R inhibitors, and treating samples with CSF1R inhibitors eliminated the presence of NLCs in long-term culture conditions. These results indicate that CSF1R small-molecule inhibitors target CD14-expressing monocytes in the CLL microenvironment, thereby depriving leukemia cells of extrinsic support signals. In addition, significant synergy was observed combining CSF1R inhibitors with idelalisib or ibrutinib, two current CLL therapies that disrupt tumor cell intrinsic B-cell receptor signaling. These findings support the concept of simultaneously targeting supportive NLCs and CLL cells and demonstrate the potential clinical utility of this combination.

  12. CRISPR/Cas9-Mediated Correction of the FANCD1 Gene in Primary Patient Cells.

    PubMed

    Skvarova Kramarzova, Karolina; Osborn, Mark J; Webber, Beau R; DeFeo, Anthony P; McElroy, Amber N; Kim, Chong Jai; Tolar, Jakub

    2017-06-14

    Fanconi anemia (FA) is an inherited condition characterized by impaired DNA repair, physical anomalies, bone marrow failure, and increased incidence of malignancy. Gene editing holds great potential to precisely correct the underlying genetic cause such that gene expression remains under the endogenous control mechanisms. This has been accomplished to date only in transformed cells or their reprogrammed induced pluripotent stem cell counterparts; however, it has not yet been reported in primary patient cells. Here we show the ability to correct a mutation in Fanconi anemia D1 ( FANCD1 ) primary patient fibroblasts. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system was employed to target and correct a FANCD1 gene deletion. Homologous recombination using an oligonucleotide donor was achieved and a pure population of modified cells was obtained by using inhibitors of poly adenosine diphosphate-ribose polymerase (poly ADP-ribose polymerase). FANCD1 function was restored and we did not observe any promiscuous cutting of the CRISPR/Cas9 at off target sites. This consideration is crucial in the context of the pre-malignant FA phenotype. Altogether we show the ability to correct a patient mutation in primary FANCD1 cells in a precise manner. These proof of principle studies support expanded application of gene editing for FA.

  13. Characteristics of a self-management support programme applicable in primary health care: a qualitative study of users' and health professionals' perceptions.

    PubMed

    Solberg, Hilde Strøm; Steinsbekk, Aslak; Solbjør, Marit; Granbo, Randi; Garåsen, Helge

    2014-11-08

    Development of more self-management support programmes in primary health care has been one option used to enhance positive outcomes in chronic disease management. At present, research results provide no consensus on what would be the best way to develop support programmes into new settings. The aim of the present study was therefore to explore users' and health professionals' perceptions of what would be the vital elements in a self - management support programme applicable in primary health care, how to account for them, and why. Four qualitative, semi-structured focus group interviews were conducted in Central Norway. The informants possessed experience in development, provision, or participation in a self-management support programme. Data was analysed by the Systematic Text Condensation method. The results showed an overall positive expectation to the potential benefits of development of a self-management support programme in primary health care. Despite somewhat different arguments and perspectives, the users and the health professionals had a joint agreement on core characteristics; a self-management support programme in primary health care should therefore be generic, not disease specific, and delivered in a group- based format. A special focus should be on the everyday- life of the participants. The most challenging aspect was a present lack of competence and experience among health professionals to moderate self-management support programmes. The development and design of a relevant and applicable self-management support programme in primary health care should balance the interests of the users with the possibilities and constraints within each municipality. It would be vital to benefit from the closeness of the patients' every-day life situations. The user informants' perception of a self-management support programme as a supplement to regular medical treatment represented an expanded understanding of the self-management support concept. An exploring

  14. Supporting Transition

    ERIC Educational Resources Information Center

    Qureshi, Asima; Petrucco, James

    2018-01-01

    Meadowbrook Primary School has explored the use of The Teacher Assessment in Primary Science (TAPS) to support transition, initially for transfer to secondary school and now for transition from Early Years Foundation Stage (EYFS) into Key Stage 1 (ages 5-7). This article will consider an example of a secondary transition project and discuss the…

  15. 26 CFR 1.678(c)-1 - Trusts for support.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Trusts for support. 1.678(c)-1 Section 1.678(c... (CONTINUED) INCOME TAXES Grantors and Others Treated As Substantial Owners § 1.678(c)-1 Trusts for support... cotrustee, to apply the income of the trust to the support or maintenance of a person whom the holder is...

  16. Patient contributions during primary care consultations for hypertension after self-reporting via a mobile phone self-management support system.

    PubMed

    Bengtsson, Ulrika; Kjellgren, Karin; Hallberg, Inger; Lundin, Mona; Mäkitalo, Åsa

    2018-03-01

    This paper reports on how the clinical consultation in primary care is performed under the new premises of patients' daily self-reporting and self-generation of data. The aim was to explore and describe the structure, topic initiation and patients' contributions in follow-up consultations after eight weeks of self-reporting through a mobile phone-based hypertension self-management support system. A qualitative, explorative study design was used, examining 20 audio- (n = 10) and video-recorded (n = 10) follow-up consultations in primary care hypertension management, through interaction analysis. Clinical trials registry: ClinicalTrials.gov NCT01510301. Four primary health care centers in Sweden. Patients with hypertension (n = 20) and their health care professional (n = 7). The consultations comprised three phases: opening, examination and closing. The most common topic was blood pressure (BP) put in relation to self-reported variables, for example, physical activity and stress. Topic initiation was distributed symmetrically between parties and BP talk was lifestyle-centered. The patients' contributed to the interpretation of BP values by connecting them to specific occasions, providing insights to the link between BP measurements and everyday life activities. Patients' contribution through interpretations of BP values to specific situations in their own lives brought on consultations where the patient as a person in context became salient. Further, the patients' and health care professionals' equal contribution during the consultations showed actively involved patients. The mobile phone-based self-management support system can thus be used to support patient involvement in consultations with a person-centered approach in primary care hypertension management Key points   The clinical consultation is important to provide opportunities for patients to gain understanding of factors affecting high blood pressure, and for health care professionals to

  17. Refining the Use of Nasal High-Flow Therapy as Primary Respiratory Support for Preterm Infants.

    PubMed

    Manley, Brett J; Roberts, Calum T; Frøisland, Dag H; Doyle, Lex W; Davis, Peter G; Owen, Louise S

    2018-05-01

    To identify clinical and demographic variables that predict nasal high-flow (nHF) treatment failure when used as a primary respiratory support for preterm infants. This secondary analysis used data from a multicenter, randomized, controlled trial comparing nHF with continuous positive airway pressure as primary respiratory support in preterm infants 28-36 completed weeks of gestation. Treatment success or failure with nHF was determined using treatment failure criteria within the first 72 hours after randomization. Infants in whom nHF treatment failed received continuous positive airway pressure, and were then intubated if failure criteria were again met. There were 278 preterm infants included, with a mean gestational age (GA) of 32.0 ± 2.1 weeks and a birth weight of 1737 ± 580 g; of these, nHF treatment failed in 71 infants (25.5%). Treatment failure was moderately predicted by a lower GA and higher prerandomization fraction of inspired oxygen (FiO 2 ): area under a receiver operating characteristic curve of 0.76 (95% CI, 0.70-0.83). Nasal HF treatment success was more likely in infants born at ≥30 weeks GA and with prerandomization FiO 2 <0.30. In preterm infants ≥28 weeks' GA enrolled in a randomized, controlled trial, lower GA and higher FiO 2 before randomization predicted early nHF treatment failure. Infants were more likely to be successfully treated with nHF from soon after birth if they were born at ≥30 weeks GA and had a prerandomization FiO 2 <0.30. However, even in this select population, continuous positive airway pressure remains superior to nHF as early respiratory support in preventing treatment failure. Australian New Zealand Clinical Trials Registry: ACTRN12613000303741. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. Development and Validation of a Primary Care-Based Family Health History and Decision Support Program (MeTree)

    PubMed Central

    Orlando, Lori A.; Buchanan, Adam H.; Hahn, Susan E.; Christianson, Carol A.; Powell, Karen P.; Skinner, Celette Sugg; Chesnut, Blair; Blach, Colette; Due, Barbara; Ginsburg, Geoffrey S.; Henrich, Vincent C.

    2016-01-01

    INTRODUCTION Family health history is a strong predictor of disease risk. To reduce the morbidity and mortality of many chronic diseases, risk-stratified evidence-based guidelines strongly encourage the collection and synthesis of family health history to guide selection of primary prevention strategies. However, the collection and synthesis of such information is not well integrated into clinical practice. To address barriers to collection and use of family health histories, the Genomedical Connection developed and validated MeTree, a Web-based, patient-facing family health history collection and clinical decision support tool. MeTree is designed for integration into primary care practices as part of the genomic medicine model for primary care. METHODS We describe the guiding principles, operational characteristics, algorithm development, and coding used to develop MeTree. Validation was performed through stakeholder cognitive interviewing, a genetic counseling pilot program, and clinical practice pilot programs in 2 community-based primary care clinics. RESULTS Stakeholder feedback resulted in changes to MeTree’s interface and changes to the phrasing of clinical decision support documents. The pilot studies resulted in the identification and correction of coding errors and the reformatting of clinical decision support documents. MeTree’s strengths in comparison with other tools are its seamless integration into clinical practice and its provision of action-oriented recommendations guided by providers’ needs. LIMITATIONS The tool was validated in a small cohort. CONCLUSION MeTree can be integrated into primary care practices to help providers collect and synthesize family health history information from patients with the goal of improving adherence to risk-stratified evidence-based guidelines. PMID:24044145

  19. Social support network, mental health and quality of life: a cross-sectional study in primary care.

    PubMed

    Portugal, Flávia Batista; Campos, Mônica Rodrigues; Correia, Celina Ragoni; Gonçalves, Daniel Almeida; Ballester, Dinarte; Tófoli, Luis Fernando; Mari, Jair de Jesus; Gask, Linda; Dowrick, Christopher; Bower, Peter; Fortes, Sandra

    2016-12-22

    The objective of this study was to identify the association between emotional distress and social support networks with quality of life in primary care patients. This was a cross-sectional study involving 1,466 patients in the cities of São Paulo and Rio de Janeiro, Brazil, in 2009/2010. The General Health Questionnaire, the Hospital Anxiety and Depression Scale and the brief version of the World Health Organization Quality of Life Instrument were used. The Social Support Network Index classified patients with the highest and lowest index as socially integrated or isolated. A bivariate analysis and four multiple linear regressions were conducted for each quality of life outcome. The means scores for the physical, psychological, social relations, and environment domains were, respectively, 64.7; 64.2; 68.5 and 49.1. In the multivariate analysis, the psychological domain was negatively associated with isolation, whereas the social relations and environment domains were positively associated with integration. Integration and isolation proved to be important factors for those in emotional distress as they minimize or maximize negative effects on quality of life.

  20. Primary care of female adolescents with type 1 diabetes mellitus and disordered eating.

    PubMed

    McCarvill, Rachael; Weaver, Kathryn

    2014-09-01

    To identify the role of the nurse practitioner in caring for female adolescents with type 1 diabetes mellitus at risk for disordered eating behaviour and to formulate clinical recommendations for nurse practitioners in the primary care setting. Transition into adulthood can be difficult for female adolescents with type 1 diabetes mellitus. Challenges associated with management of this illness may place adolescent females at an increased risk for disordered eating. Discussion paper. Sourced literature from 1991-2013, located through CINAHL, Health Source, Proquest, PubMed, PsychInfo, Web of Science and Medline databases. Nurses involved in the primary care of female adolescents with type 1 diabetes mellitus need to be aware of the increased risk for disordered eating behaviours and develop the competencies to care for both the adolescent and her family to reduce the serious consequences of these behaviours. Awareness and acquisition of the skills required to intervene will enable nurse practitioners to recognize clients at risk for disordered eating, gain appreciation of the motivation of female adolescents with type 1 diabetes mellitus towards disordered eating behaviours and give optimal opportunity for education, counselling and recovery. Future direction for research includes exploration of the experiences of adolescents with type 1 diabetes mellitus; early interventions in the primary care setting; effective educational, preventative or supportive services for adolescents with this illness and their families; and outcomes to emerging technologies for insulin therapy on disordered eating occurrence. © 2014 John Wiley & Sons Ltd.

  1. End-user support for primary care electronic medical records: a qualitative case study of users’ needs, expectations and realities

    PubMed Central

    Shachak, Aviv; Montgomery, Catherine; Dow, Rustam; Barnsley, Jan; Tu, Karen; Jadad, Alejandro R.; Lemieux-Charles, Louise

    2015-01-01

    Support is considered an important factor for realizing the benefits of health information technology (HIT) but there is a dearth of research on the topic of support, especially in primary care. We conducted a qualitative multiple case study of 4 family health teams (FHTs) and one family health organization (FHO) in Ontario, Canada in an attempt to gain insight into users’ expectations and needs, and the realities of end-user support for primary care electronic medical records (EMRs). Data were collected by semi-structured interviews, documents review, and observation of training sessions. The analysis highlights the important role of on-site information technology (IT) staff and super-users in liaising with various stakeholders to solve technical problems and providing hardware and functional (‘how to’) support; the local development of data support practices to ensure consistent documentation; and the gaps that exist in users’ and support personnel’s understanding of each other’s work processes. PMID:26225209

  2. Effectiveness of personalised support for self-management in primary care: a cluster randomised controlled trial

    PubMed Central

    Eikelenboom, Nathalie; van Lieshout, Jan; Jacobs, Annelies; Verhulst, Frank; Lacroix, Joyca; van Halteren, Aart; Klomp, Maarten; Smeele, Ivo; Wensing, Michel

    2016-01-01

    Background Self-management support is an important component of the clinical management of many chronic conditions. The validated Self-Management Screening questionnaire (SeMaS) assesses individual characteristics that influence a patient’s ability to self-manage. Aim To assess the effect of providing personalised self-management support in clinical practice on patients’ activation and health-related behaviours. Design and setting A cluster randomised controlled trial was conducted in 15 primary care group practices in the south of the Netherlands. Method After attending a dedicated self-management support training session, practice nurses in the intervention arm discussed the results of SeMaS with the patient at baseline, and tailored the self-management support. Participants completed a 13-item Patient Activation Measure (PAM-13) and validated lifestyle questionnaires at baseline and after 6 months. Data, including individual care plans, referrals to self-management interventions, self-monitoring, and healthcare use, were extracted from patients’ medical records. Multilevel multiple regression was used to assess the effect on outcomes. Results The PAM-13 score did not differ significantly between the control (n = 348) and intervention (n = 296) arms at 6 months. In the intervention arm, 29.4% of the patients performed self-monitoring, versus 15.2% in the control arm (effect size r = 0.9, P = 0.01). In the per protocol analysis (control n = 348; intervention n = 136), the effect of the intervention was significant on the number of individual care plans (effect size r = 1.3, P = 0.04) and on self-monitoring (effect size r = 1.0, P = 0.01). Conclusion This study showed that discussing SeMaS and offering tailored support did not affect patient activation or lifestyle, but did stimulate patients to self-monitor and use individual care plans. PMID:27080318

  3. Primary Care Physicians' Support of Shared Decision Making for Different Cancer Screening Decisions.

    PubMed

    Elston Lafata, Jennifer; Brown, Richard F; Pignone, Michael P; Ratliff, Scott; Shay, L Aubree

    2017-01-01

    Despite its widespread advocacy, shared decision making (SDM) is not routinely used for cancer screening. To better understand the implementation barriers, we describe primary care physicians' (PCPs') support for SDM across diverse cancer screening contexts. Surveys were mailed to a random sample of USA-based PCPs. Using multivariable logistic regression analyses, we tested for associations of PCPs' support of SDM with the US Preventive Service Task Force (USPSTF) assigned recommendation grade, assessed whether the decision pertained to not screening older patients, and the PCPs' autonomous v. controlled motivation-orientation for using SDM. PCPs (n = 278) were, on average, aged 52 years, 38% female, and 69% white. Of these, 79% endorsed discussing screening benefits as very important to SDM; 64% for discussing risks; and 31% for agreeing with patient's opinion. PCPs were most likely to rate SDM as very important for colorectal cancer screening in adults aged 50-75 years (69%), and least likely for colorectal cancer screening in adults aged >85 years (34%). Regression results indicated the importance of PCPs' having autonomous or self-determined reasons for engaging in SDM (e.g., believing in the benefits of SDM) (OR = 2.29, 95% CI, 1.87 to 2.79). PCPs' support for SDM varied by USPSTF recommendation grade (overall contrast, X 2 = 14.7; P = 0.0054), with support greatest for A-Grade recommendations. Support for SDM was lower in contexts where decisions pertained to not screening older patients (OR = 0.45, 95% CI, 0.35 to 0.56). It is unknown whether PCPs' perceptions of the importance of SDM behaviors differs with specific screening decisions or the potential limited ability to generalize findings. Our results highlight the need to document SDM benefits and consider the specific contextual challenges, such as the level of uncertainty or whether evidence supports recommending/not recommending screening, when implementing SDM across an array of cancer screening

  4. Support by trained mentor mothers for abused women: a promising intervention in primary care.

    PubMed

    Prosman, Gert-Jan; Lo Fo Wong, Sylvie H; Lagro-Janssen, Antoine L M

    2014-02-01

    Intimate partner violence (IPV) against women is a major health problem and negatively affects the victim's mental and physical health. Evidence-based interventions in family practice are scarce. We aimed to evaluate a low threshold home-visiting intervention for abused women provided by trained mentor mothers in family practice. The aim was to reduce exposure to IPV, symptoms of depression as well as to improve social support, participation in society and acceptance of mental health care. A pre-post study of a 16-week mentoring intervention with identified abused women with children was conducted. After referral by a family doctor, a mentor mother visited the abused woman weekly. Primary outcomes are IPV assessed with the Composite Abuse Scale (CAS), depressive symptoms using the Symptom Checklist (SCL 90) and social support by the Utrecht Coping List. Secondary outcomes are analysed qualitatively: participation in society defined as employment and education and the acceptance of mental health care. At baseline, 63 out of 66 abused women were referred to mentor support. Forty-three participants completed the intervention programme. IPV decreased from CASt otal 46.7 (SD 24.7) to 9.0 (SD 9.1) (P ≤ 0.001) after the mentor mother support programme. Symptoms of depression decreased from 53.3 (SD 13.7) to 34.8 (SD 11.5) (P ≤ 0.001) and social support increased from 13.2 (SD 4.0) to 15.2 (SD 3.5) (P ≤ 0.001). Participation in society and the acceptance of mental health for mother and child improved. Sixteen weekly visits by trained mentor mothers are a promising intervention to decrease exposure to IPV and symptoms of depression, as well as to improve social support, participation in society and the acceptance of professional help for abused women and their children.

  5. Morphologies of Primary Silicon in Hypereutectic Al-Si Alloys: Phase-Field Simulation Supported by Key Experiments

    NASA Astrophysics Data System (ADS)

    Wang, Kai; Wei, Ming; Zhang, Lijun; Du, Yong

    2016-04-01

    We realized a three-dimensional visualization of the morphology evolution and the growth behavior of the octahedral primary silicon in hypereutectic Al-20wtpctSi alloy during solidification in a real length scale by utilizing the phase-field simulation coupled with CALPHAD databases, and supported by key experiments. Moreover, through two-dimensional cut of the octahedral primary silicon at random angles, different morphologies observed in experiments, including triangle, square, trapezoid, rhombic, pentagon, and hexagon, were well reproduced.

  6. C-C cross-coupling of primary and secondary benzylic alcohols using supported gold-based bimetallic catalysts.

    PubMed

    Liu, Xiang; Ding, Ran-Sheng; He, Lin; Liu, Yong-Mei; Cao, Yong; He, He-Yong; Fan, Kang-Nian

    2013-04-01

    Clean alcohol-alcohol cross-coupling: A clean and efficient one-pot direct C-C cross-coupling of equimolar amounts of primary and secondary alcohols by a facile hydrogen autotransfer pathway is achieved over a robust and easily recovered hydrotalcite-supported Au-Pd bimetallic catalyst system. A variety of primary and secondary alcohols have been selectively converted into the corresponding β-alkylated ketones in good yields. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Fabrication of experimental three-meter space telescope primary and secondary mirror support structure

    NASA Technical Reports Server (NTRS)

    Mishler, H. W.

    1974-01-01

    The fabrication of prototype titanium alloy primary and secondary mirror support structures for a proposed experimental three-meter space telescope is discussed. The structure was fabricated entirely of Ti-6Al-4V tubing and plate. Fabrication included the development of procedures including welding, forming, and machining. Most of the structures was fabricated by gas-shielding tungsten-arc (GTA) welding with several major components fabricated by high frequency resistance (HFR) welding.

  8. Health Care Systems Support to Enhance Patient-Centered Care: Lessons from a Primary Care-Based Chronic Pain Management Initiative.

    PubMed

    Elder, Charles R; Debar, Lynn L; Ritenbaugh, Cheryl; Rumptz, Maureen H; Patterson, Charlotte; Bonifay, Allison; Cowan, Penney; Lancaster, Lindsay; Deyo, Richard A

    2017-01-01

    Supporting day-to-day self-care activities has emerged as a best practice when caring for patients with chronic pain, yet providing this support may introduce challenges for both patients and primary care physicians. It is essential to develop tools that help patients identify the issues and outcomes that are most important to them and to communicate this information to primary care physicians at the point of care. We describe our process to engage patients, primary care physicians, and other stakeholders in the context of a pilot randomized controlled trial of a patient-centered assessment process implemented in an everyday practice setting. We identify lessons on how to engage stakeholders and improve patient-centered care for those with chronic conditions within the primary care setting. A qualitative analysis of project minutes, interviews, and focus groups was conducted to evaluate stakeholder experiences. Stakeholders included patients, caregivers, clinicians, medical office support staff, health plan administrators, an information technology consultant, and a patient advocate. Our stakeholders included many patients with no prior experience with research. This approach enriched the applicability of feedback but necessitated extra time for stakeholder training and meeting preparation. Types of stakeholders varied over the course of the project, and more involvement of medical assistants and Information Technology staff was required than originally anticipated. Meaningful engagement of patient and physician stakeholders must be solicited in a well-coordinated manner with broad health care system supports in place to ensure full execution of patient-centered processes.

  9. Efficient Transformation of Primary Human Mesenchymal Stromal Cells by Adenovirus Early Region 1 Oncogenes.

    PubMed

    Speiseder, Thomas; Hofmann-Sieber, Helga; Rodríguez, Estefanía; Schellenberg, Anna; Akyüz, Nuray; Dierlamm, Judith; Spruss, Thilo; Lange, Claudia; Dobner, Thomas

    2017-01-01

    Previous observations that human amniotic fluid cells (AFC) can be transformed by human adenovirus type 5 (HAdV-5) E1A/E1B oncogenes prompted us to identify the target cells in the AFC population that are susceptible to transformation. Our results demonstrate that one cell type corresponding to mesenchymal stem/stroma cells (hMSCs) can be reproducibly transformed by HAdV-5 E1A/E1B oncogenes as efficiently as primary rodent cultures. HAdV-5 E1-transformed hMSCs exhibit all properties commonly associated with a high grade of oncogenic transformation, including enhanced cell proliferation, anchorage-independent growth, increased growth rate, and high telomerase activity as well as numerical and structural chromosomal aberrations. These data confirm previous work showing that HAdV preferentially transforms cells of mesenchymal origin in rodents. More importantly, they demonstrate for the first time that human cells with stem cell characteristics can be completely transformed by HAdV oncogenes in tissue culture with high efficiency. Our findings strongly support the hypothesis that undifferentiated progenitor cells or cells with stem cell-like properties are highly susceptible targets for HAdV-mediated cell transformation and suggest that virus-associated tumors in humans may originate, at least in part, from infections of these cell types. We expect that primary hMSCs will replace the primary rodent cultures in HAdV viral transformation studies and are confident that these investigations will continue to uncover general principles of viral oncogenesis that can be extended to human DNA tumor viruses as well. It is generally believed that transformation of primary human cells with HAdV-5 E1 oncogenes is very inefficient. However, a few cell lines have been successfully transformed with HAdV-5 E1A and E1B, indicating that there is a certain cell type which is susceptible to HAdV-mediated transformation. Interestingly, all those cell lines have been derived from human

  10. Psychosocial Support for Orphans and Vulnerable Children in Public Primary Schools: Challenges and Intervention Strategies

    ERIC Educational Resources Information Center

    Mwoma, Teresa; Pillay, Jace

    2015-01-01

    Much has been written about orphans and vulnerable children (OVC) with regard to their education and living. However, relatively few studies have documented the psychosocial support provided for OVC in public primary schools to enhance their psychosocial well-being. This study therefore contributes to the understanding of the challenges…

  11. Protection of Primary Dopaminergic Midbrain Neurons by GPR139 Agonists Supports Different Mechanisms of MPP+ and Rotenone Toxicity

    PubMed Central

    Bayer Andersen, Kirsten; Leander Johansen, Jens; Hentzer, Morten; Smith, Garrick Paul; Dietz, Gunnar P. H.

    2016-01-01

    The G-protein coupled receptor 139 (GPR139) is expressed specifically in the brain in areas of relevance for motor control. GPR139 function and signal transduction pathways are elusive, and results in the literature are even contradictory. Here, we examined the potential neuroprotective effect of GPR139 agonism in primary culture models of dopaminergic (DA) neuronal degeneration. We find that in vitro GPR139 agonists protected primary mesencephalic DA neurons against 1-methyl-4-phenylpyridinium (MPP+)-mediated degeneration. Protection was concentration-dependent and could be blocked by a GPR139 antagonist. However, the protection of DA neurons was not found against rotenone or 6-hydroxydopamine (6-OHDA) mediated degeneration. Our results support differential mechanisms of toxicity for those substances commonly used in Parkinson’s disease (PD) models and potential for GPR139 agonists in neuroprotection. PMID:27445691

  12. Structure–property insights into nanostructured electrodes for Li-ion batteries from local structural and diffusional probes

    DOE PAGES

    Laveda, Josefa Vidal; Johnston, Beth; Paterson, Gary W.; ...

    2017-12-04

    Microwave heating presents a faster, lower energy synthetic methodology for the realization of functional materials. Here, we demonstrate for the first time that employing this method also leads to a decrease in the occurrence of defects in olivine structured LiFe 1–xMn xPO 4. For example, the presence of antisite defects in this structure precludes Li + diffusion along the b-axis leading to a significant decrease in reversible capacities. Total scattering measurements, in combination with Li + diffusion studies using muon spin relaxation (μ+SR) spectroscopy, reveal that this synthetic method generates fewer defects in the nanostructures compared to traditional solvothermal routes.more » Our interest in developing these routes to mixed-metal phosphate LiFe 1–xMn xPO 4 olivines is due to the higher Mn 2+/ 3+ redox potential in comparison to the Fe 2+/ 3+ pair. Here, single-phase LiFe 1–xMn xPO 4 (x = 0, 0.25, 0.5, 0.75 and 1) olivines have been prepared following a microwave-assisted approach which allows for up to 4 times faster reaction times compared to traditional solvothermal methods. Interestingly, the resulting particle morphology is dependent on the Mn content. We also examine their electrochemical performance as active electrodes in Li-ion batteries. In conclusion, these results present microwave routes as highly attractive for reproducible, gram-scale syntheses of high quality nanostructured electrodes which display close to theoretical capacity for the full iron phase.« less

  13. Structure–property insights into nanostructured electrodes for Li-ion batteries from local structural and diffusional probes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Laveda, Josefa Vidal; Johnston, Beth; Paterson, Gary W.

    Microwave heating presents a faster, lower energy synthetic methodology for the realization of functional materials. Here, we demonstrate for the first time that employing this method also leads to a decrease in the occurrence of defects in olivine structured LiFe 1–xMn xPO 4. For example, the presence of antisite defects in this structure precludes Li + diffusion along the b-axis leading to a significant decrease in reversible capacities. Total scattering measurements, in combination with Li + diffusion studies using muon spin relaxation (μ+SR) spectroscopy, reveal that this synthetic method generates fewer defects in the nanostructures compared to traditional solvothermal routes.more » Our interest in developing these routes to mixed-metal phosphate LiFe 1–xMn xPO 4 olivines is due to the higher Mn 2+/ 3+ redox potential in comparison to the Fe 2+/ 3+ pair. Here, single-phase LiFe 1–xMn xPO 4 (x = 0, 0.25, 0.5, 0.75 and 1) olivines have been prepared following a microwave-assisted approach which allows for up to 4 times faster reaction times compared to traditional solvothermal methods. Interestingly, the resulting particle morphology is dependent on the Mn content. We also examine their electrochemical performance as active electrodes in Li-ion batteries. In conclusion, these results present microwave routes as highly attractive for reproducible, gram-scale syntheses of high quality nanostructured electrodes which display close to theoretical capacity for the full iron phase.« less

  14. Support Required for Primary and Secondary Students with Communication Disorders and/or Other Learning Needs

    ERIC Educational Resources Information Center

    McLeod, Sharynne; McKinnon, David H.

    2010-01-01

    Prioritization of school students with additional learning needs is a reality due to a finite resource base. Limited evidence exists regarding teachers' prioritization of primary and secondary school students with additional learning needs. The aim of the present article was to differentiate teachers' perceptions of the level of support required…

  15. Investigating the primary stability of the transversal support tibial plateau concept to retain both cruciate ligaments during total knee arthroplasty.

    PubMed

    Nowakowski, Andrej M; Stangel, Melanie; Grupp, Thomas M; Valderrabano, Victor

    2012-09-27

    The important roles of the anterior cruciate ligament regarding knee stability, physiologic kinematics, and proprioception are unquestioned. Thus, various efforts have been made to retain the ACL during total knee arthroplasty (TKA). Neither of the existing solutions to this problem, i.e. bicruciate retaining prostheses and implantation of two unicondylar prostheses, has been successful because of concept-specific problems as well as general difficulties with implant fixation. The new transversal support tibial plateau concept is a prosthesis of two individual joint surfaces reinforced beneath the articular line by joint surface supports and buttressed by a single transversal support. This configuration, which enables retention of both cruciate ligaments, should provide good bone fixation and ensure long-term alignment of the individual joint surfaces. In the current study, four prototypes based on this novel concept were developed and the resulting primary stability was analyzed using adapted load testing. The test set-up, with the model-loading of specially prepared Sawbones® and a sinusoidal oscillating load transmission with 25 000 cycles over 10 increasing load levels, achieved subsidence, which enabled comparison of the four different model variants regarding primary stability in view of bone anchoring. The model variant (TSmobile) that allowed transverse glide of the joint surface supports along the transversal support revealed the largest subsidence. A rigid attachment of the joint surface supports of the transversal support tibial plateau thus appears to offer increased primary stability regarding bone anchoring.

  16. Articulating a Deficit Perspective: A Survey of the Attitudes of Post-Primary English Language Support Teachers and Coordinators

    ERIC Educational Resources Information Center

    Lyons, Zachary

    2010-01-01

    Issues related to supporting the language of schooling have become important social and educational policy concerns in Ireland. This article reports on a three-year investigation of the micro-climate of English language support provision in 70 post-primary schools since 2007 and highlights potential points of leverage in the educational system for…

  17. Expression and function of Allergin-1 on human primary mast cells.

    PubMed

    Nagai, Kei; Tahara-Hanaoka, Satoko; Morishima, Yuko; Tokunaga, Takahiro; Imoto, Yoshimasa; Noguchi, Emiko; Kanemaru, Kazumasa; Imai, Masamichi; Shibayama, Shiro; Hizawa, Nobuyuki; Fujieda, Shigeharu; Yamagata, Kunihiro; Shibuya, Akira

    2013-01-01

    Mast cells (MC) play an important role in allergic and non-allergic immune responses. Activation of human MC is modulated by several cell surface inhibitory receptors, including recently identified Allergin-1 expressed on both human and mouse MC. Although Allergin-1 suppresses IgE-mediated, mast cell-dependent anaphylaxis in mice, the expression profile and function of Allergin-1 on human primary MC remains undetermined. Here, we established a seven-color flow cytometry method for assessing expression and function of a very small number of human primary MC. We show that Allergin-1S1, a splicing isoform of Allergin-1, is predominantly expressed on human primary MC in both bronchoalveolar lavage (BAL) fluid and nasal scratching specimens. Moreover, Allergin-1S1 inhibits IgE-mediated activation from human primary MC in BAL fluid. These results indicate that Allergin-1 on human primary MC exhibits similar characteristics as mouse Allergin-1 in the expression profile and function.

  18. Nonlinear effects of electromagnetic forces on primary resonance of a levitated elastic bar supported by high- Tc superconducting bearings

    NASA Astrophysics Data System (ADS)

    Iori, T.; Ogawa, S.; Sugiura, T.

    2007-10-01

    This research investigates nonlinear dynamics of an elastic body supported at both its ends by electromagnetic forces between superconductors and magnets. We focus on the primary resonance of each eigenmode under vertical excitation of superconducting bulks. Experiment and numerical analysis show the softening tendency in the resonance of the 3rd mode consisting of mainly deflection and slightly translation. This nonlinear response can be theoretically explained only by nonlinear coupling between the 1st and 3rd modes through their quadratic terms.

  19. Clinical support role for a pharmacy technician within a primary care resource center.

    PubMed

    Fera, Toni; Kanel, Keith T; Bolinger, Meghan L; Fink, Amber E; Iheasirim, Serah

    2018-02-01

    The creation of a clinical support role for a pharmacy technician within a primary care resource center is described. In the Primary Care Resource Center (PCRC) Project, hospital-based care transition coordination hubs staffed by nurses and pharmacist teams were created in 6 independent community hospitals. At the largest site, patient volume for targeted diseases challenged the ability of the PCRC pharmacist to provide expected elements of care to targeted patients. Creation of a new pharmacy technician clinical support role was implemented as a cost-effective option to increase the pharmacist's efficiency. The pharmacist's work processes were reviewed and technical functions identified that could be assigned to a specially trained pharmacy technician under the direction of the PCRC pharmacist. Daily tasks performed by the pharmacy technician included maintenance of the patient roster and pending discharges, retrieval and documentation of pertinent laboratory and diagnostic test information from the patient's medical record, assembly of patient medication education materials, and identification of discrepancies between disparate systems' medication records. In the 6 months after establishing the PCRC pharmacy technician role, the pharmacist's completion of comprehensive medication reviews (CMRs) for target patients increased by 40.5% ( p = 0.0223), driven largely by a 42.4% ( p < 0.0001) decrease in the time to complete each chart review. The addition of a pharmacy technician to augment pharmacist care in a PCRC team extended the reach of the pharmacist and allowed more time for the pharmacist to engage patients. Technician support enabled the pharmacist to complete more CMRs and reduced the time required for chart reviews. Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  20. 26 CFR 1.677(b)-1 - Trusts for support.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Trusts for support. 1.677(b)-1 Section 1.677(b... (CONTINUED) INCOME TAXES Grantors and Others Treated As Substantial Owners § 1.677(b)-1 Trusts for support. (a) Section 677(b) provides that a grantor is not treated as the owner of a trust merely because its...

  1. Introducing Cooperative Learning to Primary 1 and Primary 2 Pupils

    ERIC Educational Resources Information Center

    Fong, Salim; Ho, Linda; Chew, Lay See; Wong, Kok Wah; Wee, Sheila; Jacobs, George M.

    2000-01-01

    It was scary at first. Just getting P1 and 2 students to follow basic instructions is hard enough; trying to get them to work together in groups seemed like asking for extra trouble. But, a dash or two of trouble adds a bit of spice to a veteran teacher's life; so the four of us teachers at Mayflower Primary School--a neighbourhood school in Ang…

  2. Self-management support for chronic pain in primary care: a cross-sectional study of patient experiences and nursing roles.

    PubMed

    Lukewich, Julia; Mann, Elizabeth; VanDenKerkhof, Elizabeth; Tranmer, Joan

    2015-11-01

    The aim of this study was to describe chronic pain self-management from the perspective of individuals living with chronic pain in the context of primary care nursing. Self-management is a key chronic pain treatment modality and support for self-managing chronic pain is mainly provided in the context of primary care. Although nurses are optimally suited to facilitate self-management in primary care, there is a need to explore opportunities for optimizing their roles. Two cross-sectional studies. The Chronic Pain Self-Management Survey was conducted in 2011-2012 to explore the epidemiology and self-management of chronic pain in Canadian adults. The questionnaire was distributed to 1504 individuals in Ontario. In 2011, the Primary Care Nursing Roles Survey was distributed to 1911 primary care nurses in Ontario to explore their roles and to determine the extent to which chronic disease management strategies, including support for self-management, were implemented in primary care. Few respondents to the pain survey identified nurses as being the 'most helpful' facilitator of self-management while physicians were most commonly cited. Seventy-six per cent of respondents used medication to manage their chronic pain. Few respondents to the nursing survey worked in practices with specific programmes for individuals with chronic pain. Individuals with chronic pain identified barriers and facilitators to self-managing their pain and nurses identified barriers and facilitators to optimizing their role in primary care. There are several opportunities for primary care practices to facilitate self-management of chronic pain, including the optimization of the primary care nursing role. © 2015 John Wiley & Sons Ltd.

  3. Achieving Value in Primary Care: The Primary Care Value Model.

    PubMed

    Rollow, William; Cucchiara, Peter

    2016-03-01

    The patient-centered medical home (PCMH) model provides a compelling vision for primary care transformation, but studies of its impact have used insufficiently patient-centered metrics with inconsistent results. We propose a framework for defining patient-centered value and a new model for value-based primary care transformation: the primary care value model (PCVM). We advocate for use of patient-centered value when measuring the impact of primary care transformation, recognition, and performance-based payment; for financial support and research and development to better define primary care value-creating activities and their implementation; and for use of the model to support primary care organizations in transformation. © 2016 Annals of Family Medicine, Inc.

  4. Development of a Primary Care-Based Clinic to Support Adults With a History of Childhood Cancer: The Tactic Clinic.

    PubMed

    Overholser, Linda S; Moss, Kerry M; Kilbourn, Kristin; Risendal, Betsy; Jones, Alison F; Greffe, Brian S; Garrington, Timothy; Leonardi-Warren, Kristin; Yamashita, Traci E; Kutner, Jean S

    2015-01-01

    Describe the development and evolution of a primary-care-based, multidisciplinary clinic to support the ongoing care of adult survivors of childhood cancer. A consultative clinic for adult survivors of childhood cancer has been developed that is located in an adult, academic internal medicine setting and is based on a long-term follow-up clinic model available at Children's Hospital Colorado. The clinic opened in July 2008. One hundred thirty-five patients have been seen as of April 2014. Referrals and clinic capacity have gradually increased over time, and a template has been developed in the electronic medical record to help facilitate completion of individualized care plan letters. A primary care-based, multidisciplinary consultative clinic for adults with a history of childhood cancer survivor is feasible and actively engages adult primary care resources to provide risk-based care for long-term pediatric cancer survivors. This model of care planning can help support adult survivors of pediatric cancer and their primary care providers in non-academic, community settings as well. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Long-term follow-up of a randomized study of support group intervention in women with primary breast cancer.

    PubMed

    Björneklett, Helena Granstam; Rosenblad, Andreas; Lindemalm, Christina; Ojutkangas, Marja-Leena; Letocha, Henry; Strang, Peter; Bergkvist, Leif

    2013-04-01

    Despite a fairly good prognosis, many breast-cancer patients suffer from symptoms such as anxiety, depression and fatigue, which may affect health-related quality of life and may persist for several years. The aim of the present study was to perform a long-term follow-up of a randomized study of support group intervention in women after primary breast cancer treatment. Three hundred and eighty two women with primary breast cancer were randomized to support group intervention or control group, 181 in each group. Women in the intervention group participated in 1 week of intervention followed by 4 days of follow-up 2 months later. This is a long-term follow-up undertaken, in average, 6.5 years after randomization. Patients answered the questionnaires the European Organisation for Research and Treatment of Cancer, quality of life questionnaire (EORTC QLQ-C30) and the breast cancer module questionnaire (BR 23), the hospital anxiety and depression scale (HAD) and the Norwegian version of the fatigue scale (FQ). After adjusting for treatment with chemotherapy, age, marriage, education and children at home, there was a significant improvement in physical, mental and total fatigue (FQ), cognitive function, body image and future perspective (EORTC QLQ C30 and BR23) in the intervention group compared with controls. The proportion of women affected by high anxiety and depression scores were not significantly different between the groups. Support intervention significantly improved cognitive function, body image, future perspective and fatigue, compared with to the findings in the control group. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Anthropometric standards for Australian primary school children: Towards a system for monitoring and supporting children's development.

    PubMed

    Cochrane, Thomas; Davey, Rachel C; de Castella, F Robert

    2017-03-01

    To provide two foundation elements of a proposed new system to support children's physical and body status development throughout primary school: (a) age and gender appropriate achievement (anthropometric) standards and (b) a system of monitoring, feedback and support. Repeated cross-sectional sampling involving 91 schools across 5 Australian States and Territories between 2000 and 2011. Anthropometric data from 29,928 (14,643 girls, 15,285 boys) Australian children aged between 5 and 12.5 years were used to develop progression standards (norm centiles) covering the primary school years. Measures used were: height, weight, body mass index, per cent body fat, grip strength, standing long jump, cardiorespiratory fitness, sit-ups and sit-and-reach. These norms were then used to develop a Physical Activity and Lifestyle Management (PALM) system that could form the basis for progression, monitoring and reporting of anthropometric achievement standards for children. Tables and representative centile curves (3rd, 15th, 50th, 85th and 97th) for each gender and half-year age group were produced. An illustrative example of the PALM system in operation was also provided. Our research provides gender and half-year age specific anthropometric standards for Australian primary school children. Furthermore, we have developed a monitoring and progression system that could be embedded in school communities to help address the prevalence of underweight, overweight and obesity and decline in physical fitness standards. The proposed system is designed on behalf of children and families and would be administered through school settings. Change, where needed, would be delivered by the supporting school community. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

  7. Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.

    PubMed

    March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A; Shlomai, Amir; Mota, Maria M; Fleming, Heather E; Khetani, Salman R; Rice, Charles M; Bhatia, Sangeeta N

    2015-12-01

    The development of therapies and vaccines for human hepatropic pathogens requires robust model systems that enable the study of host-pathogen interactions. However, in vitro liver models of infection typically use either hepatoma cell lines that exhibit aberrant physiology or primary human hepatocytes in culture conditions in which they rapidly lose their hepatic phenotype. To achieve stable and robust in vitro primary human hepatocyte models, we developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells. By using this system, which can be established over a period of days, and maintained over multiple weeks, we demonstrate how to recapitulate in vitro hepatic life cycles for the hepatitis B and C viruses and the Plasmodium pathogens P. falciparum and P. vivax. The MPCC platform can be used to uncover aspects of host-pathogen interactions, and it has the potential to be used for drug and vaccine development.

  8. Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

    PubMed Central

    March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A.; Shlomai, Amir; Mota, Maria; Fleming, Heather E.; Khetani, Salman R.; Rice, Charles M.; Bhatia, Sangeeta N.

    2018-01-01

    Studying human hepatotropic pathogens such as hepatitis B and C viruses and malaria will be necessary for understanding host-pathogen interactions, and developing therapy and prophylaxis. Unfortunately, existing in vitro liver models typically employ either cell lines that exhibit aberrant physiology, or primary human hepatocytes in culture configurations wherein they rapidly lose their hepatic functional phenotype. Stable, robust, and reliable in vitro primary human hepatocyte models are needed as platforms for infectious disease applications. For this purpose, we describe the application of micropatterned co-cultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive cells. Using this system, we demonstrate how to recapitulate in vitro liver infection by the hepatitis B and C viruses and Plasmodium pathogens. In turn, the MPCC platform can be used to uncover aspects of host-pathogen interactions, and has the potential to be used for medium-throughput drug screening and vaccine development. PMID:26584444

  9. Analysis investigation of supporting and restraint conditions on the surface deformation of a collimator primary mirror

    NASA Astrophysics Data System (ADS)

    Chan, Chia-Yen; You, Zhen-Ting; Huang, Bo-Kai; Chen, Yi-Cheng; Huang, Ting-Ming

    2015-09-01

    For meeting the requirements of the high-precision telescopes, the design of collimator is essential. The diameter of the collimator should be larger than that of the target for the using of alignment. Special supporting structures are demanded to reduce the deformation of gravity and to control the surface deformation induced by the mounting force when inspecting large-aperture primary mirrors. By using finite element analysis, a ZERODUR® mirror of a diameter of 620 mm will be analyzed to obtain the deformation induced by the supporting structures. Zernike polynomials will also be adopted to fit the optical surface and separate corresponding aberrations. Through the studies under different boundary conditions and supporting positions of the inner ring, it is concluded that the optical performance will be excellent under a strong enough supporter.

  10. An Evaluation of Local Teacher Support Strategies for the Implementation of Inquiry-Based Science Education in French Primary Schools

    ERIC Educational Resources Information Center

    Delclaux, Monique; Saltiel, Edith

    2013-01-01

    This article presents the results of an evaluation of local teacher support strategies for implementing inquiry-based science education (IBSE) in French primary schools. The research objective was to determine which aspects of the French model of IBSE are implemented in class, and the efficiency of each teacher support strategy. Data were…

  11. Active nuclear import and passive nuclear export are the primary determinants of TDP-43 localization.

    PubMed

    Pinarbasi, Emile S; Cağatay, Tolga; Fung, Ho Yee Joyce; Li, Ying C; Chook, Yuh Min; Thomas, Philip J

    2018-05-04

    ALS (Amyotrophic Lateral Sclerosis) is a neurodegenerative disease characterized by the redistribution of the RNA binding protein TDP-43 in affected neurons: from predominantly nuclear to aggregated in the cytosol. However, the determinants of TDP-43 localization and the cellular insults that promote redistribution are incompletely understood. Here, we show that the putative Nuclear Export Signal (NES) is not required for nuclear egress of TDP-43. Moreover, when the TDP-43 domain which contains the putative NES is fused to a reporter protein, YFP, the presence of the NES is not sufficient to mediate nuclear exclusion of the fusion protein. We find that the previously studied "∆NES" mutant, in which conserved hydrophobic residues are mutated to alanines, disrupts both solubility and splicing function. We further show that nuclear export of TDP-43 is independent of the exportin XPO1. Finally, we provide evidence that nuclear egress of TDP-43 is size dependent; nuclear export of dTomato TDP-43 is significantly impaired compared to Flag TDP-43. Together, these results suggest nuclear export of TDP-43 is predominantly driven by passive diffusion.

  12. Developing a Decision Support System for Tobacco Use Counseling Using Primary Care Physicians

    PubMed Central

    Marcy, Theodore W.; Kaplan, Bonnie; Connolly, Scott W.; Michel, George; Shiffman, Richard N.; Flynn, Brian S.

    2009-01-01

    Background Clinical decision support systems (CDSS) have the potential to improve adherence to guidelines, but only if they are designed to work in the complex environment of ambulatory clinics as otherwise physicians may not use them. Objective To gain input from primary care physicians in designing a CDSS for smoking cessation to ensure that the design is appropriate to a clinical environment before attempts to test this CDSS in a clinical trial. This approach is of general interest to those designing similar systems. Design and Approach We employed an iterative ethnographic process that used multiple evaluation methods to understand physician preferences and workflow integration. Using results from our prior survey of physicians and clinic managers, we developed a prototype CDSS, validated content and design with an expert panel, and then subjected it to usability testing by physicians, followed by iterative design changes based on their feedback. We then performed clinical testing with individual patients, and conducted field tests of the CDSS in two primary care clinics during which four physicians used it for routine patient visits. Results The CDSS prototype was substantially modified through these cycles of usability and clinical testing, including removing a potentially fatal design flaw. During field tests in primary care clinics, physicians incorporated the final CDSS prototype into their workflow, and used it to assist in smoking cessation interventions up to eight times daily. Conclusions A multi-method evaluation process utilizing primary care physicians proved useful for developing a CDSS that was acceptable to physicians and patients, and feasible to use in their clinical environment. PMID:18713526

  13. Space Shuttle Flight Support Motor no. 1 (FSM-1)

    NASA Technical Reports Server (NTRS)

    Hughes, Phil D.

    1990-01-01

    Space Shuttle Flight Support Motor No. 1 (FSM-1) was static test fired on 15 Aug. 1990 at the Thiokol Corporation Static Test Bay T-24. FSM-1 was a full-scale, full-duration static test fire of a redesigned solid rocket motor. FSM-1 was the first of seven flight support motors which will be static test fired. The Flight Support Motor program validates components, materials, and manufacturing processes. In addition, FSM-1 was the full-scale motor for qualification of Western Electrochemical Corporation ammonium perchlorate. This motor was subjected to all controls and documentation requirements CTP-0171, Revision A. Inspection and instrumentation data indicate that the FSM-1 static test firing was successful. The ambient temperature during the test was 87 F and the propellant mean bulk temperature was 82 F. Ballistics performance values were within the specified requirements. The overall performance of the FSM-1 components and test equipment was nominal.

  14. Adaptation of the Information and Support Needs Questionnaire into Turkish to use in women with primary relatives with breast cancer.

    PubMed

    Tokkaya, Sedefnur; Karayurt, Ozgül

    2010-01-01

    Breast cancer is the most frequent type of cancer among women in Turkey. Because of the high incidence of breast cancer, many women have family members who have experienced breast cancer. The aim of this study was to test the validity and reliability of the Information and Support Needs Questionnaire (ISNQ) for Turkish women, which was originally developed for use in women with primary relatives who had breast cancer. The study sample included 97 women whose primary female relatives had breast cancer. Data were collected with a Demographic Questionnaire and the ISNQ. The ISNQ was developed by Chalmers et al and was composed of 2 scales: the Importance Scale and the Needs Met Scale. Linguistic validity, translation, back translation, and content validity were tested with expert opinions. Item-to-total correlation scores ranged from 0.22 to 0.72 on the Importance Scale and from 0.23 to 0.60 on the Needs Met Scale. Cronbach alpha coefficients were.81 and.83 on the Importance Scale and the Needs Met Scale. The ISNQ, adapted into Turkish, was found to have sufficient validity and reliability. The questionnaire can be used to determine information and support needs of women whose primary relatives have breast cancer. Nurses and other health professionals can conduct interventions directed toward meeting information and support needs of women whose primary relatives have breast cancer.

  15. Implementing a Primary Healthcare Framework: The Importance of Nursing Leadership in Developing and Maintaining a Brain Tumor Support Group.

    PubMed

    Nichols, Linda J; Wright, Kylie M

    2015-08-01

    Although brain tumor support groups have been available internationally for many years, Liverpool Hospital in Australia has not traditionally provided this service. As a leadership initiative, the development of a brain tumor support group that incorporates a primary healthcare framework is a sustainable approach that showcases the role of nursing leaders in changing attitudes and improving outcomes. The purpose of this review of the literature and reflection of clinical experience is to explore nursing leadership within brain tumor-specific support groups. This article will showcase a nurse-led group that incorporated a coordinated approach to delivering patient-centered care. The initiation of activities and interventions that reflected the five tenets of primary health care resulted in improved outcomes for individuals and their family caregivers throughout the trajectory of their illness. Vital to the success of this project was moving from a standalone leader to building collective and collaborative leadership more conducive to facilitating change. The support group successfully demonstrated that individuals and family caregivers may see ongoing and long-term improvements during and following treatment.

  16. How to create more supportive supervision for primary healthcare: lessons from Ngamiland district of Botswana: co-operative inquiry group.

    PubMed

    Nkomazana, Oathokwa; Mash, Robert; Wojczewski, Silvia; Kutalek, Ruth; Phaladze, Nthabiseng

    2016-01-01

    Supportive supervision is a way to foster performance, productivity, motivation, and retention of health workforce. Nevertheless there is a dearth of evidence of the impact and acceptability of supportive supervision in low- and middle-income countries. This article describes a participatory process of transforming the supervisory practice of district health managers to create a supportive environment for primary healthcare workers. The objective of the study was to explore how district health managers can change their practice to create a more supportive environment for primary healthcare providers. A facilitated co-operative inquiry group (CIG) was formed with Ngamiland health district managers. CIG belongs to the participatory action research paradigm and is characterised by a cyclic process of observation, reflection, planning, and action. The CIG went through three cycles between March 2013 and March 2014. Twelve district health managers participated in the inquiry group. The major insights and learning that emerged from the inquiry process included inadequate supervisory practice, perceptions of healthcare workers' experiences, change in the managers' supervision paradigm, recognition of the supervisors' inadequate supervisory skills, and barriers to supportive supervision. Finally, the group developed a 10-point consensus on what they had learnt regarding supportive supervision. Ngamiland health district managers have come to appreciate the value of supportive supervision and changed their management style to be more supportive of their subordinates. They also developed a consensus on supportive supervision that could be adapted for use nationally. Supportive supervision should be prioritised at all levels of the health system, and it should be adequately resourced.

  17. How to create more supportive supervision for primary healthcare: lessons from Ngamiland district of Botswana: co-operative inquiry group

    PubMed Central

    Nkomazana, Oathokwa; Mash, Robert; Wojczewski, Silvia; Kutalek, Ruth; Phaladze, Nthabiseng

    2016-01-01

    Background Supportive supervision is a way to foster performance, productivity, motivation, and retention of health workforce. Nevertheless there is a dearth of evidence of the impact and acceptability of supportive supervision in low- and middle-income countries. This article describes a participatory process of transforming the supervisory practice of district health managers to create a supportive environment for primary healthcare workers. Objective The objective of the study was to explore how district health managers can change their practice to create a more supportive environment for primary healthcare providers. Design A facilitated co-operative inquiry group (CIG) was formed with Ngamiland health district managers. CIG belongs to the participatory action research paradigm and is characterised by a cyclic process of observation, reflection, planning, and action. The CIG went through three cycles between March 2013 and March 2014. Results Twelve district health managers participated in the inquiry group. The major insights and learning that emerged from the inquiry process included inadequate supervisory practice, perceptions of healthcare workers’ experiences, change in the managers’ supervision paradigm, recognition of the supervisors’ inadequate supervisory skills, and barriers to supportive supervision. Finally, the group developed a 10-point consensus on what they had learnt regarding supportive supervision. Conclusion Ngamiland health district managers have come to appreciate the value of supportive supervision and changed their management style to be more supportive of their subordinates. They also developed a consensus on supportive supervision that could be adapted for use nationally. Supportive supervision should be prioritised at all levels of the health system, and it should be adequately resourced. PMID:27345024

  18. Gemini 8.2-m primary mirror no. 1 polishing

    NASA Astrophysics Data System (ADS)

    Cayrel, Marc; Beraud, P.; Paseri, Jacques; Dromas, E.

    1998-08-01

    The 8-m class primary mirrors of the GEMINI Telescopes are thin ULE menisci actively supported. The two mirror blanks are produced by CORNING, the optical figuring, manufacturing and assembling of interfaces are done by REOSC. REOSC is as well in charge of the transportation of the mirror blanks from CORNING to REOSC, and of the shipment of the finished optics to Hawaii and to Chile. The mirror assembly requirements are summarized, the manufacturing and testing methods are addressed. REOSC had to design and manufacture a dedicated active supporting system, representative of the one used at the telescope level. Its design and performance are presented. The manufacturing steps undertaken at REOSC and the results achieved are then detailed: mirror blank surface generating and grinding, polishing, testing. The current status of the mirrors is finally presented.

  19. Blood pressure (BP) control and perceived family support in patients with essential hypertension seen at a primary care clinic in Western Nigeria.

    PubMed

    Ojo, Oluwaseun S; Malomo, Sunday O; Sogunle, Peter T

    2016-01-01

    Nonadherence to therapeutic plans has been reported among hypertensive patients. Researchers have also shown that adherence to therapeutic plans improves if motivation in the form of social support is provided. There is a dearth of local studies that explore the influence of family support on treatment outcomes of hypertensive patients. The aim of the study was to determine the relationship between BP control and perceived family support in patients with essential hypertension seen at a primary care setting in Western Nigeria. This was a cross-sectional hospital-based study. Systematic random sampling technique was used in selecting 360 hypertensive respondents between April and July 2013. Data were collected through a pretested interviewer-administered questionnaire and a standardized tool, Perceived Social Support Family Scale, which measured the respondents' level of perceived family support. Statistical Package for Social Sciences (SPSS) version 17.0 was used to analyze data. The majority of the respondents were middle-aged (61.1%) and female (59.4%). Blood pressure (BP) was controlled in 46.4% of the respondents. Most of the respondents (79.4%) had "strong" perceived family support. Strong perceived family support (odds ratio [OR] 4.778, 95% confidence interval [CI] =2.569-8.887) and female gender (OR 1.838, 95% CI = 1.177-2.869) were independent predictors of controlled BP. The proportion of hypertensive patients with optimal BP control is low in this practice setting. The positive association between BP control and perceived family support emphasizes the need for physicians to reflect on the available family support when managing hypertensive patients.

  20. Pharmacist-led, primary care-based disease management improves hemoglobin A1c in high-risk patients with diabetes.

    PubMed

    Rothman, Russell; Malone, Robb; Bryant, Betsy; Horlen, Cheryl; Pignone, Michael

    2003-01-01

    We developed and evaluated a comprehensive pharmacist-led, primary care-based diabetes disease management program for patients with Type 2 diabetes and poor glucose control at our academic general internal medicine practice. The primary goal of this program was to improve glucose control, as measured by hemoglobin A1c (HbA1c). Clinic-based pharmacists offered support to patients with diabetes through direct teaching about diabetes, frequent phone follow-up, medication algorithms, and use of a database that tracked patient outcomes and actively identified opportunities to improve care. From September 1999, to May 2000, 159 subjects were enrolled, and complete follow-up data were available for 138 (87%) patients. Baseline HbA1c averaged 10.8%, and after an average of 6 months of intervention, the mean reduction in HbA1c was 1.9 percentage points (95% confidence interval, 1.5-2.3). In predictive regression modeling, baseline HbA1c and new onset diabetes were associated with significant improvements in HbA1c. Age, race, gender, educational level, and provider status were not significant predictors of improvement. In conclusion, a pharmacist-based diabetes care program integrated into primary care practice significantly reduced HbA1c among patients with diabetes and poor glucose control.

  1. Education on organ donation and transplantation in primary school; teachers' support and the first results of a teaching module

    PubMed Central

    Siebelink, Marion J.; Van de Wiel, Harry B. M.

    2017-01-01

    Organ and tissue donation can also involve children. Because of its sensitivity, this topic requires careful decision making. Children have the ability to carefully reflect on this subject and enjoy participating in family discussions about it. Therefore, what children need is proper information. When schools are used to educate children about this subject, information about teacher support for this type of lesson along with its effects on the depth of family discussions is important. Methods: A questionnaire was sent to all 7,542 primary schools in the Netherlands. The goal was to gather information on teachers’ perspectives about a neutral lesson devoted to organ and tissue donation, and also on the best age to start giving such a lesson. The second part of our study examined the effects of a newly developed lesson among 269 primary school pupils. The school response was 23%. Of these, 70% were positive towards a lesson; best age to start was 10–11 years. Pupils reported 20% more family discussions after school education and enjoyed learning more about this topic. There is significant support in primary schools for a school lesson on organ and tissue donation. Educational programs in schools support family discussions. PMID:28531238

  2. Effects of the Diabetes Manual 1:1 structured education in primary care.

    PubMed

    Sturt, J A; Whitlock, S; Fox, C; Hearnshaw, H; Farmer, A J; Wakelin, M; Eldridge, S; Griffiths, F; Dale, J

    2008-06-01

    To determine the effects of the Diabetes Manual on glycaemic control, diabetes-related distress and confidence to self-care of patients with Type 2 diabetes. A cluster randomized, controlled trial of an intervention group vs. a 6-month delayed-intervention control group with a nested qualitative study. Participants were 48 urban general practices in the West Midlands, UK, with high population deprivation levels and 245 adults with Type 2 diabetes with a mean age of 62 years recruited pre-randomization. The Diabetes Manual is 1:1 structured education designed for delivery by practice nurses. Measured outcomes were HbA(1c), cardiovascular risk factors, diabetes-related distress measured by the Problem Areas in Diabetes Scale and confidence to self-care measured by the Diabetes Management Self-Efficacy Scale. Outcomes were assessed at baseline and 26 weeks. There was no significant difference in HbA(1c) between the intervention group and the control group [difference -0.08%, 95% confidence interval (CI) -0.28, 0.11]. Diabetes-related distress scores were lower in the intervention group compared with the control group (difference -4.5, 95% CI -8.1, -1.0). Confidence to self-care Scores were 11.2 points higher (95% CI 4.4, 18.0) in the intervention group compared with the control group. The patient response rate was 18.5%. In this population, the Diabetes Manual achieved a small improvement in patient diabetes-related distress and confidence to self-care over 26 weeks, without a change in glycaemic control. Further study is needed to optimize the intervention and characterize those for whom it is more clinically and psychologically effective to support its use in primary care.

  3. A Comparative Study of Teachers' Pedagogical Competencies in Supporting Children with Learning Difficulties in Primary Schools in Ghana and Brunei Darussalam

    ERIC Educational Resources Information Center

    Abosi, Okechukwu; Alhassan, Abdul Razak Kuyini

    2017-01-01

    Teachers' pedagogical competencies level is increasingly affecting the implementation of inclusive education policy in many countries. The aimed at comparing primary school teachers' competence levels in supporting children with learning difficulties in Brunei Darussalam and Ghana. Descriptive survey design was used and 188 primary school teachers…

  4. A systematic review of supportive supervision as a strategy to improve primary healthcare services in Sub-Saharan Africa.

    PubMed

    Bailey, Claire; Blake, Carolyn; Schriver, Michael; Cubaka, Vincent Kalumire; Thomas, Tisa; Martin Hilber, Adriane

    2016-01-01

    It may be assumed that supportive supervision effectively builds capacity, improves the quality of care provided by frontline health workers, and positively impacts clinical outcomes. Evidence on the role of supervision in Sub-Saharan Africa has been inconclusive, despite the critical need to maximize the workforce in low-resource settings. To review the published literature from Sub-Saharan Africa on the effects of supportive supervision on quality of care, and health worker motivation and performance. A systematic review of seven databases of both qualitative and quantitative studies published in peer-reviewed journals. Selected studies were based in primary healthcare settings in Sub-Saharan Africa and present primary data concerning supportive supervision. Thematic synthesis where data from the identified studies were grouped and interpreted according to prominent themes. Supportive supervision can increase job satisfaction and health worker motivation. Evidence is mixed on whether this translates to increased clinical competence and there is little evidence of the effect on clinical outcomes. Results highlight the lack of sound evidence on the effects of supportive supervision owing to limitations in research design and the complexity of evaluating such interventions. The approaches required a high level of external inputs, which challenge the sustainability of such models. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Primary caregivers of in-home oxygen-dependent children: predictors of stress based on characteristics, needs and social support.

    PubMed

    Wang, Kai-Wei K; Lin, Hung-Ching; Lee, Chin-Ting; Lee, Kuo-Sheng

    2016-07-01

    To identify the predictors of primary caregivers' stress in caring for in-home oxygen-dependent children by examining the association between their levels of stress, caregiver needs and social support. Increasing numbers of primary caregivers of oxygen-dependent children experience caregiving stress that warrants investigation. The study used a cross-sectional design with three psychometric scales - Modified-Parenting Stress Index, Caregiver Needs Scale and Social Support Index. The data collected during 2010-2011 were from participants who were responsible for their child's care that included oxygen therapy for ≧6 hours/day; the children's ages ranged from 3 months-16 years. Descriptive statistics and multivariable linear regression were used. A total of 104 participants (M = 34, F = 70) were recruited, with an average age of 39·7 years. The average age of the oxygen-dependent children was 6·68 years and their daily use of oxygen averaged 11·39 hours. The caregivers' overall levels of stress were scored as high and information needs were scored as the highest. The most available support from family and friends was emotional support. Informational support was mostly received from health professionals, but both instrumental and emotional support were important. Levels of stress and caregiver needs were significantly correlated. Multivariable linear regression analyses identified three risk factors predicting stress, namely, the caregiver's poor health status, the child's male gender and the caregiver's greater financial need. To support these caregivers, health professionals can maintain their health status and provide instrumental, emotional, informational and financial support. © 2016 John Wiley & Sons Ltd.

  6. Supporting the Integration of HIV Testing Into Primary Care Settings

    PubMed Central

    Bradley-Springer, Lucy; Kang Dufour, Mi-Suk; Koester, Kimberly A.; Beane, Stephanie; Warren, Nancy; Beal, Jeffrey; Frank, Linda Rose

    2012-01-01

    Objectives. We examined the efforts of the US network of AIDS Education and Training Centers (AETCs) to increase HIV testing capacity across a variety of clinical settings. Methods. We used quantitative process data from 8 regional AETCs for July 1, 2008, to June 30, 2009, and qualitative program descriptions to demonstrate how AETC education helped providers integrate HIV testing into routine clinical care with the goals of early diagnosis and treatment. Results. Compared with other AETC training, HIV testing training was longer and used a broader variety of strategies to educate more providers per training. During education, providers were able to understand their primary care responsibility to address public health concerns through HIV testing. Conclusions. AETC efforts illustrate how integration of the principles of primary care and public health can be promoted through professional training. PMID:22515867

  7. Innovations in Primary Health Care: the use of communications technology and information tools to support local management.

    PubMed

    Pinto, Luiz Felipe; Rocha, Cristianne Maria Famer

    2016-05-01

    Social media has been used in different contexts as a way to streamline the flow of data and information for decision making. This has contributed to the issue of knowledge production in networks and the expansion of communication channels so that there is greater access to health services. This article describes the results of research done on 16 Information Technology and Communications Observatories in Health Care - OTICS Network in Rio - covering the Municipal Health Secretariat in Rio de Janeiro which supported the integration of primary health care and promoted the monitoring of health. It is a descriptive case study. The results relate to the support given to employees in training covering the dissemination of information, communication, training and information management in primary health care. This innovative means of communication in public health, with very little cost to the Unified Health System (SUS), allowed for a weekly registering of work processes for teams that worked in 193 primary health care units (APS) using blogs, whose total accesses reached the seven million mark in mid-2015. In the future there is a possibility that distance learning tools could be used to assist in training processes and in the continuing education of professionals in family health teams.

  8. General practitioners’ and primary care nurses’ care for people with disabilities: quality of communication and awareness of supportive services

    PubMed Central

    Storms, Hannelore; Marquet, Kristel; Claes, Neree

    2017-01-01

    Background General practitioners (GPs) and primary-care nurses (PCNs) often feel inexperienced or inadequately educated to address unmet needs of people with disabilities (PDs). In this research, GPs’ and PCNs’ communication with PDs and health care professionals, as well as their awareness of supportive measures relevant to PDs (sensory disabilities excluded), was examined. Materials and methods An electronic questionnaire was sent out to 545 GPs and 1,547 PCNs employed in Limburg (Belgium). GPs and PCNs self-reported about both communication with parties involved in care for PDs (scale very good, good, bad, very bad) and their level of awareness of supportive measures relevant for PDs (scale unaware, inadequately aware, adequately aware). Results Of the questionnaire recipients, 6.6% (36 of 545) of GPs and 37.6% (588 of 1,547) of PCNs participated: 68.8% of 32 GPs and 45.8% of 443 PCNs categorized themselves as communicating well with PDs, and attributed miscommunication to limited intellectual capacities of PDs. GPs and PCNs reported communicating well with other health care professionals. Inadequate awareness was reported for tools to communicate (88.3% of GPs, 89% of PCNs) and benefits for PDs (44.1% of GPs, 66.9% of PCNs). Conclusion GPs’ and PCNs’ lacking awareness of communication aids is problematic. Involvement in a multidisciplinary, expert network might bypass inadequate awareness of practical and social support measures. PMID:29033579

  9. General practitioners' and primary care nurses' care for people with disabilities: quality of communication and awareness of supportive services.

    PubMed

    Storms, Hannelore; Marquet, Kristel; Claes, Neree

    2017-01-01

    General practitioners (GPs) and primary-care nurses (PCNs) often feel inexperienced or inadequately educated to address unmet needs of people with disabilities (PDs). In this research, GPs' and PCNs' communication with PDs and health care professionals, as well as their awareness of supportive measures relevant to PDs (sensory disabilities excluded), was examined. An electronic questionnaire was sent out to 545 GPs and 1,547 PCNs employed in Limburg (Belgium). GPs and PCNs self-reported about both communication with parties involved in care for PDs (scale very good, good, bad, very bad) and their level of awareness of supportive measures relevant for PDs (scale unaware, inadequately aware, adequately aware). Of the questionnaire recipients, 6.6% (36 of 545) of GPs and 37.6% (588 of 1,547) of PCNs participated: 68.8% of 32 GPs and 45.8% of 443 PCNs categorized themselves as communicating well with PDs, and attributed miscommunication to limited intellectual capacities of PDs. GPs and PCNs reported communicating well with other health care professionals. Inadequate awareness was reported for tools to communicate (88.3% of GPs, 89% of PCNs) and benefits for PDs (44.1% of GPs, 66.9% of PCNs). GPs' and PCNs' lacking awareness of communication aids is problematic. Involvement in a multidisciplinary, expert network might bypass inadequate awareness of practical and social support measures.

  10. Earth and Beyond. Teacher Support for Science in the National Curriculum for Primary and Middle Schools.

    ERIC Educational Resources Information Center

    Pickwick, Alan

    The material in this book was devised in answer to a need expressed by many teachers, especially in primary (elementary) schools, for support in the teaching of astronomy. These projects and activities are aimed at fulfilling the requirements of the National Curriculum in England and Wales and the 5-14 Guidelines in Scotland. Each activity gives…

  11. Development of a web-based toolkit to support improvement of care coordination in primary care.

    PubMed

    Ganz, David A; Barnard, Jenny M; Smith, Nina Z Y; Miake-Lye, Isomi M; Delevan, Deborah M; Simon, Alissa; Rose, Danielle E; Stockdale, Susan E; Chang, Evelyn T; Noël, Polly H; Finley, Erin P; Lee, Martin L; Zulman, Donna M; Cordasco, Kristina M; Rubenstein, Lisa V

    2018-05-23

    Promising practices for the coordination of chronic care exist, but how to select and share these practices to support quality improvement within a healthcare system is uncertain. This study describes an approach for selecting high-quality tools for an online care coordination toolkit to be used in Veterans Health Administration (VA) primary care practices. We evaluated tools in three steps: (1) an initial screening to identify tools relevant to care coordination in VA primary care, (2) a two-clinician expert review process assessing tool characteristics (e.g. frequency of problem addressed, linkage to patients' experience of care, effect on practice workflow, and sustainability with existing resources) and assigning each tool a summary rating, and (3) semi-structured interviews with VA patients and frontline clinicians and staff. Of 300 potentially relevant tools identified by searching online resources, 65, 38, and 18 remained after steps one, two and three, respectively. The 18 tools cover five topics: managing referrals to specialty care, medication management, patient after-visit summary, patient activation materials, agenda setting, patient pre-visit packet, and provider contact information for patients. The final toolkit provides access to the 18 tools, as well as detailed information about tools' expected benefits, and resources required for tool implementation. Future care coordination efforts can benefit from systematically reviewing available tools to identify those that are high quality and relevant.

  12. Analysis of alternatives for using cable bolts as primary support at two low-seam coal mines

    PubMed Central

    Esterhuizen, Gabriel S.; Tulu, Ihsan B.

    2016-01-01

    Cable bolts are sometimes used in low-seam coal mines to provide support in difficult ground conditions. This paper describes cable bolting solutions at two low-seam coal mines in similar ground conditions. Both mines used support systems incorporating cable bolts as part of the primary support system. Two original cable bolt based support systems as well as two modified systems are evaluated to estimate their ability to prevent large roof falls. One of the support systems incorporated passive cable bolts, while the other used pre-tensioned cable bolts. The results and experience at the mines showed that the modified systems provided improved stability over the original support systems. The presence of the cable bolts is the most important contribution to stability against large roof falls, rather than the details of the support pattern. It was also found that a heavy steel channel can improve the safety of the system because of the ‘sling’ action it provides. Additionally, the analysis showed that fully-grouted rebar bolts load much earlier than the cable bolts, and pre-tensioning of the cable bolts can result in a more uniform distribution of loading in the roof. PMID:27722019

  13. Reliability Analysis of RSG-GAS Primary Cooling System to Support Aging Management Program

    NASA Astrophysics Data System (ADS)

    Deswandri; Subekti, M.; Sunaryo, Geni Rina

    2018-02-01

    Multipurpose Research Reactor G.A. Siwabessy (RSG-GAS) which has been operating since 1987 is one of the main facilities on supporting research, development and application of nuclear energy programs in BATAN. Until now, the RSG-GAS research reactor has been successfully operated safely and securely. However, because it has been operating for nearly 30 years, the structures, systems and components (SSCs) from the reactor would have started experiencing an aging phase. The process of aging certainly causes a decrease in reliability and safe performances of the reactor, therefore the aging management program is needed to resolve the issues. One of the programs in the aging management is to evaluate the safety and reliability of the system and also screening the critical components to be managed.One method that can be used for such purposes is the Fault Tree Analysis (FTA). In this papers FTA method is used to screening the critical components in the RSG-GAS Primary Cooling System. The evaluation results showed that the primary isolation valves are the basic events which are dominant against the system failure.

  14. Primary Care Provider Perceptions of the Effectiveness of Two Self-Management Support Programs for Vulnerable Patients with Diabetes

    PubMed Central

    Ratanawongsa, Neda; Bhandari, Vijay K; Handley, Margaret; Rundall, Thomas; Hammer, Hali; Schillinger, Dean

    2012-01-01

    Background Primary care providers (PCPs) in safety net settings face barriers to optimizing care for patients with diabetes. We conducted this study to assess PCPs' perspectives on the effectiveness of two language-concordant diabetes self-management support programs. Methods One year postintervention, we surveyed PCPs whose patients with diabetes participated in a three-arm multiclinic randomized controlled trial comparing usual care (UC), weekly automated telephone self-management (ATSM) support with nurse care management, and monthly group medical visits (GMVs). We compared PCP perspectives on patient activation to create and achieve goals, quality of care, and barriers to care using regression models accounting for within-PCP clustering. Results Of 113 eligible PCPs caring for 330 enrolled patients, 87 PCPs (77%) responded to surveys about 245 (74%) enrolled patients. Intervention patients were more likely to be perceived by PCPs as activated to create and achieve goals for chronic care when compared with UC patients (standardized effect size, ATSM vs UC, +0.41, p = 0.01; GMV vs UC, +0.31, p = 0.05). Primary care providers rated quality of care as higher for patients exposed to ATSM compared to UC (odds ratio 3.6, p < 0.01). Compared with GMV patients, ATSM patients were more likely to be perceived by PCPs as overcoming barriers related to limited English proficiency (82% ATSM vs 44% GMV, p = 0.01) and managing medications (80% ATSM vs 53% GMV, p = 0.01). Conclusions Primary care providers perceived that patients receiving ATSM support had overcome barriers, participated more actively, and received higher quality diabetes care. These views of clinician stakeholders lend additional evidence for the potential to upscale ATSM more broadly to support PCPs in their care of diverse, multilinguistic populations. PMID:22401329

  15. Students' Experiences of Collaborative Creation through Songcrafting in Primary School: Supporting Creative Agency in "School Music" Programmes

    ERIC Educational Resources Information Center

    Muhonen, Sari

    2016-01-01

    The study reported in this article investigates students' experiences (n = 41) of their primary school songcrafting, examining the potential to support creative agency within school music education programmes. Songcrafting refers to a collaborative composing practice in which everyone is considered to be a capable creator of melodies and lyrics,…

  16. Distinct roles of neuroligin-1 and SynCAM1 in synapse formation and function in primary hippocampal neuronal cultures.

    PubMed

    Burton, S D; Johnson, J W; Zeringue, H C; Meriney, S D

    2012-07-26

    Neuroligins are a family of cell adhesion molecules critical in establishing proper central nervous system connectivity; disruption of neuroligin signaling in vivo precipitates a broad range of cognitive deficits. Despite considerable recent progress, the specific synaptic function of neuroligin-1 (NL1) remains unclear. A current model proposes that NL1 acts exclusively to mature pre-existent synaptic connections in an activity-dependent manner. A second element of this activity-dependent maturation model is that an alternate molecule acts upstream of NL1 to initiate synaptic connections. SynCAM1 (SC1) is hypothesized to function in this capacity, though several uncertainties remain regarding SC1 function. Using overexpression and chronic pharmacological blockade of synaptic activity, we now demonstrate that NL1 is capable of robustly recruiting synapsin-positive terminals independent of synaptic maturation and activity in 2-week old primary hippocampal neuronal cultures. We further report that neither SC1 overexpression nor knockdown of endogenous SC1 impacts synapsin punctum densities, suggesting that SC1 is not a limiting factor of synapse initiation in maturing hippocampal neurons in vitro. Consistent with these findings, we observed profoundly greater recruitment of synapsin-positive presynaptic terminals by NL1 than SC1 in a mixed-culture assay of artificial synaptogenesis between primary neurons and heterologous cells. Collectively, our results contend multiple aspects of the proposed model of NL1 and SC1 function and motivate an alternative model whereby SC1 may mature synaptic connections forged by NL1. Supporting this model, we present evidence that combined NL1 and SC1 overexpression triggers excitotoxic neurodegeneration through SC1 signaling at synaptic connections initiated by NL1. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. 24 CFR 570.1 - Purpose and primary objective.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Purpose and primary objective. 570.1 Section 570.1 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

  18. 24 CFR 570.1 - Purpose and primary objective.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Purpose and primary objective. 570.1 Section 570.1 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT OF HOUSING AND...

  19. Assessment of the Effectiveness of the Educational Environment Supported by Computer Aided Presentations at Primary School Level

    ERIC Educational Resources Information Center

    Kose, Erdogan

    2009-01-01

    The objective of this study is to assess the effectiveness of the educational environment supported by computer aided presentations at primary school. The effectiveness of the environment has been evaluated in terms of students' learning and remembering what they have learnt. In the study, we have compared experimental group and control group in…

  20. Sphingosine-1-phosphate stimulates rat primary chondrocyte proliferation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Mi-Kyoung; Lee, Ha Young; Kwak, Jong-Young

    2006-06-23

    Rat primary chondrocytes express the sphingosine-1-phosphate (S1P) receptor, S1P{sub 2}, S1P{sub 3}, S1P{sub 4}, but not S1P{sub 1}. When chondrocytes were stimulated with S1P or phytosphingosine-1-phosphate (PhS1P, an S1P{sub 1}- and S1P{sub 4}-selective agonist), phospholipase C-mediated cytosolic calcium increase was dramatically induced. S1P and PhS1P also stimulated two kinds of mitogen-activated protein kinases, extracellular signal-regulated kinase (ERK) and p38 kinase in chondrocytes. In terms of the two phospholipids-mediated functional modulation of chondrocytes, S1P and PhS1P stimulated cellular proliferation. The two phospholipids-induced chondrocyte proliferations were almost completely blocked by PD98059 but not by SB203580, suggesting that ERK but not p38 kinasemore » is essentially required for the proliferation. Pertussis toxin almost completely inhibited the two phospholipids-induced cellular proliferation and ERK activation, indicating the crucial role of G{sub i} protein. This study demonstrates the physiological role of two important phospholipids (S1P and PhS1P) on the modulation of rat primary chondrocyte proliferation, and the crucial role played by ERK in the process.« less

  1. Predicting primary progressive aphasias with support vector machine approaches in structural MRI data.

    PubMed

    Bisenius, Sandrine; Mueller, Karsten; Diehl-Schmid, Janine; Fassbender, Klaus; Grimmer, Timo; Jessen, Frank; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, Bernhard; Ludolph, Albert; Schneider, Anja; Anderl-Straub, Sarah; Stuke, Katharina; Danek, Adrian; Otto, Markus; Schroeter, Matthias L

    2017-01-01

    Primary progressive aphasia (PPA) encompasses the three subtypes nonfluent/agrammatic variant PPA, semantic variant PPA, and the logopenic variant PPA, which are characterized by distinct patterns of language difficulties and regional brain atrophy. To validate the potential of structural magnetic resonance imaging data for early individual diagnosis, we used support vector machine classification on grey matter density maps obtained by voxel-based morphometry analysis to discriminate PPA subtypes (44 patients: 16 nonfluent/agrammatic variant PPA, 17 semantic variant PPA, 11 logopenic variant PPA) from 20 healthy controls (matched for sample size, age, and gender) in the cohort of the multi-center study of the German consortium for frontotemporal lobar degeneration. Here, we compared a whole-brain with a meta-analysis-based disease-specific regions-of-interest approach for support vector machine classification. We also used support vector machine classification to discriminate the three PPA subtypes from each other. Whole brain support vector machine classification enabled a very high accuracy between 91 and 97% for identifying specific PPA subtypes vs. healthy controls, and 78/95% for the discrimination between semantic variant vs. nonfluent/agrammatic or logopenic PPA variants. Only for the discrimination between nonfluent/agrammatic and logopenic PPA variants accuracy was low with 55%. Interestingly, the regions that contributed the most to the support vector machine classification of patients corresponded largely to the regions that were atrophic in these patients as revealed by group comparisons. Although the whole brain approach took also into account regions that were not covered in the regions-of-interest approach, both approaches showed similar accuracies due to the disease-specificity of the selected networks. Conclusion, support vector machine classification of multi-center structural magnetic resonance imaging data enables prediction of PPA subtypes with

  2. Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells.

    PubMed

    Vacharaksa, Anjalee; Asrani, Anil C; Gebhard, Kristin H; Fasching, Claudine E; Giacaman, Rodrigo A; Janoff, Edward N; Ross, Karen F; Herzberg, Mark C

    2008-07-17

    Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner. To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells) were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Deltaenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral blood mononuclear cells (PBMCs) or MOLT4 cells (CD4+ CCR5+) by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also trans infected HIV-1 to permissive cells in a donor-specific manner. Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.

  3. 41 CFR 128-1.5003 - Primary authority and responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false Primary authority and responsibility. 128-1.5003 Section 128-1.5003 Public Contracts and Property Management Federal Property Management Regulations System (Continued) DEPARTMENT OF JUSTICE 1-INTRODUCTION 1.50-Authorities and...

  4. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

    PubMed

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

    2017-10-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  5. Evaluation of the Effect of Decision Support on the Efficiency of Primary Care Providers in the Outpatient Practice

    PubMed Central

    Hankey, Ronald A.; Decker, Lindsay K.; Cha, Stephen S.; Greenes, Robert A.; Liu, Hongfang; Chaudhry, Rajeev

    2015-01-01

    Background: Clinical decision support (CDS) for primary care has been shown to improve delivery of preventive services. However, there is little evidence for efficiency of physicians due to CDS assistance. In this article, we report a pilot study for measuring the impact of CDS on the time spent by physicians for deciding on preventive services and chronic disease management. Methods: We randomly selected 30 patients from a primary care practice, and assigned them to 10 physicians. The physicians were requested to perform chart review to decide on preventive services and chronic disease management for the assigned patients. The patients assignment was done in a randomized crossover design, such that each patient received 2 sets of recommendations—one from a physician with CDS assistance and the other from a different physician without CDS assistance. We compared the physician recommendations made using CDS assistance, with the recommendations made without CDS assistance. Results: The physicians required an average of 1 minute 44 seconds, when they were they had access to the decision support system and 5 minutes when they were unassisted. Hence the CDS assistance resulted in an estimated saving of 3 minutes 16 seconds (65%) of the physicians’ time, which was statistically significant (P < .0001). There was no statistically significant difference in the number of recommendations. Conclusion: Our findings suggest that CDS assistance significantly reduced the time spent by physicians for deciding on preventive services and chronic disease management. The result needs to be confirmed by performing similar studies at other institutions. PMID:25155103

  6. Association of Psychologic and Nonpsychologic Factors With Primary Dysmenorrhea

    PubMed Central

    Faramarzi, Mahbobeh; Salmalian, Hajar

    2014-01-01

    Background: Primary dysmenorrhea seems to be one the most common gynecologic condition in women of childbearing age. Objectives: The aim of this research was to evaluate psychologic and nonpsychologic risk factors of primary dysmenorrhea. Materials and Methods: A cross-sectional study was conducted on medical sciences students of Babol University of Medical Sciences. In this study, 180 females with dysmenorrhea and 180 females without dysmenorrhea were enrolled. Psychological risk factors were evaluated in four domains including affect, social support, personality, and alexithymia. Four questionnaires were used to assessed aforementioned domains, namely, Social Support Questionnaire (SSQ), depression, anxiety, stress (DAS-21), 20-item Toronto Alexithymia Scale (TAS-20), and NEO-Five Factor Inventory of Personality (NEO-FFI). In addition, nonpsychologic factors were evaluated in three domains including demographic characteristics, habits, and gynecologic factors. Data were analyzed using the χ2 test and multiple logistic regression analysis. Results: The strongest predictor of primary dysmenorrhea was low social support (OR = 4.25; 95% CI, 2.43-7.41). Risk of dysmenorrhea was approximately 3.3 times higher in women with alexithymia (OR = 3.26; 95% CI, 1.88-5.62), 3.1 times higher in women with menstrual bleeding duration ≥ 7 days (OR = 3.06; 95% CI, 1.73-5.41), 2.5 times higher in women with a neurotic character (OR = 2.53; 95% CI, 1.42-4.50), 2.4 times higher in women with a family history of dysmenorrhea (OR = 2.43; 95% CI, 1.42-4.50), and twice higher in women with high caffeine intake (OR = 1.97; 95% CI, 1.09-3.59). Conclusions: Low social support, alexithymia, neuroticism trait, long menstrual bleeding, family history of dysmenorrhea, and high-caffeine diet are important risk factors for women with primary dysmenorrhea. This study recommended considering psychologic factors as an adjuvant to medical risks in evaluation and treatment of primary dysmenorrhea

  7. A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor.

    PubMed

    Gadd, Samantha; Huff, Vicki; Walz, Amy L; Ooms, Ariadne H A G; Armstrong, Amy E; Gerhard, Daniela S; Smith, Malcolm A; Auvil, Jaime M Guidry; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J; Moore, Richard A; Marra, Marco A; Dome, Jeffrey S; Mullighan, Charles G; Ma, Jing; Wheeler, David A; Hampton, Oliver A; Ross, Nicole; Gastier-Foster, Julie M; Arold, Stefan T; Perlman, Elizabeth J

    2017-10-01

    We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and MIRLET7A loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development.

  8. Ab initio identification of the Li-rich phase in LiFePO4.

    PubMed

    Zeng, Hua; Gu, Yue; Teng, Gaofeng; Liu, Yimeng; Zheng, Jiaxin; Pan, Feng

    2018-06-27

    A recent discovery of anionic redox activity in Li-rich layered compounds opens a new direction for the design of high-capacity cathode materials for lithium-ion batteries. Here using extensive ab initio calculations, the thermodynamic existence of the Li-rich phase in LiFePO4 to form Li1+xFe1-xPO4 with x not exceeding 12.5% has been proved. Anionic redox activity and structural stability during delithiation are further investigated. Interestingly, it is found that Li1+xFe1-xPO4 cannot be delithiated completely and thus cannot achieve extra capacity by anionic redox activity, because the local oxygen-ion redox will cause the fracture of the rigid framework formed by phosphate tetrahedral polyanions. Although an extra capacity cannot be realized, the excess Li-ions at Fe sites can enhance the Li-ion diffusivity along the adjacent [010] channel and contribute to the shift from 1D to 2D/3D diffusion. This study provides a fresh perspective on olivine-type LiFePO4 and offers some important clues on designing Li-rich cathode materials with high energy density.

  9. Common mutation underlying primary hyperoxaluria type1 in three Indian children

    PubMed Central

    Chanchlani, R.; Sinha, A.; Gulati, A.; Agarwal, V.; Bagga, A.

    2012-01-01

    Primary hyperoxaluria is an autosomal recessive disorder caused by deficiency of alanine-glyoxylate aminotransferase, which is encoded by the AGXT gene. We report three Indian children with primary hyperoxaluria type1 having a common mutation in this gene. All patients had evidence of chronic kidney disease at the time of diagnosis, with subsequent progression to end-stage renal disease. The detection of an identical mutation in the AGXT gene suggests that specific genetic screening for this mutation may be useful when considering the diagnosis of primary hyperoxaluria type1. PMID:23439734

  10. Common mutation underlying primary hyperoxaluria type1 in three Indian children.

    PubMed

    Chanchlani, R; Sinha, A; Gulati, A; Agarwal, V; Bagga, A

    2012-11-01

    Primary hyperoxaluria is an autosomal recessive disorder caused by deficiency of alanine-glyoxylate aminotransferase, which is encoded by the AGXT gene. We report three Indian children with primary hyperoxaluria type1 having a common mutation in this gene. All patients had evidence of chronic kidney disease at the time of diagnosis, with subsequent progression to end-stage renal disease. The detection of an identical mutation in the AGXT gene suggests that specific genetic screening for this mutation may be useful when considering the diagnosis of primary hyperoxaluria type1.

  11. A Children's Oncology Group and TARGET Initiative Exploring the Genetic Landscape of Wilms Tumor

    PubMed Central

    Gadd, Samantha; Huff, Vicki; Walz, Amy L.; Ooms, Ariadne H.A.G.; Armstrong, Amy E.; Gerhard, Daniela S.; Smith, Malcolm A.; Guidry Auvil, Jaime M.; Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Nguyen, Cu; Hu, Ying; Hermida, Leandro C.; Davidsen, Tanja; Gesuwan, Patee; Ma, Yussanne; Zong, Zusheng; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.; Dome, Jeffrey S.; Mullighan, Charles G.; Ma, Jing; Wheeler, David A.; Hampton, Oliver A.; Ross, Nicole; Gastier-Foster, Julie M.; Arold, Stefan T.; Perlman, Elizabeth J.

    2017-01-01

    Genome-wide sequencing, mRNA and miRNA expression, DNA copy number and methylation analyses were performed on 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, FAM123B, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), mutations were identified in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A. DNA copy number changes resulted in recurrent 1q gain, MYCN amplification, LIN28B gain, and let-7a loss. Unexpected germline variants involved PALB2 and CHEK2. Integrated analyses support two major classes of genetic changes that preserve the progenitor state and/or interrupt normal development. PMID:28825729

  12. Overexpression of genes involved in miRNA biogenesis in medullary thyroid carcinomas with RET mutation.

    PubMed

    Puppin, Cinzia; Durante, Cosimo; Sponziello, Marialuisa; Verrienti, Antonella; Pecce, Valeria; Lavarone, Elisa; Baldan, Federica; Campese, Antonio Francesco; Boichard, Amelie; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

    2014-11-01

    Abnormal expression of non-coding micro RNA (miRNA) has been described in medullary thyroid carcinoma (MTC). Expression of genes encoding factors involved in miRNA biogenesis results often deregulated in human cancer and correlates with aggressive clinical behavior. In this study, expression of four genes involved in miRNA biogenesis (DICER, DROSHA, DCGR8, and XPO5) was investigated in 54 specimens of MTC. Among them, 33 and 13 harbored RET and RAS mutations, respectively. DICER, DGCR8, and XPO5 mRNA levels were significantly overexpressed in MTC harboring RET mutations, in particular, in the presence of RET634 mutation. When MTCs with RET and RAS mutations were compared, only DGCR8 displayed a significant difference, while MTCs with RAS mutations did not show significant differences with respect to non-mutated tumors. We then attempted to correlate expression of miRNA biogenesis genes with tumor aggressiveness. According to the TNM status, MTCs were divided in two groups and compared (N0 M0 vs. N1 and/or M1): for all four genes no significant difference was detected. Cell line experiments, in which expression of a RET mutation is silenced by siRNA, suggest the existence of a causal relationship between RET mutation and overexpression of DICER, DGCR8, and XPO5 genes. These findings demonstrate that RET- but not RAS-driven tumorigenic alterations include abnormalities in the expression of some important genes involved in miRNA biogenesis that could represent new potential markers for targeted therapies in the treatment of RET-mutated MTCs aimed to restore the normal miRNA expression profile.

  13. Viral dynamics of primary HIV-1 infection in Senegal, West Africa.

    PubMed

    Sarr, Abdoulaye Dieng; Eisen, Geoffrey; Guèye-Ndiaye, Aissatou; Mullins, Christopher; Traoré, Ibrahima; Dia, Mamadou Ciré; Sankalé, Jean-Louis; Faye, Diegane; Mboup, Souleymane; Kanki, Phyllis

    2005-05-01

    Few studies have addressed primary human immunodeficiency virus (HIV) type 1 infection in sub-Saharan Africa, where the epidemic is of a predominantly heterosexual character and is caused by different subtypes. The present study examines the dynamics of viral replication in subjects infected with various HIV-1 subtypes. Seven hundred fifty-two HIV-negative Senegalese women at high risk for infection were monitored every 3 months for acute/early HIV infection; 26 infections were identified (23 HIV-1 and 3 HIV-2), with an HIV-1 incidence rate of 3.23 cases/person-years observation. Multiple viral-load measurements were taken for all seroconverters. The mean+/-standard deviation viral load for all subjects during the early stage of infection was 4.13+/-0.66 log10 copies/mL, with an overall decrease of 0.22 log10 copies/mL after the early stage; the viral set point was reached after 12 months of infection. Most subjects had relatively low viral loads during the early stage of infection. HIV-1 CRF02_AG-infected women had a significantly higher mean viral load during the early stage of infection (mean +/- SD, 4.45+/-0.60 log(10) copies/mL) than did non-HIV-1 CRF02_AG-infected women (mean+/-SD, 3.78+/-0.46 log(10) copies/mL) (P=.008). None of the subjects reported symptoms consistent with primary HIV-1 infection. Our findings in Senegalese women differ from what have been described for primary HIV-1 infection. Further investigations of primary infections with non-B subtypes are warranted, to better characterize their differences with primary infections with subtype B.

  14. Primary care physicians’ perspectives on facilitating older patients’ access to community support services

    PubMed Central

    Ploeg, Jenny; Denton, Margaret; Hutchison, Brian; McAiney, Carrie; Moore, Ainsley; Brazil, Kevin; Tindale, Joseph; Lam, Annie

    2017-01-01

    Abstract Objective To understand how family physicians facilitate older patients’ access to community support services (CSSs) and to identify similarities and differences across primary health care (PHC) models. Design Qualitative, multiple-case study design using semistructured interviews. Setting Four models of PHC delivery, specifically 2 family health teams (FHTs), 4 non-FHTs family health organizations, 4 fee-for-service practices, and 2 community health centres in urban Ontario. Participants Purposeful sampling of 23 family physicians in solo and small and large group practices within the 4 models of PHC. Methods A multiple-case study approach was used. Semistructured interviews were conducted and data were analyzed using within- and cross-case analysis. Case study tactics to ensure study rigour included memos and an audit trail, investigator triangulation, and the use of multiple, rather than single, case studies. Main findings Three main themes were identified: consulting and communicating with the health care team to create linkages; linking patients and families to CSSs; and relying on out-of-date resources and ineffective search strategies for information on CSSs. All participants worked with their team members; however, those in FHTs and community health centres generally had a broader range of health care providers available to assist them. Physicians relied on home-care case managers to help make linkages to CSSs. Physicians recommended the development of an easily searchable, online database containing available CSSs. Conclusion This study shows the importance of interprofessional teamwork in primary care settings to facilitate linkages of older patients to CSSs. The study also provides insight into the strategies physicians use to link older persons to CSSs and their recommendations for change. This understanding can be used to develop resources and approaches to better support physicians in making appropriate linkages to CSSs. PMID:28115458

  15. The Evaluation of IL6 and ESR1 Gene Polymorphisms in Primary Dysmenorrhea.

    PubMed

    Ozsoy, Asker Zeki; Karakus, Nevin; Yigit, Serbulent; Cakmak, Bulent; Nacar, Mehmet Can; Yılmaz Dogru, Hatice

    2016-01-01

    Primary dysmenorrhea is the most common gynecological complaint with painful menstrual cramps in pelvis without any pathology. It affects about half of menstruating women, and it causes significant disruption in quality of life. We investigated the association between IL6 gene promoter and ESR1 gene XbaI and PvuII polymorphisms and primary dysmenorrhea. In this case-control study, 152 unrelated young women with primary dysmenorrhea and 150 unrelated healthy age-matched controls participated. Genomic DNA was isolated and IL6 and ESR1 gene polymorphisms were genotyped using PCR-based RFLP assay. The distribution of genotype and allele frequencies of IL6 gene promoter and ESR1 gene XbaI polymorphisms were not statistically different between patients and controls (p > 0.05). However, the genotype and allele frequencies of ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls (p = 0.009 and p = 0.021, respectively). Statistically significant associations were also observed between age and married status of primary dysmenorrhea patients and ESR1 gene PvuII polymorphism (p = 0.044 and p = 0.023, respectively). In combined genotype analyses, AG at ESR1 XbaI and TC at ESR1 PvuII loci encoded a p-value of 0.027. Thus, individuals who are heterozygote at both loci have a lower risk of developing primary dysmenorrhea. Our study suggests no strong association between IL6 gene promoter and ESR1 gene XbaI polymorphisms and primary dysmenorrhea in Turkish women. However, ESR1 gene PvuII polymorphism showed statistically significant differences between primary dysmenorrhea patients and controls. The potential association between ESR1 gene PvuII polymorphism and age and married status of dysmenorrhea patients deserves further consideration.

  16. Evidence for the Effectiveness of Visual Supports in Helping Children with Disabilities Access the Mainstream Primary School Curriculum

    ERIC Educational Resources Information Center

    Foster-Cohen, Susan; Mirfin-Veitch, Brigit

    2017-01-01

    Removing barriers to learning for children with mild to moderate disabilities in mainstream primary classrooms calls for creative approaches that exploit the cognitive and sensory strengths of each child. Although their efficacy has not been fully explored, pictorial, symbolic and written supports are often used with the intention of helping…

  17. Improving Primary Care Provider Practices in Youth Concussion Management.

    PubMed

    Arbogast, Kristy B; Curry, Allison E; Metzger, Kristina B; Kessler, Ronni S; Bell, Jeneita M; Haarbauer-Krupa, Juliet; Zonfrillo, Mark R; Breiding, Matthew J; Master, Christina L

    2017-08-01

    Primary care providers are increasingly providing youth concussion care but report insufficient time and training, limiting adoption of best practices. We implemented a primary care-based intervention including an electronic health record-based clinical decision support tool ("SmartSet") and in-person training. We evaluated consequent improvement in 2 key concussion management practices: (1) performance of a vestibular oculomotor examination and (2) discussion of return-to-learn/return-to-play (RTL/RTP) guidelines. Data were included from 7284 primary care patients aged 0 to 17 years with initial concussion visits between July 2010 and June 2014. We compared proportions of visits pre- and post-intervention in which the examination was performed or RTL/RTP guidelines provided. Examinations and RTL/RTP were documented for 1.8% and 19.0% of visits pre-intervention, respectively, compared with 71.1% and 72.9% post-intervention. A total of 95% of post-intervention examinations were documented within the SmartSet. An electronic clinical decision support tool, plus in-person training, may be key to changing primary care provider behavior around concussion care.

  18. Effect of Family Supported Pre-Reading Training Program Given to Children in Preschool Education Period on Reading Success in Primary School

    ERIC Educational Resources Information Center

    Buyuktaskapu, Sema

    2012-01-01

    In this study, the effect of Family Supported Pre-Reading Program developed for 6 year olds attending nursery school on children's reading success in the future was examined. In order to fulfill this aim, reading skills of 25 primary school first-grade pupils who participated Family Supported Pre-Reading Program were compared with another 25…

  19. Quantitative Analysis Reveals that Actin and Src-Family Kinases Regulate Nuclear YAP1 and Its Export.

    PubMed

    Ege, Nil; Dowbaj, Anna M; Jiang, Ming; Howell, Michael; Hooper, Steven; Foster, Charles; Jenkins, Robert P; Sahai, Erik

    2018-06-08

    The transcriptional regulator YAP1 is critical for the pathological activation of fibroblasts. In normal fibroblasts, YAP1 is located in the cytoplasm, while in activated cancer-associated fibroblasts, it is nuclear and promotes the expression of genes required for pro-tumorigenic functions. Here, we investigate the dynamics of YAP1 shuttling in normal and activated fibroblasts, using EYFP-YAP1, quantitative photobleaching methods, and mathematical modeling. Imaging of migrating fibroblasts reveals the tight temporal coupling of cell shape change and altered YAP1 localization. Both 14-3-3 and TEAD binding modulate YAP1 shuttling, but neither affects nuclear import. Instead, we find that YAP1 nuclear accumulation in activated fibroblasts results from Src and actomyosin-dependent suppression of phosphorylated YAP1 export. Finally, we show that nuclear-constrained YAP1, upon XPO1 depletion, remains sensitive to blockade of actomyosin function. Together, these data place nuclear export at the center of YAP1 regulation and indicate that the cytoskeleton can regulate YAP1 within the nucleus. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Mapping the nuclear localization signal in the matrix protein of potato yellow dwarf virus.

    PubMed

    Anderson, Gavin; Jang, Chanyong; Wang, Renyuan; Goodin, Michael

    2018-05-01

    The ability of the matrix (M) protein of potato yellow dwarf virus (PYDV) to remodel nuclear membranes is controlled by a di-leucine motif located at residues 223 and 224 of its primary structure. This function can be uncoupled from that of its nuclear localization signal (NLS), which is controlled primarily by lysine and arginine residues immediately downstream of the LL motif. In planta localization of green fluorescent protein fusions, bimolecular fluorescence complementation assays with nuclear import receptor importin-α1 and yeast-based nuclear import assays provided three independent experimental approaches to validate the authenticity of the M-NLS. The carboxy terminus of M is predicted to contain a nuclear export signal, which is belived to be functional, given the ability of M to bind the Arabidopsis nuclear export receptor 1 (XPO1). The nuclear shuttle activity of M has implications for the cell-to-cell movement of PYDV nucleocapsids, based upon its interaction with the N and Y proteins.

  1. How primary health care staff working in rural and remote areas access skill development and expertise to support health promotion practice.

    PubMed

    McFarlane, Kathryn A; Judd, Jenni; Wapau, Hylda; Nichols, Nina; Watt, Kerrianne; Devine, Sue

    2018-05-01

    Health promotion is a key component of comprehensive primary health care. Health promotion approaches complement healthcare management by enabling individuals to increase control over their health. Many primary healthcare staff have a role to play in health promotion practice, but their ability to integrate health promotion into practice is influenced by their previous training and experience. For primary healthcare staff working in rural and remote locations, access to professional development can be limited by what is locally available and prohibitive in terms of cost for travel and accommodation. This study provides insight into how staff at a large north Queensland Aboriginal community controlled health service access skill development and health promotion expertise to support their work. A qualitative exploratory study was conducted. Small group and individual semi-structured interviews were conducted with staff at Apunipima Cape York Health Council (n=9). A purposive sampling method was used to recruit participants from a number of primary healthcare teams that were more likely to be involved in health promotion work. Both on-the-ground staff and managers were interviewed. All participants were asked how they access skill development and expertise in health promotion practice and what approaches they prefer for ongoing health promotion support. The interviews were transcribed verbatim and analysed thematically. All participants valued access to skill development, advice and support that would assist their health promotion practice. Skill development and expertise in health promotion was accessed from a variety of sources: conferences, workshops, mentoring or shared learning from internal and external colleagues, and access to online information and resources. With limited funds and limited access to professional development locally, participants fostered external and internal organisational relationships to seek in-kind advice and support. Irrespective of

  2. Primary Teacher Trainee Perspectives on a Male-Only Support Group: Moving Male Trainee Teachers beyond the "Freak Show"

    ERIC Educational Resources Information Center

    Warwick, Jane; Warwick, Paul; Hopper, Bev

    2012-01-01

    This paper reports the perspectives of male trainees on mechanisms instituted to support them during their Post-Graduate Certificate of Education in Early Years and Primary Education in England. The male trainees were interviewed towards the end of their training, using semi-structured interviews that provided scope for pursuing several lines of…

  3. Reversible Ammonia Sorption for the Primary Life Support System (PLSS)

    NASA Technical Reports Server (NTRS)

    Wojtowicz, Marek A.; Cosgrove, Joseph E.; Serio, Michael A.; Jennings, Mallory A.

    2012-01-01

    Results are presented on the development of regenerable trace-contaminant (TC) sorbent for use in Extravehicular Activities (EVAs), and more specifically in the Primary Life Support System (PLSS). Since ammonia is the most important TC to be captured, data presented in this paper are limited to ammonia sorption, with results relevant to other TCs to be reported at a later time. The currently available TC-control technology involves the use of a packed bed of acid-impregnated granular charcoal. The sorbent is non-regenerable, and its use is associated with appreciable pressure drop, i.e. power consumption. The objective of this work is to demonstrate the feasibility of using vacuum-regenerable sorbents for PLSS application. In this study, several carbon sorbent monoliths were fabricated and tested. Multiple adsorption/vacuum-regeneration cycles were demonstrated at room temperature, as well as carbon surface conditioning that enhances ammonia sorption without impairing sorbent regeneration. Depending on sorbent monolith geometry, the reduction in pressure drop with respect to granular sorbent was found to be between 50% and two orders of magnitude. Resistive heating of the carbon sorbent monolith was demonstrated by applying voltage to the opposite ends of the monolith.

  4. Anesthetic efficacy of 1.8 mL versus 3.6 mL of 4% articaine with 1:100,000 epinephrine as a primary buccal infiltration of the mandibular first molar.

    PubMed

    Martin, Matthew; Nusstein, John; Drum, Melissa; Reader, Al; Beck, Mike

    2011-05-01

    No study has compared 1.8 mL and 3.6 mL 4% articaine with 1:100,000 epinephrine in a mandibular buccal infiltration of the first molar. The authors conducted a prospective, randomized, single-blind, crossover study comparing the degree of pulpal anesthesia obtained with 1.8 mL and 3.6 mL 4% articaine with 1:100,000 epinephrine as a primary infiltration in the mandibular first molar. Eighty-six asymptomatic adult subjects randomly received a primary mandibular buccal first molar infiltration of 1.8 mL or 3.6 mL 4% articaine with 1:100,000 epinephrine in two separate appointments. The authors used an electric pulp tester to test the first molar for anesthesia in 3-minute cycles for 90 minutes after the injections. Compared with the 1.8-mL volume of 4% articaine with 1:100,000 epinephrine, the 3.6-mL volume showed a statistically higher success rate (70% vs 50%). The anesthetic efficacy of 3.6 mL 4% articaine with 1:100,000 epinephrine is better than 1.8 mL of the same anesthetic solution in a primary mandibular buccal infiltration of the first molar. However, the success rate of 70% is not high enough to support its use as a primary injection technique in the mandibular first molar. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  5. Structure of the Social Support Network of Patients with Severe and Persistent Psychiatric Disorders in Follow-Ups to Primary Health Care.

    PubMed

    de Souza, Jacqueline; de Almeida, Letícia Yamawaka; Moll, Marciana Fernandes; Silva, Lucas Duarte; Ventura, Carla Aparecida Arena

    2016-02-01

    The objective of this study is to analyze the characteristics of social support networks of patients with psychiatric disorders at follow-up to primary care. This is a cross-sectional qualitative research study. Forty-five interviews were held with patients and their supporters. The results showed small and dense networks, with a strong emphasis on the bonds with formal supporters and a scant network of informal supporters. It is recommended to develop strategies to improve social support networks and use this as an outcome indicator related to social integration of these patients and to the quality of services involved with outpatient healthcare. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Phase I Study of Selinexor, a Selective Inhibitor of Nuclear Export, in Combination With Fludarabine and Cytarabine, in Pediatric Relapsed or Refractory Acute Leukemia.

    PubMed

    Alexander, Thomas B; Lacayo, Norman J; Choi, John K; Ribeiro, Raul C; Pui, Ching-Hon; Rubnitz, Jeffrey E

    2016-12-01

    Purpose To characterize the toxicity, pharmacokinetics, and pharmacodynamics of selinexor, a selective inhibitor of nuclear export, when combined with fludarabine and cytarabine, in children with relapsed or refractory leukemia. Patients and Methods Eighteen patients with relapsed or refractory acute leukemia were enrolled in the SELHEM (Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome) clinical trial (NCT02212561). Selinexor, initially at 30 mg/m 2 per dose, was given orally on days 1, 3, 8, 10, 22, and 24 and was escalated according to a rolling-six design. Fludarabine 30 mg/m 2 and cytarabine 2 g/m 2 were administered on days 15 to 19. Pharmacokinetic and pharmacodynamic studies were performed on days 1 and 22. Response evaluations were performed on day 15 and at the completion of course 1. Results Among the 17 patients who were evaluable for toxicity, three were treated at 30 mg/m 2 , three at 40 mg/m 2 , six at 55 mg/m 2 , and five at 70 mg/m 2 . The most common grade 3 nonhematologic toxicity was asymptomatic hyponatremia. Two patients who were treated at 70 mg/m 2 experienced reversible cerebellar toxicity, thereby defining the dose-limiting toxicity. Pharmacokinetic parameters demonstrated that plasma exposure was dose proportional. Fifteen of 16 patients demonstrated at least a twofold increase of XPO1 mRNA, indicating inhibition of the XPO1 protein. In this group of heavily pretreated, relapsed, and refractory patients, seven of 15 evaluable patients (47%) achieved complete response or complete response with incomplete count recovery. Conclusion Selinexor, in combination with fludarabine and cytarabine, is tolerable at doses up to 55 mg/m 2 in pediatric patients with relapsed or refractory leukemia. All patients who received selinexor at ≥ 40 mg/m 2 demonstrated XPO1 target inhibition. Response rates are promising and will be further explored in a phase II trial.

  7. Netbook Computers as an Appropriate Solution for 1:1 Computer Use in Primary Schools

    ERIC Educational Resources Information Center

    Larkin, Kevin; Finger, Glenn

    2011-01-01

    As schools increasingly move towards 1:1 computing, research is required to inform the design and provision of this access. Utilising the Activity Theory (AT) notion of contradictions and expansion as a theoretical underpinning, this article suggests netbooks as a viable option to provide 1:1 computing for primary school students. Decisions…

  8. Optimizing psychosocial support during office-based buprenorphine treatment in primary care: patients’ experiences and preferences

    PubMed Central

    Fox, Aaron D.; Masyukova, Mariya; Cunningham, Chinazo O.

    2015-01-01

    Background Buprenorphine maintenance treatment is effective and has been successfully integrated into HIV and primary care settings. However, one key barrier to providers prescribing buprenorphine is their perception that they are unable to provide adequate counseling or psychosocial support to patients with opioid addiction. This qualitative study investigated supportive elements of office-based buprenorphine treatment that patients perceived to be most valuable. Methods We conducted five focus groups with 33 buprenorphine treatment-experienced participants. Focus groups were audio-recorded and transcribed. Iterative readings of transcripts and grounded theory analysis revealed common themes. Results Overall, participants perceived that buprenorphine treatment helped them to achieve their treatment goals and valued the flexibility, accessibility, and privacy of treatment. Participants identified interpersonal and structural elements of buprenorphine treatment that provided psychosocial support. Participants desired good physician-patient relationships, but also valued care delivery models that were patient-centered, created a safe place for self-disclosure, and utilized coordinated team-based care. Conclusions Participants derived psychosocial support from their prescribing physician, but were also open to collaborative or team-based models of care, as long as they were voluntary and confidential. Buprenorphine prescribing physicians without access to referral options for psychosocial counseling could focus on maintaining non-judgmental attitudes and shared decision making during patient encounters. Adding structure and psychosocial support to buprenorphine treatment through coordinated team-based care also seems to have great promise. PMID:26566712

  9. Copper regulates primary root elongation through PIN1-mediated auxin redistribution.

    PubMed

    Yuan, Hong-Mei; Xu, Heng-Hao; Liu, Wen-Cheng; Lu, Ying-Tang

    2013-05-01

    The heavy metal copper (Cu) is an essential microelement required for normal plant growth and development, but it inhibits primary root growth when in excess. The mechanism underlying how excess Cu functions in this process remains to be further elucidated. Here, we report that a higher concentration of CuSO4 inhibited primary root elongation of Arabidopsis seedlings by affecting both the elongation and meristem zones. In the meristem zone, meristematic cell division potential was reduced by excess Cu. Further experiments showed that Cu can modulate auxin distribution, resulting in higher auxin activities in both the elongation and meristem zones of Cu-treated roots based on DR5::GUS expression patterns. This Cu-mediated auxin redistribution was shown to be responsible for Cu-mediated inhibition of primary root elongation. Additional genetic and physiological data demonstrated that it was PINFORMED1 (PIN1), but not PIN2 or AUXIN1 (AUX1), that regulated this process. However, Cu-induced hydrogen peroxide accumulation did not contribute to Cu-induced auxin redistribution for inhibition of root elongation. When the possible role of ethylene in this process was analyzed, Cu had a similar impact on the root elongation of both the wild type and the ein2-1 mutant, implying that Cu-mediated inhibition of primary root elongation was not due to the ethylene signaling pathway.

  10. EpCAM overexpression prolongs proliferative capacity of primary human breast epithelial cells and supports hyperplastic growth

    PubMed Central

    2013-01-01

    Introduction The Epithelial Cell Adhesion Molecule (EpCAM) has been shown to be strongly expressed in human breast cancer and cancer stem cells and its overexpression has been supposed to support tumor progression and metastasis. However, effects of EpCAM overexpression on normal breast epithelial cells have never been studied before. Therefore, we analyzed effects of transient adenoviral overexpression of EpCAM on proliferation, migration and differentiation of primary human mammary epithelial cells (HMECs). Methods HMECs were transfected by an adenoviral system for transient overexpression of EpCAM. Thereafter, changes in cell proliferation and migration were studied using a real time measurement system. Target gene expression was evaluated by transcriptome analysis in proliferating and polarized HMEC cultures. A Chicken Chorioallantoic Membrane (CAM) xenograft model was used to study effects on in vivo growth of HMECs. Results EpCAM overexpression in HMECs did not significantly alter gene expression profile of proliferating or growth arrested cells. Proliferating HMECs displayed predominantly glycosylated EpCAM isoforms and were inhibited in cell proliferation and migration by upregulation of p27KIP1 and p53. HMECs with overexpression of EpCAM showed a down regulation of E-cadherin. Moreover, cells were more resistant to TGF-β1 induced growth arrest and maintained longer capacities to proliferate in vitro. EpCAM overexpressing HMECs xenografts in chicken embryos showed hyperplastic growth, lack of lumen formation and increased infiltrates of the chicken leukocytes. Conclusions EpCAM revealed oncogenic features in normal human breast cells by inducing resistance to TGF-β1-mediated growth arrest and supporting a cell phenotype with longer proliferative capacities in vitro. EpCAM overexpression resulted in hyperplastic growth in vivo. Thus, we suggest that EpCAM acts as a prosurvival factor counteracting terminal differentiation processes in normal mammary glands

  11. Effect of a computer-guided, quality improvement program for cardiovascular disease risk management in primary health care: the treatment of cardiovascular risk using electronic decision support cluster-randomized trial.

    PubMed

    Peiris, David; Usherwood, Tim; Panaretto, Kathryn; Harris, Mark; Hunt, Jennifer; Redfern, Julie; Zwar, Nicholas; Colagiuri, Stephen; Hayman, Noel; Lo, Serigne; Patel, Bindu; Lyford, Marilyn; MacMahon, Stephen; Neal, Bruce; Sullivan, David; Cass, Alan; Jackson, Rod; Patel, Anushka

    2015-01-01

    Despite effective treatments to reduce cardiovascular disease risk, their translation into practice is limited. Using a parallel arm cluster-randomized controlled trial in 60 Australian primary healthcare centers, we tested whether a multifaceted quality improvement intervention comprising computerized decision support, audit/feedback tools, and staff training improved (1) guideline-indicated risk factor measurements and (2) guideline-indicated medications for those at high cardiovascular disease risk. Centers had to use a compatible software system, and eligible patients were regular attendees (Aboriginal and Torres Strait Islander people aged ≥ 35 years and others aged ≥ 45 years). Patient-level analyses were conducted using generalized estimating equations to account for clustering. Median follow-up for 38,725 patients (mean age, 61.0 years; 42% men) was 17.5 months. Mean monthly staff support was <1 hour/site. For the coprimary outcomes, the intervention was associated with improved overall risk factor measurements (62.8% versus 53.4% risk ratio; 1.25; 95% confidence interval, 1.04-1.50; P=0.02), but there was no significant differences in recommended prescriptions for the high-risk cohort (n=10,308; 56.8% versus 51.2%; P=0.12). There were significant treatment escalations (new prescriptions or increased numbers of medicines) for antiplatelet (17.9% versus 2.7%; P<0.001), lipid-lowering (19.2% versus 4.8%; P<0.001), and blood pressure-lowering medications (23.3% versus 12.1%; P=0.02). In Australian primary healthcare settings, a computer-guided quality improvement intervention, requiring minimal support, improved cardiovascular disease risk measurement but did not increase prescription rates in the high-risk group. Computerized quality improvement tools offer an important, albeit partial, solution to improving primary healthcare system capacity for cardiovascular disease risk management. https

  12. What keeps you strong? A systematic review identifying how primary health-care and aged-care services can support the well-being of older Indigenous peoples.

    PubMed

    Davy, Carol; Kite, Elaine; Aitken, Graham; Dodd, Garth; Rigney, Janice; Hayes, Jenny; Van Emden, Jan

    2016-06-01

    The objective of this systematic review was to identify primary health-care or aged-care strategies that have or could support the well-being of older Indigenous peoples. A search was undertaken of primary databases including Medical Literature Analysis and Retrieval System Online and Cumulative Index to Nursing and Allied Health Literature. Papers which reported on the perspectives of older Indigenous peoples, community members and provider participants were included. Findings were pooled using a meta-aggregative approach. Three high-level synthesised findings - maintaining Indigenous identity, promoting independence and delivering culturally safe care - were believed to be important for supporting the well-being of older Indigenous peoples. As physical independence often diminishes with age, having the support of culturally safe primary health-care and aged-care services that understand the importance of maintaining an Indigenous identity and promoting independence will be crucial for the well-being of older Indigenous peoples. © 2016 AJA Inc.

  13. Centralized care management support for "high utilizers" in primary care practices at an academic medical center.

    PubMed

    Williams, Brent C; Paik, Jamie L; Haley, Laura L; Grammatico, Gina M

    2014-01-01

    Although evidence of effectiveness is limited, care management based outside primary care practices or hospitals is receiving increased attention. The University of Michigan (UM) Complex Care Management Program (CCMP) provides care management for uninsured and underinsured, high-utilizing patients in multiple primary care practices. To inform development of optimal care management models, we describe the CCMP model and characteristics and health care utilization patterns of its patients. Of a consecutive series of 49 patients enrolled at CCMP in 2011, the mean (SD) age was 48 (+/- 14); 23 (47%) were women; and 29 (59%) were White. Twenty-eight (57%) had two or more chronic medical conditions, 39 (80%) had one or more psychiatric condition, 28 (57%) had a substance abuse disorder, and 11 (22%) were homeless. Through phone, e-mail, and face-to-face contact with patients and primary care providers (PCPs), care managers coordinated health and social services and facilitated access to medical and mental health care. Patients had a mean (SD) number of hospitalizations and emergency room (ER) visits in 6 months prior to enrollment of2.2 (2.5) and 4.2 (4.3), respectively, with a nonstatistically significant decrease in hospitalizations, hospital days, and emergency room visits in 6 months following enrollment in CCMP. Centralized care management support for primary care practices engages high-utilizing patients with complex medical and behavioral conditions in care management that would be difficult to provide through individual practices and may decrease health care utilization by these patients.

  14. High efficiency aqueous and hybrid lithium-air batteries enabled by Li1.5Al0.5Ge1.5(PO4)3 ceramic anode-protecting membranes

    NASA Astrophysics Data System (ADS)

    Safanama, Dorsasadat; Adams, Stefan

    2017-02-01

    Due to their extremely high specific energy, rechargeable Li-air batteries could meet the demand for large-scale storage systems to integrate renewable sources into the power grid. Li-air batteries with aqueous catholytes with high solubility of discharge products have a higher potential to reach their slightly lower theoretical limits in practical devices. In this work, we demonstrate aqueous and hybrid Li-air batteries with NASICON-type Li1+xAxGe2-x(PO4)3 ceramic as anode-protecting membrane. The LAGP ceramic pellets with room temperature conductivity >10-4 S cm-1 are synthesized by melt quenching and subsequently annealed based on our optimized heat treatment cycle. Hybrid Li-air batteries are assembled by sandwiching LAGP membranes between Li-anode chamber and catholyte solutions (of various pH values) with CNT/Pt as air-cathode. When the two electron reduction mechanism prevails, overpotentials below 0.2 V are achieved for currents up to 0.07 mA cm-2 leading to energy efficiencies exceeding 98%.

  15. Evaluation of computerized decision support for oral anticoagulation management based in primary care.

    PubMed

    Fitzmaurice, D A; Hobbs, F D; Murray, E T; Bradley, C P; Holder, R

    1996-09-01

    Increasing indications for oral anticoagulation has led to pressure on general practices to undertake therapeutic monitoring. Computerized decision support (DSS) has been shown to be effective in hospitals for improving clinical management. Its usefulness in primary care has previously not been investigated. To test the effectiveness of using DSS for oral anticoagulation monitoring in primary care by measuring the proportions of patients adequately controlled, defined as within the appropriate therapeutic range of International Normalised Ratio (INR). All patients receiving warfarin from two Birmingham inner city general practices were invited to attend a practice-based anticoagulation clinic. In practice A all patients were managed using DSS. In practice B patients were randomized to receive dosing advice either through DSS or through the local hospital laboratory. Clinical outcomes, adverse events and patient acceptability were recorded. Forty-nine patients were seen in total. There were significant improvements in INR control from 23% to 86% (P > 0.001) in the practice where all patients received dosing through DSS. In the practice where patients were randomized to either DSS or hospital dosing, logistic regression showed a significant trend for improvement in intervention patients which was not apparent in the hospital-dosed patients (P < 0.001). Mean recall times were significantly extended in patients who were dosed by the practice DSS through the full 12 months (24 days to 36 days) (P = 0.033). Adverse events were comparable between hospital and practice-dosed patients, although a number of esoteric events occurred. Patient satisfaction with the practice clinics was high. Computerized DSS enables the safe and effective transfer of anticoagulation management from hospital to primary care and may result in improved patient outcome in terms of the level of control, frequency of review and general acceptability.

  16. Monitoring quality in Israeli primary care: The primary care physicians' perspective

    PubMed Central

    2012-01-01

    Background Since 2000, Israel has had a national program for ongoing monitoring of the quality of the primary care services provided by the country's four competing non-profit health plans. Previous research has demonstrated that quality of care has improved substantially since the program's inception and that the program enjoys wide support among health plan managers. However, prior to this study there were anecdotal and journalistic reports of opposition to the program among primary care physicians engaged in direct service delivery; these raised serious questions about the extent of support among physicians nationally. Goals To assess how Israeli primary care physicians experience and rate health plan efforts to track and improve the quality of care. Method The study population consisted of primary care physicians employed by the health plans who have responsibility for the quality of care of a panel of adult patients. The study team randomly sampled 250 primary-care physicians from each of the four health plans. Of the 1,000 physicians sampled, 884 met the study criteria. Every physician could choose whether to participate in the survey by mail, e-mail, or telephone. The anonymous questionnaire was completed by 605 physicians – 69% of those eligible. The data were weighted to reflect differences in sampling and response rates across health plans. Main findings The vast majority of respondents (87%) felt that the monitoring of quality was important and two-thirds (66%) felt that the feedback and subsequent remedial interventions improved medical care to a great extent. Almost three-quarters (71%) supported continuation of the program in an unqualified manner. The physicians with the most positive attitudes to the program were over age 44, independent contract physicians, and either board-certified in internal medicine or without any board-certification (i.e., residents or general practitioners). At the same time, support for the program was widespread even

  17. [Palliative care support teams and the commitment of primary care teams to terminally ill patients in their homes].

    PubMed

    Rocafort Gil, Javier; Herrera Molina, Emilio; Fernández Bermejo, Félix; Grajera Paredes María, María Eulalia; Redondo Moralo, María José; Díaz Díez, Fátima; Espinosa Rojas, José Armando

    2006-10-15

    To find out if the activity of palliative care support teams (PCST) does not negatively influences the performance of the primary care "care of terminally ill patients" service. Terminally ill patients cared for at home. Multicentre observational study. The observed variable is the increase in the number of registered patients in primary care, and the number of patients covered between the years 2002 and 2003 and the 4 intervention variables are: total visits, joint visits, assessments, and teaching sessions. The number of patients covered in 2002 was 41.19%, increasing to 45.44% in 2003. The activity rate of the PCST for each 100 000 inhabitants was 526 home visits in 2003, 86.15 joint visits, 313.68 professional assessments, and 23.14 teaching sessions. The joint visits and the teaching sessions were strongly associated with an improvement in the coverage of primary care (Pearson correlation of 0.784 and 0.759, respectively). The total visits were moderately associated (0.525) and the assessments were weakly associated (0.245). Joint visits and teaching sessions of a PCST are associated to an increase in the activity of primary care teams. Assessments and total visits did not have a negative influence.

  18. Cost-Effectiveness Analysis of Nasal Continuous Positive Airway Pressure Versus Nasal High Flow Therapy as Primary Support for Infants Born Preterm.

    PubMed

    Huang, Li; Roberts, Calum T; Manley, Brett J; Owen, Louise S; Davis, Peter G; Dalziel, Kim M

    2018-05-01

    To compare the cost-effectiveness of 2 common "noninvasive" modes of respiratory support for infants born preterm. An economic evaluation was conducted as a component of a multicenter, randomized control trial from 2013 to 2015 enrolling infants born preterm at ≥28 weeks of gestation with respiratory distress, <24 hours old, who had not previously received endotracheal intubation and mechanical ventilation or surfactant. The economic evaluation was conducted from a healthcare sector perspective and the time horizon was from birth until death or first discharge. The cost-effectiveness of continuous positive airway pressure (CPAP) vs high-flow with "rescue" CPAP backup and high-flow without rescue CPAP backup (as sole primary support) were analyzed by using the hospital cost of inpatient stay in a tertiary center and the rates of endotracheal intubation and mechanical ventilation during admission. Hospital inpatient cost records for 435 infants enrolled in all Australian centers were obtained. With "rescue" CPAP backup, an incremental cost-effectiveness ratio was estimated of A$179 000 (US$123 000) per ventilation avoided if CPAP was used compared with high flow. Without rescue CPAP backup, cost per ventilation avoided was A$7000 (US$4800) if CPAP was used compared with high flow. As sole primary support, CPAP is highly likely to be cost-effective compared with high flow. Neonatal units choosing to use only one device should apply CPAP as primary respiratory support. Compared with high-flow with rescue CPAP backup, CPAP is unlikely to be cost-effective if willingness to pay per ventilation avoided is less than A$179 000 (US$123 000). Copyright © 2018 Elsevier Inc. All rights reserved.

  19. What Teachers Want: Supporting Primary School Teachers in Teaching Science

    ERIC Educational Resources Information Center

    Fitzgerald, Angela; Schneider, Katrin

    2013-01-01

    Impending change can provide us with the opportunity to rethink and renew the things that we do. The first phase of the Australian Curriculum implementation offers primary school teachers the chance to examine their approaches to science learning and teaching. This paper focuses on the perceptions of three primary school teachers regarding what…

  20. Use of Social Support during Communication about Sickle Cell Carrier Status

    PubMed Central

    Bradford, Lisa; Roedl, Sara J.; Christopher, Stephanie A.; Farrell, Michael H.

    2012-01-01

    Objective To examine the use of social support behaviors by primary care providers during delivery of positive newborn screening results for Sickle Cell Anemia carrier status. Methods Transcripts from 125 primary care providers who conveyed Sickle Cell Anemia carrier status to standardized parents were content analyzed using categories derived from Cutrona and Suhr’s social support taxonomy. Frequencies and cross-tabulation matrices were calculated to study providers’ social support utilization. Results Results showed most primary care providers (80%) incorporate social support behaviors into delivery of Sickle Cell Anemia carrier results and most frequently employed social network (61.6%) and informational support (38.4%) behaviors. Providers used tangible aid (8%), esteem (1.6%), and emotional support (9.6%) behaviors less frequently. Conclusion Cutrona and Suhr’s taxonomy may be a useful tool for assessing supportive communication during the delivery of Sickle Cell Anemia carrier status and could be incorporated into population scale assessments of communication quality assurance. Practice Implications Primary care providers may need training in how to adapt supportive behaviors to parents’ needs during communication of Sickle Cell Anemia carrier status. They also may benefit from specific training about how to use esteem and emotional support. PMID:22658247

  1. Primary alcohols activate human TRPA1 channel in a carbon chain length-dependent manner.

    PubMed

    Komatsu, Tomoko; Uchida, Kunitoshi; Fujita, Fumitaka; Zhou, Yiming; Tominaga, Makoto

    2012-04-01

    Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is mainly expressed in primary nociceptive neurons. TRPA1 is activated by a variety of noxious stimuli, including cold temperatures, pungent compounds such as mustard oil and cinnamaldehyde, and intracellular alkalization. Here, we show that primary alcohols, which have been reported to cause skin, eye or nasal irritation, activate human TRPA1 (hTRPA1). We measured intracellular Ca(2+) changes in HEK293 cells expressing hTRPA1 induced by 1 mM primary alcohols. Higher alcohols (1-butanol to 1-octanol) showed Ca(2+) increases proportional to the carbon chain length. In whole-cell patch-clamp recordings, higher alcohols (1-hexanol to 1-octanol) activated hTRPA1 and the potency increased with the carbon chain length. Higher alcohols evoked single-channel opening of hTRPA1 in an inside-out configuration. In addition, cysteine at 665 in the N terminus and histidine at 983 in the C terminus were important for hTRPA1 activation by primary alcohols. Furthermore, straight-chain secondary alcohols increased intracellular Ca(2+) concentrations in HEK293 cells expressing hTRPA1, and both primary and secondary alcohols showed hTRPA1 activation activities that correlated highly with their octanol/water partition coefficients. On the other hand, mouse TRPA1 did not show a strong response to 1-hexanol or 1-octanol, nor did these alcohols evoke significant pain in mice. We conclude that primary and secondary alcohols activate hTRPA1 in a carbon chain length-dependent manner. TRPA1 could be a sensor of alcohols inducing skin, eye and nasal irritation in human.

  2. Primary hyperoxaluria type 1 with a novel mutation.

    PubMed

    Sethi, Sidharth Kumar; Waterham, Hans R; Sharma, Sonika; Sharma, Alok; Hari, Pankaj; Bagga, Arvind

    2009-02-01

    Primary hyperoxaluria type 1 [PH1] is an autosomal recessive disorder caused by a deficiency of alanine-glyoxylate aminotransferase AGT, which is encoded by the AGXT gene. We report an Indian family with two affected siblings having a novel mutation in the AGXT gene inherited from the parents. The index case progressed to end stage renal disease at 5 months of age. His 4 month old sibling is presently under follow up with preserved renal function.

  3. Study on lithium/air secondary batteries-Stability of NASICON-type lithium ion conducting glass-ceramics with water

    NASA Astrophysics Data System (ADS)

    Hasegawa, Satoshi; Imanishi, Nobuyuki; Zhang, Tao; Xie, Jian; Hirano, Atsushi; Takeda, Yasuo; Yamamoto, Osamu

    The water stability of the fast lithium ion conducting glass-ceramic electrolyte, Li 1+ x+ yAl xTi 2- xSi yP 3- yO 12 (LATP), has been examined in distilled water, and aqueous solutions of LiNO 3, LiCl, LiOH, and HCl. This glass-ceramics are stable in aqueous LiNO 3 and aqueous LiCl, and unstable in aqueous 0.1 M HCl and 1 M LiOH. In distilled water, the electrical conductivity slightly increases as a function of immersion time in water. The Li-Al/Li 3- xPO 4- yN y/LATP/aqueous 1 M LiCl/Pt cell, where lithium phosphors oxynitrides Li 3- xPO 4- yN y (LiPON) are used to protect the direct reaction of Li and LATP, shows a stable open circuit voltage (OCV) of 3.64 V at 25 °C, and no cell resistance change for 1 week. Lithium phosphors oxynitride is effectively used as a protective layer to suppress the reaction between the LATP and Li metal. The water-stable Li/LiPON/LATP system can be used in Li/air secondary batteries with the air electrode containing water.

  4. Meeting the needs? Perceived support of a nurse-led lifestyle programme for young adults with mental illness in a primary health-care setting.

    PubMed

    Rönngren, Ylva; Björk, Annette; Kristiansen, Lisbeth; Haage, David; Enmarker, Ingela; Audulv, Åsa

    2018-02-01

    Being a young adult with mental illness challenges all aspects of health, including an increased risk for developing lifestyle-related diseases. There is a lack of lifestyle programmes in primary health care that target physical, mental, and social needs for young adults with mental illness. The aim of the present study was to describe the experiences of young adults with mental illness receiving support from a nurse-led lifestyle programme, and how this support was related to their life context, including challenges and coping strategies. Two focus groups and six individual interviews were performed with 13 young adults (16-25 years), and analysed using a qualitative content analysis. The findings showed that the young adults experienced challenges in their daily lives, including psychiatric symptoms, lack of social understanding, and loneliness. The study indicated that the programme could support lifestyle habits with its components of supportive interpersonal relationships, awareness of coping strategies, understanding of health and illness, and cognitive support (e.g. schedules and reminders). However, the programme could not meet everyone's needs for new social relationships or more comprehensive support. Even so, this nurse-led programme provides health information-management strategies that could easily be integrated in a primary health-care setting. © 2017 Australian College of Mental Health Nurses Inc.

  5. 12. TROJAN MILL, INTERIOR SHOWING PRIMARY MILL No. 1 (MONADNOCK ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. TROJAN MILL, INTERIOR SHOWING PRIMARY MILL No. 1 (MONADNOCK CHILEAN) FROM EAST, c. 1912. ELEVATOR No. 1 ADJACENT TO MILL. CREDIT WR. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  6. Rates of Anovulation in Adolescents and Young Adults with Moderate to Severe Primary Dysmenorrhea and Those without Primary Dysmenorrhea.

    PubMed

    Seidman, Laura C; Brennan, Kathleen M; Rapkin, Andrea J; Payne, Laura A

    2018-04-01

    To evaluate rates of presumptive anovulation in eumenorrheic adolescents and young adults with moderate to severe primary dysmenorrhea and those without primary dysmenorrhea. Participants completed luteinizing hormone surge ovulation predictor test kits. Anovulatory cycles were defined by never receiving a positive result before the next menstrual period; participants were grouped as anovulatory if they experienced at least 1 anovulatory cycle during study participation. Participants rated daily level of menstrual pain on a 0-10 numeric rating scale. A university-based clinical research laboratory. Thirty-nine adolescents and young adults (ages 16-24) with primary dysmenorrhea and 52 age-matched control girls. Rates of presumptive anovulation. One hundred sixty-eight cycles were monitored, 29.8% (N = 50) of which were anovulatory (37.1% [39/105] vs 17.5% [11/63] of cycles in control and dysmenorrhea groups, respectively). During study participation, control girls were significantly more likely to have had at least 1 anovulatory cycle than were girls with primary dysmenorrhea (44.2% [23/52] vs 17.9% [7/39] of participants, respectively; P < .01). Cycle length and number of bleeding days between ovulatory and anovulatory cycles were similar. The primary dysmenorrhea group's maximum menstrual pain ratings did not differ between ovulatory and anovulatory cycles (4.77 and 4.36, respectively; P > .05). Our data support previous findings of increased rates of ovulation in primary dysmenorrhea. However, menstruation after anovulatory cycles can be as painful as menstruation after ovulatory cycles. These data support the idea that regular menses do not necessarily indicate that a normal ovulatory cycle has occurred. Previous implications that ovulation is necessary for the development of substantial menstrual pain are incomplete. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

  7. Applying STOPP Guidelines in Primary Care Through Electronic Medical Record Decision Support: Randomized Control Trial Highlighting the Importance of Data Quality.

    PubMed

    Price, Morgan; Davies, Iryna; Rusk, Raymond; Lesperance, Mary; Weber, Jens

    2017-06-15

    Potentially Inappropriate Prescriptions (PIPs) are a common cause of morbidity, particularly in the elderly. We sought to understand how the Screening Tool of Older People's Prescriptions (STOPP) prescribing criteria, implemented in a routinely used primary care Electronic Medical Record (EMR), could impact PIP rates in community (non-academic) primary care practices. We conducted a mixed-method, pragmatic, cluster, randomized control trial in research naïve primary care practices. Phase 1: In the randomized controlled trial, 40 fully automated STOPP rules were implemented as EMR alerts during a 16-week intervention period. The control group did not receive the 40 STOPP rules (but received other alerts). Participants were recruited through the OSCAR EMR user group mailing list and in person at user group meetings. Results were assessed by querying EMR data PIPs. EMR data quality probes were included. Phase 2: physicians were invited to participate in 1-hour semi-structured interviews to discuss the results. In the EMR, 40 STOPP rules were successfully implemented. Phase 1: A total of 28 physicians from 8 practices were recruited (16 in intervention and 12 in control groups). The calculated PIP rate was 2.6% (138/5308) (control) and 4.11% (768/18,668) (intervention) at baseline. No change in PIPs was observed through the intervention (P=.80). Data quality probes generally showed low use of problem list and medication list. Phase 2: A total of 5 physicians participated. All the participants felt that they were aware of the alerts but commented on workflow and presentation challenges. The calculated PIP rate was markedly less than the expected rate found in literature (2.6% and 4.0% vs 20% in literature). Data quality probes highlighted issues related to completeness of data in areas of the EMR used for PIP reporting and by the decision support such as problem and medication lists. Users also highlighted areas for better integration of STOPP guidelines with

  8. Phenotypes in siblings with homozygous mutations of TRAPPC9 and/or MCPH1 support a bifunctional model of MCPH1.

    PubMed

    Duerinckx, Sarah; Meuwissen, Marije; Perazzolo, Camille; Desmyter, Laurence; Pirson, Isabelle; Abramowicz, Marc

    2018-04-24

    Autosomal recessive intellectual disability (ARID) is vastly heterogeneous. Truncating mutations of TRAPPC9 were reported in 8 ARID families. Autosomal recessive primary microcephaly (MCPH) represents another subgroup of ARID, itself very heterogeneous, where the size of the brain is very small since birth. MCPH1 plays a role at the centrosome via a BRCT1 domain, and in DNA Damage Repair (DDR) via BRCT2 and BRCT3, and it is not clear which of these two mechanisms causes MCPH in man. We studied the phenotype and sequenced the exome in two siblings with MCPH and their unaffected sister. Homozygous mutations of TRAPPC9 (p.Leu178Pro) and of MCPH1 (p.Arg741X) were found in both affected siblings. Brain MRI showed anomalies previously associated with TRAPPC9 defects, supporting the implication of TRAPPC9 in the phenotype. Importantly, the asymptomatic sister with normal head size was homozygous for the MCPH1 truncating mutation and heterozygous for the TRAPPC9 mutation. The affected siblings represent the first ARID cases with a TRAPPC9 missense mutation and with microcephaly of prenatal onset of. Furthermore, their unaffected sister represents strong evidence that the lack of MCPH1 BRCT3 domain does not cause MCPH in man, supporting a bifunctional model of MCPH1 where the centrosomal function is involved in brain volumic development and not the DDR function. © 2018 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.

  9. Identification of new mutations in primary hyperoxaluria type 1 (PH1).

    PubMed

    von Schnakenburg, C; Rumsby, G

    1998-01-01

    Primary hyperoxaluria type 1 (PH1) is caused by deficiency of the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). The AGXT gene, which codes for the 392 amino acid protein, has been mapped to chromosome 2q37.3. In order to identify new mutations in the AGXT gene we studied 79 PH1 patients using single strand conformation polymorphism analysis. In addition to a cluster of new mutations in exon 7 we report five novel mutations in exons 2, 4, 5, 9 and 10. These are T444C, G640A, G690A, 1008-1010delGCG and G1171A. These five new mutations contribute to our knowledge of the AGXT gene. Their possible consequences for PH1 phenotype and enzyme activity are discussed.

  10. Evaluating the Implementation and Feasibility of a Web-Based Tool to Support Timely Identification and Care for the Frail Population in Primary Healthcare Settings.

    PubMed

    Lawson, Beverley; Sampalli, Tara; Wood, Stephanie; Warner, Grace; Moorhouse, Paige; Gibson, Rick; Mallery, Laurie; Burge, Fred; Bedford, Lisa G

    2017-03-07

    Understanding and addressing the needs of frail persons is an emerging health priority for Nova Scotia and internationally. Primary healthcare (PHC) providers regularly encounter frail persons in their daily clinical work. However, routine identification and measurement of frailty is not standard practice and, in general, there is a lack of awareness about how to identify and respond to frailty. A web-based tool called the Frailty Portal was developed to aid in identifying, screening, and providing care for frail patients in PHC settings. In this study, we will assess the implementation feasibility and impact of the Frailty Portal to: (1) support increased awareness of frailty among providers and patients, (2) identify the degree of frailty within individual patients, and (3) develop and deliver actions to respond to frailtyl in community PHC practice. This study will be approached using a convergent mixed method design where quantitative and qualitative data are collected concurrently, in this case, over a 9-month period, analyzed separately, and then merged to summarize, interpret and produce a more comprehensive understanding of the initiative's feasibility and scalability. Methods will be informed by the 'Implementing the Frailty Portal in Community Primary Care Practice' logic model and questions will be guided by domains and constructs from an implementation science framework, the Consolidated Framework for Implementation Research (CFIR). The 'Frailty Portal' aims to improve access to, and coordination of, primary care services for persons experiencing frailty. It also aims to increase primary care providers' ability to care for patients in the context of their frailty. Our goal is to help optimize care in the community by helping community providers gain the knowledge they may lack about frailty both in general and in their practice, support improved identification of frailty with the use of screening tools, offer evidence based severity-specific care goals

  11. Quality tools and resources to support organisational improvement integral to high-quality primary care: a systematic review of published and grey literature.

    PubMed

    Janamian, Tina; Upham, Susan J; Crossland, Lisa; Jackson, Claire L

    2016-04-18

    To conduct a systematic review of the literature to identify existing online primary care quality improvement tools and resources to support organisational improvement related to the seven elements in the Primary Care Practice Improvement Tool (PC-PIT), with the identified tools and resources to progress to a Delphi study for further assessment of relevance and utility. Systematic review of the international published and grey literature. CINAHL, Embase and PubMed databases were searched in March 2014 for articles published between January 2004 and December 2013. GreyNet International and other relevant websites and repositories were also searched in March-April 2014 for documents dated between 1992 and 2012. All citations were imported into a bibliographic database. Published and unpublished tools and resources were included in the review if they were in English, related to primary care quality improvement and addressed any of the seven PC-PIT elements of a high-performing practice. Tools and resources that met the eligibility criteria were then evaluated for their accessibility, relevance, utility and comprehensiveness using a four-criteria appraisal framework. We used a data extraction template to systematically extract information from eligible tools and resources. A content analysis approach was used to explore the tools and resources and collate relevant information: name of the tool or resource, year and country of development, author, name of the organisation that provided access and its URL, accessibility information or problems, overview of each tool or resource and the quality improvement element(s) it addresses. If available, a copy of the tool or resource was downloaded into the bibliographic database, along with supporting evidence (published or unpublished) on its use in primary care. This systematic review identified 53 tools and resources that can potentially be provided as part of a suite of tools and resources to support primary care practices in

  12. Investigations of systems ThO 2-MO 2-P 2O 5 (M=U, Ce, Zr, Pu). Solid solutions of thorium-uranium (IV) and thorium-plutonium (IV) phosphate-diphosphates

    NASA Astrophysics Data System (ADS)

    Dacheux, N.; Podor, R.; Brandel, V.; Genet, M.

    1998-02-01

    In the framework of nuclear waste management aiming at the research of a storage matrix, the chemistry of thorium phosphates has been completely re-examined. In the ThO 2-P 2O 5 system a new compound thorium phosphate-diphosphate Th 4(PO 4) 4P 2O 7 has been synthesized. The replacement of Th 4+ by a smaller cation like U 4+ and Pu 4+ in the thorium phosphate-diphosphate (TPD) lattice has been achieved. Th 4- xU x(PO 4) 4P 2O 7 and Th 4- xPu x(PO 4) 4P 2O 7 solid solutions have been synthesized through wet and dry processes with 0< x<3.0 for uranium and 0< x<1.0 for plutonium. From the variation of the unit cell parameters, an upper x value equal to 1.67 has been estimated for the thorium-plutonium (IV) phosphate-diphosphate solid solutions. Two other tetravalent cations, Ce 4+ and Zr 4+, cannot be incorporated in the TPD lattice: cerium (IV) because of its reduction into Ce (III) at high temperature, and zirconium probably because of its too small radius compared to thorium.

  13. Ulcerative colitis outpatient management: development and evaluation of tools to support primary care practitioners.

    PubMed

    Bennett, A L; Buckton, S; Lawrance, I; Leong, R W; Moore, G; Andrews, J M

    2015-12-01

    Current models of care for ulcerative colitis (UC) across healthcare systems are inconsistent with a paucity of existing guidelines or supportive tools for outpatient management. This study aimed to produce and evaluate evidence-based outpatient management tools for UC to guide primary care practitioners and patients in clinical decision-making. Three tools were developed after identifying current gaps in the provision of healthcare services for patients with UC at a Clinical Insights Meeting in 2013. Draft designs were further refined through consultation and consolidation of feedback by the steering committee. Final drafts were developed following feasibility testing in three key stakeholder groups (gastroenterologists, general practitioners and patients) by questionnaire. The tools were officially launched into mainstream use in Australia in 2014. Three quarters of all respondents liked the layout and content of each tool. Minimal safety concerns were aired and those, along with pieces of information that were felt to be omitted, that were reviewed by the steering committee and incorporated into the final documents. The majority (over 80%) of respondents felt that the tools would be useful and would improve outpatient management of UC. Evidence-based outpatient clinical management tools for UC can be developed. The concept and end-product have been well received by all stakeholder groups. These tools should support non-specialist clinicians to optimise UC management and empower patients by facilitating them to safely self-manage and identify when medical support is needed. © 2015 Royal Australasian College of Physicians.

  14. Use of a computerized decision support system for primary and secondary prevention of work-related MSD disability.

    PubMed

    Womack, Sarah K; Armstrong, Thomas J

    2005-09-01

    The present study evaluates the effectiveness of a decision support system used to evaluate and control physical job stresses and prevent re-injury of workers who have experienced or are concerned about work-related musculoskeletal disorders. The software program is a database that stores detailed job information such as standardized work data, videos, and upper-extremity physical stress ratings for over 400 jobs in the plant. Additionally, the database users were able to record comments about the jobs and related control issues. The researchers investigated the utility and effectiveness of the software by analyzing its use over a 20-month period. Of the 197 comments entered by the users, 25% pertained to primary prevention, 75% pertained to secondary prevention, and 94 comments (47.7%) described ergonomic interventions. Use of the software tool improved primary and secondary prevention by improving the quality and efficiency of the ergonomic job analysis process.

  15. Differentiation of Enhancing Glioma and Primary Central Nervous System Lymphoma by Texture-Based Machine Learning.

    PubMed

    Alcaide-Leon, P; Dufort, P; Geraldo, A F; Alshafai, L; Maralani, P J; Spears, J; Bharatha, A

    2017-06-01

    Accurate preoperative differentiation of primary central nervous system lymphoma and enhancing glioma is essential to avoid unnecessary neurosurgical resection in patients with primary central nervous system lymphoma. The purpose of the study was to evaluate the diagnostic performance of a machine-learning algorithm by using texture analysis of contrast-enhanced T1-weighted images for differentiation of primary central nervous system lymphoma and enhancing glioma. Seventy-one adult patients with enhancing gliomas and 35 adult patients with primary central nervous system lymphomas were included. The tumors were manually contoured on contrast-enhanced T1WI, and the resulting volumes of interest were mined for textural features and subjected to a support vector machine-based machine-learning protocol. Three readers classified the tumors independently on contrast-enhanced T1WI. Areas under the receiver operating characteristic curves were estimated for each reader and for the support vector machine classifier. A noninferiority test for diagnostic accuracy based on paired areas under the receiver operating characteristic curve was performed with a noninferiority margin of 0.15. The mean areas under the receiver operating characteristic curve were 0.877 (95% CI, 0.798-0.955) for the support vector machine classifier; 0.878 (95% CI, 0.807-0.949) for reader 1; 0.899 (95% CI, 0.833-0.966) for reader 2; and 0.845 (95% CI, 0.757-0.933) for reader 3. The mean area under the receiver operating characteristic curve of the support vector machine classifier was significantly noninferior to the mean area under the curve of reader 1 ( P = .021), reader 2 ( P = .035), and reader 3 ( P = .007). Support vector machine classification based on textural features of contrast-enhanced T1WI is noninferior to expert human evaluation in the differentiation of primary central nervous system lymphoma and enhancing glioma. © 2017 by American Journal of Neuroradiology.

  16. Integrated Clinical Decision Support Systems Promote Absolute Cardiovascular Risk Assessment: An Important Primary Prevention Measure in Aboriginal and Torres Strait Islander Primary Health Care.

    PubMed

    Matthews, Veronica; Burgess, Christopher P; Connors, Christine; Moore, Elizabeth; Peiris, David; Scrimgeour, David; Thompson, Sandra C; Larkins, Sarah; Bailie, Ross

    2017-01-01

    Aboriginal and Torres Strait Islander Australians experience a greater burden of disease compared to non-Indigenous Australians. Around one-fifth of the health disparity is caused by cardiovascular disease (CVD). Despite the importance of absolute cardiovascular risk assessment (CVRA) as a screening and early intervention tool, few studies have reported its use within the Australian Indigenous primary health care (PHC) sector. This study utilizes data from a large-scale quality improvement program to examine variation in documented CVRA as a primary prevention strategy for individuals without prior CVD across four Australian jurisdictions. We also examine the proportion with elevated risk and follow-up actions recorded. We undertook cross-sectional analysis of 2,052 client records from 97 PHC centers to assess CVRA in Indigenous adults aged ≥20 years with no recorded chronic disease diagnosis (2012-2014). Multilevel regression was used to quantify the variation in CVRA attributable to health center and client level factors. The main outcome measure was the proportion of eligible adults who had CVRA recorded. Secondary outcomes were the proportion of clients with elevated risk that had follow-up actions recorded. Approximately 23% ( n  = 478) of eligible clients had documented CVRA. Almost all assessments (99%) were conducted in the Northern Territory. Within this jurisdiction, there was wide variation between centers in the proportion of clients with documented CVRA (median 38%; range 0-86%). Regression analysis showed health center factors accounted for 48% of the variation. Centers with integrated clinical decision support systems were more likely to document CVRA (OR 21.1; 95% CI 5.4-82.4; p  < 0.001). Eleven percent ( n  = 53) of clients were found with moderate/high CVD risk, of whom almost one-third were under 35 years ( n  = 16). Documentation of follow-up varied with respect to the targeted risk factor. Fewer than 30% with abnormal

  17. Tobacco use disorder treatment in primary care

    PubMed Central

    Kunyk, Diane; Els, Charl; Papadakis, Sophia; Selby, Peter

    2014-01-01

    Abstract Objective To test a team-based, site-specific, multicomponent clinical system pathway designed for enhancing tobacco use disorder treatment by primary care physicians. Design A prospective cohort study. Setting Sixty primary care sites in Alberta. Participants A convenience sample of 198 primary care physicians from the population of 2857. Main outcome measures Data collection occurred between September 2010 and February 2012 on 3 distinct measures. Twenty-four weeks after the intervention, audits of the primary care practices assessed the adoption and sustainability of 10 tobacco clinical system pathway components, a survey measured changes in physicians’ treatment intentions, and patient chart reviews examined changes in physicians’ consistency with the treatment algorithm. Results The completion rate by physicians was 89.4%. An intention-to-treat approach was undertaken for statistical analysis. Intervention uptake was demonstrated by positive changes at 4 weeks in how many of the 10 clinical system measures were performed (mean [SD] = 4.22 [1.60] vs 8.57 [1.46]; P < .001). Physicians demonstrated significant favourable changes in 9 of the 12 measures of treatment intention (P < .05). The 18 282 chart reviews documented significant increases in 6 of the 8 algorithm components. Conclusion Our findings suggest that the provision of a tobacco clinical system pathway that incorporates other members of the health care team and builds on existing office infrastructures will support positive and sustainable changes in tobacco use disorder treatment by physicians in primary care. This study reaffirms the substantive and important role of supporting how treatment is delivered in physicians’ practices. PMID:25022640

  18. An outbreak of influenza A(H1N1)pdm09 virus in a primary school in Vietnam.

    PubMed

    Duong, Tran Nhu; Tho, Nguyen Thi Thi; Hien, Nguyen Tran; Olowokure, Babatunde

    2015-10-15

    Despite school pupils being at greatest risk during the 2009 influenza pandemic there are limited data on outbreaks of influenza A(H1N1)pdm09 in primary schools in South-East Asia. This prospective cohort study describes an outbreak of influenza A(H1N1)pdm09 in a primary school in rural Vietnam. In total 103 cases of influenza-like illness were found among the 407 pupils in the primary school. Ten of these were laboratory confirmed cases of influenza A(H1N1)pdm09 virus. The overall attack rate (AR) was 25% (103/407), and was highest (41%) in grade 4 pupils, where the outbreak started. All cases in the outbreak presented with a mild and self-limiting illness, acute respiratory symptoms and fever. Public health interventions to contain the outbreak could explain the lower attack rates in other grades. Ill pupils were asked to stay at home. Oseltamivir was not given to pupils and the school did not close during the outbreak. The last detected case occurred 12 days following identification of the first case. This is the first report of an outbreak of influenza A(H1N1)pdm09 among pupils in a primary school in Vietnam. High attack rates in Grade 4 pupils suggest shared activities contributed to transmission. The public health response using non-pharmaceutical measures may have played a role in ending the outbreak.

  19. Primary outcomes reporting in trials of paediatric type 1 diabetes mellitus: a systematic review.

    PubMed

    Khanpour Ardestani, Samaneh; Karkhaneh, Mohammad; Yu, Hai Chuan; Hydrie, Muhammad Zafar Iqbal; Vohra, Sunita

    2017-12-19

    Our objective was to systematically review randomised clinical trials (RCTs) of paediatric type 1 diabetes mellitus (T1DM) to assess reporting of (1) primary outcome, (2) outcome measurement properties and (3) presence or absence of adverse events. Electronic searches in MEDLINE, EMBASE, CINAHL, Cochrane SR and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were undertaken. The search period was between 2001 and 2017. English-language RCTs on children younger than 21 years with T1DM were selected. We excluded studies of diagnostic or screening tools, multiple phase studies, protocols, and follow-up or secondary analysis of data. Of 11 816 unique references, 231 T1DM RCTs were included. Of total 231 included studies, 117 (50.6%) trials failed to report what their primary outcome was. Of 114 (49.4%) studies that reported primary outcome, 88 (77.2%) reported one and 26 (22.8%) more than one primary outcomes. Of 114 studies that clearly stated their primary outcome, 101 (88.6%) used biological/physiological measurements and 13 (11.4%) used instruments (eg, questionnaires, scales, etc) to measure their primary outcome; of these, 12 (92.3%) provided measurement properties or related citation. Of the 231 included studies, 105 (45.5%) reported that adverse events occurred, 39 (16.9%) reported that no adverse events were identified and 87 (37.7%) did not report on the presence or absence of adverse events. Despite tremendous efforts to improve reporting of clinical trials, clear reporting of primary outcomes of RCTs for paediatric T1DM is still lacking. Adverse events due to DM interventions were often not reported in the included trials. Transparent reporting of primary outcome, validity of measurement tools and adverse events need to be improved in paediatric T1DM trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise

  20. The Nitrate Transporter MtNPF6.8 (MtNRT1.3) Transports Abscisic Acid and Mediates Nitrate Regulation of Primary Root Growth in Medicago truncatula1[W

    PubMed Central

    Pellizzaro, Anthoni; Clochard, Thibault; Cukier, Caroline; Bourdin, Céline; Juchaux, Marjorie; Montrichard, Françoise; Thany, Steeve; Raymond, Valérie; Planchet, Elisabeth; Morère-Le Paven, Marie-Christine

    2014-01-01

    Elongation of the primary root during postgermination of Medicago truncatula seedlings is a multigenic trait that is responsive to exogenous nitrate. A quantitative genetic approach suggested the involvement of the nitrate transporter MtNPF6.8 (for Medicago truncatula NITRATE TRANSPORTER1/PEPTIDE TRANSPORTER Family6.8) in the inhibition of primary root elongation by high exogenous nitrate. In this study, the inhibitory effect of nitrate on primary root elongation, via inhibition of elongation of root cortical cells, was abolished in npf6.8 knockdown lines. Accordingly, we propose that MtNPF6.8 mediates nitrate inhibitory effects on primary root growth in M. truncatula. pMtNPF6.8:GUS promoter-reporter gene fusion in Agrobacterium rhizogenes-generated transgenic roots showed the expression of MtNPF6.8 in the pericycle region of primary roots and lateral roots, and in lateral root primordia and tips. MtNPF6.8 expression was insensitive to auxin and was stimulated by abscisic acid (ABA), which restored the inhibitory effect of nitrate in npf6.8 knockdown lines. It is then proposed that ABA acts downstream of MtNPF6.8 in this nitrate signaling pathway. Furthermore, MtNPF6.8 was shown to transport ABA in Xenopus spp. oocytes, suggesting an additional role of MtNPF6.8 in ABA root-to-shoot translocation. 15NO3−-influx experiments showed that only the inducible component of the low-affinity transport system was affected in npf6.8 knockdown lines. This indicates that MtNPF6.8 is a major contributor to the inducible component of the low-affinity transport system. The short-term induction by nitrate of the expression of Nitrate Reductase1 (NR1) and NR2 (genes that encode two nitrate reductase isoforms) was greatly reduced in the npf6.8 knockdown lines, supporting a role of MtNPF6.8 in the primary nitrate response in M. truncatula. PMID:25367858

  1. CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma

    PubMed Central

    Wadkin, James C. R.; Patten, Daniel A.; Kamarajah, Sivesh K.; Shepherd, Emma L.; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H.; Weston, Chris J.

    2017-01-01

    CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

  2. A de novo mutation in the AGXT gene causing primary hyperoxaluria type 1.

    PubMed

    Williams, Emma L; Kemper, Markus J; Rumsby, Gill

    2006-09-01

    Primary hyperoxaluria type 1 is caused by mutations in the alanine-glyoxylate aminotransferase (AGXT) gene. In cases in which no mutation was identified, linkage analysis can be used to confirm or exclude the diagnosis in other siblings. We present a family in which a sibling of the index case predicted to have primary hyperoxaluria type 1 by means of linkage analysis failed to show hyperoxaluria during the following 7 years, putting the diagnosis into question. Whole-gene sequence analysis identified 2 causative mutations in the index case, of which only 1, c.646A (Gly216Arg), was inherited. The other sequence change, c.33_34insC, was a de novo mutation occurring on the paternal allele. This particular mutation is a relatively common cause of primary hyperoxaluria type 1. It occurs in a run of 8 cytosines and therefore potentially is susceptible to polymerase slippage. This case illustrates 2 important points. First, biochemical confirmation of a genetic diagnosis should always be made in siblings diagnosed by using genetic tests. Second, de novo mutations should be considered as a potential, albeit rare, cause of primary hyperoxaluria type 1.

  3. The Coming Primary Care Revolution.

    PubMed

    Ellner, Andrew L; Phillips, Russell S

    2017-04-01

    The United States has the most expensive, technologically advanced, and sub-specialized healthcare system in the world, yet it has worse population health status than any other high-income country. Rising healthcare costs, high rates of waste, the continued trend towards chronic non-communicable disease, and the growth of new market entrants that compete with primary care services have set the stage for fundamental change in all of healthcare, driven by a revolution in primary care. We believe that the coming primary care revolution ought to be guided by the following design principles: 1) Payment must adequately support primary care and reward value, including non-visit-based care. 2) Relationships will serve as the bedrock of value in primary care, and will increasingly be fostered by teams, improved clinical operations, and technology, with patients and non-physicians assuming an ever-increasing role in most aspects of healthcare. 3) Generalist physicians will increasingly focus on high-acuity and high-complexity presentations, and primary care teams will increasingly manage conditions that specialists managed in the past. 4) Primary care will refocus on whole-person care, and address health behaviors as well as vision, hearing, dental, and social services. Design based on these principles should lead to higher-value healthcare, but will require new approaches to workforce training.

  4. A randomized-control trial for the teachers' diploma programme on psychosocial care, support and protection in Zambian government primary schools.

    PubMed

    Kaljee, Linda; Zhang, Liying; Langhaug, Lisa; Munjile, Kelvin; Tembo, Stephen; Menon, Anitha; Stanton, Bonita; Li, Xiaoming; Malungo, Jacob

    2017-04-01

    Orphaned and vulnerable children (OVC) experience poverty, stigma, and abuse resulting in poor physical, emotional, and psychological outcomes. The Teachers' Diploma Programme on Psychosocial Care, Support, and Protection is a child-centered 15-month long-distance learning program focused on providing teachers with the knowledge and skills to enhance their school environments, foster psychosocial support, and facilitate school-community relationships. A randomized controlled trial was implemented in 2013-2014. Both teachers (n=325) and students (n=1378) were assessed at baseline and 15-months post-intervention from randomly assigned primary schools in Lusaka and Eastern Provinces, Zambia. Multilevel linear mixed models (MLM) indicate positive significant changes for intervention teachers on outcomes related to self-care, teaching resources, safety, social support, and gender equity. Positive outcomes for intervention students related to future orientation, respect, support, safety, sexual abuse, and bullying. Outcomes support the hypothesis that teachers and students benefit from a program designed to enhance teachers' psychosocial skills and knowledge.

  5. Comprehensive Evaluation of Programmed Death-Ligand 1 Expression in Primary and Metastatic Prostate Cancer.

    PubMed

    Haffner, Michael C; Guner, Gunes; Taheri, Diana; Netto, George J; Palsgrove, Doreen N; Zheng, Qizhi; Guedes, Liana Benevides; Kim, Kunhwa; Tsai, Harrison; Esopi, David M; Lotan, Tamara L; Sharma, Rajni; Meeker, Alan K; Chinnaiyan, Arul M; Nelson, William G; Yegnasubramanian, Srinivasan; Luo, Jun; Mehra, Rohit; Antonarakis, Emmanuel S; Drake, Charles G; De Marzo, Angelo M

    2018-06-01

    Antibodies targeting the programmed cell death protein 1/programmed death-ligand 1 (PD-L1) interaction have shown clinical activity in multiple cancer types. PD-L1 protein expression is a clinically validated predictive biomarker of response for such therapies. Prior studies evaluating the expression of PD-L1 in primary prostate cancers have reported highly variable rates of PD-L1 positivity. In addition, limited data exist on PD-L1 expression in metastatic castrate-resistant prostate cancer (mCRPC). Here, we determined PD-L1 protein expression by immunohistochemistry using a validated PD-L1-specific antibody (SP263) in a large and representative cohort of primary prostate cancers and prostate cancer metastases. The study included 539 primary prostate cancers comprising 508 acinar adenocarcinomas, 24 prostatic duct adenocarcinomas, 7 small-cell carcinomas, and a total of 57 cases of mCRPC. PD-L1 positivity was low in primary acinar adenocarcinoma, with only 7.7% of cases showing detectable PD-L1 staining. Increased levels of PD-L1 expression were noted in 42.9% of small-cell carcinomas. In mCRPC, 31.6% of cases showed PD-L1-specific immunoreactivity. In conclusion, in this comprehensive evaluation of PD-L1 expression in prostate cancer, PD-L1 expression is rare in primary prostate cancers, but increased rates of PD-L1 positivity were observed in mCRPC. These results will be important for the future clinical development of programmed cell death protein 1/PD-L1-targeting therapies in prostate cancer. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  6. Supporting Patient Behavior Change: Approaches Used by Primary Care Clinicians Whose Patients Have an Increase in Activation Levels.

    PubMed

    Greene, Jessica; Hibbard, Judith H; Alvarez, Carmen; Overton, Valerie

    2016-03-01

    We aimed to identify the strategies used to support patient behavior change by clinicians whose patients had an increase in patient activation. This mixed methods study was conducted in collaboration with Fairview Health Services, a Pioneer Accountable Care Organization. We aggregated data on the change in patient activation measure (PAM) score for 7,144 patients to the primary care clinician level. We conducted in-depth interviews with 10 clinicians whose patients' score increases were among the highest and 10 whose patients' score changes were among the lowest. Transcripts of the interviews were analyzed to identify key strategies that differentiated the clinicians whose patients had top PAM change scores. Clinicians whose patients had relatively large activation increases reported using 5 key strategies to support patient behavior change (mean = 3.9 strategies): emphasizing patient ownership; partnering with patients; identifying small steps; scheduling frequent follow-up visits to cheer successes, problem solve, or both; and showing caring and concern for patients. Clinicians whose patients had lesser change in activation were far less likely to describe using these approaches (mean = 1.3 strategies). Most clinicians, regardless of group, reported developing their own approach to support patient behavior change. Those whose patients showed high activation change reported spending more time with patients on counseling and education than did those whose patients showed less improvement in activation. Clinicians vary in the strategies they use to promote behavior change and in the time spent with patients on such activities. The 5 key strategies used by clinicians with high patient activation change are promising approaches to supporting patient behavior change that should be tested in a larger sample of clinicians to validate their effectiveness. © 2016 Annals of Family Medicine, Inc.

  7. An internet-based intervention with brief nurse support to manage obesity in primary care (POWeR+): a pragmatic, parallel-group, randomised controlled trial.

    PubMed

    Little, Paul; Stuart, Beth; Hobbs, Fd Richard; Kelly, Jo; Smith, Emily R; Bradbury, Katherine J; Hughes, Stephanie; Smith, Peter W F; Moore, Michael V; Lean, Mike E J; Margetts, Barrie M; Byrne, Chris D; Griffin, Simon; Davoudianfar, Mina; Hooper, Julie; Yao, Guiqing; Zhu, Shihua; Raftery, James; Yardley, Lucy

    2016-10-01

    The obesity epidemic has major public health consequences. Expert dietetic and behavioural counselling with intensive follow-up is effective, but resource requirements severely restrict widespread implementation in primary care, where most patients are managed. We aimed to estimate the effectiveness and cost-effectiveness of an internet-based behavioural intervention (POWeR+) combined with brief practice nurse support in primary care. We did this pragmatic, parallel-group, randomised controlled trial at 56 primary care practices in central and south England. Eligible adults aged 18 years or older with a BMI of 30 kg/m(2) or more (or ≥28 kg/m(2) with hypertension, hypercholesterolaemia, or diabetes) registered online with POWeR+-a 24 session, web-based, weight management intervention lasting 6 months. After registration, the website automatically randomly assigned patients (1:1:1), via computer-generated random numbers, to receive evidence-based dietetic advice to swap foods for similar, but healthier, choices and increase fruit and vegetable intake, in addition to 6 monthly nurse follow-up (control group); web-based intervention and face-to-face nurse support (POWeR+Face-to-face [POWeR+F]; up to seven nurse contacts over 6 months); or web-based intervention and remote nurse support (POWeR+Remote [POWeR+R]; up to five emails or brief phone calls over 6 months). Participants and investigators were masked to group allocation at the point of randomisation; masking of participants was not possible after randomisation. The primary outcome was weight loss averaged over 12 months. We did a secondary analysis of weight to measure maintenance of 5% weight loss at months 6 and 12. We modelled the cost-effectiveness of each intervention. We did analysis by intention to treat, with multiple imputation for missing data. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN21244703. Between Jan 30, 2013, and March 20, 2014, 818

  8. RNA Export through the NPC in Eukaryotes.

    PubMed

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-03-20

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC.

  9. Differential expression of c-Met between primary and metastatic sites in clear-cell renal cell carcinoma and its association with PD-L1 expression.

    PubMed

    Lalani, Aly-Khan A; Gray, Kathryn P; Albiges, Laurence; Callea, Marcella; Pignon, Jean-Christophe; Pal, Soumitro; Gupta, Mamta; Bhatt, Rupal S; McDermott, David F; Atkins, Michael B; Woude, G F Vande; Harshman, Lauren C; Choueiri, Toni K; Signoretti, Sabina

    2017-11-28

    In preclinical models, c-Met promotes survival of renal cancer cells through the regulation of programmed death-ligand 1 (PD-L1). However, this relationship in human clear cell renal cell carcinoma (ccRCC) is not well characterized. We evaluated c-Met expression in ccRCC patients using paired primary and metastatic samples and assessed the association with PD-L1 expression and other clinical features. Areas with predominant and highest Fuhrman nuclear grade (FNG) were selected. c-Met expression was evaluated by IHC using an anti-Met monoclonal antibody (MET4 Ab) and calculated by a combined score (CS, 0-300): intensity of c-Met staining (0-3) x % of positive cells (0-100). PD-L1 expression in tumor cells was previously assessed by IHC and PD-L1+ was defined as PD-L1 > 0% positive cells. Our cohort consisted of 45 pairs of primary and metastatic ccRCC samples. Overall, c-Met expression was higher in metastatic sites compared to primary sites (average c-Met CS: 55 vs. 28, p = 0.0003). Higher c-Met expression was associated with higher FNG (4 vs. 3) in primary tumors (average c-Met CS: 52 vs. 20, p = 0.04). c-Met expression was numerically greater in PD-L1+ vs. PD-L1- tumors. Higher c-Met expression in metastatic sites compared to primary tumors suggests that testing for biomarkers of response to c-Met inhibitors should be conducted in metastases. While higher c-Met expression in PD-L1+ tumors requires further investigation, it supports exploring these targets in combination clinical trials.

  10. Timing of intra-aortic balloon pump support and 1-year survival.

    PubMed

    Ramnarine, Ian R; Grayson, Antony D; Dihmis, Walid C; Mediratta, Neeraj K; Fabri, Brian M; Chalmers, John A C

    2005-05-01

    The relationship between the timing of intra-aortic balloon pump (IABP) support and surgical outcome remains a subject of debate. Peri-operative mechanical circulatory support is commenced either prophylactically or after increasing inotropic support has proved inadequate. This study evaluates the effect timing of IABP support on the 1-year survival of patients undergoing cardiac surgery. From April 1997 to September 2002, 7698 consecutive cardiac surgical procedures were performed. This included 5678 isolated coronary artery bypasses (CABGs), 1245 isolated valve procedures and 775 simultaneous CABG and valve procedures. IABP support was required in 237 patients (3.1%). Twenty-seven patients (0.35%) were classed as high-risk and received preoperative IABP support, 25 patients (0.32%) were haemodynamically compromised and required preoperative IABP support, 120 patients (1.56%) required intra-operative IABP support, and 65 patients (0.84%) required post-operative IABP support. Multiple variables were offered to a Cox proportional hazards model and significant predictors of 1-year survival were identified. These were used to risk adjust Kaplan-Meier survival curves. 1-year follow-up was complete and 450 deaths (5.8%) were recorded. The significant independent predictors of increased mortality at 1-year (P<0.05, HR=hazard ratio) were post-operative renal failure (HR=3.5), increasing EuroSCORE (HR=1.2), post-operative myocardial infarction (HR=3.7), post-operative IABP (HR=4.1) intra-operative IABP (HR=2.8), post-operative stroke (HR=2.5), increasing number of valves (HR=1.6), ejection fraction <30% (HR=1.3) and triple-vessel disease (HR=1.3). After risk-adjustment, 1-year survival for patients who required intra-operative IABP support was significantly greater than for those patients who required IABP support in the post-operative period. Patients who warrant IABP support in the post-operative setting have a significantly increased mortality at 1-year when compared to

  11. Support and performance improvement for primary health care workers in low- and middle-income countries: a scoping review of intervention design and methods

    PubMed Central

    Mabey, David C.; Chaudhri, Simran; Brown Epstein, Helen-Ann; Lawn, Stephen D.

    2017-01-01

    Abstract Primary health care workers (HCWs) in low- and middle-income settings (LMIC) often work in challenging conditions in remote, rural areas, in isolation from the rest of the health system and particularly specialist care. Much attention has been given to implementation of interventions to support quality and performance improvement for workers in such settings. However, little is known about the design of such initiatives and which approaches predominate, let alone those that are most effective. We aimed for a broad understanding of what distinguishes different approaches to primary HCW support and performance improvement and to clarify the existing evidence as well as gaps in evidence in order to inform decision-making and design of programs intended to support and improve the performance of health workers in these settings. We systematically searched the literature for articles addressing this topic, and undertook a comparative review to document the principal approaches to performance and quality improvement for primary HCWs in LMIC settings. We identified 40 eligible papers reporting on interventions that we categorized into five different approaches: (1) supervision and supportive supervision; (2) mentoring; (3) tools and aids; (4) quality improvement methods, and (5) coaching. The variety of study designs and quality/performance indicators precluded a formal quantitative data synthesis. The most extensive literature was on supervision, but there was little clarity on what defines the most effective approach to the supervision activities themselves, let alone the design and implementation of supervision programs. The mentoring literature was limited, and largely focused on clinical skills building and educational strategies. Further research on how best to incorporate mentorship into pre-service clinical training, while maintaining its function within the routine health system, is needed. There is insufficient evidence to draw conclusions about coaching

  12. 7 CFR 1710.152 - Primary support documents.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... capital investments required to serve a borrower's planned new loads, improve service reliability and... manager to guide the system toward its financial goals. The forecast submitted in support of a loan...

  13. Resveratrol Differentially Regulates NAMPT and SIRT1 in Hepatocarcinoma Cells and Primary Human Hepatocytes

    PubMed Central

    Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Petzold-Quinque, Stefanie; Damm, Georg; Gebhardt, Rolf; Kiess, Wieland; Garten, Antje

    2014-01-01

    Resveratrol is reported to possess chemotherapeutic properties in several cancers. In this study, we wanted to investigate the molecular mechanisms of resveratrol-induced cell cycle arrest and apoptosis as well as the impact of resveratrol on NAMPT and SIRT1 protein function and asked whether there are differences in hepatocarcinoma cells (HepG2, Hep3B cells) and non-cancerous primary human hepatocytes. We found a lower basal NAMPT mRNA and protein expression in hepatocarcinoma cells compared to primary hepatocytes. In contrast, SIRT1 was significantly higher expressed in hepatocarcinoma cells than in primary hepatocytes. Resveratrol induced cell cycle arrest in the S- and G2/M- phase and apoptosis was mediated by activation of p53 and caspase-3 in HepG2 cells. In contrast to primary hepatocytes, resveratrol treated HepG2 cells showed a reduction of NAMPT enzymatic activity and increased p53 acetylation (K382). Resveratrol induced NAMPT release from HepG2 cells which was associated with increased NAMPT mRNA expression. This effect was absent in primary hepatocytes where resveratrol was shown to function as NAMPT and SIRT1 activator. SIRT1 inhibition by EX527 resembled resveratrol effects on HepG2 cells. Furthermore, a SIRT1 overexpression significantly decreased both p53 hyperacetylation and resveratrol-induced NAMPT release as well as S-phase arrest in HepG2 cells. We could show that NAMPT and SIRT1 are differentially regulated by resveratrol in hepatocarcinoma cells and primary hepatocytes and that resveratrol did not act as a SIRT1 activator in hepatocarcinoma cells. PMID:24603648

  14. Relationship between health-related quality of life, perceived family support and unmet health needs in adult patients with multimorbidity attending primary care in Portugal: a multicentre cross-sectional study.

    PubMed

    Prazeres, Filipe; Santiago, Luiz

    2016-11-11

    Multimorbidity has a high prevalence in the primary care context and it is frequently associated with worse health-related quality of life (HRQoL). Few studies evaluated the variables that could have a potential effect on HRQoL of primary care patients with multimorbidity. The purpose of this study, the first of its kind ever undertaken in Portugal, is to analyse the relationship between multimorbidity, health-related quality of life, perceived family support and unmet health needs in adult patients attending primary care. Multicentre, cross-sectional survey conducted among primary care patients with multimorbidity. It included 521 participants (64.1 % females) who met the inclusion criteria. HRQoL was evaluated using the Portuguese Short Form-12 Health Status Questionnaire. The Portuguese Family APGAR was used to measure the perceived family support. A patients' unmet health needs questionnaire was used. The unmet needs for medical, surgical and dental care; prescription medications; mental healthcare or counselling; and eyeglasses or other technical aid was assessed. Descriptive and multivariate analyses were performed. The sample had an overall average of 4.5 chronic health problems. Increased multimorbidity levels were linked to worse health-related quality of life, particularly the physical health. Some variables were confirmed as playing a role on health-related quality of life. Male patients with high monthly incomes and highly functional families had better physical and mental health. High levels of education and the presence of asthma were also associated with better physical health. Contrariwise, elderly patients with high levels of multimorbidity and with osteoarthritis had lower physical health. The majority of the patients did not have unmet health needs. When health needs were stated they were mostly for generalist medical care, dental care, and eyeglasses/other technical aid. Financial insufficiency was the primary reason for not fulfilling their

  15. Social Support and Psychosocial Well-being Among Low-Income, Adolescent, African American, First-Time Mothers.

    PubMed

    Hudson, Diane Brage; Campbell-Grossman, Christie; Kupzyk, Kevin A; Brown, Sara E; Yates, Bernice C; Hanna, Kathleen M

    2016-01-01

    The aims of this study are to describe for single, low-income, adolescent, African American new mothers how (1) primary sources of social support changed over time, (2) the level of social support (emotional, informational, tangible, and problematic) from these primary sources changed over time, and (3) social support from the primary supporter was associated with mothers' psychosocial well-being (self-esteem and loneliness) over time. A secondary analysis was conducted of data from a previous social support intervention study. The sample consisted of 35 single, low-income, adolescent (mean [SD] age, 18.3 [1.7] years), African American new mothers. Mothers completed social support, self-esteem, and loneliness instruments at 1 and 6 weeks and 3 and 6 months postpartum. Most mothers (64.7%) had changes in their primary social support provider during the first 6 months postpartum. The combination of the adolescent's mother and boyfriend provided the highest level of support, no matter the type, relative to any other source of support. At every time point, positive correlations were found between emotional support and self-esteem and between problematic support and loneliness. Single, low-income, African American, adolescent new mothers are at risk for not having a consistent source of support, which may lead to lower self-esteem and greater loneliness. Clinical nurse specialists could facilitate care guidelines for these new mothers to identify their sources of support at each home visit and advocate for the adolescent's mother and boyfriend to work together to provide support. Bolstering the mothers' natural sources of support can potentially improve self-esteem and reduce loneliness. Improvement in these sources of support could prevent a decline in the mothers' psychosocial well-being. Development and testing support interventions are advocated; findings could guide clinical nurse specialists in addressing these new mothers' needs.

  16. Social Support and Psychosocial Well-Being among Low-Income, Adolescent, African American, First-Time Mothers

    PubMed Central

    Hudson, Diane Brage; Campbell-Grossman, Christie; Kupzyk, Kevin A.; Brown, Sara E; Yates, Bernice; Hanna, Kathleen M.

    2016-01-01

    Aims Aims of this study were to describe for single, low-income, adolescent, African American new mothers how (1) primary sources of social support changed over time; (2) the level of social support (emotional, informational, tangible, and problematic) from these primary sources changed over time; and (3) social support from the primary supporter was associated with mothers' psychosocial well-being (self-esteem and loneliness) over time. Design A secondary analysis was conducted of data from a previous social support intervention study. Sample The sample consisted of 35 single, low-income, adolescent (M age = 18.3 years; SD = 1.7), African American new mothers. Methods Mothers completed social support, self-esteem, and loneliness instruments at 1 and 6 weeks and 3 and 6 months postpartum. Results Most mothers (64.7%) had changes in their primary social support provider during the first 6 months postpartum. The combination of the adolescent's mother and boyfriend provided the highest level of support, no matter the type, relative to any other source of support. At every time point, positive correlations were found between emotional support and self-esteem and between problematic support and loneliness. Conclusion Single, low-income, African American, adolescent new mothers are at risk for not having a consistent source of support which may lead to lower self-esteem and greater loneliness. Implications Clinical nurse specialists could facilitate care guidelines for these new mothers to identify their sources of support at each home visit and advocate for the adolescent's mother and boyfriend to work together to provide support. Bolstering the mothers' natural sources of support can potentially improve self-esteem and reduce loneliness. Improvement in these sources of support could prevent a decline in the mothers' psychosocial well-being. Development and testing support interventions are advocated; findings could guide clinical nurse specialists in addressing these

  17. Space Suit Portable Life Support System Test Bed (PLSS 1.0) Development and Testing

    NASA Technical Reports Server (NTRS)

    Watts, Carly; Campbell, Colin; Vogel, Matthew; Conger, Bruce

    2012-01-01

    A multi-year effort has been carried out at NASA-JSC to develop an advanced extra-vehicular activity Portable Life Support System (PLSS) design intended to further the current state of the art by increasing operational flexibility, reducing consumables, and increasing robustness. Previous efforts have focused on modeling and analyzing the advanced PLSS architecture, as well as developing key enabling technologies. Like the current International Space Station Extra-vehicular Mobility Unit PLSS, the advanced PLSS comprises three subsystems required to sustain the crew during extra-vehicular activity including the Thermal, Ventilation, and Oxygen Subsystems. This multi-year effort has culminated in the construction and operation of PLSS 1.0, a test bed that simulates full functionality of the advanced PLSS design. PLSS 1.0 integrates commercial off the shelf hardware with prototype technology development components, including the primary and secondary oxygen regulators, Ventilation Subsystem fan, Rapid Cycle Amine swingbed carbon dioxide and water vapor removal device, and Spacesuit Water Membrane Evaporator heat rejection device. The overall PLSS 1.0 test objective was to demonstrate the capability of the Advanced PLSS to provide key life support functions including suit pressure regulation, carbon dioxide and water vapor removal, thermal control and contingency purge operations. Supplying oxygen was not one of the specific life support functions because the PLSS 1.0 test was not oxygen rated. Nitrogen was used for the working gas. Additional test objectives were to confirm PLSS technology development components performance within an integrated test bed, identify unexpected system level interactions, and map the PLSS 1.0 performance with respect to key variables such as crewmember metabolic rate and suit pressure. Successful PLSS 1.0 testing completed 168 test points over 44 days of testing and produced a large database of test results that characterize system level

  18. Somatization among older primary care attenders.

    PubMed

    Sheehan, B; Bass, C; Briggs, R; Jacoby, R

    2003-07-01

    The importance of somatization among older primary care attenders is unclear. We aimed to establish the prevalence, persistence and associations of somatization among older primary care attenders, and the associations of frequent attendance. One hundred and forty primary care attenders over 65 years were rated twice, 10 months apart, on measures of somatization, psychiatric status, physical health and attendance. The syndrome of GMS hypochondriacal neurosis had a prevalence of 5% but was transient. Somatized symptoms and attributions were persistent and associated with depression, physical illness and perceived poor social support. Frequent attenders (top third) had higher rates of depression, physical illness and somatic symptoms, and lower perceived support. Somatization is common among older primary care attenders and has similar correlates to younger primary care somatizers. Psychological distress among older primary care attenders is associated with frequent attendance. Improved recognition should result in benefits to patients and services.

  19. Feasibility study of a clinical decision support system for the management of multimorbid seniors in primary care: study protocol.

    PubMed

    Weltermann, Birgitta; Kersting, Christine

    2016-01-01

    Care for seniors is complex because patients often have more than one disease, one medication, and one physician. It is a key challenge for primary care physicians to structure the various aspects of each patient's care, to integrate each patient's preferences, and to maintain a long-term overview. This article describes the design for the development and feasibility testing of the clinical decision support system (CDSS) eCare*Seniors© which is electronic health record (EHR)-based allowing for a long-term, comprehensive, evidence-based, and patient preference-oriented management of multimorbid seniors. This mixed-methods study is designed in three steps. First, focus groups and practice observations will be conducted to develop criteria for software design from a physicians' and practice assistants' perspective. Second, based on these criteria, a CDSS prototype will be developed. Third, the prototype's feasibility will be tested by five primary care practices in the care of 30 multimorbid seniors. Primary outcome is the usability of the software measured by the validated system usability scale (SUS) after 3 months. Secondary outcomes are the (a) willingness to routinely use the CDSS, (b) degree of utilization of the CDSS, (c) acceptance of the CDSS, (d) willingness of the physicians to purchase the CDSS, and (e) willingness of the practice assistants to use the CDSS in the long term. These outcomes will be measured using semi-structured interviews and software usage data. If the SUS score reaches ≥70 %, feasibility testing will be judged successful. Otherwise, the CDSS prototype will be refined according to the users' needs and retested by the physicians and practice assistants until it is fully adapted to their requirements and reaches a usability score ≥70 %. The study will support the development of a CDSS which is primary care-defined, user-friendly, easy-to-comprehend, workflow-oriented, and comprehensive. The software will assist physicians and

  20. 17 CFR Appendix 1 to Part 45 - Tables of Minimum Primary Economic Terms Data

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 1 2012-04-01 2012-04-01 false Tables of Minimum Primary Economic Terms Data 1 Appendix 1 to Part 45 Commodity and Securities Exchanges COMMODITY FUTURES TRADING... Minimum Primary Economic Terms Data ER13JA12.003 ER13JA12.004 ER13JA12.005 ER13JA12.006 ER13JA12.007...

  1. 17 CFR Appendix 1 to Part 45 - Tables of Minimum Primary Economic Terms Data

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 1 2013-04-01 2013-04-01 false Tables of Minimum Primary Economic Terms Data 1 Appendix 1 to Part 45 Commodity and Securities Exchanges COMMODITY FUTURES TRADING... Minimum Primary Economic Terms Data ER13JA12.003 ER13JA12.004 ER13JA12.005 ER13JA12.006 ER13JA12.007...

  2. GSTM1 null polymorphism at the glutathione S-transferase M1 locus: phenotype and genotype studies in patients with primary biliary cirrhosis.

    PubMed Central

    Davies, M H; Elias, E; Acharya, S; Cotton, W; Faulder, G C; Fryer, A A; Strange, R C

    1993-01-01

    Studies were carried out to test the hypothesis that the GSTM1 null phenotype at the mu (mu) class glutathione S-transferase 1 locus is associated with an increased predisposition to primary biliary cirrhosis. Starch gel electrophoresis was used to compare the prevalence of GSTM1 null phenotype 0 in patients with end stage primary biliary cirrhosis and a group of controls without evidence of liver disease. The prevalence of GSTM1 null phenotype in the primary biliary cirrhosis and control groups was similar; 39% and 45% respectively. In the primary biliary cirrhosis group all subjects were of the common GSTM1 0, GSTM1 A, GSTM1 B or GSTM1 A, B phenotypes while in the controls, one subject showed an isoform with an anodal mobility compatible with it being a product of the putative GSTM1*3 allele. As the GSTM1 phenotype might be changed by the disease process, the polymerase chain reaction was used to amplify the exon 4-exon 5 region of GSTM1 and show that in 13 control subjects and 11 patients with primary biliary cirrhosis, GSTM1 positive and negative genotypes were associated with corresponding GSTM1 expressing and non-expressing phenotypes respectively. The control subject with GSTM1 3 phenotype showed a positive genotype. Images Figure 1 Figure 2 PMID:8491405

  3. Service, training, mentorship: first report of an innovative education-support program to revitalize primary care social service in Chiapas, Mexico.

    PubMed

    Van Wieren, Andrew; Palazuelos, Lindsay; Elliott, Patrick F; Arrieta, Jafet; Flores, Hugo; Palazuelos, Daniel

    2014-01-01

    The Mexican mandatory year of social service following medical school, or pasantía, is designed to provide a safety net for the underserved. However, social service physicians (pasantes) are typically unpracticed, unsupervised, and unsupported. Significant demotivation, absenteeism, and underperformance typically plague the social service year. Compañeros en Salud (CES) aimed to create an education-support package to turn the pasantía into a transformative learning experience. CES recruited pasantes to complete their pasantía in CES-supported Ministry of Health clinics in rural Chiapas. The program aims to: 1) train pasantes to more effectively deliver primary care, 2) expose pasantes to central concepts of global health and social medicine, and 3) foster career development of pasantes. Program components include supportive supervision, on-site mentorship, clinical information resources, monthly interactive seminars, and improved clinic function. We report quantitative and qualitative pasante survey data collected from February 2012 to August 2013 to discuss strengths and weaknesses of this program and its implications for the pasante workforce in Mexico. Pasantes reported that their medical knowledge, and clinical and leadership skills all improved during the CES education-support program. Most pasantes felt the program had an overall positive effect on their career goals and plans, although their self-report of preparedness for the Mexican residency entrance exam (ENARM) decreased during the social service year. One hundred percent reported they were satisfied with the CES-supported pasantía experience and wished to help the poor and underserved in their careers. Education-support programs similar to the CES program may encourage graduating medical students to complete their social service in underserved areas, improve the quality of care provided by pasantes, and address many of the known shortcomings of the pasantía. Additional efforts should focus on

  4. 40 CFR Table 1 to Subpart Gggggg... - Applicability of General Provisions to Primary Zinc Production Area Sources

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Primary Zinc Production Area Sources 1 Table 1 to Subpart GGGGGG of Part 63 Protection of Environment... Pollutants for Primary Nonferrous Metals Area Sources-Zinc, Cadmium, and Beryllium Pt. 63, Subpt. GGGGGG, Table 1 Table 1 to Subpart GGGGGG of Part 63—Applicability of General Provisions to Primary Zinc...

  5. 40 CFR Table 1 to Subpart Gggggg... - Applicability of General Provisions to Primary Zinc Production Area Sources

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Primary Zinc Production Area Sources 1 Table 1 to Subpart GGGGGG of Part 63 Protection of Environment... Pollutants for Primary Nonferrous Metals Area Sources-Zinc, Cadmium, and Beryllium Pt. 63, Subpt. GGGGGG, Table 1 Table 1 to Subpart GGGGGG of Part 63—Applicability of General Provisions to Primary Zinc...

  6. Bifurcating effects of hope and support in short- and long-term health outcomes among primary care patients without mental illness.

    PubMed

    Katerndahl, David

    2014-08-01

    Adverse life events and stressors can lead to symptoms, increased alcohol intake, and impaired functional status, while hope and social support can mitigate such adverse effects. Yet, there is reason to question such simple, linear relationships among healthy adults. The purpose of this study was to assess whether short-term or long-term changes in alcohol intake, psychological symptoms or functional status were better modelled as cusp catastrophic or linear processes among primary care patients without mental illness. This secondary analysis of a study on the stability of psychological symptoms among primary care patients without mental disorders included 38 subjects who completed baseline, and 2-month and/or 6-month assessments of psychological symptoms, functional status and stressors as well as hope and social support. The analyses modelled short-term and long-term changes in alcohol intake, psychological symptoms and functional status using cusp catastrophe (CCM) and linear modelling. Overall, four of the nine 2-month analyses found CCM superior to linear models; however, only one 6-month analysis (alcohol intake) found that CCM was superior. The 2-month cusp phenomena included both symptomatology and functional status. The asymmetry variables were often not significant in the CCM models; in fact, only distress was significant at all. While hope was a significant bifurcation variable at both the 2-month and 6-month levels, social support was a significant bifurcation variable for three of the four 2-month CCMs. In conclusion, while 6-month outcomes were rarely explained through CCM, half of 2-month outcomes were. Hope and support demonstrated bifurcation effects. © 2013 John Wiley & Sons, Ltd.

  7. Effect of a Primary Care Walking Intervention with and without Nurse Support on Physical Activity Levels in 45- to 75-Year-Olds: The Pedometer And Consultation Evaluation (PACE-UP) Cluster Randomised Clinical Trial

    PubMed Central

    Harris, Tess; Iliffe, Steve; Whincup, Peter H.; Ekelund, Ulf; Furness, Cheryl; Anokye, Nana; Ibison, Judith; DeWilde, Steve; David, Lee; Dale, Rebecca; Cook, Derek G.

    2017-01-01

    (min/wk) were 33 for postal (95% CI 17–49) and 35 for nurse support (95% CI 19–51). There were no significant differences between the two interventions at 12 mo. The 10% (1,023/10,467) recruitment rate was a study limitation. Conclusions A primary care pedometer-based walking intervention in predominantly inactive 45- to 75-y-olds increased step-counts by about one-tenth and time in MVPA in bouts by about one-third. Nurse and postal delivery achieved similar 12-mo PA outcomes. A primary care pedometer intervention delivered by post or with minimal support could help address the public health physical inactivity challenge. Clinical Trial Registration isrctn.com ISRCTN98538934. PMID:28045890

  8. Decellularized extracellular matrices produced from immortal cell lines derived from different parts of the placenta support primary mesenchymal stem cell expansion

    PubMed Central

    Kusuma, Gina D.; Brennecke, Shaun P.; O’Connor, Andrea J.; Kalionis, Bill

    2017-01-01

    Mesenchymal stem/stromal cells (MSCs) exhibit undesired phenotypic changes during ex vivo expansion, limiting production of the large quantities of high quality primary MSCs needed for both basic research and cell therapies. Primary MSCs retain many desired MSC properties including proliferative capacity and differentiation potential when expanded on decellularized extracellular matrix (dECM) prepared from primary MSCs. However, the need to use low passage number primary MSCs (passage 3 or lower) to produce the dECM drastically limits the utility and impact of this technology. Here, we report that primary MSCs expanded on dECM prepared from high passage number (passage 25) human telomerase reverse transcriptase (hTERT) transduced immortal MSC cell lines also exhibit increased proliferation and osteogenic differentiation. Two hTERT-transduced placenta-derived MSC cell lines, CMSC29 and DMSC23 [derived from placental chorionic villi (CMSCs) and decidua basalis (DMSCs), respectively], were used to prepare dECM-coated substrates. These dECM substrates showed structural and biochemical differences. Primary DMSCs cultured on dECM-DMSC23 showed a three-fold increase in cell number after 14 days expansion in culture and increased osteogenic differentiation compared with controls. Primary CMSCs cultured on the dECM-DMSC23 exhibited a two-fold increase in cell number and increased osteogenic differentiation. We conclude that immortal MSC cell lines derived from different parts of the placenta produce dECM with varying abilities for supporting increased primary MSC expansion while maintaining important primary MSC properties. Additionally, this is the first demonstration of using high passage number cells to produce dECM that can promote primary MSC expansion, and this advancement greatly increases the feasibility and applicability of dECM-based technologies. PMID:28152107

  9. Decellularized extracellular matrices produced from immortal cell lines derived from different parts of the placenta support primary mesenchymal stem cell expansion.

    PubMed

    Kusuma, Gina D; Brennecke, Shaun P; O'Connor, Andrea J; Kalionis, Bill; Heath, Daniel E

    2017-01-01

    Mesenchymal stem/stromal cells (MSCs) exhibit undesired phenotypic changes during ex vivo expansion, limiting production of the large quantities of high quality primary MSCs needed for both basic research and cell therapies. Primary MSCs retain many desired MSC properties including proliferative capacity and differentiation potential when expanded on decellularized extracellular matrix (dECM) prepared from primary MSCs. However, the need to use low passage number primary MSCs (passage 3 or lower) to produce the dECM drastically limits the utility and impact of this technology. Here, we report that primary MSCs expanded on dECM prepared from high passage number (passage 25) human telomerase reverse transcriptase (hTERT) transduced immortal MSC cell lines also exhibit increased proliferation and osteogenic differentiation. Two hTERT-transduced placenta-derived MSC cell lines, CMSC29 and DMSC23 [derived from placental chorionic villi (CMSCs) and decidua basalis (DMSCs), respectively], were used to prepare dECM-coated substrates. These dECM substrates showed structural and biochemical differences. Primary DMSCs cultured on dECM-DMSC23 showed a three-fold increase in cell number after 14 days expansion in culture and increased osteogenic differentiation compared with controls. Primary CMSCs cultured on the dECM-DMSC23 exhibited a two-fold increase in cell number and increased osteogenic differentiation. We conclude that immortal MSC cell lines derived from different parts of the placenta produce dECM with varying abilities for supporting increased primary MSC expansion while maintaining important primary MSC properties. Additionally, this is the first demonstration of using high passage number cells to produce dECM that can promote primary MSC expansion, and this advancement greatly increases the feasibility and applicability of dECM-based technologies.

  10. Primary DNA damage and genetic polymorphisms for CYP1A1, EPHX and GSTM1 in workers at a graphite electrode manufacturing plant

    PubMed Central

    Moretti, Massimo; Dell'Omo, Marco; Villarini, Milena; Pastorelli, Roberta; Muzi, Giacomo; Airoldi, Luisa; Pasquini, Rossana

    2007-01-01

    Background The results of a cross-sectional study aimed to evaluate whether genetic polymorphisms (biomarkers of susceptibility) for CYP1A1, EPHX and GSTM1 genes that affect polycyclic aromatic hydrocarbons (PAH) activation and detoxification might influence the extent of primary DNA damage (biomarker of biologically effective dose) in PAH exposed workers are presented. PAH-exposure of the study populations was assessed by determining the concentration of 1-hydroxypyrene (1OHP) in urine samples (biomarker of exposure dose). Methods The exposed group consisted of workers (n = 109) at a graphite electrode manufacturing plant, occupationally exposed to PAH. Urinary 1OHP was measured by HPLC. Primary DNA damage was evaluated by the alkaline comet assay in peripheral blood leukocytes. Genetic polymorphisms for CYP1A1, EPHX and GSTM1 were determined by PCR or PCR/RFLP analysis. Results 1OHP and primary DNA damage were significantly higher in electrode workers compared to reference subjects. Moreover, categorization of subjects as normal or outlier highlighted an increased genotoxic risk OR = 2.59 (CI95% 1.32–5.05) associated to exposure to PAH. Polymorphisms in EPHX exons 3 and 4 was associated to higher urinary concentrations of 1OHP, whereas none of the genotypes analyzed (CYP1A1, EPHX, and GSTM1) had any significant influence on primary DNA damage as evaluated by the comet assay. Conclusion The outcomes of the present study show that molecular epidemiology approaches (i.e. cross-sectional studies of genotoxicity biomarkers) can play a role in identifying common genetic risk factors, also attempting to associate the effects with measured exposure data. Moreover, categorization of subjects as normal or outlier allowed the evaluation of the association between occupational exposure to PAH and DNA damage highlighting an increased genotoxic risk. PMID:17908297

  11. Therapeutically targeting cyclin D1 in primary tumors arising from loss of Ini1

    PubMed Central

    Smith, Melissa E.; Cimica, Velasco; Chinni, Srinivasa; Jana, Suman; Koba, Wade; Yang, Zhixia; Fine, Eugene; Zagzag, David; Montagna, Cristina; Kalpana, Ganjam V.

    2011-01-01

    Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1 directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors p16Ink4a and p21CIP. RTs are exquisitely dependent on cyclin D1 for genesis and survival. To facilitate translation of unique therapeutic strategies, we have used genetically engineered, Ini1+/− mice for therapeutic testing. We found that PET can be used to noninvasively and accurately detect primary tumors in Ini1+/− mice. In a PET-guided longitudinal study, we found that treating Ini1+/− mice bearing primary tumors with the pan-cdk inhibitor flavopiridol resulted in complete and stable regression of some tumors. Other tumors showed resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol used was not sufficient to down-modulate the high level of cyclin D1 and failed to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses indicated that there is aneuploidy and increased CCND1 copy number in resistant cells. These studies indicate that resistance to flavopiridol may be correlated to elevated cyclin D1 levels. Our studies also indicate that Ini1+/− mice are valuable tools for testing unique therapeutic strategies and for understanding mechanisms of drug resistance in tumors that arise owing to loss of Ini1, which is essential for developing effective treatment strategies against these aggressive tumors. PMID:21173237

  12. Primary total hip arthroplasty in Catalonia: What is the clinical evidence that supports our prosthesis?

    PubMed

    Chaverri-Fierro, D; Lobo-Escolar, L; Espallargues, M; Martínez-Cruz, O; Domingo, L; Pons-Cabrafiga, M

    The implementation of National Prostheses Registries allows us to obtain a large amount of data and make conclusions in order to improve the use of them. Sweden was the first country to implement a National Prostheses Registry in 1979. Catalonia has been doing this since 2005. The aim of our study is to analyse the evidence that supports primary total hip replacement in Catalonia in the last 9 years, based on the Arthroplasty Registry of Catalonia (RACat). A review of the literature was carried out of the prosthesis (acetabular cups/stems) reported in the RACat between the period 2005 to 2013 in the following databases: ODEP (Orthopaedic Data Evaluation Panel), TRIP database, PubMed, and Google Scholar. Those prostheses implanted in less than 10 units (182 acetabular components corresponding to 49 models/228 stems corresponding to 63 models) were excluded. A total of 18,634 (99%) implanted acetabular cups were analysed out of a total number of 18,816, corresponding to 74 different models. In 18 models (2527 acetabular cups) no clinical evidence to support its use was found. An analysis was performed on 19,367 (98.84%) out of a total number of 19,595 implanted stems, corresponding to 75 different models. In 16 models (1845 stems) no clinical evidence was found to support their use. Variable evidence was found in the 56 models of acetabular cups (16,107) and 59 models of stems (17,522), most of it corresponding to level iv clinical evidence. There was a significant number implanted prostheses evaluated (13.56% acetabular cups/9.5% stems) for which no clinical evidence was found. The elevated number of models is highlighted (49 types for acetabular cups/63 types for stems) with less than 10 units implanted, which corresponds to only 1% of the total implants. The use of arthroplasty registers is shown to be an extremely helpful tool that allows analyses and conclusions to be made for the follow-up and post-marketing surveillance period. Copyright © 2016 SECOT

  13. Smoking cessation in primary care clinics.

    PubMed

    Sippel, J M; Osborne, M L; Bjornson, W; Goldberg, B; Buist, A S

    1999-11-01

    To document smoking cessation rates achieved by applying the 1996 Agency for Health Care Policy and Research (AHCPR) smoking cessation guidelines for primary care clinics, compare these quit rates with historical results, and determine if quit rates improve with an additional motivational intervention that includes education as well as spirometry and carbon monoxide measurements. Randomized clinical trial. Two university-affiliated community primary care clinics. Two hundred five smokers with routinely scheduled appointments. All smokers were given advice and support according to AHCPR guidelines. Half of the subjects received additional education with spirometry and carbon monoxide measurements. Quit rate was evaluated at 9-month follow-up. Eleven percent of smokers were sustained quitters at follow-up. Sustained quit rate was no different for intervention and control groups (9% vs 14%; [OR] 0.6; 95% [CI] 0.2, 1.4). Nicotine replacement therapy was strongly associated with sustained cessation (OR 6.7; 95% CI 2.3, 19.6). Subjects without insurance were the least likely to use nicotine replacement therapy ( p =.05). Historical data from previously published studies showed that 2% of smokers quit following physician advice, and additional support similar to AHCPR guidelines increased the quit rate to 5%. The sustained smoking cessation rate achieved by following AHCPR guidelines was 11% at 9 months, which compares favorably with historical results. Additional education with spirometry did not improve the quit rate. Nicotine replacement therapy was the strongest predictor of cessation, yet was used infrequently owing to cost. These findings support the use of AHCPR guidelines in primary care clinics, but do not support routine spirometry for motivating patients similar to those studied here.

  14. Molecular Characterization of TaFAR1 Involved in Primary Alcohol Biosynthesis of Cuticular Wax in Hexaploid Wheat.

    PubMed

    Wang, Yong; Wang, Meiling; Sun, Yulin; Hegebarth, Daniela; Li, Tingting; Jetter, Reinhard; Wang, Zhonghua

    2015-10-01

    Cuticular waxes are complex mixtures of very long chain (VLC) fatty acids and their derivatives in which primary alcohols are the most abundant components in the leaf surface of common wheat (Triticum aestivum L.). However, the genes involved in primary alcohol biosynthesis in wheat are still largely unknown. Here we identified, via a homology-based approach, the TaFAR1 gene belonging to the fatty acyl-CoA reductases (FARs) from wheat. Heterologous expression of TaFAR1 in yeast (Saccharomyces cerevisiae) and in the Arabidopsis (Arabidopsis thaliana) cer4-3 mutant afforded production of C22 primary alcohol and C22-C24 primary alcohols, respectively, and transgenic expression of TaFAR1 in tomato (Solanum lycopersicum) cv MicroTom leaves and fruits resulted in the accumulation of C26-C30 primary alcohols and C30-C34 primary alcohols, respectively. The TaFAR1 protein was localized to the endoplasmic reticulum (ER) in rice (Oryza sativa L.) leaf protoplasts. Moreover, the TaFAR1 expression pattern across various organs correlated with the levels of primary alcohols accumulating in corresponding waxes, and with the presence of platelet-shaped epicuticular wax crystals formed by primary alcohols. A nullisomic-tetrasomic wheat line lacking TaFAR1 had significantly reduced levels of primary alcohols in its leaf blade and anther wax. TaFAR1 was located on chromosome 4AL and appeared to be highly conserved, with only one haplotype among 32 wheat cultivars. Finally, TaFAR1 expression was induced by drought and cold stress in an ABA-dependent manner. Taken together, our results show that TaFAR1 is an active enzyme forming primary alcohols destined for the wheat cuticle. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. 13. TROJAN MILL, INTERIOR SHOWING PRIMARY MILL No. 1 (ALLIS ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. TROJAN MILL, INTERIOR SHOWING PRIMARY MILL No. 1 (ALLIS CHALMERS BALL MILL) FROM EAST, c. 1919. ELECTRIC MOTOR AND DRIVE SHAFT CLEARLY VISIBLE. CREDIT WR. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  16. Evaluating Teachers' Support Requests When Just-in-Time Instructional Support is Provided to Introduce a Primary Level Web-Based Reading Program

    ERIC Educational Resources Information Center

    Wood, Eileen; Anderson, Alissa; Piquette-Tomei, Noella; Savage, Robert; Mueller, Julie

    2011-01-01

    Support requests were documented for 10 teachers (4 kindergarten, 4 grade one, and 2 grade one/two teachers) who received just-in-time instructional support over a 2 1/2 month period while implementing a novel reading software program as part of their literacy instruction. In-class observations were made of each instructional session. Analysis of…

  17. Molecular insights into primary hyperoxaluria type 1 pathogenesis.

    PubMed

    Cellini, Barbara; Oppici, Elisa; Paiardini, Alessandro; Montioli, Riccardo

    2012-01-01

    Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disorder of glyoxylate metabolism caused by the deficiency of liver peroxisomal alanine:glyoxylate aminotransferase (AGT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. The PH1 pathogenesis is mostly due to single point mutations (more than 150 so far identified) on the AGXT gene, and is characterized by a marked heterogeneity in terms of genotype, enzymatic and clinical phenotypes. This article presents an up to date review of selected aspects of the biochemical properties of the two allelic forms of AGT and of some PH1-causing variants. These recent discoveries highlight the effects at the protein level of the pathogenic mutations, and, together with previous cell biology and clinical data, (i) improve the understanding of the molecular basis of PH1 pathogenesis, and (ii) help to delineate perspectives for predicting the response to pyridoxine treatment or for suggesting new strategies for PH1 patients bearing the analyzed mutations.

  18. Effectiveness of computerized clinical decision support systems for asthma and chronic obstructive pulmonary disease in primary care: a systematic review.

    PubMed

    Fathima, Mariam; Peiris, David; Naik-Panvelkar, Pradnya; Saini, Bandana; Armour, Carol Lyn

    2014-12-02

    The use of computerized clinical decision support systems may improve the diagnosis and ongoing management of chronic diseases, which requires recurrent visits to multiple health professionals, disease and medication monitoring and modification of patient behavior. The aim of this review was to systematically review randomized controlled trials evaluating the effectiveness of computerized clinical decision systems (CCDSS) in the care of people with asthma and COPD. Randomized controlled trials published between 2003 and 2013 were searched using multiple electronic databases Medline, EMBASE, CINAHL, IPA, Informit, PsychINFO, Compendex, and Cochrane Clinical Controlled Trials Register databases. To be included, RCTs had to evaluate the role of the CCDSSs for asthma and/or COPD in primary care. Nineteen studies representing 16 RCTs met our inclusion criteria. The majority of the trials were conducted in patients with asthma. Study quality was generally high. Meta-analysis was not conducted because of methodological and clinical heterogeneity. The use of CCDSS improved asthma and COPD care in 14 of the 19 studies reviewed (74%). Nine of the nineteen studies showed statistically significant (p < 0.05) improvement in the primary outcomes measured. The majority of the studies evaluated health care process measures as their primary outcomes (10/19). Evidence supports the effectiveness of CCDSS in the care of people with asthma. However there is very little information of its use in COPD care. Although there is considerable improvement in the health care process measures and clinical outcomes through the use of CCDSSs, its effects on user workload and efficiency, safety, costs of care, provider and patient satisfaction remain understudied.

  19. Developing a corss-project support system during mission operations: Deep Space 1 extended mission flight control

    NASA Technical Reports Server (NTRS)

    Scarffe, V. A.

    2002-01-01

    NASA is focusing on small, low-cost spacecraft for both planetary and earth science missions. Deep Space 1 (DS1) was the first mission to be launched by the NMP. The New Millennium Project (NMP) is designed to develop and test new technology that can be used on future science missions with lower cost and risk. The NMP is finding ways to reduce cost not only in development, but also in operations. DS 1 was approved for an extended mission, but the budget was not large, so the project began looking into part time team members shared with other projects. DS1 launched on October 24, 1998, in it's primary mission it successfully tested twelve new technologies. The extended mission started September 18, 1999 and ran through the encounter with Comet Borrelly on September 22,2001. The Flight Control Team (FCT) was one team that needed to use part time or multi mission people. Circumstances led to a situation where for the few months before the Borrelly encounter in September of 2001 DSl had no certified full time Flight Control Engineers also known as Aces. This paper examines how DS 1 utilized cross-project support including the communication between different projects, and the how the tools used by the Flight Control Engineer fit into cross-project support.

  20. Evidence for Altered Glutamine Metabolism in Human Immunodeficiency Virus Type 1 Infected Primary Human CD4+ T Cells

    PubMed Central

    Hegedus, Andrea; Kavanagh Williamson, Maia; Khan, Mariam B.; Dias Zeidler, Julianna; Da Poian, Andrea T.; El-Bacha, Tatiana; Struys, Eduard A.

    2017-01-01

    Abstract Glutamine is a conditionally essential amino acid that is an important metabolic resource for proliferating tissues by acting as a proteinogenic amino acid, a nitrogen donor for biosynthetic reactions and as a substrate for the citric acid or tricarboxylic acid cycle. The human immunodeficiency virus type 1 (HIV-1) productively infects activated CD4+ T cells that are known to require glutamine for proliferation and for carrying out effector functions. As a virus, HIV-1 is furthermore entirely dependent on host metabolism to support its replication. In this study, we compared HIV-1 infected with uninfected activated primary human CD4+ T cells with regard to glutamine metabolism. We report that glutamine concentrations are elevated in HIV-1-infected cells and that glutamine is important to support HIV-1 replication, although the latter is closely linked to the glutamine dependency of cell survival. Metabolic tracer experiments showed that entry of glutamine-derived carbon into the citric acid cycle is unaffected by HIV-1 infection, but that there is an increase in the secretion of glutamine-derived glutamic acid from HIV-1-infected cells. Western blotting of key enzymes that metabolize glutamine revealed marked differences in the expression of glutaminase isoforms, KGA and CAG, as well as the PPAT enzyme that targets glutamine-derived nitrogen toward nucleotide synthesis. Altogether, this demonstrates that infection of CD4+ T cells with HIV-1 leads to considerable changes in the cellular glutamine metabolism. PMID:28844150

  1. Evidence for Altered Glutamine Metabolism in Human Immunodeficiency Virus Type 1 Infected Primary Human CD4+ T Cells.

    PubMed

    Hegedus, Andrea; Kavanagh Williamson, Maia; Khan, Mariam B; Dias Zeidler, Julianna; Da Poian, Andrea T; El-Bacha, Tatiana; Struys, Eduard A; Huthoff, Hendrik

    2017-12-01

    Glutamine is a conditionally essential amino acid that is an important metabolic resource for proliferating tissues by acting as a proteinogenic amino acid, a nitrogen donor for biosynthetic reactions and as a substrate for the citric acid or tricarboxylic acid cycle. The human immunodeficiency virus type 1 (HIV-1) productively infects activated CD4 + T cells that are known to require glutamine for proliferation and for carrying out effector functions. As a virus, HIV-1 is furthermore entirely dependent on host metabolism to support its replication. In this study, we compared HIV-1 infected with uninfected activated primary human CD4 + T cells with regard to glutamine metabolism. We report that glutamine concentrations are elevated in HIV-1-infected cells and that glutamine is important to support HIV-1 replication, although the latter is closely linked to the glutamine dependency of cell survival. Metabolic tracer experiments showed that entry of glutamine-derived carbon into the citric acid cycle is unaffected by HIV-1 infection, but that there is an increase in the secretion of glutamine-derived glutamic acid from HIV-1-infected cells. Western blotting of key enzymes that metabolize glutamine revealed marked differences in the expression of glutaminase isoforms, KGA and CAG, as well as the PPAT enzyme that targets glutamine-derived nitrogen toward nucleotide synthesis. Altogether, this demonstrates that infection of CD4 + T cells with HIV-1 leads to considerable changes in the cellular glutamine metabolism.

  2. CD151 supports VCAM-1-mediated lymphocyte adhesion to liver endothelium and is upregulated in chronic liver disease and hepatocellular carcinoma.

    PubMed

    Wadkin, James C R; Patten, Daniel A; Kamarajah, Sivesh K; Shepherd, Emma L; Novitskaya, Vera; Berditchevski, Fedor; Adams, David H; Weston, Chris J; Shetty, Shishir

    2017-08-01

    CD151, a member of the tetraspanin family of receptors, is a lateral organizer and modulator of activity of several families of transmembrane proteins. It has been implicated in the development and progression of several cancers, but its role in chronic inflammatory disease is less well understood. Here we show that CD151 is upregulated by distinct microenvironmental signals in a range of chronic inflammatory liver diseases and in primary liver cancer, in which it supports lymphocyte recruitment. CD151 was highly expressed in endothelial cells of the hepatic sinusoids and neovessels developing in fibrotic septa and tumor margins. Primary cultures of human hepatic sinusoidal endothelial cells (HSECs) expressed CD151 at the cell membrane and in intracellular vesicles. CD151 was upregulated by VEGF and HepG2 conditioned media but not by proinflammatory cytokines. Confocal microscopy confirmed that CD151 colocalized with the endothelial adhesion molecule/immunoglobulin superfamily member, VCAM-1. Functional flow-based adhesion assays with primary human lymphocytes and HSECs demonstrated a 40% reduction of lymphocyte adhesion with CD151 blockade. Inhibition of lymphocyte adhesion was similar between VCAM-1 blockade and a combination of CD151/VCAM-1 blockade, suggesting a collaborative role between the two receptors. These studies demonstrate that CD151 is upregulated within the liver during chronic inflammation, where it supports lymphocyte recruitment via liver endothelium. We propose that CD151 regulates the activity of VCAM-1 during lymphocyte recruitment to the human liver and could be a novel anti-inflammatory target in chronic liver disease and hepatocellular cancer prevention. NEW & NOTEWORTHY Chronic hepatitis is characterized by lymphocyte accumulation in liver tissue, which drives fibrosis and carcinogenesis. Here, we demonstrate for the first time that the tetraspanin CD151 supports lymphocyte adhesion to liver endothelium. We show that CD151 is upregulated

  3. 26 CFR 1.509(a)-3 - Broadly, publicly supported organizations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Broadly, publicly supported organizations. 1.509(a)-3 Section 1.509(a)-3 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Private Foundations § 1.509(a)-3 Broadly, publicly supported organizations. (a) In general—(1)...

  4. Why high tech needs high touch: Supporting continuity of community primary health care.

    PubMed

    Meyer, Ellenore D; Hugo, Johannes F M; Marcus, Tessa S; Molebatsi, Rebaone; Komana, Kabelo

    2018-06-21

     Integrated care through community-oriented primary care (COPC) deployed through municipal teams of community health workers (CHWs) has been part of health reform in South Africa since 2011. The role of COPC and integration of information and communication technology (ICT) information to improve patient health and access to care, require a better understanding of patient social behaviour. Aim: The study sought to understand how COPC with CHWs visiting households offering health education can support antenatal follow-up and what the barriers for access to care would be. Method: A mixed methodological approach was followed. Quantitative patient data were recorded on an electronic health record-keeping system. Qualitative data collection was performed through interviews of the COPC teams at seven health posts in Mamelodi and telephonic patient interviews. Interviews were analysed according to themes and summarised as barriers to access care from a social and community perspective. Results: An integrated COPC approach increased the number of traceable pregnant women followed up at home from 2016 - 2017. Wrong addresses or personal identification were given at the clinic because of fear of being denied care. Allocating patients correctly to a ward-based outreach team (WBOT) proved to be a challenge as many patients did not know their street address. Conclusion: Patient health data available to a health worker on a smartphone as part of COPC improve patient traceability and follow-up at home making timely referral possible. Health system developments that support patient care on community level could strengthen patient health access and overall health.

  5. Exploration of the contexts surrounding the implementation of an intervention supporting return-to-work after breast cancer in a primary care setting: starting point for an intervention development.

    PubMed

    Bilodeau, Karine; Tremblay, Dominique; Durand, Marie-José

    2018-01-01

    Many recommendations have been made regarding survivorship care provided by teams of primary care professionals. However, the nature of that follow-up, including support for return-to-work (RTW) after cancer, remains largely undefined. As implementation problems are frequently context-related, a pilot study was conducted to describe the contexts, according to Grol and Wensing, in which a new intervention is to be implemented. This pilot study is the first of three steps in intervention development planning. In-depth semi-structured interviews (n=6) were carried out with stakeholders selected for their knowledgeable perspective of various settings, such as hospitals, primary care, employers, and community-based organizations. Interviews focused on participants' perceptions of key contextual facilitators and barriers to consider for the deployment of an RTW intervention in a primary care setting. Data from interviews were transcribed and analyzed. A content analysis was performed based on an iterative process. An intervention supporting the process of RTW in primary care makes sense for participants. Results suggest that important levers are present in organizational, professional, and social settings. However, many barriers, mainly related to organizational settings, have been identified, eg, distribution of tasks for survivor follow-up, continuity of information, and coordination of care between specialized oncology care and general primary care. To develop and deploy the intervention, recommendations that emerged from this pilot study for overcoming barriers were identified, eg, training (professionals, survivors, and employers), the use of communication tools, and adopting a practice guide for survivor care. The results were also helpful in focusing on the relevance of an intervention supporting the RTW process as a component of primary care for survivors.

  6. Parents' level of support for adults' purchase and consumption of alcohol at primary school events when children are present.

    PubMed

    Ward, Bernadette; Kippen, Rebecca; Buykx, Penny; Gilligan, Conor; Chapman, Kathy

    2015-03-01

    Environmental and societal factors are significant determinants of children's initiation to and use of alcohol. Schools are important settings for promoting well-being and substantial resources have been devoted to curriculum-based alcohol programs, but the effects of these in reducing the misuse of alcohol have been modest. Adults can and do consume alcohol at school events when students are present, but there is a dearth of evidence about parents' level of support for the practice. The aim of this study was to examine parents' level of support for the purchase and consumption of alcohol at primary school fundraising events when children are present. Four hundred seventy-nine Australian parents of children aged 0-12 years participated in an online survey. Logistic regression was used to assess the impact of parent characteristics on the level of agreement with parental purchase and consumption of alcohol at school fundraising events when children are present. The majority of parents (60%) disagreed/strongly disagreed with the practice of adults being able to purchase and consume alcohol at school fundraising events when children were present. The 21% of parents who supported the practice were more likely to be daily smokers and/or have higher (>6) Alcohol Use Disorders Identification Test-alcohol consumption scores. Despite the fact that the majority of parents disagree with this practice, published reports suggest that adults' use of alcohol at primary school events is an emerging issue. It is important that school decision-makers are mindful of the financial and educational value of fundraising activities. © 2014 Australasian Professional Society on Alcohol and other Drugs.

  7. Support and performance improvement for primary health care workers in low- and middle-income countries: a scoping review of intervention design and methods.

    PubMed

    Vasan, Ashwin; Mabey, David C; Chaudhri, Simran; Brown Epstein, Helen-Ann; Lawn, Stephen D

    2017-04-01

    Primary health care workers (HCWs) in low- and middle-income settings (LMIC) often work in challenging conditions in remote, rural areas, in isolation from the rest of the health system and particularly specialist care. Much attention has been given to implementation of interventions to support quality and performance improvement for workers in such settings. However, little is known about the design of such initiatives and which approaches predominate, let alone those that are most effective. We aimed for a broad understanding of what distinguishes different approaches to primary HCW support and performance improvement and to clarify the existing evidence as well as gaps in evidence in order to inform decision-making and design of programs intended to support and improve the performance of health workers in these settings. We systematically searched the literature for articles addressing this topic, and undertook a comparative review to document the principal approaches to performance and quality improvement for primary HCWs in LMIC settings. We identified 40 eligible papers reporting on interventions that we categorized into five different approaches: (1) supervision and supportive supervision; (2) mentoring; (3) tools and aids; (4) quality improvement methods, and (5) coaching. The variety of study designs and quality/performance indicators precluded a formal quantitative data synthesis. The most extensive literature was on supervision, but there was little clarity on what defines the most effective approach to the supervision activities themselves, let alone the design and implementation of supervision programs. The mentoring literature was limited, and largely focused on clinical skills building and educational strategies. Further research on how best to incorporate mentorship into pre-service clinical training, while maintaining its function within the routine health system, is needed. There is insufficient evidence to draw conclusions about coaching in this

  8. 17 CFR Appendix 1 to Part 45 - Tables of Minimum Primary Economic Terms Data

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 2 2014-04-01 2014-04-01 false Tables of Minimum Primary Economic Terms Data 1 Appendix 1 to Part 45 Commodity and Securities Exchanges COMMODITY FUTURES TRADING... 45—Tables of Minimum Primary Economic Terms Data ER13JA12.003 ER13JA12.004 ER13JA12.005 ER13JA12.006...

  9. Scaling Gross Primary Production (GPP) over boreal and deciduous forest landscapes in support of MODIS GPP product validation.

    Treesearch

    David P. Turner; William D. Ritts; Warren B. Cohen; Stith T. Gower; Maosheng Zhao; Steve W. Running; Steven C. Wofsy; Shawn Urbanski; Allison L. Dunn; J.W. Munger

    2003-01-01

    The Moderate Resolution Imaging Radiometer (MODIS) is the primary instrument in the NASA Earth Observing System for monitoring the seasonality of global terrestrial vegetation. Estimates of 8-day mean daily gross primary production (GPP) at the 1 km spatial resolution are now operationally produced by the MODIS Land Science Team for the global terrestrial surface using...

  10. RISQy business (Relationships, Incentives, Supports, and Quality): evolution of the British Columbia Model of Primary Care (patient-centered medical home).

    PubMed

    MacCarthy, Dan; Hollander, Marcus J

    2014-01-01

    In 2002, the British Columbia Ministry of Health and the British Columbia Medical Association (now Doctors of BC) came together to form the British Columbia General Practice Services Committee to bring about transformative change in primary care in British Columbia, Canada. This committee's approach to primary care was to respond to an operational problem--the decline of family practice in British Columbia--with an operational solution--assist general practitioners to provide better care by introducing new incentive fees into the fee-for-service payment schedule, and by providing additional training to general practitioners. This may be referred to as a "soft power" approach, which can be summarized in the abbreviation RISQ: focus on Relationships; provide Incentives for general practitioners to spend more time with their patients and provide guidelines-based care; Support general practitioners by developing learning modules to improve their practices; and, through the incentive payments and learning modules, provide better Quality care to patients and improved satisfaction to physicians. There are many similarities between the British Columbian approach to primary care and the US patient-centered medical home.

  11. Effects of Mg doping on the remarkably enhanced electrochemical performance of Na 3V 2(PO 4) 3 cathode materials for sodium ion batteries

    DOE PAGES

    Li, Hui; Yu, Xiqian; Bai, Ying; ...

    2015-01-01

    Na 3V 2-xMg x(PO 4) 3/C composites with different Mg 2+ doping contents (x=0, 0.01, 0.03, 0.05, 0.07 and 0.1) were prepared by a facile sol-gel method. The doping effects on the crystal structure were investigated by XRD, XPS and EXAFS. The results show that low dose doping Mg 2+ does not alter the structure of the material, and magnesium is successfully substituted for vanadium site. The Mg doped Na 3V 2-xMg x(PO 4) 3/C composites exhibit significant improvements on the electrochemistry performances in terms of the rate capability and cycle performance, especially for the Na 3V 1.95Mg 0.05(PO 4)more » 3/C. For example, when the current density increased from 1 C to 30 C, the specific capacity only decreased from 112.5 mAh g-1 to 94.2 mAh g -1 showing very good rate capability. Moreover, even cycling at a high rate of 20 C, an excellent capacity retention of 81% is maintained from the initial value of 106.4 mAh g-1 to 86.2 mAh g-1 at the 50th cycle. Enhanced rate capability and cycle performance can be attributed to the optimized particle size, structural stability and enhanced ionic and electronic conductivity induced by Mg doping.« less

  12. 25. PRIMARY POWER TRANSMISSION BELT HOLES IN 1st FLOOR MILL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    25. PRIMARY POWER TRANSMISSION BELT HOLES IN 1st FLOOR MILL NO. 1 CEILING. WATER-POWERED MACHINERY LOCATED IN BASEMENT RAN LEATHER BELTS THROUGH THESE HOLES. POWER WAS THEN TRANSMITTED TO SHAFTS AND PULLEYS TO RUN MACHINERY ON MILL FLOORS. - Prattville Manufacturing Company, Number One, 242 South Court Street, Prattville, Autauga County, AL

  13. c-Myc Represses Transcription of Epstein-Barr Virus Latent Membrane Protein 1 Early after Primary B Cell Infection.

    PubMed

    Price, Alexander M; Messinger, Joshua E; Luftig, Micah A

    2018-01-15

    Recent evidence has shown that the Epstein-Barr virus (EBV) oncogene LMP1 is not expressed at high levels early after EBV infection of primary B cells, despite its being essential for the long-term outgrowth of immortalized lymphoblastoid cell lines (LCLs). In this study, we found that expression of LMP1 increased 50-fold between 7 days postinfection and the LCL state. Metabolic labeling of nascent transcribed mRNA indicated that this was primarily a transcription-mediated event. EBNA2, the key viral transcription factor regulating LMP1, and CTCF, an important chromatin insulator, were recruited to the LMP1 locus similarly early and late after infection. However, the activating histone H3K9Ac mark was enriched at the LMP1 promoter in LCLs relative to that in infected B cells early after infection. We found that high c-Myc activity in EBV-infected lymphoma cells as well as overexpression of c-Myc in an LCL model system repressed LMP1 transcription. Finally, we found that chemical inhibition of c-Myc both in LCLs and early after primary B cell infection increased LMP1 expression. These data support a model in which high levels of endogenous c-Myc activity induced early after primary B cell infection directly repress LMP1 transcription. IMPORTANCE EBV is a highly successful pathogen that latently infects more than 90% of adults worldwide and is also causally associated with a number of B cell malignancies. During the latent life cycle, EBV expresses a set of viral oncoproteins and noncoding RNAs with the potential to promote cancer. Critical among these is the viral latent membrane protein LMP1. Prior work suggests that LMP1 is essential for EBV to immortalize B cells, but our recent work indicates that LMP1 is not produced at high levels during the first few weeks after infection. Here we show that transcription of the LMP1 gene can be negatively regulated by a host transcription factor, c-Myc. Ultimately, understanding the regulation of EBV oncogenes will allow us

  14. 6. TROJAN MILL, PRIMARY THICKENER No. 1 FROM WEST, c. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. TROJAN MILL, PRIMARY THICKENER No. 1 FROM WEST, c. 1914. TANK COMPLETED PRIOR TO ADDITION OF ENCLOSURE. ADDITION FOR BARREN SOLUTION TANK JUST VISIBLE BETWEEN THICKENER AND CRUSHED ORE BIN. CREDIT WR. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD

  15. Genetic heterogeneity and minor CYP1B1 involvement in the molecular basis of primary congenital glaucoma in Gypsies.

    PubMed

    Sivadorai, P; Cherninkova, S; Bouwer, S; Kamenarova, K; Angelicheva, D; Seeman, P; Hollingsworth, K; Mihaylova, V; Oscar, A; Dimitrova, G; Kaneva, R; Tournev, I; Kalaydjieva, L

    2008-07-01

    Primary congenital glaucoma (PCG) is a genetically heterogeneous disorder of autosomal recessive inheritance, with mutations in the cytochrome P450 1B1 (CYP1B1) gene detected in an average of approximately 50% of cases worldwide. The Roma/Gypsies are considered to be a rare example of a single founder CYP1B1 mutation, E387K (identified in the Slovak Roma), accounting for 100% of disease alleles. Contrary to this concept, unusual genetic heterogeneity was revealed in this study of 21 Gypsy PCG patients from Bulgaria and 715 controls from the general Gypsy population. In our small sample of affected subjects, we identified five different CYP1B1 mutations - four known (E229K, R368H, E387K and R390C) and one novel and potentially pathogenic (F445I), which together accounted for approximately 30% of disease alleles. E387K was rare in both the patient and the control group, indicating that its high frequency in the Slovak Roma is the product of local founder effect not representative of the overall molecular pattern of PCG in the Gypsy population. Data on other Mendelian disorders and on the population genetics of the Gypsies suggest that a true founder mutation is likely to exist and has remained undetected. Our analysis of another candidate gene, MYOC, and the GLC3B and GLC3C loci did not provide support for their involvement. The molecular basis of PCG in the Gypsies is thus unresolved, and diagnostic analyses should be extended beyond the E387K mutation.

  16. Activity of [des-Aspartyl1]-Angiotensin II in Primary Aldosteronism

    PubMed Central

    Carey, Robert M.; Ayers, Carlos R.; Vaughan, E. Darracott; Peach, Michael J.; Herf, Steven M.

    1979-01-01

    This study describes the effects of [des-Aspartyl1]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6±1 to 14±3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33±8 to 65±13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III. Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two

  17. Primary Progressive Aphasia

    MedlinePlus

    ... condition has three types, which cause different symptoms. Semantic variant primary progressive aphasia Symptoms include these difficulties: ... a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does ...

  18. 1-norm support vector novelty detection and its sparseness.

    PubMed

    Zhang, Li; Zhou, WeiDa

    2013-12-01

    This paper proposes a 1-norm support vector novelty detection (SVND) method and discusses its sparseness. 1-norm SVND is formulated as a linear programming problem and uses two techniques for inducing sparseness, or the 1-norm regularization and the hinge loss function. We also find two upper bounds on the sparseness of 1-norm SVND, or exact support vector (ESV) and kernel Gram matrix rank bounds. The ESV bound indicates that 1-norm SVND has a sparser representation model than SVND. The kernel Gram matrix rank bound can loosely estimate the sparseness of 1-norm SVND. Experimental results show that 1-norm SVND is feasible and effective. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Immunoprecipitation of Tri-methylated Capped RNA.

    PubMed

    Hayes, Karen E; Barr, Jamie A; Xie, Mingyi; Steitz, Joan A; Martinez, Ivan

    2018-02-05

    Cellular quiescence (also known as G 0 arrest) is characterized by reduced DNA replication, increased autophagy, and increased expression of cyclin-dependent kinase p27 Kip1 . Quiescence is essential for wound healing, organ regeneration, and preventing neoplasia. Previous findings indicate that microRNAs (miRNAs) play an important role in regulating cellular quiescence. Our recent publication demonstrated the existence of an alternative miRNA biogenesis pathway in primary human foreskin fibroblast (HFF) cells during quiescence. Indeed, we have identified a group of pri-miRNAs (whose mature miRNAs were found induced during quiescence) modified with a 2,2,7-trimethylguanosine (TMG)-cap by the trimethylguanosine synthase 1 (TGS1) protein and transported to the cytoplasm by the Exportin-1 (XPO1) protein. We used an antibody against (TMG)-caps (which does not cross-react with the (m 7 G)-caps that most pri-miRNAs or mRNAs contain [Luhrmann et al ., 1982]) to perform RNA immunoprecipitations from total RNA extracts of proliferating or quiescent HFFs. The novelty of this assay is the specific isolation of pri-miRNAs as well as other non-coding RNAs containing a TMG-cap modification.

  20. Nurse practitioner organizational climate in primary care settings: implications for professional practice.

    PubMed

    Poghosyan, Lusine; Nannini, Angela; Stone, Patricia W; Smaldone, Arlene

    2013-01-01

    The expansion of the nurse practitioner (NP) workforce in primary care is key to meeting the increased demand for care. Organizational climates in primary care settings affect NP professional practice and the quality of care. This study investigated organizational climate and its domains affecting NP professional practice in primary care settings. A qualitative descriptive design, with purposive sampling, was used to recruit 16 NPs practicing in primary care settings in Massachusetts. An interview guide was developed and pretested with two NPs and in 1 group interview with 7 NPs. Data collection took place in spring of 2011. Individual interviews lasted from 30-70 minutes, were audio recorded, and transcribed. Data were analyzed using Atlas.ti 6.0 software by 3 researchers. Content analysis was applied. Three previously identified themes, NP-physician relations, independent practice and autonomy, and professional visibility, as well as two new themes, organizational support and resources and NP-administration relations emerged from the analyses. NPs reported collegial relations with physicians, challenges in establishing independent practice, suboptimal relationships with administration, and lack of support. NP contributions to patient care were invisible. Favorable organizational climates should be promoted to support the expanding of NP workforce in primary care and to optimize recruitment and retention efforts. © 2013.

  1. Different patterns of social support perceived and their association with physical (hypertension, diabetes) or mental diseases in the context of primary health care.

    PubMed

    Aragão, Ellen Ingrid Souza; Portugal, Flávia Batista; Campos, Mônica Rodrigues; Lopes, Claudia de Souza; Fortes, Sandra Lúcia Correia Lima

    2017-07-01

    This work discusses the relationship between hypertension, diabetes, anxiety, depression, and social support in primary health care. This research aimed to identify the association between physical disease, mental disease, support network and perceived social support in the research sample. This is a cross-sectional study inserted in a larger research project funded by the Pan American Health Organization and carried out in 2002 in Petrópolis, RJ. The sample consisted of 714 patients with ages ranging from 18 to 65 years old. Results showed association between variables from support network either with evidence of hypertension or diabetes, or with the existence of common mental disorders, but with different patterns. Associations with the perceived support were positive in patients with hypertension and diabetes; Common Mental Disorder patients showed negative associations, inversely associated to the level of mental disease.

  2. Social support for diabetes illness management: supporting adolescents and caregivers.

    PubMed

    Idalski Carcone, April; Ellis, Deborah A; Weisz, Arlene; Naar-King, Sylvie

    2011-10-01

    The aim of this research study was to examine the relationship between 4 sources of social support (support for the adolescent from family, support for the adolescent from friends, support for the caregiver from another adult, and support to the family from the health care provider) and adolescents' diabetes outcomes (illness management behavior and health status) using a diverse sample of urban adolescents. One hundred forty-one adolescents with insulin-managed diabetes and their primary caregivers completed questionnaires assessing social support and illness management behavior. Glucose meters were downloaded and hemoglobin A1c assays were obtained. Structural equation modeling was used to test a model social support informed by social ecological theory. The results of the structural equation modeling indicated that support for the caregiver from another adult was directly and positively related to support for the adolescent from family and indirectly related to better illness management. Support for the adolescent from family was directly related to better diabetes management and, through better management, to better diabetes health. Support to the family from the health care provider was not related to support for the adolescent and support to the adolescent from friends was not related to illness management, as hypothesized. This study identifies a novel target for social support intervention to improve adolescents' illness management behavior-the caregivers of adolescents with diabetes. By enhancing the social support caregivers receive from other adults in their lives, caregivers' ability to support their adolescent children with diabetes might also be improved which, in turn, improves adolescents' illness outcomes.

  3. Transferrin receptor 1 upregulation in primary tumor and downregulation in benign kidney is associated with progression and mortality in renal cell carcinoma patients

    PubMed Central

    Greene, Christopher J.; Attwood, Kristopher; Sharma, Nitika J.; Gross, Kenneth W.; Smith, Gary J.; Xu, Bo; Kauffman, Eric C.

    2017-01-01

    The central dysregulated pathway of clear cell (cc) renal cell carcinoma (RCC), the von Hippel Lindau/hypoxia inducible factor-α axis, is a key regulator of intracellular iron levels, however the role of iron uptake in human RCC tumorigenesis and progression remains unknown. We conducted a thorough, large-scale investigation of the expression and prognostic significance of the primary iron uptake protein, transferrin receptor 1 (TfR1/CD71/TFRC), in RCC patients. TfR1 immunohistochemistry was performed in over 1500 cores from 574 renal cell tumor patient tissues (primary tumors, matched benign kidneys, metastases) and non-neoplastic tissues from 36 different body sites. TfR1 levels in RCC tumors, particularly ccRCC, were significantly associated with adverse clinical prognostic features (anemia, lower body mass index, smoking), worse tumor pathology (size, stage, grade, multifocality, sarcomatoid dedifferentiation) and worse survival outcomes, including after adjustments for tumor pathology. Highest TfR1 tissue levels in the non-gravid body were detected in benign renal tubule epithelium. Opposite to TfR1 changes in the primary tumor, TfR1 levels in benign kidney dropped during tumor progression and were inversely associated with worse survival outcomes, independent of tumor pathology. Quantitative measurement of TfR1 subcellular localization in cell lines demonstrated mixed cytoplasmic and membranous expression with increased TfR1 in clusters in ccRCC versus benign renal cell lines. Results of this study support an important role for TfR1 in RCC progression and identify TfR1 as a novel RCC biomarker and therapeutic target. PMID:29291011

  4. Transition of Students with Autistic Spectrum Disorders from Primary to Post-Primary School: A Framework for Success

    ERIC Educational Resources Information Center

    Deacy, Evelyn; Jennings, Fiona; O'Halloran, Ailbhe

    2015-01-01

    The purpose of this research was to investigate best practice in relation to the planning, process and strategies that support the transition of students with ASD from primary to post-primary school. A questionnaire survey was sent to graduates of a postgraduate Certificate/Diploma in SEN (ASD) in Ireland who were working in primary and…

  5. Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells

    PubMed Central

    Raab, Monika; Kappel, Sven; Krämer, Andrea; Sanhaji, Mourad; Matthess, Yves; Kurunci-Csacsko, Elisabeth; Calzada-Wack, Julia; Rathkolb, Birgit; Rozman, Jan; Adler, Thure; Busch, Dirk H.; Esposito, Irene; Fuchs, Helmut; Gailus-Durner, Valérie; Klingenspor, Martin; Wolf, Eckhard; Sänger, Nicole; Prinz, Florian; Angelis, Martin Hrabě de; Seibler, Jost; Yuan, Juping; Bergmann, Martin; Knecht, Rainald; Kreft, Bertolt; Strebhardt, Klaus

    2011-01-01

    High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions. PMID:21772266

  6. RNA Export through the NPC in Eukaryotes

    PubMed Central

    Okamura, Masumi; Inose, Haruko; Masuda, Seiji

    2015-01-01

    In eukaryotic cells, RNAs are transcribed in the nucleus and exported to the cytoplasm through the nuclear pore complex. The RNA molecules that are exported from the nucleus into the cytoplasm include messenger RNAs (mRNAs), ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), small nuclear RNAs (snRNAs), micro RNAs (miRNAs), and viral mRNAs. Each RNA is transported by a specific nuclear export receptor. It is believed that most of the mRNAs are exported by Nxf1 (Mex67 in yeast), whereas rRNAs, snRNAs, and a certain subset of mRNAs are exported in a Crm1/Xpo1-dependent manner. tRNAs and miRNAs are exported by Xpot and Xpo5. However, multiple export receptors are involved in the export of some RNAs, such as 60S ribosomal subunit. In addition to these export receptors, some adapter proteins are required to export RNAs. The RNA export system of eukaryotic cells is also used by several types of RNA virus that depend on the machineries of the host cell in the nucleus for replication of their genome, therefore this review describes the RNA export system of two representative viruses. We also discuss the NPC anchoring-dependent mRNA export factors that directly recruit specific genes to the NPC. PMID:25802992

  7. Formative and summative assessment of science in English primary schools: evidence from the Primary Science Quality Mark

    NASA Astrophysics Data System (ADS)

    Earle, Sarah

    2014-05-01

    Background:Since the discontinuation of Standard Attainment Tests (SATs) in science at age 11 in England, pupil performance data in science reported to the UK government by each primary school has relied largely on teacher assessment undertaken in the classroom. Purpose:The process by which teachers are making these judgements has been unclear, so this study made use of the extensive Primary Science Quality Mark (PSQM) database to obtain a 'snapshot' (as of March 2013) of the approaches taken by 91 English primary schools to the formative and summative assessment of pupils' learning in science. 1" sec-type="S0003" id="S0003">PSQM is an award scheme for UK primary schools. It requires the science subject leader (co-ordinator) in each school to reflect upon and develop practice over the course of one year, then upload a set of reflections and supporting evidence to the database to support their application. One of the criteria requires the subject leader to explain how science is assessed within the school. Sample:The data set consists of the electronic text in the assessment section of all 91 PSQM primary schools which worked towards the Quality Mark in the year April 2012 to March 2013. Design and methods:Content analysis of a pre-existing qualitative data set. Text in the assessment section of each submission was first coded as describing formative or summative processes, then sub-coded into different strategies used. Results:A wide range of formative and summative approaches were reported, which tended to be described separately, with few links between them. Talk-based strategies are widely used for formative assessment, with some evidence of feedback to pupils. Whilst the use of tests or tracking grids for summative assessment is widespread, few schools rely on one system alone. Enquiry skills and conceptual knowledge were often assessed separately. 1" id="S0007">Conclusions:There is little consistency in the approaches</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20018477','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20018477"><span>On the sparseness of <span class="hlt">1</span>-norm <span class="hlt">support</span> vector machines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhang, Li; Zhou, Weida</p> <p>2010-04-01</p> <p>There is some empirical evidence available showing that <span class="hlt">1</span>-norm <span class="hlt">Support</span> Vector Machines (<span class="hlt">1</span>-norm SVMs) have good sparseness; however, both how good sparseness <span class="hlt">1</span>-norm SVMs can reach and whether they have a sparser representation than that of standard SVMs are not clear. In this paper we take into account the sparseness of <span class="hlt">1</span>-norm SVMs. Two upper bounds on the number of nonzero coefficients in the decision function of <span class="hlt">1</span>-norm SVMs are presented. First, the number of nonzero coefficients in <span class="hlt">1</span>-norm SVMs is at most equal to the number of only the exact <span class="hlt">support</span> vectors lying on the +<span class="hlt">1</span> and -<span class="hlt">1</span> discriminating surfaces, while that in standard SVMs is equal to the number of <span class="hlt">support</span> vectors, which implies that <span class="hlt">1</span>-norm SVMs have better sparseness than that of standard SVMs. Second, the number of nonzero coefficients is at most equal to the rank of the sample matrix. A brief review of the geometry of linear programming and the primal steepest edge pricing simplex method are given, which allows us to provide the proof of the two upper bounds and evaluate their tightness by experiments. Experimental results on toy data sets and the UCI data sets illustrate our analysis. Copyright 2009 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29742291','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29742291"><span>PD-<span class="hlt">1</span> and PD-L<span class="hlt">1</span> expression in HNSCC <span class="hlt">primary</span> cancer and related lymph node metastasis - impact on clinical outcome.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Schneider, Sven; Kadletz, Lorenz; Wiebringhaus, Robert; Kenner, Lukas; Selzer, Edgar; Füreder, Thorsten; Rajky, Orsolya; Berghoff, Anna S; Preusser, Matthias; Heiduschka, Gregor</p> <p>2018-05-09</p> <p>Expression profiles and clinical impact of programmed cell death ligand <span class="hlt">1</span> (PD-L<span class="hlt">1</span>) and programmed cell death <span class="hlt">1</span> (PD-<span class="hlt">1</span>) expressing tumour infiltrating lymphocytes (TILs) in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. This study evaluates expression patterns in <span class="hlt">primary</span> HNSCC and related lymph node metastasis and impact on patients' clinical outcome. Immunohistochemical staining patterns of PD-L<span class="hlt">1</span> and PD-<span class="hlt">1</span> were evaluated in 129 specimens of <span class="hlt">primary</span> HNSCC and 77 lymph node metastases. Results were correlated to patients' clinical data. PD-L<span class="hlt">1</span> expression was observed in 36% of <span class="hlt">primary</span> carcinoma and 33% of lymph node metastasis and significantly correlates with decreased overall survival (OS) (p=0.01) and disease free survival (DFS) (p=0.001) in oral cavity squamous cell carcinoma patients. PD-L<span class="hlt">1</span> expression was associated with presence of lymph node metastasis (p=0.0223). Infiltration of PD-<span class="hlt">1</span> expressing lymphocytes significantly correlates with favorable OS (p=0.001) and DFS (p=0.001) in oropharyngeal cancer and hypopharyngeal cancer patients OS (p=0.007) and DFS (p=0.001). Presence of PD-<span class="hlt">1</span> TILs significantly correlates with better OS (p=0.005) and DFS (p=0) also in the HPV negative cohort. Cox regression multivariate analysis revealed PD-<span class="hlt">1</span> TIL expression as an independent prognostic marker for OS (p=0.004) and DFS (p=0.001) and T stage was validated as negative prognostic marker for OS (p=0.011). PD-<span class="hlt">1</span> expressing lymphocytes (p=0.0412) and PD-L<span class="hlt">1</span> expression (p=0.0022) patterns correlate significantly in <span class="hlt">primary</span> cancers and matched lymph node metastases. Our results characterize the expression profiles of PD-<span class="hlt">1</span> axis proteins in HNSCC which might serve as possible clinical prognostic markers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28018871','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28018871"><span>Integration of chronic disease prevention and management services into <span class="hlt">primary</span> care: a pragmatic randomized controlled trial (PR<span class="hlt">1</span>MaC).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Fortin, Martin; Chouinard, Maud-Christine; Dubois, Marie-France; Bélanger, Martin; Almirall, José; Bouhali, Tarek; Sasseville, Maxime</p> <p>2016-01-01</p> <p>Chronic disease prevention and management programs are usually single-disease oriented. Our objective was to evaluate an intervention that targeted multiple chronic conditions and risk factors. We conducted a pragmatic randomized controlled trial involving patients aged 18-75 years with at least <span class="hlt">1</span> of the targeted chronic conditions or risk factors from 8 <span class="hlt">primary</span> care practices in the Saguenay region of Quebec, Canada, to evaluate an intervention that included self-management <span class="hlt">support</span> and patient-centred motivational approaches. Self-management (<span class="hlt">primary</span> outcome) was evaluated using the Health Education Impact Questionnaire (heiQ). Secondary outcomes included self-efficacy, health-related quality of life, psychological distress and health behaviours. Three hundred thirty-two patients were recruited and randomly assigned ( n = 166 for both intervention and control groups) and evaluated after 3 months. The intervention group showed improvement in 6 of the 8 heiQ domains: health-directed behaviour (relative risk [RR] <span class="hlt">1</span>.71, 95% confidence interval [CI] <span class="hlt">1</span>.13 to 2.59), emotional well-being (RR <span class="hlt">1</span>.73, 95% CI <span class="hlt">1</span>.07 to 2.79), self-monitoring and insight (RR 2.40, 95% CI <span class="hlt">1</span>.19 to 4.86), constructive attitudes and approaches (RR 2.40, 95% CI <span class="hlt">1</span>.37 to 4.21), skill and technique acquisition (RR <span class="hlt">1</span>.70, 95% CI <span class="hlt">1</span>.14 to 2.53), and health service navigation (RR <span class="hlt">1</span>.93, 95% CI <span class="hlt">1</span>.08 to 3.47). Improvement was also observed in the Physical Component Summary ( p = 0.017) and the Single Index ( p = 0.041) of the 12-Item Short Form Health Survey (version 2). The intervention group improved in fruit and vegetable consumption (odds ratio [OR] 2.36, 95% CI <span class="hlt">1</span>.41 to 3.95) and physical activity (OR 3.81, 95% CI <span class="hlt">1</span>.65 to 8.76). One-year improvement was maintained in the intervention group for several outcomes. It is possible to implement an intervention integrating chronic disease prevention and management services into <span class="hlt">primary</span> care settings. We obtained positive and promising results using this</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23692212','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23692212"><span><span class="hlt">Supporting</span> adolescents with type <span class="hlt">1</span> diabetes mellitus: a qualitative study.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rostami, Shahnaz; Parsa-Yekta, Zohreh; Najafi Ghezeljeh, Tahereh; Vanaki, Zohreh</p> <p>2014-03-01</p> <p>Without sufficient <span class="hlt">support</span>, type <span class="hlt">1</span> diabetes mellitus often disturbs patients' normal lives. This study describes and explores the <span class="hlt">support</span> that Iranian adolescents with type <span class="hlt">1</span> diabetes mellitus experienced. Semistructured interviews were conducted with ten adolescents, seven family members, one dietitian, one nurse, and one school nurse. Participants were chosen using purposive sampling from two teaching hospitals and one high school in two urban areas of Iran. Using standard procedures for content analysis, three main themes were identified: maintaining a normal life; receiving tangible, informational, and emotional <span class="hlt">support</span> from the family and society; and advancement of life toward normalization. The cornerstone of maintaining a normal life for adolescents with type <span class="hlt">1</span> diabetes mellitus is to adopt an active role in taking care of themselves within their systems of <span class="hlt">support</span>. © 2013 Wiley Publishing Asia Pty Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24723877','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24723877"><span>Enhanced peripheral visual processing in congenitally deaf humans is <span class="hlt">supported</span> by multiple brain regions, including <span class="hlt">primary</span> auditory cortex.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Scott, Gregory D; Karns, Christina M; Dow, Mark W; Stevens, Courtney; Neville, Helen J</p> <p>2014-01-01</p> <p>Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems <span class="hlt">supporting</span> this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of <span class="hlt">primary</span> auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11-15° vs. 2-7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined <span class="hlt">primary</span> auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including <span class="hlt">primary</span> auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including <span class="hlt">primary</span> auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf adults.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=payment+AND+system&pg=7&id=EJ473318','ERIC'); return false;" href="https://eric.ed.gov/?q=payment+AND+system&pg=7&id=EJ473318"><span>Providing <span class="hlt">Primary</span> Health Care to Children: Integrating <span class="hlt">Primary</span> Care Services with Health Insurance Principles.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Rosenbaum, Sara</p> <p>1993-01-01</p> <p>Examines how health care reform might be structured to provide <span class="hlt">support</span> for a package of <span class="hlt">primary</span> care services for children of all socioeconomic strata. An insurance-like financing system, such as the special Medicaid payment system adopted by New York State for public and nonprofit <span class="hlt">primary</span> health care programs, may be useful as a model for a…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/pages/biblio/1326043-numerical-simulations-primary-secondary-hydrogen-ena-fluxes-au','SCIGOV-DOEP'); return false;" href="https://www.osti.gov/pages/biblio/1326043-numerical-simulations-primary-secondary-hydrogen-ena-fluxes-au"><span>Numerical simulations of <span class="hlt">primary</span> and secondary hydrogen ENA fluxes at <span class="hlt">1</span> AU</span></a></p> <p><a target="_blank" href="http://www.osti.gov/pages">DOE PAGES</a></p> <p>Zirnstein, Eric; Heerikhuisen, Jacob; Pogorelov, Nikolai</p> <p>2012-11-20</p> <p>The interaction between the solar wind (SW) and the local interstellar medium (LISM) creates energetic neutral atoms (ENAs), mainly Hydrogen (H), at energies similar to ions in the SW. H ENAs are born from charge exchanges between SW protons and LISM H atoms. A large portion of measurable <span class="hlt">primary</span> ENAs are born in the inner heliosheath (IHS), where the heated and condensed SW plasma has a large thermal component to direct ENAs back toward <span class="hlt">1</span> AU. Secondary ENAs, however, require secondary charge exchanges before being detected at <span class="hlt">1</span> AU. <span class="hlt">Primary</span> ENAs born in the supersonic and subsonic SW may exitmore » the HP, charge exchange into pick-up ions (PUIs), and charge exchange again to become secondary ENAs. Recent IBEX observations show a ribbon of flux dominating the entire sky. It is possible that the IBEX ribbon is created through secondary charge exchange processes. In this article we present a numerical code that calculates <span class="hlt">primary</span> and secondary H ENA fluxes by integrating along ENA trajectories. Here we will provide descriptions of the code and preliminary results.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29846859','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29846859"><span>Type I collagen-induced YAP nuclear expression promotes <span class="hlt">primary</span> cilia growth and contributes to cell migration in confluent mouse embryo fibroblast 3T3-L<span class="hlt">1</span> cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Xu, Qian; Liu, Xiaoling; Liu, Weiwei; Hayashi, Toshihiko; Yamato, Masayuki; Fujisaki, Hitomi; Hattori, Shunji; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi</p> <p>2018-05-30</p> <p>The extracellular matrix (ECM) is a major biomechanical environment for all cells in vivo, and tightly controls wound healing and cancer progression. Type I collagen (Col I) is the most abundant component in ECM and plays an essential role for cell motility control and migration beyond structural <span class="hlt">support</span>. Our previous results showed that Col I increased the length of <span class="hlt">primary</span> cilia and the expression of <span class="hlt">primary</span> cilia-associated proteins in 3T3-L<span class="hlt">1</span> cells. The Hippo/YAP pathway serves as a major integrator of cell surface-mediated signals and regulates key processes for the development and maintenance of tissue functions. In this study, we investigated the role of Hippo/YAP signaling in <span class="hlt">primary</span> cilia growth of cells cultured on Col I-coated plate, as well as the potential link between <span class="hlt">primary</span> cilia and migration. At 2-day post-confluence, YAP localization in the nucleus was dramatically increased when the cells were cultured on Col I-coated plate, accompanied by cilia growth. YAP inhibitor verteporfin repressed the growth of <span class="hlt">primary</span> cilia as well as the expressions of ciliogenesis-associated proteins in confluent 3T3-L<span class="hlt">1</span> cells cultured on Col I-coated plate. Moreover, knockdown of either YAP or IFT88, one of the ciliogenesis-associated proteins, reversed the migration of confluent 3T3-L<span class="hlt">1</span> cells promoted by Col I-coating. In conclusion, activation of YAP pathway by Col I-coating of culture plate for confluent 3T3-L<span class="hlt">1</span> cells is positively associated with the <span class="hlt">primary</span> cilia growth, which eventually results in promoted migration.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.epa.gov/air-emissions-modeling/2005-v41-technical-support-document','PESTICIDES'); return false;" href="https://www.epa.gov/air-emissions-modeling/2005-v41-technical-support-document"><span>2005 v4.<span class="hlt">1</span> Technical <span class="hlt">Support</span> Document</span></a></p> <p><a target="_blank" href="http://www.epa.gov/pesticides/search.htm">EPA Pesticide Factsheets</a></p> <p></p> <p></p> <p>Preparation of Emission Inventories for the Version 4.<span class="hlt">1</span>, 2005-based Platform describes how emissions from the 2005 NEI, version 2 and were processed for air quality modeling in <span class="hlt">support</span> of the Boiler MACT and the Mercury and Air Toxics Standards.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19730015543','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19730015543"><span>Tracking and data system <span class="hlt">support</span> for the Mariner Mars 1971 mission. Volume 3: Orbit insertion through end of <span class="hlt">primary</span> mission</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Barnum, P. W.; Renzetti, N. A.; Textor, G. P.; Kelly, L. B.</p> <p>1973-01-01</p> <p>The Tracking and Data System (TDS) <span class="hlt">Support</span> for the Mariner Mars 1971 Mission final report contains the deep space tracking and data acquisition activities in <span class="hlt">support</span> of orbital operations. During this period a major NASA objective was accomplished: completion of the 180th revolution and 90th day of data gathering with the spacecraft about the planet Mars. Included are presentations of the TDS flight <span class="hlt">support</span> pass chronology data for each of the Deep Space Stations used, and performance evaluation for the Deep Space Network Telemetry, Tracking, Command, and Monitor Systems. With the loss of Mariner 8 at launch, Mariner 9 assumed the mission plan of Mariner 8, which included the TV mapping cycles and a 12-hr orbital period. The mission plan was modified as a result of a severe dust storm on the surface of Mars, which delayed the start of the TV mapping cycles. Thus, the end of <span class="hlt">primary</span> mission date was extended to complete the TV mapping cycles.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28186056','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28186056"><span>A Conceptual Model for Increasing Use of Electronic Medical Records by <span class="hlt">Primary</span> Care Physicians Through End-User <span class="hlt">Support</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Randhawa, Gurprit K</p> <p>2017-01-01</p> <p>A conceptual model for exploring the relationship between end-user <span class="hlt">support</span> (EUS) and electronic medical record (EMR) use by <span class="hlt">primary</span> care physicians is presented. The model was developed following a review of conceptual and theoretical frameworks related to technology adoption/use and EUS. The model includes (a) one core construct (facilitating conditions), (b) four antecedents and one postcedent of facilitating conditions, and (c) four moderators. EMR use behaviour is the key outcome of the model. The proposed conceptual model should be tested. The model may be used to inform planning and decision-making for EMR implementations to increase EMR use for benefits realization.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22240033','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22240033"><span>Corticosteroid therapy in patients with <span class="hlt">primary</span> viral pneumonia due to pandemic (H<span class="hlt">1</span>N<span class="hlt">1</span>) 2009 influenza.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Diaz, Emili; Martin-Loeches, Ignacio; Canadell, Laura; Vidaur, Loreto; Suarez, David; Socias, Lorenzo; Estella, Angel; Gil Rueda, Bernardo; Guerrero, José Eugenio; Valverdú-Vidal, Montserrat; Vergara, Juan Carlos; López-Pueyo, María Jesús; Magret, Mónica; Recio, Teresa; López, Diego; Rello, Jordi; Rodriguez, Alejandro</p> <p>2012-03-01</p> <p>During the first pandemic, some patients with pandemic (H<span class="hlt">1</span>N<span class="hlt">1</span>) 2009 influenza were treated with corticosteroids. The objective of this study was to assess the effect on survival of corticosteroid therapy in patients with pandemic (H<span class="hlt">1</span>N<span class="hlt">1</span>) 2009 influenza. Prospective, observational, multicenter study performed in 148 ICU. Data were recorded in the GTEI/SEMICYUC registry. Adult patients with pandemic (H<span class="hlt">1</span>N<span class="hlt">1</span>) 2009 influenza confirmed by rt-PCR were included in the analysis. Database records specified corticosteroid type and reason for corticosteroid treatment. 372 patients with the diagnosis of <span class="hlt">primary</span> viral pneumonia and completed outcomes treated in an ICU were included in the database. Mechanical ventilation was used in 70.2% of the patients. 136 (36.6%) patients received corticosteroids after a diagnosis of <span class="hlt">primary</span> viral pneumonia. Obesity (35.6% vs 47.8% p = 0.021) and asthma (7.6% vs 15.4% p = 0.018), were more frequent in the group treated with corticosteroids. A Cox regression analysis adjusted for severity and potential confounding factors found that the use of corticosteroid therapy was not significantly associated with mortality (HR = <span class="hlt">1</span>.06, 95% CI 0.626-<span class="hlt">1</span>.801; p = 0.825). Corticosteroid therapy in a selected group of patients with <span class="hlt">primary</span> viral pneumonia due to pandemic (H<span class="hlt">1</span>N<span class="hlt">1</span>) 2009 influenza does not improve survival. Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.loc.gov/pictures/collection/hh/item/sd0019.photos.189325p/','SCIGOV-HHH'); return false;" href="https://www.loc.gov/pictures/collection/hh/item/sd0019.photos.189325p/"><span>5. TROJAN MILL, <span class="hlt">PRIMARY</span> THICKENER No. <span class="hlt">1</span> FROM WEST, c. ...</span></a></p> <p><a target="_blank" href="http://www.loc.gov/pictures/collection/hh/">Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey</a></p> <p></p> <p></p> <p>5. TROJAN MILL, <span class="hlt">PRIMARY</span> THICKENER No. <span class="hlt">1</span> FROM WEST, c. 1914. TANK BARREL IS COMPLETE, BUT ADDITION ENCLOSURE NOT YET BEGUN. SAMPLING ADDITION SOUTH OF CRUSHED ORE BIN (CHANGE OF SIDING COLOR SHOWN AS COMPLETE. ROCK BIN VISIBLE ON FAR RIGHT. CREDIT WR. - Bald Mountain Gold Mill, Nevada Gulch at head of False Bottom Creek, Lead, Lawrence County, SD</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_15");'>15</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li class="active"><span>17</span></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_17 --> <div id="page_18" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="341"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25613929','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25613929"><span>[Professional quality of life in workers of the Toledo <span class="hlt">primary</span> care health area].</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Villarín Castro, A; Méndez García, T; Zuzuárregui Gironés, M S; Sánchez Serrano, S; Conejo Ocaña, R</p> <p>2015-01-01</p> <p>To determine the professional quality of life in the workers of the Toledo <span class="hlt">Primary</span> Care Health Area and to analyse its components. Descriptive, cross-sectional study, performed on workers of the Toledo <span class="hlt">Primary</span> Care Health Area with an online self-administered questionnaire. age, sex, health centre, professional group, seniority, management experience, collaboration in working groups, employment situation, and the PQL-35 professional quality of life questionnaire. A total of 430 completed questionnaires were received (45.3%), of which 68.4% were women. The mean age was 47.7±8.6 years old. Mean seniority was 21.5±9.7 years. PQL-35 results were: perception of management <span class="hlt">support</span> 4.8±<span class="hlt">1</span>.5; perception of workload 6.2±<span class="hlt">1</span>.3; intrinsic motivation 7.9±<span class="hlt">1.1</span>; job disconnection capacity 6.3±2.6; and professional quality of life 5.2±2.<span class="hlt">1</span>. Gender differences were found in perception of management <span class="hlt">support</span> (4.5±<span class="hlt">1</span>.5 in males vs 4.9±<span class="hlt">1</span>.5 in females; P=.031) and professional quality of life (4.9±2.0 vs 5.3±2.<span class="hlt">1</span>; p=.044). Depending on the professional group, differences were found in the perception of workload (6.4±<span class="hlt">1.1</span> in physicians, 6.3±<span class="hlt">1</span>.3 in nurses, 5.9±<span class="hlt">1</span>.6 in non-sanitary professionals, and 5.3±<span class="hlt">1</span>.2 in <span class="hlt">support</span> units professionals; P<.001). Depending on the employment situation, differences were found in the intrinsic motivation (7.8±<span class="hlt">1.1</span> in proprietors, 8.3±<span class="hlt">1.1</span> in temporary workers, and 8.2±<span class="hlt">1.1</span> in substitutes; P=.002). The professional quality of life in the workers of the Toledo <span class="hlt">Primary</span> Care Health Area is similar to that of other Spanish Health Areas, even in a time of economic crisis. The intrinsic motivation of the professionals is very high, in contrast with their high perception of workload and their low perception of management <span class="hlt">support</span>. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22888130','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22888130"><span>The peach (Prunus persica L. Batsch) genome harbours 10 KNOX genes, which are differentially expressed in stem development, and the class <span class="hlt">1</span> KNOPE<span class="hlt">1</span> regulates elongation and lignification during <span class="hlt">primary</span> growth.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Testone, Giulio; Condello, Emiliano; Verde, Ignazio; Nicolodi, Chiara; Caboni, Emilia; Dettori, Maria Teresa; Vendramin, Elisa; Bruno, Leonardo; Bitonti, Maria Beatrice; Mele, Giovanni; Giannino, Donato</p> <p>2012-09-01</p> <p>The KNOTTED-like (KNOX) genes encode homeodomain transcription factors and regulate several processes of plant organ development. The peach (Prunus persica L. Batsch) genome was found to contain 10 KNOX members (KNOPE genes); six of them were experimentally located on the Prunus reference map and the class <span class="hlt">1</span> KNOPE<span class="hlt">1</span> was found to link to a quantitative trait locus (QTL) for the internode length in the peach×Ferganensis population. All the KNOPE genes were differentially transcribed in the internodes of growing shoots; the KNOPE<span class="hlt">1</span> mRNA abundance decreased progressively from <span class="hlt">primary</span> (elongation) to secondary growth (radial expansion). During <span class="hlt">primary</span> growth, the KNOPE<span class="hlt">1</span> mRNA was localized in the cortex and in the procambium/metaphloem zones, whereas it was undetected in incipient phloem and xylem fibres. KNOPE<span class="hlt">1</span> overexpression in the Arabidopsis bp4 loss-of-function background (35S:KNOPE<span class="hlt">1</span>/bp genotype) restored the rachis length, suggesting, together with the QTL association, a role for KNOPE<span class="hlt">1</span> in peach shoot elongation. Several lignin biosynthesis genes were up-regulated in the bp4 internodes but repressed in the 35S:KNOPE<span class="hlt">1</span>/bp lines similarly to the wild type. Moreover, the lignin deposition pattern of the 35S:KNOPE<span class="hlt">1</span>/bp and the wild-type internodes were the same. The KNOPE<span class="hlt">1</span> protein was found to recognize in vitro one of the typical KNOX DNA-binding sites that recurred in peach and Arabidopsis lignin genes. KNOPE<span class="hlt">1</span> expression was inversely correlated with that of lignin genes and lignin deposition along the peach shoot stems and was down-regulated in lignifying vascular tissues. These data strongly <span class="hlt">support</span> that KNOPE<span class="hlt">1</span> prevents cell lignification by repressing lignin genes during peach stem <span class="hlt">primary</span> growth.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3444263','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3444263"><span>The peach (Prunus persica L. Batsch) genome harbours 10 KNOX genes, which are differentially expressed in stem development, and the class <span class="hlt">1</span> KNOPE<span class="hlt">1</span> regulates elongation and lignification during <span class="hlt">primary</span> growth</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Giannino, Donato</p> <p>2012-01-01</p> <p>The KNOTTED-like (KNOX) genes encode homeodomain transcription factors and regulate several processes of plant organ development. The peach (Prunus persica L. Batsch) genome was found to contain 10 KNOX members (KNOPE genes); six of them were experimentally located on the Prunus reference map and the class <span class="hlt">1</span> KNOPE<span class="hlt">1</span> was found to link to a quantitative trait locus (QTL) for the internode length in the peach×Ferganensis population. All the KNOPE genes were differentially transcribed in the internodes of growing shoots; the KNOPE<span class="hlt">1</span> mRNA abundance decreased progressively from <span class="hlt">primary</span> (elongation) to secondary growth (radial expansion). During <span class="hlt">primary</span> growth, the KNOPE<span class="hlt">1</span> mRNA was localized in the cortex and in the procambium/metaphloem zones, whereas it was undetected in incipient phloem and xylem fibres. KNOPE<span class="hlt">1</span> overexpression in the Arabidopsis bp4 loss-of-function background (35S:KNOPE<span class="hlt">1</span>/bp genotype) restored the rachis length, suggesting, together with the QTL association, a role for KNOPE<span class="hlt">1</span> in peach shoot elongation. Several lignin biosynthesis genes were up-regulated in the bp4 internodes but repressed in the 35S:KNOPE<span class="hlt">1</span>/bp lines similarly to the wild type. Moreover, the lignin deposition pattern of the 35S:KNOPE<span class="hlt">1</span>/bp and the wild-type internodes were the same. The KNOPE<span class="hlt">1</span> protein was found to recognize in vitro one of the typical KNOX DNA-binding sites that recurred in peach and Arabidopsis lignin genes. KNOPE<span class="hlt">1</span> expression was inversely correlated with that of lignin genes and lignin deposition along the peach shoot stems and was down-regulated in lignifying vascular tissues. These data strongly <span class="hlt">support</span> that KNOPE<span class="hlt">1</span> prevents cell lignification by repressing lignin genes during peach stem <span class="hlt">primary</span> growth. PMID:22888130</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/EJ1001071.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/EJ1001071.pdf"><span>The Effects of a Family <span class="hlt">Support</span> Program Including Respite Care on Parenting Stress and Family Quality of Life Perceived by <span class="hlt">Primary</span> Caregivers of Children with Disabilities in Korea</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Sung, Minjung; Park, Jiyeon</p> <p>2012-01-01</p> <p>In this study, a family <span class="hlt">support</span> program was carried out for <span class="hlt">primary</span> caregivers of children with disabilities. The program included respite care, recreation programs, counseling, and social <span class="hlt">support</span> coordination based on individual needs of each family. In order to verify the intervention effects, parenting stress and family quality of life were…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/EJ908189.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/EJ908189.pdf"><span><span class="hlt">Supporting</span> <span class="hlt">Primary</span> and Secondary Beginning Teachers Online: Key Findings of the Education Alumni <span class="hlt">Support</span> Project</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Maxwell, T. W.; Harrington, I.; Smith, H. J.</p> <p>2010-01-01</p> <p>During 2005, the Education Alumni <span class="hlt">Support</span> Project (EdASP) (Maxwell, Smith, Baxter, Boyd, Harrington, Jenkins, Sargeant & Tamatea 2006) provided online <span class="hlt">support</span> for University of New England (UNE) graduand, and later, graduate, teachers as they commenced their careers. The project was based on research which reported that many beginning teachers…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25648301','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25648301"><span>A cluster randomised controlled trial evaluating the effectiveness of eHealth-<span class="hlt">supported</span> patient recruitment in <span class="hlt">primary</span> care research: the TRANSFoRm study protocol.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mastellos, Nikolaos; Andreasson, Anna; Huckvale, Kit; Larsen, Mark; Curcin, Vasa; Car, Josip; Agreus, Lars; Delaney, Brendan</p> <p>2015-02-03</p> <p>Opportunistic recruitment is a highly laborious and time-consuming process that is currently performed manually, increasing the workload of already busy practitioners and resulting in many studies failing to achieve their recruitment targets. The Translational Medicine and Patient Safety in Europe (TRANSFoRm) platform enables automated recruitment, data collection and follow-up of patients, potentially improving the efficiency, time and costs of clinical research. This study aims to assess the effectiveness of TRANSFoRm in improving patient recruitment and follow-up in <span class="hlt">primary</span> care trials. This multi-centre, parallel-arm cluster randomised controlled trial will compare TRANSFoRm-<span class="hlt">supported</span> with standard opportunistic recruitment. Participants will be general practitioners and patients with gastro-oesophageal reflux disease from 40 <span class="hlt">primary</span> care centres in five European countries. Randomisation will take place at the care centre level. The intervention arm will use the TRANSFoRm tools for recruitment, baseline data collection and follow-up. The control arm will use web-based case report forms and paper self-completed questionnaires. The <span class="hlt">primary</span> outcome will be the proportion of eligible patients successfully recruited at the end of the 16-week recruitment period. Secondary outcomes will include the proportion of recruited patients with complete baseline and follow-up data and the proportion of participants withdrawn or lost to follow-up. The study will also include an economic evaluation and measures of technology acceptance and user experience. The study should shed light on the use of eHealth to improve the effectiveness of recruitment and follow-up in <span class="hlt">primary</span> care research and provide an evidence base for future eHealth-<span class="hlt">supported</span> recruitment initiatives. Reporting of results is expected in October 2015. EudraCT: 2014-001314-25.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078662','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3078662"><span>Electronic decision <span class="hlt">support</span> for diagnostic imaging in a <span class="hlt">primary</span> care setting</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Reed, Martin H</p> <p>2011-01-01</p> <p>Methods Clinical guideline adherence for diagnostic imaging (DI) and acceptance of electronic decision <span class="hlt">support</span> in a rural community family practice clinic was assessed over 36 weeks. Physicians wrote 904 DI orders, 58% of which were addressed by the Canadian Association of Radiologists guidelines. Results Of those orders with guidelines, 76% were ordered correctly; 24% were inappropriate or unnecessary resulting in a prompt from clinical decision <span class="hlt">support</span>. Physicians followed suggestions from decision <span class="hlt">support</span> to improve their DI order on 25% of the initially inappropriate orders. The use of decision <span class="hlt">support</span> was not mandatory, and there were significant variations in use rate. Initially, 40% reported decision <span class="hlt">support</span> disruptive in their work flow, which dropped to 16% as physicians gained experience with the software. Conclusions Physicians <span class="hlt">supported</span> the concept of clinical decision <span class="hlt">support</span> but were reluctant to change clinical habits to incorporate decision <span class="hlt">support</span> into routine work flow. PMID:21486884</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5927103','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5927103"><span>Hypermethylation of the TSLC<span class="hlt">1</span> Gene Promoter in <span class="hlt">Primary</span> Gastric Cancers and Gastric Cancer Cell Lines</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Honda, Teiichiro; Waki, Takayoshi; Jin, Zhe; Sato, Kiyoshi; Motoyama, Teiichi; Kawata, Sumio; Kimura, Wataru; Nishizuka, Satoshi; Murakami, Yoshinori</p> <p>2002-01-01</p> <p>The TSLC<span class="hlt">1</span> (tumor suppressor in lung cancer–<span class="hlt">1</span>) gene is a novel tumor suppressor gene on chromosomal region 11q23.2, and is frequently inactivated by concordant promoter hypermethylation and loss of heterozygosity (LOH) in non‐small cell lung cancer (NSCLC). Because LOH on 11q has also been observed frequently in other human neoplasms including gastric cancer, we investigated the promoter methylation status of TSLC<span class="hlt">1</span> in 10 gastric cancer cell lines and 97 <span class="hlt">primary</span> gastric cancers, as well as the corresponding non‐cancerous gastric tissues, by bisulfite‐SSCP analysis followed by direct sequencing. Allelic status of the TSLC<span class="hlt">1</span> gene was also investigated in these cell lines and <span class="hlt">primary</span> gastric cancers. The TSLC<span class="hlt">1</span> promoter was methylated in two gastric cancer cell lines, KATO‐III and ECC10, and in 15 out of 97 (16%) <span class="hlt">primary</span> gastric cancers. It was not methylated in non‐cancerous gastric tissues, suggesting that this hypermethylation is a cancer‐specific alteration. KATO‐III and ECC10 cells retained two alleles of TSLC<span class="hlt">1</span>, both of which showed hypermethylation, associated with complete loss of gene expression. Most of the <span class="hlt">primary</span> gastric cancers with promoter methylation also retained heterozygosity at the TSLC<span class="hlt">1</span> locus on 11q23.2. These data indicate that bi‐allelic hypermethylation of the TSLC<span class="hlt">1</span> promoter and resulting gene silencing occur in a subset of <span class="hlt">primary</span> gastric cancers. PMID:12716461</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3044708','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3044708"><span>Comparative Profiling of <span class="hlt">Primary</span> Colorectal Carcinomas and Liver Metastases Identifies LEF<span class="hlt">1</span> as a Prognostic Biomarker</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Lin, Albert Y.; Chua, Mei-Sze; Choi, Yoon-La; Yeh, William; Kim, Young H.; Azzi, Raymond; Adams, Gregg A.; Sainani, Kristin; van de Rijn, Matt; So, Samuel K.; Pollack, Jonathan R.</p> <p>2011-01-01</p> <p>Purpose We sought to identify genes of clinical significance to predict survival and the risk for colorectal liver metastasis (CLM), the most common site of metastasis from colorectal cancer (CRC). Patients and Methods We profiled gene expression in 31 specimens from <span class="hlt">primary</span> CRC and 32 unmatched specimens of CLM, and performed Significance Analysis of Microarrays (SAM) to identify genes differentially expressed between these two groups. To characterize the clinical relevance of two highly-ranked differentially-expressed genes, we analyzed the expression of secreted phosphoprotein <span class="hlt">1</span> (SPP<span class="hlt">1</span> or osteopontin) and lymphoid enhancer factor-<span class="hlt">1</span> (LEF<span class="hlt">1</span>) by immunohistochemistry using a tissue microarray (TMA) representing an independent set of 154 patients with <span class="hlt">primary</span> CRC. Results Supervised analysis using SAM identified 963 genes with significantly higher expression in CLM compared to <span class="hlt">primary</span> CRC, with a false discovery rate of <0.5%. TMA analysis showed SPP<span class="hlt">1</span> and LEF<span class="hlt">1</span> protein overexpression in 60% and 44% of CRC cases, respectively. Subsequent occurrence of CLM was significantly correlated with the overexpression of LEF<span class="hlt">1</span> (chi-square p = 0.042), but not SPP<span class="hlt">1</span> (p = 0.14). Kaplan Meier analysis revealed significantly worse survival in patients with overexpression of LEF<span class="hlt">1</span> (p<0.01), but not SPP<span class="hlt">1</span> (p = 0.11). Both univariate and multivariate analyses identified stage (p<0.0001) and LEF<span class="hlt">1</span> overexpression (p<0.05) as important prognostic markers, but not tumor grade or SPP<span class="hlt">1</span>. Conclusion Among genes differentially expressed between CLM and <span class="hlt">primary</span> CRC, we demonstrate overexpression of LEF<span class="hlt">1</span> in <span class="hlt">primary</span> CRC to be a prognostic factor for poor survival and increased risk for liver metastasis. PMID:21383983</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/18505591','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/18505591"><span>Describing and analysing <span class="hlt">primary</span> health care system <span class="hlt">support</span> for chronic illness care in Indigenous communities in Australia's Northern Territory - use of the Chronic Care Model.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Si, Damin; Bailie, Ross; Cunningham, Joan; Robinson, Gary; Dowden, Michelle; Stewart, Allison; Connors, Christine; Weeramanthri, Tarun</p> <p>2008-05-28</p> <p>Indigenous Australians experience disproportionately high prevalence of, and morbidity and mortality from chronic illness such as diabetes, renal disease and cardiovascular disease. Improving the understanding of how Indigenous <span class="hlt">primary</span> care systems are organised to deliver chronic illness care will inform efforts to improve the quality of care for Indigenous people. This cross-sectional study was conducted in 12 Indigenous communities in Australia's Northern Territory. Using the Chronic Care Model as a framework, we carried out a mail-out survey to collect information on material, financial and human resources relating to chronic illness care in participating health centres. Follow up face-to-face interviews with health centre staff were conducted to identify successes and difficulties in the systems in relation to providing chronic illness care to community members. Participating health centres had distinct areas of strength and weakness in each component of systems: <span class="hlt">1</span>) organisational influence - strengthened by inclusion of chronic illness goals in business plans, appointment of designated chronic disease coordinators and introduction of external clinical audits, but weakened by lack of training in disease prevention and health promotion and limited access to Medicare funding; 2) community linkages - facilitated by working together with community organisations (e.g. local stores) and running community-based programs (e.g. "health week"), but detracted by a shortage of staff especially of Aboriginal health workers working in the community; 3) self management - promoted through patient education and goal setting with clients, but impeded by limited focus on family and community-based activities due to understaffing; 4) decision <span class="hlt">support</span> - facilitated by distribution of clinical guidelines and their integration with daily care, but limited by inadequate access to and <span class="hlt">support</span> from specialists; 5) delivery system design - strengthened by provision of transport for</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23528530','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23528530"><span>Acceptance of H<span class="hlt">1</span>N<span class="hlt">1</span> vaccine among healthcare workers at <span class="hlt">primary</span> healthcare centres in Abha, KSA.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Alsaleem, Mohammed Abadi</p> <p>2013-04-01</p> <p>One of the major concerns related to the pandemic outbreak of H<span class="hlt">1</span>N<span class="hlt">1</span> influenza in 2009 was the cost burden on medical resources, which led to a negative impact on mortality and morbidity. This situation placed healthcare workers (HCWs) in an unusual position of being both the main actors and one of the main targets of the prevention strategies against the 2009 pandemic influenza A (H<span class="hlt">1</span>N<span class="hlt">1</span>). The aim of the study was to find out and compare the acceptance of H<span class="hlt">1</span>N<span class="hlt">1</span> vaccine among different categories of <span class="hlt">primary</span> HCWs in <span class="hlt">primary</span> healthcare centres in Abha as well as to explore the reasons among them for not accepting the HINI vaccine. A cross-sectional study was conducted including all HCWs serving at <span class="hlt">primary</span> healthcare centres in Abha. A self-administered validated questionnaire was used to collect data reflecting the intake of H<span class="hlt">1</span>N<span class="hlt">1</span> vaccine and its association with other parameters that may influence the uptake of this vaccine. The overall response rate was 347/402 (86.3%). The age of the participants ranged between 22 and 59 years with a mean of 34.9 years and SD of 8.4 years. The percentage of physicians, nurses and technicians who took the H<span class="hlt">1</span>N<span class="hlt">1</span> vaccination was 32.6, 28 and 10%, respectively. The overall vaccine intake rate was 28.2%. The main reasons given by HCWs for being immunized were personal protection (51%), fear of transmitting disease to their family and relatives (49%) and fear of transmitting the disease to their patients (43.9%). The main reasons given by HCWs for rejecting H<span class="hlt">1</span>N<span class="hlt">1</span> vaccination were fear of side effects (70.3%) and doubts regarding the safety of the vaccine (68.3%). In general, knowledge about H<span class="hlt">1</span>N<span class="hlt">1</span> was insufficient. However, it was better among physicians than among nurses and technicians. The low rate of acceptance of the pandemic vaccine and the insufficient level of knowledge about the H<span class="hlt">1</span>N<span class="hlt">1</span> virus among Saudi HCWs were alarming given that they were considered models for patients and the public.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29642964','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29642964"><span>Strengthening <span class="hlt">primary</span> health care through <span class="hlt">primary</span> care and public health collaboration: the influence of intrapersonal and interpersonal factors.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Valaitis, Ruta K; O'Mara, Linda; Wong, Sabrina T; MacDonald, Marjorie; Murray, Nancy; Martin-Misener, Ruth; Meagher-Stewart, Donna</p> <p>2018-04-12</p> <p>AimThe aim of this paper is to examine Canadian key informants' perceptions of intrapersonal (within an individual) and interpersonal (among individuals) factors that influence successful <span class="hlt">primary</span> care and public health collaboration. <span class="hlt">Primary</span> health care systems can be strengthened by building stronger collaborations between <span class="hlt">primary</span> care and public health. Although there is literature that explores interpersonal factors that can influence successful inter-organizational collaborations, a few of them have specifically explored <span class="hlt">primary</span> care and public health collaboration. Furthermore, no papers were found that considered factors at the intrapersonal level. This paper aims to explore these gaps in a Canadian context. This interpretative descriptive study involved key informants (service providers, managers, directors, and policy makers) who participated in one h telephone interviews to explore their perceptions of influences on successful <span class="hlt">primary</span> care and public health collaboration. Transcripts were analyzed using NVivo 9.FindingsA total of 74 participants [from the provinces of British Columbia (n=20); Ontario (n=19); Nova Scotia (n=21), and representatives from other provinces or national organizations (n=14)] participated. Five interpersonal factors were found that influenced public health and <span class="hlt">primary</span> care collaborations including: (<span class="hlt">1</span>) trusting and inclusive relationships; (2) shared values, beliefs and attitudes; (3) role clarity; (4) effective communication; and (5) decision processes. There were two influencing factors found at the intrapersonal level: (<span class="hlt">1</span>) personal qualities, skills and knowledge; and (2) personal values, beliefs, and attitudes. A few differences were found across the three core provinces involved. There were several complex interactions identified among all inter and intra personal influencing factors: One key factor - effective communication - interacted with all of them. Results <span class="hlt">support</span> and extend our understanding of what influences</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=%22Beverage+Industry%22&id=ED134919','ERIC'); return false;" href="https://eric.ed.gov/?q=%22Beverage+Industry%22&id=ED134919"><span>Issues in <span class="hlt">Primary</span> Prevention in Substance Abuse. A Statement.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Phelps, Donald G.</p> <p></p> <p>The purpose of the National Institute on Alcohol Abuse and Alcoholism is to reduce the incidence of social, psychological, and health problems due to the use of alcohol. Soliciting financial <span class="hlt">support</span> for <span class="hlt">primary</span> prevention programs is difficult because of: (<span class="hlt">1</span>) Federal, state, and local revenues derived from sales of alcoholic beverages; (2) The…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27113328','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27113328"><span>GPER<span class="hlt">1</span> mediates estrogen-induced neuroprotection against oxygen-glucose deprivation in the <span class="hlt">primary</span> hippocampal neurons.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhao, Tian-Zhi; Shi, Fei; Hu, Jun; He, Shi-Ming; Ding, Qian; Ma, Lian-Ting</p> <p>2016-07-22</p> <p>It is well-known that the neuroprotective effects of estrogen have potential in the prevention and amelioration of ischemic and degenerative neurological disorders, while the underlying mechanisms for estrogen actions are undefined. As an important mediator for the non-genomic functions of estrogen, GPER<span class="hlt">1</span> (G Protein-coupled Estrogen Receptor <span class="hlt">1</span>) has been suggested to involve in the beneficial roles of estrogen in neural cells. Here our studies on <span class="hlt">primary</span> hippocampal neurons have focused on GPER<span class="hlt">1</span> in an in vitro model of ischemia using oxygen-glucose deprivation (OGD). GPER<span class="hlt">1</span> expression in the <span class="hlt">primary</span> hippocampal neurons was stimulated by the OGD treatments. Both E2 (estradiol) and E2-BSA (membrane impermeable estradiol by covalent conjugation of bovine serum albumin) attenuated OGD-induced cell death in <span class="hlt">primary</span> cultures of hippocampal neurons. Importantly, this membrane-mediated estrogen function requires GPER<span class="hlt">1</span> protein. Knocking down of GPER<span class="hlt">1</span> diminished, while overexpression of GPER<span class="hlt">1</span> potentiated, the protective roles of E2/E2-BSA following OGD. Additionally, the downstream mechanisms employed by membrane-associated estrogen signaling were found to include PI3K/Akt-dependent Ask<span class="hlt">1</span> inhibition in the <span class="hlt">primary</span> hippocampal neurons. Overall, these research results could enhance our understanding of the neuroprotective actions for estrogen, and provide a new therapeutic target for improving stroke outcome and ameliorating degenerative neurological diseases. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29753036','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29753036"><span>Explaining the amount and consistency of medical care and self-management <span class="hlt">support</span> in asthma: a survey of <span class="hlt">primary</span> care providers in France and the United Kingdom.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>de Bruin, Marijn; Dima, Alexandra L; Texier, Nathalie; van Ganse, Eric</p> <p>2018-05-09</p> <p>The quality of asthma <span class="hlt">primary</span> care may vary between countries, health care practices, and health care professionals (HCPs). Identifying and explaining such differences is critical for health services improvement. To examine the quality of asthma <span class="hlt">primary</span> care in France and United Kingdom, and identify within-country and between-country predictors amenable to intervention. An online questionnaire to capture asthma medical care and self-management <span class="hlt">support</span>, practice characteristics, and psychosocial determinants, was completed by 276 HCPs. Mokken Scaling analyses were used to examine item structure and consistency. Hierarchical regression analyses were used to identify predictors of the amount (number of asthma care activities HCPs delivered) and consistency (the degree to which HCPs deliver similar care) of asthma medical care and self-management <span class="hlt">support</span>. On average, HCPs reported delivering 74,2% of guideline-recommended care. Consistency of medical care and self-management <span class="hlt">support</span> was lower among HCPs delivering a lower amount of care (r=.58 and r=.57, p<.001). UK HCPs provided more and more consistent asthma self-management <span class="hlt">support</span> -but not medical care- than French HCPs, which was explained by the presence of practice nurses in the UK. More training, positive social norms, and higher behavioural control explained better quality of care across all HCPs. Using carefully-developed questionnaires and advanced psychometric analyses, this study suggests that involving practice nurses, making social expectations visible, and providing more training to enhance skills and confidence in asthma care delivery could enhance the amount and consistency of asthma <span class="hlt">primary</span> care. This needs to be corroborated in a future intervention trial. Copyright © 2018. Published by Elsevier Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15499210','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15499210"><span>Molecular aetiology of <span class="hlt">primary</span> hyperoxaluria type <span class="hlt">1</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Danpure, Christopher J</p> <p>2004-01-01</p> <p><span class="hlt">Primary</span> hyperoxaluria type <span class="hlt">1</span> (PH<span class="hlt">1</span>) is a rare autosomal-recessive disorder, caused by a deficiency of the liver-specific intermediary-metabolic enzyme alanine:glyoxylate aminotransferase (AGT). AGT deficiency results in increased synthesis and excretion of the metabolic end-product oxalate and the deposition of insoluble calcium oxalate in the kidney and urinary tract. Numerous mutations and polymorphisms have been identified in the gene (AGXT) that encodes AGT, some of which interact synergistically to cause a variety of complex enzyme phenotypes, including AGT intraperoxisomal aggregation, accelerated degradation, and peroxisome-to-mitochondrion mistargeting. The latter is the single most common cause of PH<span class="hlt">1</span> and results from the functional interaction between a common Pro11Leu polymorphism and a disease-specific Gly170Arg mutation. The recent solution of the crystal structure of AGT has enabled the effects of several mutations and polymorphisms to be rationalised in terms of their likely effects on AGT conformation. Increased understanding of the molecular aetiology of PH<span class="hlt">1</span> has led to significant improvements in all aspects of the clinical management of the disorder, including diagnosis (by enzyme assay of percutaneous needle liver biopsies), prenatal diagnosis (by DNA analysis of chorionic villus samples) and treatment (by liver transplantation as a form of enzyme replacement therapy). Copyright (c) 2004 S. Karger AG, Basel.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5640868','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5640868"><span>HIV-<span class="hlt">1</span> Cross-Reactive <span class="hlt">Primary</span> Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Wang, Yimeng; O'Dell, Sijy; Turner, Hannah L.; Chiang, Chi-I; Lei, Lin; Guenaga, Javier; Wilson, Richard; Martinez-Murillo, Paola; Doria-Rose, Nicole; Ward, Andrew B.; Mascola, John R.; Wyatt, Richard T.; Karlsson Hedestam, Gunilla B.</p> <p>2017-01-01</p> <p> a subset of individuals. To achieve this goal, an improved understanding of vaccine-elicited responses, including at the monoclonal Ab level, is essential. Here, we isolated and characterized a panel of vaccine-elicited cross-reactive neutralizing MAbs targeting the Env V3 loop that moderately neutralized several <span class="hlt">primary</span> viruses and recapitulated the serum neutralizing antibody response. Striking similarities between the cross-reactive V3 NAbs elicited by vaccination in macaques and natural infections in humans illustrate commonalities between the vaccine- and infection-induced responses to V3 and <span class="hlt">support</span> the feasibility of exploring the V3 epitope as a HIV-<span class="hlt">1</span> vaccine target in nonhuman primates. PMID:28835491</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol2/pdf/CFR-2013-title40-vol2-sec50-9.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title40-vol2/pdf/CFR-2013-title40-vol2-sec50-9.pdf"><span>40 CFR 50.9 - National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>... ambient air quality standards for ozone. 50.9 Section 50.9 Protection of Environment ENVIRONMENTAL....9 National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone. (a) The level of the national <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone measured by a...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol2/pdf/CFR-2012-title40-vol2-sec50-9.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title40-vol2/pdf/CFR-2012-title40-vol2-sec50-9.pdf"><span>40 CFR 50.9 - National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>... ambient air quality standards for ozone. 50.9 Section 50.9 Protection of Environment ENVIRONMENTAL....9 National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone. (a) The level of the national <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone measured by a...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol2/pdf/CFR-2011-title40-vol2-sec50-9.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title40-vol2/pdf/CFR-2011-title40-vol2-sec50-9.pdf"><span>40 CFR 50.9 - National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>... ambient air quality standards for ozone. 50.9 Section 50.9 Protection of Environment ENVIRONMENTAL....9 National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone. (a) The level of the national <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone measured by a...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_16");'>16</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li class="active"><span>18</span></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_18 --> <div id="page_19" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="361"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol2/pdf/CFR-2010-title40-vol2-sec50-9.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title40-vol2/pdf/CFR-2010-title40-vol2-sec50-9.pdf"><span>40 CFR 50.9 - National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>... ambient air quality standards for ozone. 50.9 Section 50.9 Protection of Environment ENVIRONMENTAL....9 National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone. (a) The level of the national <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone measured by a...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol2/pdf/CFR-2014-title40-vol2-sec50-9.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title40-vol2/pdf/CFR-2014-title40-vol2-sec50-9.pdf"><span>40 CFR 50.9 - National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>... ambient air quality standards for ozone. 50.9 Section 50.9 Protection of Environment ENVIRONMENTAL....9 National <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone. (a) The level of the national <span class="hlt">1</span>-hour <span class="hlt">primary</span> and secondary ambient air quality standards for ozone measured by a...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=%22relativistic+fluid%22+OR+%22relativistic+hydrodynamic%22+OR+%22problem+of+time%22+OR+%22equivalence+principl%22&pg=7&id=ED467229','ERIC'); return false;" href="https://eric.ed.gov/?q=%22relativistic+fluid%22+OR+%22relativistic+hydrodynamic%22+OR+%22problem+of+time%22+OR+%22equivalence+principl%22&pg=7&id=ED467229"><span>The <span class="hlt">Primary</span> Headteacher's Handbook: The Essential Guide for <span class="hlt">Primary</span> Heads. <span class="hlt">Primary</span> Essentials Series.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Smith, Roger</p> <p></p> <p>Although the setting is British, the <span class="hlt">primary</span> head's problems are similar to those faced by U.S. elementary principals. This is a guidebook for managing <span class="hlt">primary</span> schools. It shows the day-to-day running of a <span class="hlt">primary</span> school and the organizational structures in which staff and pupils can be inspired. Chapter <span class="hlt">1</span> considers the creation of a positive…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29038854','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29038854"><span>Who is a survivor? Perceptions from individuals who experienced pediatric cancer and their <span class="hlt">primary</span> <span class="hlt">support</span> persons.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Molinaro, Monica L; Fletcher, Paula C</p> <p>2018-04-01</p> <p>The purpose of this research was to examine the lived experiences of individuals who had cancer as children, as well as lived experiences of their current <span class="hlt">primary</span> <span class="hlt">support</span> persons. Based on van Manen's "new" interpretive phenomenology, interviews were conducted with ten pediatric cancer survivors and nine of their <span class="hlt">support</span> persons to gain a more holistic understanding of the pediatric cancer experiences of children and their families. Four themes emerged from the data; however, only the topic of the use of the term "survivor" and identification with the term will be discussed. All participants in the study described their personal definition of the term survivor and what it meant to be a survivor. Additionally, all individuals in the study discussed the concept of being a survivor and if they would consider themselves, or their loved ones, to be "survivors." The results of this study provide health care professionals, family members, and individuals fundraising or advocating for cancer causes with insights on how the term survivor may be interpreted. This study may provide insight to individuals who had cancer as children, in showing that their personal perspective shapes their identity; although "survivor" is common cancer vernacular, individuals can choose not to identify with their illness experiences.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26469986','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26469986"><span>Rapid Antiretroviral Therapy Initiation for Women in an HIV-<span class="hlt">1</span> Prevention Clinical Trial Experiencing <span class="hlt">Primary</span> HIV-<span class="hlt">1</span> Infection during Pregnancy or Breastfeeding.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M</p> <p>2015-01-01</p> <p>During an HIV-<span class="hlt">1</span> prevention clinical trial in East Africa, we observed 16 cases of <span class="hlt">primary</span> HIV-<span class="hlt">1</span> infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during <span class="hlt">primary</span> HIV-<span class="hlt">1</span> infection during pregnancy and breastfeeding is feasible in this setting.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21676023','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21676023"><span><span class="hlt">Primary</span> health care in Canada: systems in motion.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hutchison, Brian; Levesque, Jean-Frederic; Strumpf, Erin; Coyle, Natalie</p> <p>2011-06-01</p> <p>During the 1980s and 1990s, innovations in the organization, funding, and delivery of <span class="hlt">primary</span> health care in Canada were at the periphery of the system rather than at its core. In the early 2000s, a new policy environment emerged. This policy analysis examines <span class="hlt">primary</span> health care reform efforts in Canada during the last decade, drawing on descriptive information from published and gray literature and from a series of semistructured interviews with informed observers of <span class="hlt">primary</span> health care in Canada. <span class="hlt">Primary</span> health care in Canada has entered a period of potentially transformative change. Key initiatives include <span class="hlt">support</span> for interprofessional <span class="hlt">primary</span> health care teams, group practices and networks, patient enrollment with a <span class="hlt">primary</span> care provider, financial incentives and blended-payment schemes, development of <span class="hlt">primary</span> health care governance mechanisms, expansion of the <span class="hlt">primary</span> health care provider pool, implementation of electronic medical records, and quality improvement training and <span class="hlt">support</span>. Canada's experience suggests that <span class="hlt">primary</span> health care transformation can be achieved voluntarily in a pluralistic system of private health care delivery, given strong government and professional leadership working in concert. © 2011 Milbank Memorial Fund. Published by Wiley Periodicals Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://www.dtic.mil/docs/citations/AD1007630','DTIC-ST'); return false;" href="http://www.dtic.mil/docs/citations/AD1007630"><span>Oligodendroglial MCT<span class="hlt">1</span> and Metabolic <span class="hlt">Support</span> of Axons in Multiple Sclerosis</span></a></p> <p><a target="_blank" href="http://www.dtic.mil/">DTIC Science & Technology</a></p> <p></p> <p>2015-10-01</p> <p>AWARD NUMBER: W81XWH-14-<span class="hlt">1</span>-0524 TITLE:Oligodendroglial MCT<span class="hlt">1</span> and Metabolic <span class="hlt">Support</span> of Axons in Multiple Sclerosis PRINCIPAL INVESTIGATOR: Jeffrey D...29 Sep 2015 4. TITLE AND SUBTITLE Oligodendroglial MCT<span class="hlt">1</span> and Metabolic <span class="hlt">Support</span> of Axons in Multiple Sclerosis 5a. CONTRACT NUMBER W81XWH-14-<span class="hlt">1</span>-0524...MCT<span class="hlt">1</span> in injured oligodendroglia of multiple sclerosis patients contributes to axon neurodegeneration and that increasing MCT<span class="hlt">1</span> will be protective in the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3007624','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3007624"><span>Regulation of Cellular Calcium in Vestibular <span class="hlt">Supporting</span> Cells by Otopetrin <span class="hlt">1</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kim, Euysoo; Hyrc, Krzysztof L.; Speck, Judith; Lundberg, Yunxia W.; Salles, Felipe T.; Kachar, Bechara; Goldberg, Mark P.; Warchol, Mark E.</p> <p>2010-01-01</p> <p>Otopetrin <span class="hlt">1</span> (OTOP<span class="hlt">1</span>) is a multitransmembrane domain protein, which is essential for mineralization of otoconia, the calcium carbonate biominerals required for vestibular function, and the normal sensation of gravity. The mechanism driving mineralization of otoconia is poorly understood, but it has been proposed that <span class="hlt">supporting</span> cells and a mechanism to maintain high concentrations of calcium are critical. Using Otop<span class="hlt">1</span> knockout mice and a utricular epithelial organ culture system, we show that OTOP<span class="hlt">1</span> is expressed at the apex of <span class="hlt">supporting</span> cells and functions to increase cytosolic calcium in response to purinergic agonists, such as adenosine 5′-triphosphate (ATP). This is achieved by blocking mobilization of calcium from intracellular stores in an extracellular calcium-dependent manner and by mediating influx of extracellular calcium. These data <span class="hlt">support</span> a model in which OTOP<span class="hlt">1</span> acts as a sensor of the extracellular calcium concentration near <span class="hlt">supporting</span> cells and responds to ATP in the endolymph to increase intracellular calcium levels during otoconia mineralization. PMID:20554841</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2001SPIE.4451..126G','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2001SPIE.4451..126G"><span>SOFIA <span class="hlt">primary</span> mirror fabrication and testing</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Geyl, Roland; Tarreau, Michel; Plainchamp, Patrick</p> <p>2001-12-01</p> <p>The Stratospheric Observatory for Infrared Astronomy (SOFIA) is a joint American-German project dedicated to performing IR astronomy on board a Boeing Aircraft, in near space condition. First flight of the Observatory is planned for 2003. The REOSC Products Unit of SAGEM SA (France) has been contracted by Kayser Threde (Germany) for the design and fabrication of the 2.7-meter diameter, F/<span class="hlt">1</span>.19 parabolic lightweight SOFIA <span class="hlt">primary</span> mirror as well as the M3 dichroic and folding mirror assembly. This paper will report the design, fabrication and test of the lightweight <span class="hlt">primary</span> mirror. The mirror structure has been obtained by machining it out from a solid Zerodur blank. It is the world's largest of this type today. Axial and lateral mirror <span class="hlt">support</span> system has been conceptually designed and engineered by SAGEM-REOSC engineers in relation with Kayser Threde team. The optical surface is an F/<span class="hlt">1</span>.19 parabola polished to a high level of quality.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/10906312','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/10906312"><span>The connections of layer 4 subdivisions in the <span class="hlt">primary</span> visual cortex (V<span class="hlt">1</span>) of the owl monkey.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Boyd, J D; Mavity-Hudson, J A; Casagrande, V A</p> <p>2000-07-01</p> <p>The <span class="hlt">primary</span> visual cortex (V<span class="hlt">1</span>) of primates receives signals from parallel lateral geniculate nucleus (LGN) channels. These signals are utilized by the laminar and compartmental [i.e. cytochrome oxidase (CO) blob and interblob] circuitry of V<span class="hlt">1</span> to synthesize new output pathways appropriate for the next steps of analysis. Within this framework, this study had two objectives: (i) to analyze the con- nections between <span class="hlt">primary</span> input and output layers and compartments of V<span class="hlt">1</span>; and (ii) to determine differences in connection patterns that might be related to species differences in physiological properties in an effort to link specific pathways to visual functions. In this study we examined the intrinsic interlaminar connections of V<span class="hlt">1</span> in the owl monkey, a nocturnal New World monkey, with a special emphasis on the projections from layer 4 to layer 3. Interlaminar connections were labeled via small iontophoretic or pressure injections of tracers [horseradish peroxidase, biocytin, biotinylated dextrine amine (BDA) or cholera toxin subunit B conjugated to colloidal gold particles]. Our most significant finding was that layer 4 (4C of Brodmann) can be divided into three tiers based upon projections to the superficial layers. Specifically, we find that 4alpha (4Calpha), 4beta (4Cbeta) and 4ctr send <span class="hlt">primary</span> projections to layers 3C (4B), 3Bbeta (4A) and 3Balpha (3B), respectively. Examination of laminar structure with Nissl staining <span class="hlt">supports</span> a tripartite organization of layer 4. The cortical output layer above layer 3Balpha (3B) (e.g. layer 3A) does not appear to receive any direct connections from layer 4 but receives heavy input from layers 3Balpha (3B) and 3C (4B). Some connectional differences also were observed between the subdivisions of layer 3 and the infragranular layers. No consistent differences in connections were observed that distinguished CO blobs from interblobs or that could be correlated with differences in visual lifestyle (nocturnal versus diurnal) when compared</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2843600','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2843600"><span>Female partners of patients after surgical prostate cancer treatment: interactions with physicians and <span class="hlt">support</span> needs</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2010-01-01</p> <p>Background Few studies have explored the women's experiences as a result of a partners' diagnosis of prostate cancer. This study begins to explore women's interactions with physicians (<span class="hlt">primary</span> care and urologist) and the <span class="hlt">support</span> needs associated with the diagnosis and treatment of their partners' prostate cancer. Methods Two focus groups (n = 14) of women whose partners were diagnosed with prostate cancer (diagnoses' <span class="hlt">1</span> - 18 months). A trained facilitator used open-ended questions to explore ideas. The framework approach was used to analyze the transcripts. Results Three main themes emerged: <span class="hlt">1</span>. More <span class="hlt">support</span>. Validation and information is needed for women including emotional <span class="hlt">support</span> and opportunities to share experiences. 2. Role of the physician. The transfer of care once specialized treatment is no longer needed remained poorly defined, which increased confusion and feelings of abandonment related to the role of the <span class="hlt">primary</span> physician. 3. Partners' relationship changes. Men became more dependent on their partners for <span class="hlt">support</span> and to act as the <span class="hlt">primary</span> communicator and caregiver. Conclusions Additional research is needed in this field to confirm the importance of training <span class="hlt">primary</span> care physicians to consider holistic treatment approaches that recognize the partner and family needs as important in the complete physical and emotional healing of their patients. PMID:20211019</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4935460','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4935460"><span>CRM-<span class="hlt">1</span> knockdown inhibits extrahepatic cholangiocarcinoma tumor growth by blocking the nuclear export of p27Kip<span class="hlt">1</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Luo, Jian; Chen, Yongjun; Li, Qiang; Wang, Bing; Zhou, Yanqiong; Lan, Hongzhen</p> <p>2016-01-01</p> <p>Cholangiocarcinoma is a deadly disease which responds poorly to surgery and conventional chemotherapy or radiotherapy. Early diagnosis is difficult due to the anatomical and biological characteristics of cholangiocarcinoma. Cyclin-dependent kinase inhibitor <span class="hlt">1</span>B (p27Kip<span class="hlt">1</span>) is a cyclin-dependent kinase inhibitor and in the present study, we found that p27Kip<span class="hlt">1</span> expression was suppressed in the nucleus and increased in the cytoplasm in 53 samples of cholangiocarcinoma from patients with highly malignant tumors (poorly-differentiated and tumor-node-metastsis (TNM) stage III–IV) compared with that in samples from 10 patients with chronic cholangitis. The expression of phosphorylated (p-)p27Kip<span class="hlt">1</span> (Ser10), one of the phosphorylated forms of p27Kip<span class="hlt">1</span>, was increased in the patient samples with increasing malignancy and clinical stage. Coincidentally, chromosome region maintenance <span class="hlt">1</span> (CRM-<span class="hlt">1</span>; also referred to as exportin <span class="hlt">1</span> or <span class="hlt">Xpo</span><span class="hlt">1</span>), a critical protein responsible for protein translocation from the nucleus to the cytoplasm, was also overexpressed in the tumor samples which were poorly differentiated and of a higher clinical stage. Through specific short hairpin RNA (shRNA)-mediated knockdown of CRM-<span class="hlt">1</span> in the cholangiocarcinoma cell line QBC939, we identified an elevation of cytoplasmic p27Kip<span class="hlt">1</span> and a decrease of nuclear p27Kip<span class="hlt">1</span>. Furthermore, the viability and colony formation ability of QBC939 cells was largely reduced with G<span class="hlt">1</span> arrest. Consistent with the findings of the in vitro experiments, in a xenograft mouse model, the tumors formed in the CRM-<span class="hlt">1</span> knockdown group were markedly smaller and weighed less than those in the control group in vivo. Taken together, these findings demonstrated that the interplay between CRM-<span class="hlt">1</span> and p27Kip<span class="hlt">1</span> may provide potentially potent biomarkers and functional targets for the development of future cholangiocarcinoma treatments. PMID:27279267</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4705310','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4705310"><span><span class="hlt">Primary</span> prevention of type 2 diabetes: integrative public health and <span class="hlt">primary</span> care opportunities, challenges and strategies</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Green, Lawrence W; Brancati, Frederick L; Albright, Ann</p> <p>2012-01-01</p> <p>Type 2 diabetes imposes a large and growing burden on the public’s health. This burden, combined with the growing evidence for <span class="hlt">primary</span> prevention from randomized controlled trials of structured lifestyle programs leads to recommendations to include caloric reduction, increased physical activity and specific assistance to patients in problem solving to achieve modest weight loss as well as pharmacotherapy. These recommendations demand exploration of new ways to implement such <span class="hlt">primary</span> prevention strategies through more integrated community organization, medical practice and policy. The US experience with control of tobacco use and high blood pressure offers valuable lessons for policy, such as taxation on products, and for practice in a variety of settings, such as coordination of referrals for lifestyle <span class="hlt">supports</span>. We acknowledge also some notable exceptions to their generalizability. This paper presents possible actions proposed by an expert panel, summarized in Table <span class="hlt">1</span> as recommendations for immediate action, strategic action and research. The collaboration of <span class="hlt">primary</span> care and public health systems will be required to make many of these recommendations a reality. This paper also provides information on the progress made in recent years by the Division of Diabetes Translation at the US Centers for Disease Control and Prevention (CDC) to implement or facilitate such integration of <span class="hlt">primary</span> care and public health for <span class="hlt">primary</span> prevention. PMID:22399542</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24251372','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24251372"><span>'I am stronger, I'm no longer afraid…', an evaluation of a home-visiting mentor mother <span class="hlt">support</span> programme for abused women in <span class="hlt">primary</span> care.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Prosman, Gert-Jan; Lo Fo Wong, Sylvie H; Römkens, Renée; Lagro-Janssen, Antoine L M</p> <p>2014-12-01</p> <p>We aimed to investigate which factors make a mentor mother <span class="hlt">support</span> programme for abused women successful. We used semi-structured interviews with abused women and focus group discussions with the mentor mothers to evaluate their experiences and needs within a mentor <span class="hlt">support</span> programme (MeMoSA). Fourteen abused women were interviewed 6 months after the <span class="hlt">support</span> programme ended. Mentor mothers participated in two focus group discussions. Abused women emphasised that nonjudgmental listening, equivalence, involvement and bonding are important factors for successful <span class="hlt">support</span>. Mentor mothers described that empathy, availability, persistence and advocacy fitted the needs of women best to empower them and help them to cope with their violent situation at home. A safe place to meet each other was also an important factor. A good relationship, tailored <span class="hlt">support</span> provided by home visiting, advocacy and safety are required to effectively help abused women. MeMoSA, a home-visiting <span class="hlt">support</span> programme, is a promising valuable new <span class="hlt">support</span> programme in <span class="hlt">primary</span> care for abused women. © 2013 Nordic College of Caring Science.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=mobile+AND+strategy&pg=2&id=EJ1128657','ERIC'); return false;" href="https://eric.ed.gov/?q=mobile+AND+strategy&pg=2&id=EJ1128657"><span>Bring Your Own Device--A Snapshot of Two Australian <span class="hlt">Primary</span> Schools</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Maher, Damian; Twining, Peter</p> <p>2017-01-01</p> <p>Background: The use of <span class="hlt">1:1</span> and Bring Your Own Device strategies in schools is in its infancy and little is known about how mobile devices such as tablets are being used to <span class="hlt">support</span> educational practice. Purpose: In this article, two suburban <span class="hlt">primary</span> schools in Sydney, Australia were focused on with an aim to understand how mobile device strategies…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/14638730','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/14638730"><span>Interactions of endothelin-<span class="hlt">1</span> with dexamethasone in <span class="hlt">primary</span> cultured human trabecular meshwork cells.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhang, Xinyu; Clark, Abbot F; Yorio, Thomas</p> <p>2003-12-01</p> <p>Concentrations of aqueous humor endothelin (ET)-<span class="hlt">1</span> are increased in patients with <span class="hlt">primary</span> open-angle glaucoma (POAG) as well as in animal models of glaucoma. Glucocorticoids have also been associated with glaucoma, in that topical administration of glucocorticoids can increase intraocular pressure by increasing outflow resistance in the trabecular meshwork (TM) in some individuals. Recent research has shown that dexamethasone (Dex), a synthetic glucocorticoid, can increase the release of ET-<span class="hlt">1</span> from human nonpigmented ciliary epithelial (HNPE) cells, a source of aqueous ET-<span class="hlt">1</span>. In the present study, the downstream interaction of ET-<span class="hlt">1</span> with Dex in target TM cells, an action that may alter outflow resistance, was investigated. A normal <span class="hlt">primary</span> human TM (NTM) cell line and a TM cell line derived from a glaucomatous eye (GTM) were used. The cells were treated with vehicle or Dex. The mRNA levels of prepro-ET-<span class="hlt">1</span>, endothelin receptor A (ET(A)), and endothelin receptor B (ET(B)) were measured by quantitative RT-PCR (QPCR). The protein expression of ET(A) and ET(B) receptors were investigated by Western blot analysis using polyclonal anti-ET(A) and anti-ET(B) antibodies, respectively, on plasma membrane fractions. Intracellular Ca(2+) ([Ca(2+)](i)) mobilization mediated by ET-<span class="hlt">1</span> was measured using the Fura-2 AM fluorescent probe technique as an index of ET receptor function. ET-<span class="hlt">1</span>-stimulated nitric oxide (NO) release was measured using a Griess colorimetric NO synthase assay kit. Both NTM and GTM cultured cells expressed prepro-ET-<span class="hlt">1</span> mRNA less abundantly than did HNPE cells, and Dex treatment had no effect on the mRNA expression of the ET-<span class="hlt">1</span> gene. TM cells expressed mRNA of ET(A) receptors as detected by QPCR, whereas the ET(B) message was not clearly delineated. Western blot analysis showed that both ET(A) and ET(B) receptor proteins were present. The ET(A) receptor was linked to calcium mobilization as ET-<span class="hlt">1</span> produced an increase in intracellular calcium release, and this increase</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26618365','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26618365"><span>Innovative approach to patient-centered care coordination in <span class="hlt">primary</span> care practices.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Clarke, Robin; Bharmal, Nazleen; Di Capua, Paul; Tseng, Chi-Hong; Mangione, Carol M; Mittman, Brian; Skootsky, Samuel A</p> <p>2015-09-01</p> <p>Although care coordination is an essential component of the patient-centered medical home structure, current case manager models have limited usefulness to population health because they typically serve a small group of patients defined based on disease or utilization. Our objective was to <span class="hlt">support</span> our health system's population health by implementing and evaluating a program that embedded nonlicensed coordinators within our <span class="hlt">primary</span> care practices to <span class="hlt">support</span> physicians in executing care plans and communicating with patients. Matched case-control differences-in-differences. Comprehensive care coordinators (CCC) were introduced into 14 of the system's 28 practice sites in 2 waves. After a structured training program, CCCs identified, engaged, and intervened among patients within the practice in conjunction with practice <span class="hlt">primary</span> care providers. We counted and broadly coded CCC activities that were documented in the intervention database. We examined the impact of CCC intervention on emergency department (ED) utilization at the practice level using a negative binomial multivariate regression model controlling for age, gender, and medical complexity. CCCs touched 10,500 unique patients over a <span class="hlt">1</span>-year period. CCC interventions included execution of care (38%), coordination of transitions (32%), self-management <span class="hlt">support</span>/link to community resources (15%), monitor and follow-up (10%), and patient assessment (<span class="hlt">1</span>%). The CCC intervention group had a 20% greater reduction in its prepost ED visit rate compared with the control group (P < .0001). Our CCC intervention demonstrated a significant reduction in ED visits by focusing on the centrality of the <span class="hlt">primary</span> care provider and practice. Our model may serve as a cost-effective and scalable alternative for care coordination in <span class="hlt">primary</span> care.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24188617','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24188617"><span>HOBE+, a case study: a virtual community of practice to <span class="hlt">support</span> innovation in <span class="hlt">primary</span> care in Basque Public Health Service.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Abos Mendizabal, Galder; Nuño Solinís, Roberto; Zaballa González, Irune</p> <p>2013-11-05</p> <p>A virtual professional community of practice (VCoP), HOBE+, has been set up to foster and facilitate innovation in <span class="hlt">primary</span> care. It is aimed at all <span class="hlt">primary</span> care professionals of the Basque Public Health Service (Osakidetza) in the provinces of Biscay and Araba. HOBE + is a VCoP that incorporates innovation management from the generation of ideas to their implementation in <span class="hlt">primary</span> care practice. We used a case study method, based on the data provided by the technology platform that <span class="hlt">supports</span> the VCoP, and from a survey completed by HOBE + users. The target population was all <span class="hlt">primary</span> care staff (including all professional categories) from Araba and Biscay provinces of the Basque Country (Spain), who represent the target users of the VCoP. From a total of 5190 professionals across all the professional categories invited to join, 1627 (31.3%) actually registered in the VCoP and, during the study period, 90 (5.5% of the registered users) participated actively in some way. The total number of ideas proposed by the registered users was 133. Of these, 23 ideas (17.2%) are being implemented. Finally, 80% of the users who answered the satisfaction survey about their experience with HOBE + considered the initiative useful in order to achieve continuous improvement and real innovation in clinical and managerial processes. The experience shows that it is possible to create a virtual CoP for innovation in <span class="hlt">primary</span> care where professionals from different professional categories propose ideas for innovation that are ultimately implemented.This manuscript objectives are to assess the process of developing and implementing a VCoP open to all <span class="hlt">primary</span> care professionals in Osakidetza, including the take-up, participation and use of this VCoP in the first 15 months after its launch in October 2011. In addition, the usefulness of the VCoP was assessed through a survey gathering the opinions of the professionals involved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3868317','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3868317"><span>HOBE+, a case study: a virtual community of practice to <span class="hlt">support</span> innovation in <span class="hlt">primary</span> care in Basque Public Health Service</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2013-01-01</p> <p>Background A virtual professional community of practice (VCoP), HOBE+, has been set up to foster and facilitate innovation in <span class="hlt">primary</span> care. It is aimed at all <span class="hlt">primary</span> care professionals of the Basque Public Health Service (Osakidetza) in the provinces of Biscay and Araba. HOBE + is a VCoP that incorporates innovation management from the generation of ideas to their implementation in <span class="hlt">primary</span> care practice. Methods We used a case study method, based on the data provided by the technology platform that <span class="hlt">supports</span> the VCoP, and from a survey completed by HOBE + users. The target population was all <span class="hlt">primary</span> care staff (including all professional categories) from Araba and Biscay provinces of the Basque Country (Spain), who represent the target users of the VCoP. Results From a total of 5190 professionals across all the professional categories invited to join, 1627 (31.3%) actually registered in the VCoP and, during the study period, 90 (5.5% of the registered users) participated actively in some way. The total number of ideas proposed by the registered users was 133. Of these, 23 ideas (17.2%) are being implemented. Finally, 80% of the users who answered the satisfaction survey about their experience with HOBE + considered the initiative useful in order to achieve continuous improvement and real innovation in clinical and managerial processes. Conclusions The experience shows that it is possible to create a virtual CoP for innovation in <span class="hlt">primary</span> care where professionals from different professional categories propose ideas for innovation that are ultimately implemented. This manuscript objectives are to assess the process of developing and implementing a VCoP open to all <span class="hlt">primary</span> care professionals in Osakidetza, including the take-up, participation and use of this VCoP in the first 15 months after its launch in October 2011. In addition, the usefulness of the VCoP was assessed through a survey gathering the opinions of the professionals involved. PMID:24188617</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/19790006358','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/19790006358"><span><span class="hlt">Primary</span> reflector for solar energy collection systems</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Miller, C. G. (Inventor); Stephens, J. B.</p> <p>1978-01-01</p> <p>A fixed, linear, ground-based <span class="hlt">primary</span> reflector is disclosed which has an extended curved sawtooth-contoured surface covered with a metalized polymeric reflecting material. The device reflects solar energy to a movably <span class="hlt">supported</span> collector that is kept at the concentrated line focus of the reflector <span class="hlt">primary</span>. The <span class="hlt">primary</span> reflector may be constructed by a process utilizing well-known freeway paving machinery.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_17");'>17</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li class="active"><span>19</span></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_19 --> <div id="page_20" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="381"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1514510','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1514510"><span>Possible <span class="hlt">Primary</span> Lymph Node Gastrinoma: Occurrence, Natural History, and Predictive Factors</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Norton, Jeffrey A.; Alexander, H. Richard; Fraker, Douglas L.; Venzon, David J.; Gibril, Fathia; Jensen, Robert T.</p> <p>2003-01-01</p> <p>Objective To analyze the results of a prospective study of 176 patients with Zollinger-Ellison syndrome (ZES) (138 sporadic, 38 MEN<span class="hlt">1</span>) undergoing 207 operations over a 17-year period. Summary Background Data The existence of lymph node (LN) <span class="hlt">primary</span> gastrinoma causing ZES is controversial. Methods Three groups of patients were compared: LN only resected, cured, and no relapse (likely LN <span class="hlt">primary</span>); same criteria but relapse (unlikely LN <span class="hlt">primary</span>); and duodenal <span class="hlt">primary</span> and LN metastases (Duo-LN). Results Forty-five (26%) had only LN(s) as the initial tumor found. Twenty-six of the 45 (58%) fit the definition of a likely LN <span class="hlt">primary</span> because they were apparently cured postresection. At 10.4 ± <span class="hlt">1</span>.2 years, 69% of the 26 patients with likely LN <span class="hlt">primary</span> tumors have remained cured and have LN <span class="hlt">primaries</span>. In the 8 of 26 with recurrent ZES, it occurred at 5 ± <span class="hlt">1</span> years, and 3 had duodenal gastrinoma that had been missed. Ten percent (13/138) of all patients with sporadic ZES and 0% (0/38) with ZES and MEN<span class="hlt">1</span> remained cured with only a LN tumor removed. In patients with sporadic gastrinomas no clinical, laboratory, or radiographic localization feature differed among patients with likely LN <span class="hlt">primary</span> (n = 16) and those with unlikely LN <span class="hlt">primary</span> (n = 6) or those with Duo-LN (n = 37). In the likely LN <span class="hlt">primary</span> group, the largest LN was 2.2 ± 0.2 cm, the number of LNs removed was <span class="hlt">1</span>.3 ± 0.<span class="hlt">1</span> (25% ≥<span class="hlt">1</span> LN), and 78% were in the gastrinoma triangle, which also did not differ from the other 2 groups. Disease-free survival was similar in the likely LN <span class="hlt">primary</span> group, patients with Duo-LN, and those with pancreatic <span class="hlt">primaries</span>. Conclusions These results <span class="hlt">support</span> the conclusion that <span class="hlt">primary</span> LN gastrinomas occur and are not rare (approximately 10% of sporadic cases). These results suggest that a proportion (25%) of these tumors are either multiple or malignant. Because no clinical, laboratory, or tumoral characteristic distinguishes patients with LN <span class="hlt">primary</span> tumors, all patients with ZES undergoing surgery</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4939126','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4939126"><span><span class="hlt">Primary</span> care physicians’ perspectives on the prescription opioid epidemic*</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Kennedy-Hendricks, Alene; Busch, Susan H.; McGinty, Emma E.; Bachhuber, Marcus A.; Niederdeppe, Jeff; Gollust, Sarah E.; Webster, Daniel W.; Fiellin, David A.; Barry, Colleen L.</p> <p>2016-01-01</p> <p>Background Prescription opioid use disorder and overdose have risen substantially in the U.S. <span class="hlt">Primary</span> care physicians are critical to many ongoing and proposed efforts to address the prescription opioid epidemic. Yet, little is known about their attitudes and beliefs surrounding this issue. This study aimed to determine <span class="hlt">primary</span> care physicians’ perceptions of the seriousness of the problem, its causes, groups responsible for addressing it, attitudes toward individuals with prescription opioid use disorder, beliefs about the effectiveness of addiction treatments, and <span class="hlt">support</span> for various policies. Methods We conducted a national web-based survey in 2014 among <span class="hlt">1</span>,010 <span class="hlt">primary</span> care physicians. We gauged responses to attitude and belief items on 7-point Likert scales. We examined the proportion agreeing with each statement, and whether responses differed among physicians prescribing higher and lower volumes of opioids. Results Respondents largely attributed the causes of prescription opioid use disorder to individual-oriented factors and certain physician-oriented factors, and believed that individuals with prescription opioid use disorder and physicians were primarily responsible for addressing the problem. Negative attitudes toward people with prescription opioid use disorder were prevalent, but a majority believed that treatment could be effective. There was majority <span class="hlt">support</span> for all measured policies, with the highest levels of <span class="hlt">support</span> for policies to monitor prescribing among patients potentially at risk for an opioid use disorder and to improve physician education and training. Conclusions Given strong endorsement of recommended policies, physician <span class="hlt">support</span> could be leveraged to advance efforts to curb prescription opioid use disorder and overdose. PMID:27261154</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1338437','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1338437"><span>Secondary reinforcement and number of <span class="hlt">primary</span> reinforcements<span class="hlt">1</span></span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Fantino, Edmund; Herrnstein, R. J.</p> <p>1968-01-01</p> <p>Pigeons' pecks on either of two concurrently available response keys produced secondary reinforcers according to independent one-minute variable-interval schedules. Different secondary reinforcers, in the presence of which the rates of <span class="hlt">primary</span> reinforcement were equal, were associated with each key. The rate of pecking maintained by each secondary reinforcer varied directly, but nonproportionally, with the number of <span class="hlt">primary</span> reinforcements given in the presence of the secondary reinforcer. PMID:5636860</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4778022','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4778022"><span>DHA Suppresses <span class="hlt">Primary</span> Macrophage Inflammatory Responses via Notch <span class="hlt">1</span>/ Jagged <span class="hlt">1</span> Signaling</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K.</p> <p>2016-01-01</p> <p>Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. <span class="hlt">Primary</span> macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch <span class="hlt">1</span> and Jagged <span class="hlt">1</span> protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box <span class="hlt">1</span> and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch <span class="hlt">1</span>/Jagged <span class="hlt">1</span> protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture. PMID:26940787</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26940787','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26940787"><span>DHA Suppresses <span class="hlt">Primary</span> Macrophage Inflammatory Responses via Notch <span class="hlt">1</span>/ Jagged <span class="hlt">1</span> Signaling.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Ali, Mehboob; Heyob, Kathryn; Rogers, Lynette K</p> <p>2016-03-04</p> <p>Persistent macrophages were observed in the lungs of murine offspring exposed to maternal LPS and neonatal hyperoxia. Maternal docosahexaenoic acid (DHA) supplementation prevented the accumulation of macrophages and improved lung development. We hypothesized that these macrophages are responsible for pathologies observed in this model and the effects of DHA supplementation. <span class="hlt">Primary</span> macrophages were isolated from adult mice fed standard chow, control diets, or DHA supplemented diets. Macrophages were exposed to hyperoxia (O2) for 24 h and LPS for 6 h or 24 h. Our data demonstrate significant attenuation of Notch <span class="hlt">1</span> and Jagged <span class="hlt">1</span> protein levels in response to DHA supplementation in vivo but similar results were not evident in macrophages isolated from mice fed standard chow and supplemented with DHA in vitro. Co-culture of activated macrophages with MLE12 epithelial cells resulted in the release of high mobility group box <span class="hlt">1</span> and leukotriene B4 from the epithelial cells and this release was attenuated by DHA supplementation. Collectively, our data indicate that long term supplementation with DHA as observed in vivo, resulted in deceased Notch <span class="hlt">1</span>/Jagged <span class="hlt">1</span> protein expression however, DHA supplementation in vitro was sufficient to suppress release LTB4 and to protect epithelial cells in co-culture.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28667042','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28667042"><span>R132H Mutation in IDH<span class="hlt">1</span> Gene is Associated with Increased Tumor HIF<span class="hlt">1</span>-Alpha and Serum VEGF Levels in <span class="hlt">Primary</span> Glioblastoma Multiforme.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yalaza, Cem; Ak, Handan; Cagli, Mehmet Sedat; Ozgiray, Erkin; Atay, Sevcan; Aydin, Hikmet Hakan</p> <p>2017-05-01</p> <p>Glioblastoma multiforme (GBM) is the most common form of <span class="hlt">primary</span> brain tumors. Although mutations in isocitrate dehydrogenase-<span class="hlt">1</span> (IDH<span class="hlt">1</span>) have been identified in a number of cancers, their role in tumor development has not been fully elucidated. In this study, we aimed to investigate the association between IDH<span class="hlt">1</span> mutations, tumor tissue HIF-<span class="hlt">1</span> alpha, and serum VEGF levels in patients with <span class="hlt">primary</span> GBM for the first time. 32 patients (mean age, years: 58±14.0) diagnosed with <span class="hlt">primary</span> glioblastoma multiforme were screened for IDH<span class="hlt">1</span> mutations (R132H, R132S, R132C and R132L) by direct sequencing. Serum VEGF and tumor tissue HIF<span class="hlt">1</span>-alpha levels were measured by enzyme-linked immunosorbent assay. Associations between categoric variables were determined using chi-square tests. Differences between two groups were compared with t test for continuous variables. Six percent of patients were found to be heterozygous for R132H mutation. Tumor HIF<span class="hlt">1</span>-alpha and serum VEGF levels were found to be significantly increased in IDH<span class="hlt">1</span> -mutated tumor tissues ( p <0.0001 and p =0.0454, respectively). Our results suggest that mutated IDH<span class="hlt">1</span> may contribute to carcinogenesis via induction of HIF-<span class="hlt">1</span> alpha pathway in <span class="hlt">primary</span> GBM. © 2017 by the Association of Clinical Scientists, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ocg.cancer.gov/news-publications/publications/childrens-oncology-group-and-target-initiative-exploring-genetic','NCI'); return false;" href="https://ocg.cancer.gov/news-publications/publications/childrens-oncology-group-and-target-initiative-exploring-genetic"><span>A Children's Oncology Group and TARGET initiative exploring the genetic landscape of Wilms tumor. | Office of Cancer Genomics</span></a></p> <p><a target="_blank" href="http://www.cancer.gov">Cancer.gov</a></p> <p></p> <p></p> <p>We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT<span class="hlt">1</span>, CTNNB<span class="hlt">1</span>, AMER<span class="hlt">1</span>, DROSHA, DGCR8, <span class="hlt">XPO</span>5, DICER<span class="hlt">1</span>, SIX<span class="hlt">1</span>, SIX2, MLLT<span class="hlt">1</span>, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL<span class="hlt">1</span>, NONO, MAX, COL6A3, ASXL<span class="hlt">1</span>, MAP3K4, and ARID<span class="hlt">1</span>A.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29090598','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29090598"><span>Care Coordination for Youth With Mental Health Disorders in <span class="hlt">Primary</span> Care.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hobbs Knutson, Katherine; Meyer, Mark J; Thakrar, Nisha; Stein, Bradley D</p> <p>2018-01-01</p> <p>Many children are treated for mental health disorders in <span class="hlt">primary</span> care settings. The system of care (SOC) provides a framework for collaboration among pediatric mental health providers, but it is unclear if youth treated for mental health disorders in <span class="hlt">primary</span> care receive such coordination. At the South Boston Community Health Center from September /2012 to August 2013 for 74 individuals ≤18 years, the odds of contact with SOC agencies (mental health, education, child protective services, juvenile justice and developmental disabilities) were compared for mental health treatment in <span class="hlt">primary</span> versus specialty care. The odds of SOC contact within <span class="hlt">primary</span> care were lower compared to specialty care (OR = 0.43, 95% CI = 0.29-0.66), specifically for mental health (OR = 0.54, 95% CI = 0.25-<span class="hlt">1</span>.2), education (OR = 0.12, 95% CI = 0.050-0.28), and child protective services (OR = 0.64, 95% CI = 0.22-<span class="hlt">1</span>.9). As care coordination may improve health outcomes, increased <span class="hlt">support</span> and education for care coordination specific to youth treated for mental health disorders in <span class="hlt">primary</span> care settings may be warranted.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28867253','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28867253"><span>Estrogen decreases tight junction protein ZO-<span class="hlt">1</span> expression in human <span class="hlt">primary</span> gut tissues.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei</p> <p>2017-10-01</p> <p>Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens <span class="hlt">1</span> (ZO-<span class="hlt">1</span>) and estrogen receptor (ER)-α/β in human <span class="hlt">primary</span> gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-<span class="hlt">1</span> and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-<span class="hlt">1</span> expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-<span class="hlt">1</span> mRNA and protein expression, ZO-<span class="hlt">1</span> promoter activity, IL-6 production, and NF-κB activation in human <span class="hlt">primary</span> gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://hdl.handle.net/2060/20060028172','NASA-TRS'); return false;" href="http://hdl.handle.net/2060/20060028172"><span>Invasive Species Forecasting System: A Decision <span class="hlt">Support</span> Tool for the U.S. Geological Survey: FY 2005 Benchmarking Report v.<span class="hlt">1</span>.6</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Stohlgren, Tom; Schnase, John; Morisette, Jeffrey; Most, Neal; Sheffner, Ed; Hutchinson, Charles; Drake, Sam; Van Leeuwen, Willem; Kaupp, Verne</p> <p>2005-01-01</p> <p>The National Institute of Invasive Species Science (NIISS), through collaboration with NASA's Goddard Space Flight Center (GSFC), recently began incorporating NASA observations and predictive modeling tools to fulfill its mission. These enhancements, labeled collectively as the Invasive Species Forecasting System (ISFS), are now in place in the NIISS in their initial state (V<span class="hlt">1</span>.0). The ISFS is the <span class="hlt">primary</span> decision <span class="hlt">support</span> tool of the NIISS for the management and control of invasive species on Department of Interior and adjacent lands. The ISFS is the backbone for a unique information services line-of-business for the NIISS, and it provides the means for delivering advanced decision <span class="hlt">support</span> capabilities to a wide range of management applications. This report describes the operational characteristics of the ISFS, a decision <span class="hlt">support</span> tool of the United States Geological Survey (USGS). Recent enhancements to the performance of the ISFS, attained through the integration of observations, models, and systems engineering from the NASA are benchmarked; i.e., described quantitatively and evaluated in relation to the performance of the USGS system before incorporation of the NASA enhancements. This report benchmarks Version <span class="hlt">1</span>.0 of the ISFS.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1060665','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/1060665"><span>Technical <span class="hlt">Support</span> Document for Version 3.9.<span class="hlt">1</span> of the COMcheck Software</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Bartlett, Rosemarie; Connell, Linda M.; Gowri, Krishnan</p> <p>2012-09-01</p> <p>COMcheck provides an optional way to demonstrate compliance with commercial and high-rise residential building energy codes. Commercial buildings include all use groups except single family and multifamily not over three stories in height. COMcheck was originally based on ANSI/ASHRAE/IES Standard 90.<span class="hlt">1</span>-1989 (Standard 90.<span class="hlt">1</span>-1989) requirements and is intended for use with various codes based on Standard 90.<span class="hlt">1</span>, including the Codification of ASHRAE/IES Standard 90.<span class="hlt">1</span>-1989 (90.<span class="hlt">1</span>-1989 Code) (ASHRAE 1989a, 1993b) and ASHRAE/IESNA Standard 90.<span class="hlt">1</span>-1999 (Standard 90.<span class="hlt">1</span>-1999). This includes jurisdictions that have adopted the 90.<span class="hlt">1</span>-1989 Code, Standard 90.<span class="hlt">1</span>-1989, Standard 90.<span class="hlt">1</span>-1999, or their own code based on one of these. We view Standard 90.<span class="hlt">1</span>-1989more » and the 90.<span class="hlt">1</span>-1989 Code as having equivalent technical content and have used both as source documents in developing COMcheck. This technical <span class="hlt">support</span> document (TSD) is designed to explain the technical basis for the COMcheck software as originally developed based on the ANSI/ASHRAE/IES Standard 90.<span class="hlt">1</span>-1989 (Standard 90.<span class="hlt">1</span>-1989). Documentation for other national model codes and standards and specific state energy codes <span class="hlt">supported</span> in COMcheck has been added to this report as appendices. These appendices are intended to provide technical documentation for features specific to the <span class="hlt">supported</span> codes and for any changes made for state-specific codes that differ from the standard features that <span class="hlt">support</span> compliance with the national model codes and standards. Beginning with COMcheck version 3.8.0, <span class="hlt">support</span> for 90.<span class="hlt">1</span>-1989, 90.<span class="hlt">1</span>-1999, and the 1998 IECC and version 3.9.0 <span class="hlt">support</span> for 2000 and 2001 IECC are no longer included, but those sections remain in this document for reference purposes.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=335362&Lab=IO&keyword=cycles&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50','EPA-EIMS'); return false;" href="https://cfpub.epa.gov/si/si_public_record_report.cfm?dirEntryId=335362&Lab=IO&keyword=cycles&actType=&TIMSType=+&TIMSSubTypeID=&DEID=&epaNumber=&ntisID=&archiveStatus=Both&ombCat=Any&dateBeginCreated=&dateEndCreated=&dateBeginPublishedPresented=&dateEndPublishedPresented=&dateBeginUpdated=&dateEndUpdated=&dateBeginCompleted=&dateEndCompleted=&personID=&role=Any&journalID=&publisherID=&sortBy=revisionDate&count=50"><span>Water Systems Project <span class="hlt">1</span>: Current Systems and Regulatory <span class="hlt">Support</span></span></a></p> <p><a target="_blank" href="http://oaspub.epa.gov/eims/query.page">EPA Science Inventory</a></p> <p></p> <p></p> <p>Water Systems Project <span class="hlt">1</span> objectives: <span class="hlt">1</span>) Supply research results to <span class="hlt">support</span> federal regulations and guidance; 2) provide strategies to regions, states, and communities for improved regulatory compliance, and 3) provide rapid and effective emergency response where appropriate (e.g. ...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/1245994','SCIGOV-DOEDE'); return false;" href="https://www.osti.gov/servlets/purl/1245994"><span>AmeriFlux BR-Sa<span class="hlt">1</span> Santarem-Km67-<span class="hlt">Primary</span> Forest</span></a></p> <p><a target="_blank" href="http://www.osti.gov/dataexplorer">DOE Data Explorer</a></p> <p>Saleska, Scott [University of Arizona</p> <p>2016-01-01</p> <p>This is the AmeriFlux version of the carbon flux data for the site BR-Sa<span class="hlt">1</span> Santarem-Km67-<span class="hlt">Primary</span> Forest. Site Description - The LBA Tapajos KM67 Mature Forest site is located in the Tapajos National Forest, a 450,000 ha closed-canopy upland forest in Amazonian Brazil. Bounded by the Tapajos River in the west and highway BR-163 to the east, the tower is located on a flat plateau (or planalto) that extends up to 150 km to the north, south, and east. Within the confines of the National Forest, anthropogenic disturbances are limited to a few small hunting trails. The surrounding stand is classified as <span class="hlt">primary</span> or "old-growth"" predominantly by its uneven age distribution, emergent trees, numerous epiphytes and abundant large logs. In 2007 falling trees hit the tower guy wires rendering all instrumentation in-operational. After a complete restoration tower measurements resumed in August of 2008.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26086805','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26086805"><span>Enhancing spatial resolution of (18)F positron imaging with the Timepix detector by classification of <span class="hlt">primary</span> fired pixels using <span class="hlt">support</span> vector machine.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Wang, Qian; Liu, Zhen; Ziegler, Sibylle I; Shi, Kuangyu</p> <p>2015-07-07</p> <p>Position-sensitive positron cameras using silicon pixel detectors have been applied for some preclinical and intraoperative clinical applications. However, the spatial resolution of a positron camera is limited by positron multiple scattering in the detector. An incident positron may fire a number of successive pixels on the imaging plane. It is still impossible to capture the <span class="hlt">primary</span> fired pixel along a particle trajectory by hardware or to perceive the pixel firing sequence by direct observation. Here, we propose a novel data-driven method to improve the spatial resolution by classifying the <span class="hlt">primary</span> pixels within the detector using <span class="hlt">support</span> vector machine. A classification model is constructed by learning the features of positron trajectories based on Monte-Carlo simulations using Geant4. Topological and energy features of pixels fired by (18)F positrons were considered for the training and classification. After applying the classification model on measurements, the <span class="hlt">primary</span> fired pixels of the positron tracks in the silicon detector were estimated. The method was tested and assessed for [(18)F]FDG imaging of an absorbing edge protocol and a leaf sample. The proposed method improved the spatial resolution from 154.6   ±   4.2 µm (energy weighted centroid approximation) to 132.3   ±   3.5 µm in the absorbing edge measurements. For the positron imaging of a leaf sample, the proposed method achieved lower root mean square error relative to phosphor plate imaging, and higher similarity with the reference optical image. The improvements of the preliminary results <span class="hlt">support</span> further investigation of the proposed algorithm for the enhancement of positron imaging in clinical and preclinical applications.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2015PMB....60.5261W','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2015PMB....60.5261W"><span>Enhancing spatial resolution of 18F positron imaging with the Timepix detector by classification of <span class="hlt">primary</span> fired pixels using <span class="hlt">support</span> vector machine</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Wang, Qian; Liu, Zhen; Ziegler, Sibylle I.; Shi, Kuangyu</p> <p>2015-07-01</p> <p>Position-sensitive positron cameras using silicon pixel detectors have been applied for some preclinical and intraoperative clinical applications. However, the spatial resolution of a positron camera is limited by positron multiple scattering in the detector. An incident positron may fire a number of successive pixels on the imaging plane. It is still impossible to capture the <span class="hlt">primary</span> fired pixel along a particle trajectory by hardware or to perceive the pixel firing sequence by direct observation. Here, we propose a novel data-driven method to improve the spatial resolution by classifying the <span class="hlt">primary</span> pixels within the detector using <span class="hlt">support</span> vector machine. A classification model is constructed by learning the features of positron trajectories based on Monte-Carlo simulations using Geant4. Topological and energy features of pixels fired by 18F positrons were considered for the training and classification. After applying the classification model on measurements, the <span class="hlt">primary</span> fired pixels of the positron tracks in the silicon detector were estimated. The method was tested and assessed for [18F]FDG imaging of an absorbing edge protocol and a leaf sample. The proposed method improved the spatial resolution from 154.6   ±   4.2 µm (energy weighted centroid approximation) to 132.3   ±   3.5 µm in the absorbing edge measurements. For the positron imaging of a leaf sample, the proposed method achieved lower root mean square error relative to phosphor plate imaging, and higher similarity with the reference optical image. The improvements of the preliminary results <span class="hlt">support</span> further investigation of the proposed algorithm for the enhancement of positron imaging in clinical and preclinical applications.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=Science&pg=4&id=EJ1156405','ERIC'); return false;" href="https://eric.ed.gov/?q=Science&pg=4&id=EJ1156405"><span><span class="hlt">Primary</span> Science Quality Mark--2016 Update</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Turner, Jane</p> <p>2016-01-01</p> <p>Back in May 2011, an article in "<span class="hlt">Primary</span> Science" described how the idea for a quality mark for <span class="hlt">primary</span> science was developed from an initial conversation at an Association for Science Education annual conference (Turner, Marshall and Elsmore, 2011). Its intention then, as now, was to <span class="hlt">support</span> and champion good practice and raise the…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=primary+AND+care+AND+coordination&pg=3&id=EJ614310','ERIC'); return false;" href="https://eric.ed.gov/?q=primary+AND+care+AND+coordination&pg=3&id=EJ614310"><span>Counselling in <span class="hlt">Primary</span> Care: Past, Present, and Future.</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Eatock, John</p> <p>2000-01-01</p> <p>Presents a brief history of the growth of counseling in <span class="hlt">primary</span> care. Discusses the challenges for <span class="hlt">primary</span> care counselors and counseling, as well as the need for coordination, regulation and management. Also discusses the imperative for research <span class="hlt">support</span> and the unique nature of counseling in <span class="hlt">primary</span> care including challenges to its survival. (MKA)</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4316236','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4316236"><span>Dermatoglyphics and Karyotype Analysis in <span class="hlt">Primary</span> Amenorrhoea</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sontakke, Bharat R; Waghmare, Jwalant E; Tarnekar, Aditya M; Shende, Moreshwar R; Pal, Asoke K</p> <p>2014-01-01</p> <p>Background: Dermatoglyphics is the scientific study of the skin ridge patterns on the fingers, toes, palms of the hands and soles of feet. Dermatoglyphics is in use as a <span class="hlt">supportive</span> diagnostic tool in genetic or chromosomal disorders as well as in clinical conditions with genetic etiologies. <span class="hlt">Primary</span> amenorrhoea and Dermatoglyphics, both have the suspected multifactorial (genetic and environmental) aetiologies. Objective: In the present study the finger dermatoglyphic patterns were studied in <span class="hlt">primary</span> amenorrhoea cases and age matched fertile control females and also attention was given to find out whether a specific dermatoglyphic trait exists in <span class="hlt">primary</span> amenorrhoea cases and whether it was statistically significant. Materials and Methods: To study the role of dermatoglyphics in <span class="hlt">primary</span> amenorrhoea, a study was conducted on 30 subjects with <span class="hlt">primary</span> amenorrhoea (as cases) and compared it with equal number of age matched fertile females (as controls). We studied fingertip patterns in all the subjects enrolled. Simultaneously we have assessed the Karyotype of <span class="hlt">primary</span> amenorrhoea cases. Result and Conclusion: Two subjects in experimental group have shown abnormal Karyotypes. The most significant finding in present study was increased total finger ridge count (TFRC) in <span class="hlt">primary</span> amenorrhoea cases which was statistically significant. We also found higher frequency of loops and arches in <span class="hlt">primary</span> amenorrhoea with abnormal karyotypes. This type of study may be quite useful as a <span class="hlt">supportive</span> investigation, in stating the predisposition of an individual to <span class="hlt">primary</span> amenorrhoea and referral of an individual for karyotyping. PMID:25653930</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29760028','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29760028"><span>Roles and Functions of Community Health Workers in <span class="hlt">Primary</span> Care.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hartzler, Andrea L; Tuzzio, Leah; Hsu, Clarissa; Wagner, Edward H</p> <p>2018-05-01</p> <p>Community health workers have potential to enhance <span class="hlt">primary</span> care access and quality, but remain underutilized. To provide guidance on their integration, we characterized roles and functions of community health workers in <span class="hlt">primary</span> care through a literature review and synthesis. Analysis of 30 studies identified 12 functions (ie, care coordination, health coaching, social <span class="hlt">support</span>, health assessment, resource linking, case management, medication management, remote care, follow-up, administration, health education, and literacy <span class="hlt">support</span>) and 3 prominent roles representing clusters of functions: clinical services, community resource connections, and health education and coaching. We discuss implications for community health worker training and clinical <span class="hlt">support</span> in <span class="hlt">primary</span> care. © 2018 Annals of Family Medicine, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15084379','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15084379"><span>The utility and limitation of thyroid transcription factor-<span class="hlt">1</span> protein in <span class="hlt">primary</span> and metastatic pulmonary neoplasms.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chang, Yih-Leong; Lee, Yung-Chie; Liao, Wei-Yu; Wu, Chen-Tu</p> <p>2004-05-01</p> <p>Thyroid transcription factor-<span class="hlt">1</span> (TTF-<span class="hlt">1</span>) is a tissue-specific transcription factor expressed in the thyroid and lung. The clinical utility and limitation of TTF-<span class="hlt">1</span> in <span class="hlt">primary</span> or metastatic carcinomas of the lung have not been previously studied in detail. We examined TTF-<span class="hlt">1</span> expression in 510 <span class="hlt">primary</span> lung and 107 metastatic neoplasms. TTF-<span class="hlt">1</span> was detectable in 4/99 (4%) squamous cell carcinomas, 169/176 (96%) solitary adenocarcinomas, 34/34 (100%) multifocal adenocarcinomas, <span class="hlt">1/1</span> (100%) signet ring cell carcinoma, 16/20 (80%) mucinous adenocarcinomas, 23/23 (100%) nonmucinous bronchioloalveolar carcinomas, 19/36 (53%) small cell carcinomas, and 39/44 (89%) sclerosing hemangioma. TTF-<span class="hlt">1</span> was absent in all eight carcinoids, three atypical carcinoids, 23 pleomorphic carcinomas, 25 lymphoepithelioma-like carcinomas, the sarcomatous component of one pseudomesotheliomatous carcinoma, and one mesothelioma. In four combined small cell carcinomas and 12 adenosquamous carcinomas, TTF-<span class="hlt">1</span> expression was only demonstrated in the adenocarcinoma component. There were 78 TTF-<span class="hlt">1</span> non-immunoreactive metastatic cases from 22 livers, 20 colorectums, 10 breasts, six nasopharynx, four larynx, four ovaries, three salivary glands, three esophagus, two adrenal glands, two kidneys, one bile duct, and one endometrium. TTF-<span class="hlt">1</span> was also detected in all 10 cervical lymph nodes, seven brain, and 6/7 (86%) bony tissues of 24 patients with metastatic carcinomas of unknown <span class="hlt">primary</span> site, but it was absent in 125 patients with metastatic carcinomas other than lung origin in cervical lymph nodes, brain, and bony tissues. These results indicate the clinical usefulness and limitation in certain <span class="hlt">primary</span> and metastatic lung neoplasms.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_18");'>18</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li class="active"><span>20</span></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_20 --> <div id="page_21" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="401"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21824381','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21824381"><span>Computerized clinical decision <span class="hlt">support</span> systems for <span class="hlt">primary</span> preventive care: a decision-maker-researcher partnership systematic review of effects on process of care and patient outcomes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Souza, Nathan M; Sebaldt, Rolf J; Mackay, Jean A; Prorok, Jeanette C; Weise-Kelly, Lorraine; Navarro, Tamara; Wilczynski, Nancy L; Haynes, R Brian</p> <p>2011-08-03</p> <p>Computerized clinical decision <span class="hlt">support</span> systems (CCDSSs) are claimed to improve processes and outcomes of <span class="hlt">primary</span> preventive care (PPC), but their effects, safety, and acceptance must be confirmed. We updated our previous systematic reviews of CCDSSs and integrated a knowledge translation approach in the process. The objective was to review randomized controlled trials (RCTs) assessing the effects of CCDSSs for PPC on process of care, patient outcomes, harms, and costs. We conducted a decision-maker-researcher partnership systematic review. We searched MEDLINE, EMBASE, Ovid's EBM Reviews Database, Inspec, and other databases, as well as reference lists through January 2010. We contacted authors to confirm data or provide additional information. We included RCTs that assessed the effect of a CCDSS for PPC on process of care and patient outcomes compared to care provided without a CCDSS. A study was considered to have a positive effect (i.e., CCDSS showed improvement) if at least 50% of the relevant study outcomes were statistically significantly positive. We added 17 new RCTs to our 2005 review for a total of 41 studies. RCT quality improved over time. CCDSSs improved process of care in 25 of 40 (63%) RCTs. Cumulative scientifically strong evidence <span class="hlt">supports</span> the effectiveness of CCDSSs for screening and management of dyslipidaemia in <span class="hlt">primary</span> care. There is mixed evidence for effectiveness in screening for cancer and mental health conditions, multiple preventive care activities, vaccination, and other preventive care interventions. Fourteen (34%) trials assessed patient outcomes, and four (29%) reported improvements with the CCDSS. Most trials were not powered to evaluate patient-important outcomes. CCDSS costs and adverse events were reported in only six (15%) and two (5%) trials, respectively. Information on study duration was often missing, limiting our ability to assess sustainability of CCDSS effects. Evidence <span class="hlt">supports</span> the effectiveness of CCDSSs for screening and</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29760025','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29760025"><span>Association of the Social Determinants of Health With Quality of <span class="hlt">Primary</span> Care.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Katz, Alan; Chateau, Dan; Enns, Jennifer E; Valdivia, Jeff; Taylor, Carole; Walld, Randy; McCulloch, Scott</p> <p>2018-05-01</p> <p>In <span class="hlt">primary</span> care, there is increasing recognition of the difficulty of treating patients' immediate health concerns when their overall well-being is shaped by underlying social determinants of health. We assessed the association of social complexity factors with the quality of care patients received in <span class="hlt">primary</span> care settings. Eleven social complexity factors were defined using administrative data on poverty, mental health, newcomer status, and justice system involvement from the Manitoba Population Research Data Repository. We measured the distribution of these factors among <span class="hlt">primary</span> care patients who made at least 3 visits during 2010-2013 to clinicians in Manitoba, Canada. Using generalized linear mixed modeling, we measured 26 <span class="hlt">primary</span> care indicators to compare the quality of care received by patients with 0 to 5 or more social complexity factors. Among 626,264 <span class="hlt">primary</span> care patients, 54% were living with at least <span class="hlt">1</span> social complexity factor, and 4% were living with 5 or more. Social complexity factors were strongly associated with poorer outcomes with respect to <span class="hlt">primary</span> care indicators for prevention (eg, breast cancer screening; odds ratio [OR] = 0.77; 99% CI, 0.73-0.81), chronic disease management (eg, diabetes management; OR = 0.86; 99% CI, 0.79-0.92), geriatric care (eg, benzodiazepine prescriptions; OR = <span class="hlt">1</span>.63; 99% CI, <span class="hlt">1.48-1</span>.80), and use of health services (eg, ambulatory visits; OR = <span class="hlt">1</span>.09; 99% CI, <span class="hlt">1.08-1</span>.09). Linking health and social data demonstrates how social determinants are associated with <span class="hlt">primary</span> care service provision. Our findings provide insight into the social needs of <span class="hlt">primary</span> care populations, and may <span class="hlt">support</span> the development of focused interventions to address social complexity in <span class="hlt">primary</span> care. © 2018 Annals of Family Medicine, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=104231','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=104231"><span>Role of CXCR4 in Cell-Cell Fusion and Infection of Monocyte-Derived Macrophages by <span class="hlt">Primary</span> Human Immunodeficiency Virus Type <span class="hlt">1</span> (HIV-<span class="hlt">1</span>) Strains: Two Distinct Mechanisms of HIV-<span class="hlt">1</span> Dual Tropism</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Yi, Yanjie; Isaacs, Stuart N.; Williams, Darlisha A.; Frank, Ian; Schols, Dominique; De Clercq, Erik; Kolson, Dennis L.; Collman, Ronald G.</p> <p>1999-01-01</p> <p>Dual-tropic human immunodeficiency virus type <span class="hlt">1</span> (HIV-<span class="hlt">1</span>) strains infect both <span class="hlt">primary</span> macrophages and transformed T-cell lines. Prototype T-cell line-tropic (T-tropic) strains use CXCR4 as their principal entry coreceptor (X4 strains), while macrophagetropic (M-tropic) strains use CCR5 (R5 strains). Prototype dual tropic strains use both coreceptors (R5X4 strains). Recently, CXCR4 expressed on macrophages was found to <span class="hlt">support</span> infection by certain HIV-<span class="hlt">1</span> isolates, including the dual-tropic R5X4 strain 89.6, but not by T-tropic X4 prototypes like 3B. To better understand the cellular basis for dual tropism, we analyzed the macrophage coreceptors used for Env-mediated cell-cell fusion as well as infection by several dual-tropic HIV-<span class="hlt">1</span> isolates. Like 89.6, the R5X4 strain DH12 fused with and infected both wild-type and CCR5-negative macrophages. The CXCR4-specific inhibitor AMD3100 blocked DH12 fusion and infection in macrophages that lacked CCR5 but not in wild-type macrophages. This finding indicates two independent entry pathways in macrophages for DH12, CCR5 and CXCR4. Three <span class="hlt">primary</span> isolates that use CXCR4 but not CCR5 (tybe, UG021, and UG024) replicated efficiently in macrophages regardless of whether CCR5 was present, and AMD3100 blocking of CXCR4 prevented infection in both CCR5 negative and wild-type macrophages. Fusion mediated by UG021 and UG024 Envs in both wild-type and CCR5-deficient macrophages was also blocked by AMD3100. Therefore, these isolates use CXCR4 exclusively for entry into macrophages. These results confirm that macrophage CXCR4 can be used for fusion and infection by <span class="hlt">primary</span> HIV-<span class="hlt">1</span> isolates and indicate that CXCR4 may be the sole macrophage coreceptor for some strains. Thus, dual tropism can result from two distinct mechanisms: utilization of both CCR5 and CXCR4 on macrophages and T-cell lines, respectively (dual-tropic R5X4), or the ability to efficiently utilize CXCR4 on both macrophages and T-cell lines (dual-tropic X4). PMID:10438797</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25750510','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25750510"><span>CYP<span class="hlt">1</span>B<span class="hlt">1</span> copy number variation is not a major contributor to <span class="hlt">primary</span> congenital glaucoma.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Souzeau, Emmanuelle; Hayes, Melanie; Ruddle, Jonathan B; Elder, James E; Staffieri, Sandra E; Kearns, Lisa S; Mackey, David A; Zhou, Tiger; Ridge, Bronwyn; Burdon, Kathryn P; Dubowsky, Andrew; Craig, Jamie E</p> <p>2015-01-01</p> <p>To evaluate the prevalence and the diagnostic utility of testing for CYP<span class="hlt">1</span>B<span class="hlt">1</span> copy number variation (CNV) in <span class="hlt">primary</span> congenital glaucoma (PCG) cases unexplained by CYP<span class="hlt">1</span>B<span class="hlt">1</span> point mutations in The Australian and New Zealand Registry of Advanced Glaucoma. In total, 50 PCG cases either heterozygous for disease-causing variants or with no CYP<span class="hlt">1</span>B<span class="hlt">1</span> sequence variants were included in the study. CYP<span class="hlt">1</span>B<span class="hlt">1</span> CNV was analyzed by Multiplex Ligation-dependent Probe Amplification (MLPA). No deletions or duplications were found in any of the cases. This is the first study to report on CYP<span class="hlt">1</span>B<span class="hlt">1</span> CNV in PCG cases. Our findings show that this mechanism is not a major contributor to the phenotype and is of limited diagnostic utility.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25542273','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25542273"><span>Preventing the spread of H<span class="hlt">1</span>N<span class="hlt">1</span> influenza infection during a pandemic: autonomy-<span class="hlt">supportive</span> advice versus controlling instruction.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chan, Derwin King-Chung; Yang, Sophie Xin; Mullan, Barbara; Du, Xiumin; Zhang, Xin; Chatzisarantis, Nikos L D; Hagger, Martin S</p> <p>2015-06-01</p> <p>Wearing facemask is an effective strategy for preventing the spread of the H<span class="hlt">1</span>N<span class="hlt">1</span> in enclosed public spaces. This quasi-experiment examined the effects of University professor 'autonomy <span class="hlt">support</span> on students' motivation, social cognitive factors, and intention to wear facemasks in the lecture hall during a hypothetical H<span class="hlt">1</span>N<span class="hlt">1</span> pandemic. University students (N = 705) completed self-report measures of motivation, social cognitive factors, and intention according to a hypothetical H<span class="hlt">1</span>N<span class="hlt">1</span> pandemic scenario in which their professors asked them to wear facemasks in the lecture hall, using either an 'autonomy-<span class="hlt">supportive</span>' interpersonal style or a 'controlling' style. The results showed that the manipulation of professors' autonomy <span class="hlt">support</span> exerted a positive effect on students' perception of autonomy <span class="hlt">support</span>, which positively predicted their self-determined motivation, social cognitive factors, and intentions to wear facemasks. In conclusion, promoting self-determined motivation using autonomy-<span class="hlt">supportive</span> communication styles might be an effective means of fostering individuals' adaptive beliefs and motivation of H<span class="hlt">1</span>N<span class="hlt">1</span> prevention.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17489907','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17489907"><span><span class="hlt">Primary</span> care practice organization influences colorectal cancer screening performance.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Yano, Elizabeth M; Soban, Lynn M; Parkerton, Patricia H; Etzioni, David A</p> <p>2007-06-01</p> <p>To identify <span class="hlt">primary</span> care practice characteristics associated with colorectal cancer (CRC) screening performance, controlling for patient-level factors. <span class="hlt">Primary</span> care director survey (1999-2000) of 155 VA <span class="hlt">primary</span> care clinics linked with 38,818 eligible patients' sociodemographics, utilization, and CRC screening experience using centralized administrative and chart-review data (2001). Practices were characterized by degrees of centralization (e.g., authority over operations, staffing, outside-practice influence); resources (e.g., sufficiency of nonphysician staffing, space, clinical <span class="hlt">support</span> arrangements); and complexity (e.g., facility size, academic status, managed care penetration), adjusting for patient-level covariates and contextual factors. Chart-based evidence of CRC screening through direct colonoscopy, sigmoidoscopy, or consecutive fecal occult blood tests, eliminating cases with documented histories of CRC, polyps, or inflammatory bowel disease. After adjusting for sociodemographic characteristics and health care utilization, patients were significantly more likely to be screened for CRC if their <span class="hlt">primary</span> care practices had greater autonomy over the internal structure of care delivery (p<.04), more clinical <span class="hlt">support</span> arrangements (p<.03), and smaller size (p<.001). Deficits in <span class="hlt">primary</span> care clinical <span class="hlt">support</span> arrangements and local autonomy over operational management and referral procedures are associated with significantly lower CRC screening performance. Competition with hospital resource demands may impinge on the degree of internal organization of their affiliated <span class="hlt">primary</span> care practices.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24987047','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24987047"><span>Management of pediatric tachyarrhythmias on mechanical <span class="hlt">support</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Silva, Jennifer N A; Erickson, Christopher C; Carter, Christopher D; Greene, E Anne; Kantoch, Michal; Collins, Kathryn K; Miyake, Christina Y; Carboni, Michael P; Rhee, Edward K; Papez, Andrew; Anand, Vijay; Bowman, Tammy M; Van Hare, George F</p> <p>2014-08-01</p> <p>Pediatric patients with persistent arrhythmias may require mechanical cardiopulmonary <span class="hlt">support</span>. We sought to classify the population, spectrum, and success of current treatment strategies. A multicenter retrospective chart review was undertaken at 11 sites. Inclusion criteria were (<span class="hlt">1</span>) patients <21 years, (2) initiation of mechanical <span class="hlt">support</span> for a <span class="hlt">primary</span> diagnosis of arrhythmias, and (3) actively treated on mechanical <span class="hlt">support</span>. A total of 39 patients were identified with a median age of 5.5 months and median weight of 6 kg. A total of 69% of patients were cannulated for supraventricular tachycardia with a median rate of 230 beats per minute. A total of 90% of patients were <span class="hlt">supported</span> with extracorporeal membrane oxygenation for an average of 5 days. The remaining 10% were <span class="hlt">supported</span> with ventricular assist devices for an average of 38 (20-60) days. A total of 95% of patients were treated with antiarrhythmics, with 43% requiring ><span class="hlt">1</span> antiarrhythmic. Amiodarone was the most frequently used medication alone or in combination. A total of 33% patients underwent electrophysiology study/transcatheter ablation. Radiofrequency ablation was successful in 9 patients on full flow extracorporeal membrane oxygenation with 3 radiofrequency-failures/conversion to cryoablation. One patient underwent <span class="hlt">primary</span> cryoablation. A total of 15% of complications were related to electrophysiology study/ablation. At follow-up, 23 patients were alive, 8 expired, and 8 transplanted. Younger patients were more likely to require <span class="hlt">support</span> in the presented population. Most patients were treated with antiarrhythmics and one third required electrophysiology study/ablation. Radiofrequency ablation is feasible without altering extracorporeal membrane oxygenation flows. There was a low frequency of acute adverse events in patients undergoing electrophysiology study/ablation, while on extracorporeal membrane oxygenation. © 2014 American Heart Association, Inc.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3683648','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3683648"><span>Cooperative roles for emmprin and LYVE-<span class="hlt">1</span> in the regulation of chemoresistance for <span class="hlt">primary</span> effusion lymphoma</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Qin, Z; Dai, L; Bratoeva, M; Slomiany, MG; Toole, BP; Parsons, C</p> <p>2013-01-01</p> <p>The Kaposi’s sarcoma-associated herpesvirus is the causative agent of <span class="hlt">primary</span> effusion lymphoma (PEL), for which cytotoxic chemotherapy represents the standard of care. The high mortality associated with PEL may be explained in part by resistance of these tumors to chemotherapy. The membrane-bound glycoprotein emmprin (CD147) enhances chemoresistance in tumors through effects on transporter expression, trafficking and interactions. Interactions between hyaluronan and hyaluronan receptors on the cell surface also facilitate emmprin-mediated chemoresistance. Whether emmprin or hyaluronan-receptor interactions regulate chemotherapeutic resistance for virus-associated malignancies is unknown. Using human PEL tumor cells, we found that PEL sensitivity to chemotherapy is directly proportional to expression of emmprin, the lymphatic vessel endothelial hyaluronan receptor-<span class="hlt">1</span> (LYVE-<span class="hlt">1</span>) and a drug transporter known as the breast cancer resistance protein/ABCG2 (BCRP), and that emmprin, LYVE-<span class="hlt">1</span> and BCRP interact with each other and colocalize on the PEL cell surface. In addition, we found that emmprin induces chemoresistance in PEL cells through upregulation of BCRP expression, and RNA interference targeting of emmprin, LYVE-<span class="hlt">1</span> or BCRP enhances PEL cell apoptosis induced by chemotherapy. Finally, disruption of hyaluronan-receptor interactions using small hyaluronan oligosaccharides reduces expression of emmprin and BCRP while sensitizing PEL cells to chemotherapy. Collectively, these data <span class="hlt">support</span> interdependent roles for emmprin, LYVE-<span class="hlt">1</span> and BCRP in chemotherapeutic resistance for PEL. PMID:21660043</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2010JCrGr.312.1334F','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2010JCrGr.312.1334F"><span>Factors influencing the purity of electronic grade phosphine delivered to MOCVD tools</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Feng, Jun; Owens, Mitch; Raynor, Mark W.</p> <p>2010-04-01</p> <p>Increasing mobility of InP films with usage time of one PH 3 cylinder prompted an investigation into factors influencing the purity of delivered PH 3. The presence of hygroscopic H <span class="hlt">xPO</span> y residues in a delivery system greatly increases the dry-down time compared to that of a clean system. Static delivery system tests show increasing H 2O concentration with time and twice the increase in PH 3 versus N 2 over 48 h indicating reaction of metal oxides in components with PH 3 to generate H 2O. Gas purity may also vary during cylinder usage. Depletion of a high-purity PH 3 cylinder shows consistently low gas phase H 2O levels before phase-break but increasing levels after phase-break, as the cylinder depressurizes. The results highlight the importance of using pure PH 3, employing rigorous cycle-purging procedures to prevent H <span class="hlt">xPO</span> y contamination, switching out cylinders in good time and using purification technology to control H 2O.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22927586','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22927586"><span>Socialization and organizational citizenship behavior among Turkish <span class="hlt">primary</span> and secondary school teachers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Çavuş, Mustafa Fedai</p> <p>2012-01-01</p> <p>The aim of the present study is to investigate the effects of organizational socialization levels of employees on organizational citizenship behavior (OCB). A total of 185 (70 female, 115 male) teachers were sampled at 27 <span class="hlt">primary</span> and secondary schools. Their ages ranged from 23 to 55 years, with a mean (SD) of 36 (5.<span class="hlt">1</span>). In this sample, 100 (54.<span class="hlt">1</span>%) worked in <span class="hlt">primary</span> schools, and 85 (45.9%) worked in secondary schools. A three-part questionnaire was designed for the study. The research scales were self-report measures of organizational socialization, OCB, and demographic variables. The hypothesized model was tested using Pearson correlation analyses and multiple regression analyses. The teachers demonstrated high level socialization (Mean 4.2, SD 0.7) and OCB (Mean 4.0, SD 0.54). Understanding, coworker <span class="hlt">support</span>, and performance proficiency explained significant variance in organizational citizenship behavior; however, there was no relationship (p=0.286) between the organizational goals and values and OCB. The findings contribute to our understanding of the relationship between the level of organizational socialization and organizational citizenship behavior in educational settings. These findings suggest that high level organizational socialization <span class="hlt">supports</span> organizational citizenship behavior in <span class="hlt">primary</span> and secondary school teachers.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21673577','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21673577"><span>A health insurance company-initiated practice <span class="hlt">support</span> intervention for optimizing acid-suppressing drug prescriptions in <span class="hlt">primary</span> care.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Smeets, Hugo M; Hoes, Arno W; Zuithoff, Nicolaas P A; van Dijk, Paul C M; van der Lee, Arnold P M; de Wit, Niek J</p> <p>2011-08-01</p> <p>A health insurance-initiated programme to improve cost-effectiveness of acid-suppressing drugs (ASDs). To evaluate the effect of two different interventions of general practitioner <span class="hlt">support</span> in reducing drug prescription. A sequential cluster randomized controlled trial with 90 participating general practitioners in a telephone <span class="hlt">support</span> (TS) group or practice visit (PV) group. TS group received <span class="hlt">support</span> in phase-<span class="hlt">1</span> (first 6 months), but served as control group in phase-2 (6-12 months period). PV group received no intervention in phase-<span class="hlt">1</span>, serving as the control group for the TS group, but received <span class="hlt">support</span> in phase-2. Prescription data were extracted from Agis Health Insurance Database. Outcomes were the proportion of responders to drug reduction and the number of defined daily dose (DDD). Differences in users and DDD were analysed using multilevel regression analysis. At baseline, 3424 patients used ASD chronically (211 DDDs, on average). The difference between TS and control groups among responders was 3.2% [95% confidence interval (CI): 0.8; 5.6] and relative risk was <span class="hlt">1</span>.26 (95% CI: <span class="hlt">1</span>.06; <span class="hlt">1</span>.51). The difference between PV and control groups was not relevant (0.4%, 95% CI: -<span class="hlt">1</span>.99; 2.79 and relative risk: <span class="hlt">1</span>.01, 95% CI: 0.82; <span class="hlt">1</span>.20). The difference in DDD per patient was -3.0 (95% CI: -8.9; 2.9) and -5.82 (95% CI: -12.4; 0.73), respectively. This health insurance company-initiated intervention had a moderate effect on ASD prescription. In contrast to TS, PVs did not seem to reduce ASD prescription rates.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2018Metro..55...84S','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2018Metro..55...84S"><span>A <span class="hlt">primary</span> method for the complex calibration of a hydrophone from <span class="hlt">1</span> Hz to 2 kHz</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Slater, W. H.; E Crocker, S.; Baker, S. R.</p> <p>2018-02-01</p> <p>A <span class="hlt">primary</span> calibration method is demonstrated to obtain the magnitude and phase of the complex sensitivity for a hydrophone at frequencies between <span class="hlt">1</span> Hz and 2 kHz. The measurement is performed in a coupler reciprocity chamber (‘coupler’) a closed test chamber where time harmonic oscillations in pressure can be achieved and the reciprocity conditions required for a <span class="hlt">primary</span> calibration can be realized. Relevant theory is reviewed and the reciprocity parameter updated for the complex measurement. Systematic errors and corrections for magnitude are reviewed and more added for phase. The combined expanded uncertainties of the magnitude and phase of the complex sensitivity at <span class="hlt">1</span> Hz were 0.<span class="hlt">1</span> dB re <span class="hlt">1</span> V μ Pa-<span class="hlt">1</span> and  ± <span class="hlt">1</span>\\circ , respectively. Complex sensitivity, sensitivity magnitude, and phase measurements are presented on an example <span class="hlt">primary</span> reference hydrophone.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29807696','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29807696"><span>ESR<span class="hlt">1</span> methylation in <span class="hlt">primary</span> tumors and paired circulating tumor DNA of patients with high-grade serous ovarian cancer.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Giannopoulou, Lydia; Mastoraki, Sophia; Buderath, Paul; Strati, Areti; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S</p> <p>2018-05-25</p> <p>Estrogen receptor, coded by the ESR<span class="hlt">1</span> gene, is highly expressed in epithelial ovarian cancer. ESR<span class="hlt">1</span> gene is frequently methylated in many types of gynecological malignancies. However, only a few studies attempted to investigate the role of ESR<span class="hlt">1</span> methylation and its clinical significance in ovarian cancer so far. The aim of our study was to examine ESR<span class="hlt">1</span> methylation status in <span class="hlt">primary</span> tumors and corresponding circulating tumor DNA of patients with high-grade serous ovarian cancer (HGSC). ESR<span class="hlt">1</span> methylation was detected by a highly specific and sensitive real-time methylation-specific PCR assay. Two groups of HGSC samples were analyzed: group A (n = 66 <span class="hlt">primary</span> tumors) and group B (n = 53 <span class="hlt">primary</span> tumors and 50 corresponding plasma samples). ESR<span class="hlt">1</span> was found methylated in both groups of <span class="hlt">primary</span> tumors: in 32/66 (48.5%) of group A and in 15/53 (28.3%) of group B. 19/50 (38.0%) corresponding plasma samples of group B were also methylated for ESR<span class="hlt">1</span>. A significant agreement for ESR<span class="hlt">1</span> methylation was observed between <span class="hlt">primary</span> tumors and paired plasma ctDNA samples (P = 0.004). Interestingly, the presence of ESR<span class="hlt">1</span> methylation in <span class="hlt">primary</span> tumor samples of group B was significantly correlated with a better overall survival (P = 0.027) and progression-free survival (P = 0.041). We report for the first time the presence of ESR<span class="hlt">1</span> methylation in plasma ctDNA of patients with HGSC. The agreement between ESR<span class="hlt">1</span> methylation in <span class="hlt">primary</span> tumors and paired ctDNA is statistically significant. Our results indicate a correlation between the presence of ESR<span class="hlt">1</span> methylation and a better clinical outcome in HGSC patients. Copyright © 2018 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://adsabs.harvard.edu/abs/2016AGUOSHI51A..06T','NASAADS'); return false;" href="http://adsabs.harvard.edu/abs/2016AGUOSHI51A..06T"><span>Do Offshore Wind Farms Influence Marine <span class="hlt">Primary</span> Production?</span></a></p> <p><a target="_blank" href="http://adsabs.harvard.edu/abstract_service.html">NASA Astrophysics Data System (ADS)</a></p> <p>Tweddle, J. F.; Murray, R. B. O.; Gubbins, M.; Scott, B. E.</p> <p>2016-02-01</p> <p><span class="hlt">Primary</span> producers (phytoplankton) form the basis of marine food-webs, <span class="hlt">supporting</span> production of higher trophic levels, and act as a sink of CO2. We considered the impact of proposed large scale offshore wind farms in moderately deep waters (> 45 m) off the east coast of Scotland on rates of <span class="hlt">primary</span> production. A 2 stage modelling process was used, employing state-of-the-art 3-D hydrographic models with the ability to capture flow at the spatial resolution of 10 m combined with <span class="hlt">1</span>-D vertical modelling using 7 years of local forcing data. Through influencing the strength of stratification via changes in current flow, large (100 m) modelled wind turbine foundations had a significant effect on <span class="hlt">primary</span> producers, consistently reducing total annual <span class="hlt">primary</span> production, although within the range of natural interannual variability. The percentage reduction was largest over submarine banks less than 54 m in depth, and was outside the range of natural interannual variability. Smaller (10 m) turbine foundations had no discernible effect on total annual <span class="hlt">primary</span> production. The results indicate that smaller foundations should be favored as a mitigation measure, in terms of effects on <span class="hlt">primary</span> production, and this type of analysis should be considered within sectoral planning and licensing processes for future renewable energy developments.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4106384','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4106384"><span><span class="hlt">Support</span> for e-Health Services Among Elderly <span class="hlt">Primary</span> Care Patients</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Pirogowicz, Iwona</p> <p>2014-01-01</p> <p>Abstract Background: E-health has a substantial potential to improve access to as well as <span class="hlt">support</span> efficient and effective care for the elderly. Questions remain and must be addressed, however, regarding the challenges faced by the elderly in the use of this technology. The aim of the study was to assess the attitude (needs) and preferences of the elderly in a selected region of Poland regarding selected e-health services and the factors associated with them. Materials and Methods: The study was conducted among 286 patients over 60 years of age being served by general practitioners in southwest Poland's Lower Silesia Province. The assessment pertaining to e-health was based on a specially designed questionnaire. Results: Nearly one-third of the study respondents had a computer at home, and 61% of these (19% of all surveyed elderly) used it. Twenty-two percent of respondents used the Internet, at least occasionally, whereas 62% used mobile phones. Approximately 41% (n=116) of the elderly had a favorable attitude toward e-health services (labeled here as <span class="hlt">supporters</span>) and were willing to use it if/when offered an opportunity to do so. A substantial majority (84%) of <span class="hlt">supporters</span> expressed a desire to receive simple medical recommendations via mobile phone or a computer, although significant majorities (61% and 60%, respectively) would like to receive the results of tests by e-mail or short message service reminders for scheduled visits or prescribed medications. Slightly less than half (47%) of e-health <span class="hlt">supporters</span> would request appointments online. Among the more important factors associated with <span class="hlt">support</span> of e-health services were urban residence, higher education, and normal cognitive function, as well as having a computer, Internet access, or a mobile phone. Conclusions: The majority of elderly patients in this Polish community are not overly enthusiastic about using information and communications technology tools in their healthcare. Nevertheless, a substantial</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20073174','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20073174"><span>Delegating work in <span class="hlt">primary</span> care: a false ideal?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Dobson, Gregory; Pinker, Edieal J</p> <p>2009-01-01</p> <p><span class="hlt">Primary</span> care physicians are advised to delegate as much work as possible to <span class="hlt">support</span> staff enabling them to serve larger patient panels and handle more patient visits, and thus generate more revenue. We explain that this advice is based on several fallacies and show evidence that dividing work processes among different types of <span class="hlt">support</span> staff actually reduces productivity and profitability of <span class="hlt">primary</span> care practices. We conclude that the efficient operation of large practices requires sophisticated practice management skills.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1790708','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1790708"><span>ABCA<span class="hlt">1</span>, ABCG<span class="hlt">1</span> and SR-BI: hormonal regulation in <span class="hlt">primary</span> rat hepatocytes and human cell lines</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Sporstøl, Marita; Mousavi, Seyed Ali; Eskild, Winnie; Roos, Norbert; Berg, Trond</p> <p>2007-01-01</p> <p>Background Scavenger receptor type B class I (SR-BI), ABC transporter A<span class="hlt">1</span> (ABCA<span class="hlt">1</span>) -and G<span class="hlt">1</span> (ABCG<span class="hlt">1</span>) all play important roles in the reverse cholesterol transport. Reverse cholesterol transport is a mechanism whereby the body can eliminate excess cholesterol. Here, the regulation of SR-BI, ABCA<span class="hlt">1</span>, and ABCG<span class="hlt">1</span> by dexamethasone (a synthetic glucocorticoid) and insulin were studied in order to gain more insight into the role of these two hormones in the cholesterol metabolism. Results By use of real time RT-PCR and Western blotting we examined the expression of our target genes. The results show that SR-BI, ABCA<span class="hlt">1</span> and ABCG<span class="hlt">1</span> mRNA expression increased in response to dexamethasone while insulin treatment reduced the expression in <span class="hlt">primary</span> rat hepatocytes. The stimulatory effect of dexamethasone was reduced by the addition of the anti-glucocorticoid mifepristone. In HepG2 cells and THP-<span class="hlt">1</span> macrophages, however, the effect of dexamethasone was absent or inhibitory with no significant change in the presence of mifepristone. The latter observation may be a result of the low protein expression of glucocorticoid receptor (GR) in these cell lines. Conclusion Our results illustrates that insulin and glucocorticoids, two hormones crucial in the carbohydrate metabolism, also play an important role in the regulation of genes central in reverse cholesterol transport. We found a marked difference in mRNA expression between the <span class="hlt">primary</span> cells and the two established cell lines when studying the effect of dexamethasone which may result from the varying expression levels of GR. PMID:17241464</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17241464','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17241464"><span>ABCA<span class="hlt">1</span>, ABCG<span class="hlt">1</span> and SR-BI: hormonal regulation in <span class="hlt">primary</span> rat hepatocytes and human cell lines.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sporstøl, Marita; Mousavi, Seyed Ali; Eskild, Winnie; Roos, Norbert; Berg, Trond</p> <p>2007-01-22</p> <p>Scavenger receptor type B class I (SR-BI), ABC transporter A<span class="hlt">1</span> (ABCA<span class="hlt">1</span>) -and G<span class="hlt">1</span> (ABCG<span class="hlt">1</span>) all play important roles in the reverse cholesterol transport. Reverse cholesterol transport is a mechanism whereby the body can eliminate excess cholesterol. Here, the regulation of SR-BI, ABCA<span class="hlt">1</span>, and ABCG<span class="hlt">1</span> by dexamethasone (a synthetic glucocorticoid) and insulin were studied in order to gain more insight into the role of these two hormones in the cholesterol metabolism. By use of real time RT-PCR and Western blotting we examined the expression of our target genes. The results show that SR-BI, ABCA<span class="hlt">1</span> and ABCG<span class="hlt">1</span> mRNA expression increased in response to dexamethasone while insulin treatment reduced the expression in <span class="hlt">primary</span> rat hepatocytes. The stimulatory effect of dexamethasone was reduced by the addition of the anti-glucocorticoid mifepristone. In HepG2 cells and THP-<span class="hlt">1</span> macrophages, however, the effect of dexamethasone was absent or inhibitory with no significant change in the presence of mifepristone. The latter observation may be a result of the low protein expression of glucocorticoid receptor (GR) in these cell lines. Our results illustrates that insulin and glucocorticoids, two hormones crucial in the carbohydrate metabolism, also play an important role in the regulation of genes central in reverse cholesterol transport. We found a marked difference in mRNA expression between the <span class="hlt">primary</span> cells and the two established cell lines when studying the effect of dexamethasone which may result from the varying expression levels of GR.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-56.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-56.pdf"><span>28 CFR 79.56 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.56... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical documentation. In all...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-64.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-64.pdf"><span>28 CFR 79.64 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.64... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_19");'>19</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li class="active"><span>21</span></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_21 --> <div id="page_22" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="421"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-66.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-66.pdf"><span>28 CFR 79.66 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-45.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-45.pdf"><span>28 CFR 79.45 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.45... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-54.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title28-vol2/pdf/CFR-2010-title28-vol2-sec79-54.pdf"><span>28 CFR 79.54 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-07-01</p> <p>... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.54... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-64.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-64.pdf"><span>28 CFR 79.64 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.64... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-54.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-54.pdf"><span>28 CFR 79.54 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.54... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-45.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-45.pdf"><span>28 CFR 79.45 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.45... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-66.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-66.pdf"><span>28 CFR 79.66 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-56.pdf','CFR2011'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2011-title28-vol2/pdf/CFR-2011-title28-vol2-sec79-56.pdf"><span>28 CFR 79.56 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2011&page.go=Go">Code of Federal Regulations, 2011 CFR</a></p> <p></p> <p>2011-07-01</p> <p>... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.56... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical documentation. In all...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-45.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-45.pdf"><span>28 CFR 79.45 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.45... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-45.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-45.pdf"><span>28 CFR 79.45 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.45... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-64.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-64.pdf"><span>28 CFR 79.64 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.64... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-54.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-54.pdf"><span>28 CFR 79.54 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.54... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-56.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-56.pdf"><span>28 CFR 79.56 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.56... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical documentation. In all...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-66.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-66.pdf"><span>28 CFR 79.66 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-66.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-66.pdf"><span>28 CFR 79.66 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-54.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-54.pdf"><span>28 CFR 79.54 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.54... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-45.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-45.pdf"><span>28 CFR 79.45 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.45... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-66.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-66.pdf"><span>28 CFR 79.66 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.66... renal cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-56.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-56.pdf"><span>28 CFR 79.56 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.56... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical documentation. In all...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-54.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-54.pdf"><span>28 CFR 79.54 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.54... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical documentation. To prove...</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_20");'>20</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li class="active"><span>22</span></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_22 --> <div id="page_23" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="441"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-64.pdf','CFR2014'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2014-title28-vol2/pdf/CFR-2014-title28-vol2-sec79-64.pdf"><span>28 CFR 79.64 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2014&page.go=Go">Code of Federal Regulations, 2014 CFR</a></p> <p></p> <p>2014-07-01</p> <p>... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.64... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-56.pdf','CFR2013'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2013-title28-vol2/pdf/CFR-2013-title28-vol2-sec79-56.pdf"><span>28 CFR 79.56 - Proof of <span class="hlt">primary</span> renal cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2013&page.go=Go">Code of Federal Regulations, 2013 CFR</a></p> <p></p> <p>2013-07-01</p> <p>... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Proof of <span class="hlt">primary</span> renal cancer. 79.56... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> renal cancer following pertinent... conclusion that a claimant developed <span class="hlt">primary</span> renal cancer must be <span class="hlt">supported</span> by medical documentation. In all...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-64.pdf','CFR2012'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2012-title28-vol2/pdf/CFR-2012-title28-vol2-sec79-64.pdf"><span>28 CFR 79.64 - Proof of <span class="hlt">primary</span> lung cancer.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2012&page.go=Go">Code of Federal Regulations, 2012 CFR</a></p> <p></p> <p>2012-07-01</p> <p>... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Proof of <span class="hlt">primary</span> lung cancer. 79.64... cancer. (a) In determining whether a claimant developed <span class="hlt">primary</span> lung cancer following pertinent... claimant. A conclusion that a claimant developed <span class="hlt">primary</span> lung cancer must be <span class="hlt">supported</span> by medical...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3423116','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3423116"><span>Cystogenesis and elongated <span class="hlt">primary</span> cilia in Tsc<span class="hlt">1</span>-deficient distal convoluted tubules</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Armour, Eric A.; Carson, Robert P.</p> <p>2012-01-01</p> <p>Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC<span class="hlt">1</span> or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc<span class="hlt">1</span> gene in the distal convoluted tubules (DCT). At young ages, Tsc<span class="hlt">1</span> conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)<span class="hlt">1</span> but decreased mTORC2 signaling. Treatment with the mTORC<span class="hlt">1</span> inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined <span class="hlt">primary</span> cilia in the DCT. Cilia were longer in Tsc<span class="hlt">1</span> CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc<span class="hlt">1</span> gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC<span class="hlt">1</span> but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of <span class="hlt">primary</span> cilia. PMID:22674026</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22674026','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22674026"><span>Cystogenesis and elongated <span class="hlt">primary</span> cilia in Tsc<span class="hlt">1</span>-deficient distal convoluted tubules.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Armour, Eric A; Carson, Robert P; Ess, Kevin C</p> <p>2012-08-15</p> <p>Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC<span class="hlt">1</span> or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc<span class="hlt">1</span> gene in the distal convoluted tubules (DCT). At young ages, Tsc<span class="hlt">1</span> conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)<span class="hlt">1</span> but decreased mTORC2 signaling. Treatment with the mTORC<span class="hlt">1</span> inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined <span class="hlt">primary</span> cilia in the DCT. Cilia were longer in Tsc<span class="hlt">1</span> CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc<span class="hlt">1</span> gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC<span class="hlt">1</span> but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of <span class="hlt">primary</span> cilia.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/16957746','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/16957746"><span>Is there a genotype-phenotype correlation in <span class="hlt">primary</span> hyperoxaluria type <span class="hlt">1</span>?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Beck, B B; Hoppe, B</p> <p>2006-09-01</p> <p>There is ongoing debate about a genotype-phenotype correlation in patients with <span class="hlt">primary</span> hyperoxaluria type <span class="hlt">1</span> and specific AGXT mutations. However, other determinants like environmental factors or modifer genes may play a pivotal role in the heterogeneity of the disease. The report of Lorenzo and co-workers highlights this situation, presenting data of a whole population with just one specific AGXT mutation.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28928859','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28928859"><span>IDH<span class="hlt">1</span> R132H Mutation Is Accompanied with Malignant Progression of Paired <span class="hlt">Primary</span>-Recurrent Astrocytic Tumours.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Mu, Luyan; Xu, Wanzhen; Li, Qingla; Ge, Haitao; Bao, Hongbo; Xia, Songsong; Ji, Jingjing; Jiang, Jie; Song, Yuwen; Gao, Qiang</p> <p>2017-01-01</p> <p>IDH<span class="hlt">1</span> R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH<span class="hlt">1</span> R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH<span class="hlt">1</span> R132H mutations were assessed by immunohistochemistry in 55 paired <span class="hlt">primary</span>-recurrent astrocytomas tissues, including 5 paired <span class="hlt">primary</span> pilocytic astrocytoma (pPA, WHO grade I), 35 paired <span class="hlt">primary</span> low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired <span class="hlt">primary</span> high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH<span class="hlt">1</span> exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH<span class="hlt">1</span> R132H mutation was 68.6% (24/35) in pLGA group, but no IDH<span class="hlt">1</span> mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with <span class="hlt">primary</span> astrocytoma, there was no change of IDH<span class="hlt">1</span> status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups ( p<0.01 ), while the pHGA group has the shortest ones ( p<0.01 ). In pLGA group, the IDH<span class="hlt">1</span> R132H mutation subgroup has longer RFP than IDH<span class="hlt">1</span> wild type subgroup ( p<0.01 ), but the OS has no statistical difference between two subgroups ( p>0.6 ). Additionally, IDH<span class="hlt">1</span> R132H mutation independently predicted a long RFP in patients with pLGA (HR <span class="hlt">1</span>.073, 95% CI 0.151-0.775, p<0.01 ).</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5604202','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5604202"><span>IDH<span class="hlt">1</span> R132H Mutation Is Accompanied with Malignant Progression of Paired <span class="hlt">Primary</span>-Recurrent Astrocytic Tumours</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Mu, Luyan; Xu, Wanzhen; Li, Qingla; Ge, Haitao; Bao, Hongbo; Xia, Songsong; Ji, Jingjing; Jiang, Jie; Song, Yuwen; Gao, Qiang</p> <p>2017-01-01</p> <p>IDH<span class="hlt">1</span> R132H mutation is an important marker of survival in patients with gliomas. Although there are many changes of genes in tumour malignant progression, IDH<span class="hlt">1</span> R132H mutation status in glioma progression remained unclear. Here, an in-depth characterization of IDH<span class="hlt">1</span> R132H mutations were assessed by immunohistochemistry in 55 paired <span class="hlt">primary</span>-recurrent astrocytomas tissues, including 5 paired <span class="hlt">primary</span> pilocytic astrocytoma (pPA, WHO grade I), 35 paired <span class="hlt">primary</span> low grade astrocytoma (pLGA, WHO grade II and III) and 15 paired <span class="hlt">primary</span> high grade astrocytoma (pHGA/ Glioblastoma, WHO grade IV). Meanwhile, the DNA was isolated from paired samples, and PCR amplification was used for IDH<span class="hlt">1</span> exon4 sequencing. Nonparametric test, KM and Cox models were used to examine the statistical difference and survival function. We found that the percent of IDH<span class="hlt">1</span> R132H mutation was 68.6% (24/35) in pLGA group, but no IDH<span class="hlt">1</span> mutation was found in pPA and pHGA groups. Meanwhile, the results from immunohistochemistry and DNA sequencing showed that, compared with <span class="hlt">primary</span> astrocytoma, there was no change of IDH<span class="hlt">1</span> status in recurrent astrocytoma whatever tumour pathological grade raise or indolent. The pPA group has the longest recurrence-free period (RFP) and overall survival (OS) in three groups (p<0.01), while the pHGA group has the shortest ones (p<0.01). In pLGA group, the IDH<span class="hlt">1</span> R132H mutation subgroup has longer RFP than IDH<span class="hlt">1</span> wild type subgroup (p<0.01), but the OS has no statistical difference between two subgroups (p>0.6). Additionally, IDH<span class="hlt">1</span> R132H mutation independently predicted a long RFP in patients with pLGA (HR <span class="hlt">1</span>.073, 95% CI 0.151-0.775, p<0.01). PMID:28928859</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/11089616','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/11089616"><span>Viral dynamics in <span class="hlt">primary</span> HIV-<span class="hlt">1</span> infection. Karolinska Institutet <span class="hlt">Primary</span> HIV Infection Study Group.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Lindbäck, S; Karlsson, A C; Mittler, J; Blaxhult, A; Carlsson, M; Briheim, G; Sönnerborg, A; Gaines, H</p> <p>2000-10-20</p> <p>To study the natural course of viremia during <span class="hlt">primary</span> HIV infection (PHI). Eight patients were followed from a median of 5 days from the onset of PHI illness. Plasma HIV-<span class="hlt">1</span> RNA levels were measured frequently and the results were fitted to mathematical models. HIV-<span class="hlt">1</span> RNA levels were also monitored in nine patients given two reverse transcriptase inhibitors and a protease inhibitor after a median of 7 days from the onset of PHI illness. HIV-<span class="hlt">1</span> RNA appeared in the blood during the week preceding onset of PHI illness and increased rapidly during the first viremic phase, reaching a peak at a mean of 7 days after onset of illness. This was followed by a phase of rapidly decreasing levels of HIV-<span class="hlt">1</span> RNA to an average of 21 days after onset. Viral density continued to decline thereafter but at a 5- to 50-fold lower rate; a steady-state level was reached at a median of 2 months after onset of PHI. Peak viral density levels correlated significantly with levels measured between days 50 and 600. Initiation of antiretroviral treatment during PHI resulted in rapidly declining levels to below 50 copies/mL. This study demonstrates the kinetic phases of viremia during PHI and indicates two new contributions to the natural history of HIV-<span class="hlt">1</span> infection: PHI peak levels correlate with steady-state levels and HIV-<span class="hlt">1</span> RNA declines biphasically; an initial rapid decay is usually followed by a slow decay, which is similar to the initial changes seen with antiviral treatment.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=purpose+AND+science&id=EJ1165107','ERIC'); return false;" href="https://eric.ed.gov/?q=purpose+AND+science&id=EJ1165107"><span>The Use of Organising Purposes in Science Instruction as a Scaffolding Mechanism to <span class="hlt">Support</span> Progressions: A Study of Talk in Two <span class="hlt">Primary</span> Science Classrooms</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Johansson, Annie-Maj; Wickman, Per-Olof</p> <p>2018-01-01</p> <p>Purpose: This study examines how different purposes can <span class="hlt">support</span> teachers in their work with progressions as a part of a teaching sequences in science in <span class="hlt">primary</span> school. Design/Method: The study was carried out in two classes working with inquiry and the events that took place in the classroom were filmed. In the study, we have chosen to use the…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26177524','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26177524"><span>Are Time-Limited Grants Likely to Stimulate Sustained Growth in <span class="hlt">Primary</span> Care Residency Training? A Study of the <span class="hlt">Primary</span> Care Residency Expansion Program.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Chen, Rossan Melissa; Petterson, Stephen; Bazemore, Andrew; Grumbach, Kevin</p> <p>2015-09-01</p> <p>To examine the perceived likelihood of sustaining new residency positions funded by five-year (2010-2015) <span class="hlt">Primary</span> Care Residency Expansion (PCRE) grants from the Health Resources and Services Administration, which aimed to increase training output to address <span class="hlt">primary</span> care workforce issues. During September-December 2013, the authors administered an online or telephone survey to program directors whose residency programs received PCRE grants. The main outcome measure was perceived likelihood of sustaining the expanded residency positions beyond the expiration of the grant, in the outlying years of 2016 and 2017 (when the positions will be partially <span class="hlt">supported</span>) and after 2017 (when the positions will be unsupported). Of 78 eligible program directors, 62 responded (response rate = 79.5%). Twenty-eight (45.<span class="hlt">1</span>%; 95% CI 32.9%-57.9%) reported that their programs were unlikely to, very unlikely to, or not planning to continue the expanded positions after the PCRE grant expires. Overall, 14 (22.5%) reported having secured full funding to <span class="hlt">support</span> the expanded positions beyond 2017. Family medicine and pediatrics program directors were significantly less likely than internal medicine program directors to report having secured funding for the outlying years (P = .02). This study suggests that an approach to <span class="hlt">primary</span> care residency training expansion that relies on time-limited grants is unlikely to produce sustainable growth of the <span class="hlt">primary</span> care pipeline. Policy makers should instead implement systemic reform of graduate medical education (GME) financing and designate reliable sources of funding, such as Medicare and Medicaid GME funds, for new <span class="hlt">primary</span> care residency positions.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28371581','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28371581"><span>Single-Particle Tracking of Human Immunodeficiency Virus Type <span class="hlt">1</span> Productive Entry into Human <span class="hlt">Primary</span> Macrophages.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Li, Qin; Li, Wei; Yin, Wen; Guo, Jia; Zhang, Zhi-Ping; Zeng, Dejun; Zhang, Xiaowei; Wu, Yuntao; Zhang, Xian-En; Cui, Zongqiang</p> <p>2017-04-25</p> <p>Macrophages are one of the major targets of human immunodeficiency virus (HIV-<span class="hlt">1</span>), but the viral entry pathway remains poorly understood in these cells. Noninvasive virus labeling and single-virus tracking are effective tools for studying virus entry. Here, we constructed a quantum dot (QD)-encapsulated infectious HIV-<span class="hlt">1</span> particle to track viral entry at a single-particle level in live human <span class="hlt">primary</span> macrophages. QDs were encapsulated in HIV-<span class="hlt">1</span> virions by incorporating viral accessory protein Vpr-conjugated QDs during virus assembly. With the HIV-<span class="hlt">1</span> particles encapsulating QDs, we monitored the early phase of viral infection in real time and observed that, during infection, HIV-<span class="hlt">1</span> was endocytosed in a clathrin-mediated manner; the particles were translocated into Rab5A-positive endosomes, and the core was released into the cytoplasm by viral envelope-mediated endosomal fusion. Drug inhibition assays verified that endosome fusion contributes to HIV-<span class="hlt">1</span> productive infection in <span class="hlt">primary</span> macrophages. Additionally, we observed that a dynamic actin cytoskeleton is critical for HIV-<span class="hlt">1</span> entry and intracellular migration in <span class="hlt">primary</span> macrophages. HIV-<span class="hlt">1</span> dynamics and infection could be blocked by multiple different actin inhibitors. Our study revealed a productive entry pathway in macrophages that requires both endosomal function and actin dynamics, which may assist in the development of inhibitors to block the HIV entry in macrophages.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24666438','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24666438"><span>Intervention to improve social and family <span class="hlt">support</span> for caregivers of dependent patients: ICIAS study protocol.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Rosell-Murphy, Magdalena; Bonet-Simó, Josep M; Baena, Esther; Prieto, Gemma; Bellerino, Eva; Solé, Francesc; Rubio, Montserrat; Krier, Ilona; Torres, Pascuala; Mimoso, Sonia</p> <p>2014-03-25</p> <p>Despite the existence of formal professional <span class="hlt">support</span> services, informal <span class="hlt">support</span> (mainly family members) continues to be the main source of eldercare, especially for those who are dependent or disabled. Professionals on the <span class="hlt">primary</span> health care are the ideal choice to educate, provide psychological <span class="hlt">support</span>, and help to mobilize social resources available to the informal caregiver.Controversy remains concerning the efficiency of multiple interventions, taking a holistic approach to both the patient and caregiver, and optimum utilization of the available community resources. .For this reason our goal is to assess whether an intervention designed to improve the social <span class="hlt">support</span> for caregivers effectively decreases caregivers burden and improves their quality of life. CONTROLled, multicentre, community intervention trial, with patients and their caregivers randomized to the intervention or control group according to their assigned <span class="hlt">Primary</span> Health Care Team (PHCT). <span class="hlt">Primary</span> Health Care network (9 PHCTs). <span class="hlt">Primary</span> informal caregivers of patients receiving home health care from participating PHCTs. Required sample size is 282 caregivers (141 from PHCTs randomized to the intervention group and 141 from PHCTs randomized to the control group. a) PHCT professionals: standardized training to implement caregivers intervention. b) Caregivers: <span class="hlt">1</span> individualized counselling session, <span class="hlt">1</span> family session, and 4 educational group sessions conducted by participating PHCT professionals; in addition to usual home health care visits, periodic telephone follow-up contact and unlimited telephone <span class="hlt">support</span>. Caregivers and dependent patients: usual home health care, consisting of bimonthly scheduled visits, follow-up as needed, and additional attention upon request.Data analysisDependent variables: Caregiver burden (short-form Zarit test), caregivers' social <span class="hlt">support</span> (Medical Outcomes Study), and caregivers' reported quality of life (SF-12)INDEPENDENT VARIABLES: a) Caregiver: sociodemographic data</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5505452','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5505452"><span>Delivery of Brief Interventions for Heavy Drinking in <span class="hlt">Primary</span> Care: Outcomes of the ODHIN 5-Country Cluster Randomized Trial</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Anderson, Peter; Coulton, Simon; Kaner, Eileen; Bendtsen, Preben; Kłoda, Karolina; Reynolds, Jillian; Segura, Lidia; Wojnar, Marcin; Mierzecki, Artur; Deluca, Paolo; Newbury-Birch, Dorothy; Parkinson, Kathryn; Okulicz-Kozaryn, Katarzyna; Drummond, Colin; Gual, Antoni</p> <p>2017-01-01</p> <p>PURPOSE We aimed to test whether 3 strategies—training and <span class="hlt">support</span>, financial reimbursement, and an option to direct screen-positive patients to an Internet-based method of giving brief advice—have a longer-term effect on <span class="hlt">primary</span> care clinicians’ delivery of screening and advice to heavy drinkers operationalized with the Alcohol Use Disorders Identification Test–Consumption (AUDIT-C) tool. METHODS We undertook a cluster randomized factorial trial with a 12-week implementation period in 120 <span class="hlt">primary</span> health care units throughout Catalonia, England, Netherlands, Poland, and Sweden. Units were randomized to 8 groups: care as usual (control); training and <span class="hlt">support</span> alone; financial reimbursement alone; electronic brief advice alone; paired combinations of these conditions; and all 3 combined. The <span class="hlt">primary</span> outcome was the proportion of consulting adult patients (aged 18 years and older) receiving intervention—screening and, if screen-positive, advice—at 9 months. RESULTS Based on the factorial design, the ratio of the log of the proportion of patients given intervention at the 9-month follow-up was <span class="hlt">1</span>.39 (95% CI, <span class="hlt">1</span>.03–<span class="hlt">1</span>.88) in units that received training and <span class="hlt">support</span> as compared with units that did not. Neither financial reimbursement nor directing screen-positive patients to electronic brief advice led to a higher proportion of patients receiving intervention. CONCLUSIONS Training and <span class="hlt">support</span> of <span class="hlt">primary</span> health care units has a lasting, albeit small, impact on the proportion of adult patients given an alcohol intervention at 9 months. PMID:28694269</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27638213','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27638213"><span>Low-cost functional plasticity of TRPV<span class="hlt">1</span> <span class="hlt">supports</span> heat tolerance in squirrels and camels.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Laursen, Willem J; Schneider, Eve R; Merriman, Dana K; Bagriantsev, Sviatoslav N; Gracheva, Elena O</p> <p>2016-10-04</p> <p>The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40 °C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid <span class="hlt">1</span> (TRPV<span class="hlt">1</span>) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by <span class="hlt">primary</span> afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV<span class="hlt">1</span> orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV<span class="hlt">1</span> as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV<span class="hlt">1</span> orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV<span class="hlt">1</span>, <span class="hlt">supporting</span> functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV<span class="hlt">1</span>-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV<span class="hlt">1</span> molecule, which can undergo profound tuning at the minimal cost of a single amino acid change.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5056056','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5056056"><span>Low-cost functional plasticity of TRPV<span class="hlt">1</span> <span class="hlt">supports</span> heat tolerance in squirrels and camels</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Laursen, Willem J.; Merriman, Dana K.; Bagriantsev, Sviatoslav N.; Gracheva, Elena O.</p> <p>2016-01-01</p> <p>The ability to sense heat is crucial for survival. Increased heat tolerance may prove beneficial by conferring the ability to inhabit otherwise prohibitive ecological niches. This phenomenon is widespread and is found in both large and small animals. For example, ground squirrels and camels can tolerate temperatures more than 40 °C better than many other mammalian species, yet a molecular mechanism subserving this ability is unclear. Transient receptor potential vanilloid <span class="hlt">1</span> (TRPV<span class="hlt">1</span>) is a polymodal ion channel involved in the detection of noxious thermal and chemical stimuli by <span class="hlt">primary</span> afferents of the somatosensory system. Here, we show that thirteen-lined ground squirrels (Ictidomys tridecemlineatus) and Bactrian camels (Camelus ferus) express TRPV<span class="hlt">1</span> orthologs with dramatically reduced temperature sensitivity. The loss of sensitivity is restricted to temperature and does not affect capsaicin or acid responses, thereby maintaining a role for TRPV<span class="hlt">1</span> as a detector of noxious chemical cues. We show that heat sensitivity can be reengineered in both TRPV<span class="hlt">1</span> orthologs by a single amino acid substitution in the N-terminal ankyrin-repeat domain. Conversely, reciprocal mutations suppress heat sensitivity of rat TRPV<span class="hlt">1</span>, <span class="hlt">supporting</span> functional conservation of the residues. Our studies suggest that squirrels and camels co-opt a common molecular strategy to adapt to hot environments by suppressing the efficiency of TRPV<span class="hlt">1</span>-mediated heat detection at the level of somatosensory neurons. Such adaptation is possible because of the remarkable functional flexibility of the TRPV<span class="hlt">1</span> molecule, which can undergo profound tuning at the minimal cost of a single amino acid change. PMID:27638213</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29743224','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29743224"><span>Implementation of Health Insurance <span class="hlt">Support</span> Tools in Community Health Centers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Huguet, Nathalie; Hatch, Brigit; Sumic, Aleksandra; Tillotson, Carrie; Hicks, Elizabeth; Nelson, Joan; DeVoe, Jennifer E</p> <p>2018-01-01</p> <p>Health information technology (HIT) provides new opportunities for <span class="hlt">primary</span> care clinics to <span class="hlt">support</span> patients with health insurance enrollment and maintenance. We present strategies, early findings, and clinic reflections on the development and implementation of HIT tools designed to streamline and improve health insurance tracking at community health centers. We are conducting a hybrid implementation-effectiveness trial to assess novel health insurance enrollment and <span class="hlt">support</span> tools in <span class="hlt">primary</span> care clinics. Twenty-three clinics in 7 health centers from the OCHIN practice-based research network are participating in the implementation component of the trial. Participating health centers were randomized to <span class="hlt">1</span> of 2 levels of implementation <span class="hlt">support</span>, including arm <span class="hlt">1</span> (n = 4 health centers, 11 clinic sites) that received HIT tools and educational materials and arm 2 (n = 3 health centers, 12 clinic sites) that received HIT tools, educational materials, and individualized implementation <span class="hlt">support</span> with a practice coach. We used mixed-methods (qualitative and quantitative) to assess tool use rates and facilitators and barriers to implementation in the first 6 months. Clinics reported favorable attitudes toward the HIT tools, which replace less efficient and more cumbersome processes, and reflect on the importance of clinic engagement in tool development and refinement. Five of 7 health centers are now regularly using the tools and are actively working to increase tool use. Six months after formal implementation, arm 2 clinics demonstrated higher rates of tool use, compared with arm <span class="hlt">1</span>. These results highlight the value of early clinic input in tool development, the potential benefit of practice coaching during HIT tool development and implementation, and a novel method for coupling a hybrid implementation-effectiveness design with principles of improvement science in <span class="hlt">primary</span> care research. © Copyright 2018 by the American Board of Family Medicine.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21800139','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21800139"><span>THAP<span class="hlt">1</span>/DYT6 sequence variants in non-DYT<span class="hlt">1</span> early-onset <span class="hlt">primary</span> dystonia in China and their effects on RNA expression.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cheng, Fu Bo; Ozelius, Laurie J; Wan, Xin Hua; Feng, Jia Chun; Ma, Ling Yan; Yang, Ying Mai; Wang, Lin</p> <p>2012-02-01</p> <p>Mutations in the THAP<span class="hlt">1</span> gene were recently identified as the cause of DYT6 <span class="hlt">primary</span> dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP<span class="hlt">1</span> gene. In addition, the mutation frequency in Chinese early-onset <span class="hlt">primary</span> dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT<span class="hlt">1</span> early-onset <span class="hlt">primary</span> dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP<span class="hlt">1</span> gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP<span class="hlt">1</span> sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP<span class="hlt">1</span> in human lymphocytes. Our findings indicated that THAP<span class="hlt">1</span> sequence variants are not common in non-DYT<span class="hlt">1</span> early-onset <span class="hlt">primary</span> dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP<span class="hlt">1</span> expression.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4820171','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4820171"><span><span class="hlt">Support</span> Group for Parents Coping with Children with Type <span class="hlt">1</span> Diabetes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>PATE, Tanja; RUTAR, Miha; BATTELINO, Tadej; DROBNIČ RADOBULJAC, Maja; BRATINA, Nataša</p> <p>2015-01-01</p> <p>Objectives Type <span class="hlt">1</span> diabetes is one of the most common chronic diseases in childhood. Active parental involvement, parental <span class="hlt">support</span> in the diabetes management and family functioning are associated with optimal diabetes management and glycemic control. The purpose of this study was to assess parental satisfaction with participation in the group and their perceptions of the impact of the intervention on living and coping with childrens T<span class="hlt">1</span>D. Methods A sample of 34 parents of children with T<span class="hlt">1</span>D participated in this trend study. The participants’ experience and satisfaction with <span class="hlt">support</span> group was measured by a self- evaluation questionnaire, designed for the purpose of the present study. Results Quantitative data show that parents were overall satisfied with almost all measured items of the evaluation questionnaire (wellbeing in the group, feeling secure, experiencing new things, being able to talk and feeling being heard) during the 4-year period. However, parents from the second and third season, on average, found that the <span class="hlt">support</span> group has better fulfilled their expectations than the parents from the first season (p = 0,010). The qualitative analysis of the participants’ responses to the open-ended questions was underpinned by four themes: <span class="hlt">support</span> when confronting the diagnosis, transformation of the family dynamics, me as a parent, exchange of experience and good practice and facing the world outside the family. Discussion The presented parent <span class="hlt">support</span> group showed to be a promising <span class="hlt">supportive</span>, therapeutic and psychoeducative space where parents could strengthen their role in the upbringing of their child with T<span class="hlt">1</span>D. PMID:27646912</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27646912','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27646912"><span><span class="hlt">Support</span> Group for Parents Coping with Children with Type <span class="hlt">1</span> Diabetes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Pate, Tanja; Rutar, Miha; Battelino, Tadej; Drobnič Radobuljac, Maja; Bratina, Nataša</p> <p>2015-06-01</p> <p>Type <span class="hlt">1</span> diabetes is one of the most common chronic diseases in childhood. Active parental involvement, parental <span class="hlt">support</span> in the diabetes management and family functioning are associated with optimal diabetes management and glycemic control. The purpose of this study was to assess parental satisfaction with participation in the group and their perceptions of the impact of the intervention on living and coping with childrens T<span class="hlt">1</span>D. A sample of 34 parents of children with T<span class="hlt">1</span>D participated in this trend study. The participants' experience and satisfaction with <span class="hlt">support</span> group was measured by a self- evaluation questionnaire, designed for the purpose of the present study. Quantitative data show that parents were overall satisfied with almost all measured items of the evaluation questionnaire (wellbeing in the group, feeling secure, experiencing new things, being able to talk and feeling being heard) during the 4-year period. However, parents from the second and third season, on average, found that the <span class="hlt">support</span> group has better fulfilled their expectations than the parents from the first season (p = 0,010). The qualitative analysis of the participants' responses to the open-ended questions was underpinned by four themes: <span class="hlt">support</span> when confronting the diagnosis, transformation of the family dynamics, me as a parent, exchange of experience and good practice and facing the world outside the family. The presented parent <span class="hlt">support</span> group showed to be a promising <span class="hlt">supportive</span>, therapeutic and psychoeducative space where parents could strengthen their role in the upbringing of their child with T<span class="hlt">1</span>D.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li class="active"><span>23</span></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_23 --> <div id="page_24" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="461"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/biblio/22204962-cpeb1-modulates-lipopolysaccharide-mediated-inos-induction-rat-primary-astrocytes','SCIGOV-STC'); return false;" href="https://www.osti.gov/biblio/22204962-cpeb1-modulates-lipopolysaccharide-mediated-inos-induction-rat-primary-astrocytes"><span>CPEB<span class="hlt">1</span> modulates lipopolysaccharide-mediated iNOS induction in rat <span class="hlt">primary</span> astrocytes</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young, E-mail: chanyshin@kku.ac.kr</p> <p>2011-06-17</p> <p>Highlights: {yields} Expression and phosphorylation of CPEB<span class="hlt">1</span> is increased by LPS stimulation in rat <span class="hlt">primary</span> astrocytes. {yields} JNK regulates expression and phosphorylation of CPEB<span class="hlt">1</span> in reactive astrocytes. {yields} Down-regulation of CPEB<span class="hlt">1</span> using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. {yields} CPEB<span class="hlt">1</span> may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury,more » yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein <span class="hlt">1</span> (CPEB<span class="hlt">1</span>) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB<span class="hlt">1</span> is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB<span class="hlt">1</span> was increased in rat <span class="hlt">primary</span> astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB<span class="hlt">1</span> expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB<span class="hlt">1</span> is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.« less</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28729620','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28729620"><span>Self-management behaviour and <span class="hlt">support</span> among <span class="hlt">primary</span> care COPD patients: cross-sectional analysis of data from the Birmingham Chronic Obstructive Pulmonary Disease Cohort.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Khan, Ainee; Dickens, Andrew P; Adab, Peymane; Jordan, Rachel E</p> <p>2017-07-20</p> <p>Self-management <span class="hlt">support</span> for chronic obstructive pulmonary disease (COPD) patients is recommended by UK national guidelines, but extent of implementation is unknown. We aimed to describe self-management behaviour and <span class="hlt">support</span> among COPD patients and explore behaviour associated with having a self-management plan. We undertook cross-sectional analysis of self-reported data from diagnosed COPD patients in the Birmingham COPD Cohort study. Questionnaire items relevant to self-management behaviour, knowledge of COPD, receipt of self-management plans and advice from healthcare professionals were examined. Multiple regression models were used to identify behaviour associated with having a self-management plan. One-thousand seventy-eight participants (676 males, 62.7%, mean age 69.8 (standard deviation 9.0) years) were included. The majority reported taking medications as instructed (940, 94.0%) and receiving annual influenza vaccinations (962, 89.2%). Only 400 (40.4%) participants had self-management plans, 538 (49.9%) reported never having received advice on diet/exercise and 110 (42.7%) current smokers had been offered practical help to stop smoking in the previous year. General knowledge about COPD was moderate (mean total Bristol COPD Knowledge Questionnaire score: 31.5 (standard deviation 10.7); max score 65), corresponding to 48.5% of questions answered correctly. Having a self-management plan was positively associated with self-reported adherence to medication (odds ratio 3.10, 95% confidence interval <span class="hlt">1</span>.43 to 6.72), attendance at a training course (odds ratio 2.72, 95% confidence interval <span class="hlt">1</span>.81 to 4.12), attendance at a <span class="hlt">support</span> group (odds ratio 6.28, 95% confidence interval 2.96 to 13.35) and better disease knowledge (mean difference 4.87, 95% confidence interval 3.16 to 6.58). <span class="hlt">Primary</span> care healthcare professionals should ensure more widespread implementation of individualised self-management plans for all patients and improve the lifestyle advice provided. CALL FOR</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/17045302','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/17045302"><span>Setting nutrient thresholds to <span class="hlt">support</span> an ecological assessment based on nutrient enrichment, potential <span class="hlt">primary</span> production and undesirable disturbance.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Devlin, Michelle; Painting, Suzanne; Best, Mike</p> <p>2007-01-01</p> <p>The EU Water Framework Directive recognises that ecological status is <span class="hlt">supported</span> by the prevailing physico-chemical conditions in each water body. This paper describes an approach to providing guidance on setting thresholds for nutrients taking account of the biological response to nutrient enrichment evident in different types of water. Indices of pressure, state and impact are used to achieve a robust nutrient (nitrogen) threshold by considering each individual index relative to a defined standard, scale or threshold. These indices include winter nitrogen concentrations relative to a predetermined reference value; the potential of the waterbody to <span class="hlt">support</span> phytoplankton growth (estimated as <span class="hlt">primary</span> production); and detection of an undesirable disturbance (measured as dissolved oxygen). Proposed reference values are based on a combination of historical records, offshore (limited human influence) nutrient concentrations, literature values and modelled data. Statistical confidence is based on a number of attributes, including distance of confidence limits away from a reference threshold and how well the model is populated with real data. This evidence based approach ensures that nutrient thresholds are based on knowledge of real and measurable biological responses in transitional and coastal waters.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/29530173','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/29530173"><span>Exploration of funding models to <span class="hlt">support</span> hybridisation of Australian <span class="hlt">primary</span> health care organisations.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Reddy, Sandeep</p> <p>2017-09-01</p> <p><span class="hlt">Primary</span> Health Care (PHC) funding in Australia is complex and fragmented. The focus of PHC funding in Australia has been on volume rather than comprehensive <span class="hlt">primary</span> care and continuous quality improvement. As PHC in Australia is increasingly delivered by hybrid style organisations, an appropriate funding model that matches this set-up while addressing current issues with PHC funding is required. This article discusses and proposes an appropriate funding model for hybrid PHC organisations.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27025557','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27025557"><span>Electrocardiogram interpretation and arrhythmia management: a <span class="hlt">primary</span> and secondary care survey.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Begg, Gordon; Willan, Kathryn; Tyndall, Keith; Pepper, Chris; Tayebjee, Muzahir</p> <p>2016-05-01</p> <p>There is increasing desire among service commissioners to treat arrhythmia in <span class="hlt">primary</span> care. Accurate interpretation of the electrocardiogram (ECG) is fundamental to this. ECG interpretation has previously been shown to vary widely but there is little recent data. To examine the interpretation of ECGs in <span class="hlt">primary</span> and secondary care. A cross-sectional survey of participants' interpretation of six ECGs and hypothetical management of patients based on those ECGs, at <span class="hlt">primary</span> care educational events, and a cardiology department in Leeds. A total of 262 <span class="hlt">primary</span> care clinicians and 20 cardiology clinicians were surveyed via questionnaire. Answers were compared with expert electrophysiologist opinion. In <span class="hlt">primary</span> care, abnormal ECGs were interpreted as normal by 23% of responders. ST elevation and prolonged QT were incorrectly interpreted as normal by <span class="hlt">1</span>% and 22%, respectively. In cardiology, abnormal ECGs were interpreted as normal by 3%. ECG provision and interpretation remains inconsistent in both <span class="hlt">primary</span> and secondary care. <span class="hlt">Primary</span> care practitioners are less experienced and less confident with ECG interpretation than cardiologists, and require <span class="hlt">support</span> in this area. © British Journal of General Practice 2016.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24165402','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24165402"><span>COPD self-management <span class="hlt">supportive</span> care: chaos and complexity theory.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Cornforth, Amber</p> <p></p> <p>This paper uses the emergent theories of chaos and complexity to explore the self-management <span class="hlt">supportive</span> care of chronic obstructive pulmonary disease (COPD) patients within the evolving <span class="hlt">primary</span> care setting. It discusses the concept of self-management <span class="hlt">support</span>, the complexity of the <span class="hlt">primary</span> care context and consultations, smoking cessation, and the impact of acute exacerbations and action planning. The author hopes that this paper will enable the acquisition of new insight and better understanding in this clinical area, as well as <span class="hlt">support</span> meaningful learning and facilitate more thoughtful, effective and high quality patient-centred care within the context of <span class="hlt">primary</span> care.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/ED580216.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/ED580216.pdf"><span>Fast Facts about Early <span class="hlt">Support</span> for Infants and Toddlers (ESIT)</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Washington State Department of Early Learning, 2017</p> <p>2017-01-01</p> <p>This brief report provides facts about Early <span class="hlt">Support</span> for Infants and Toddlers (ESIT) on the following topics: (<span class="hlt">1</span>) What is the purpose of the IDEA Part C early intervention?; (2) Early intervention service delivery in Washington, July <span class="hlt">1</span>, 2015 through June 30, 2016; (3) <span class="hlt">Primary</span> early intervention services; (4) What are the expected child outcomes?;…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23703681','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23703681"><span>Population-based estimates of the prevalence of FMR<span class="hlt">1</span> expansion mutations in women with early menopause and <span class="hlt">primary</span> ovarian insufficiency.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Murray, Anna; Schoemaker, Minouk J; Bennett, Claire E; Ennis, Sarah; Macpherson, James N; Jones, Michael; Morris, Danielle H; Orr, Nick; Ashworth, Alan; Jacobs, Patricia A; Swerdlow, Anthony J</p> <p>2014-01-01</p> <p><span class="hlt">Primary</span> ovarian insufficiency before the age of 40 years affects <span class="hlt">1</span>% of the female population and is characterized by permanent cessation of menstruation. Genetic causes include FMR<span class="hlt">1</span> expansion mutations. Previous studies have estimated mutation prevalence in clinical referrals for <span class="hlt">primary</span> ovarian insufficiency, but these are likely to be biased as compared with cases in the general population. The prevalence of FMR<span class="hlt">1</span> expansion mutations in early menopause (between the ages of 40 and 45 years) has not been published. We studied FMR<span class="hlt">1</span> CGG repeat number in more than 2,000 women from the Breakthrough Generations Study who underwent menopause before the age of 46 years. We determined the prevalence of premutation (55-200 CGG repeats) and intermediate (45-54 CGG repeats) alleles in women with <span class="hlt">primary</span> ovarian insufficiency (n = 254) and early menopause (n = <span class="hlt">1</span>,881). The prevalence of the premutation was 2.0% in <span class="hlt">primary</span> ovarian insufficiency, 0.7% in early menopause, and 0.4% in controls, corresponding to odds ratios of 5.4 (95% confidence interval = <span class="hlt">1</span>.7-17.4; P = 0.004) for <span class="hlt">primary</span> ovarian insufficiency and 2.0 (95% confidence interval = 0.8-5.<span class="hlt">1</span>; P = 0.12) for early menopause. Combining <span class="hlt">primary</span> ovarian insufficiency and early menopause gave an odds ratio of 2.4 (95% confidence interval = <span class="hlt">1</span>.02-5.8; P = 0.04). Intermediate alleles were not significant risk factors for either early menopause or <span class="hlt">primary</span> ovarian insufficiency. FMR<span class="hlt">1</span> premutations are not as prevalent in women with ovarian insufficiency as previous estimates have suggested, but they still represent a substantial cause of <span class="hlt">primary</span> ovarian insufficiency and early menopause.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4958295','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4958295"><span>The N-terminus of survivin is a mitochondrial-targeting sequence and Src regulator</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Dunajová, Lucia; Cash, Emily; Markus, Robert; Rochette, Sophie; Townley, Amelia R.</p> <p>2016-01-01</p> <p>ABSTRACT Survivin (also known as BIRC5) is a cancer-associated protein that exists in several locations in the cell. Its cytoplasmic residence in interphase cells is governed by CRM<span class="hlt">1</span> (also known as <span class="hlt">XPO</span><span class="hlt">1</span>)-mediated nuclear exportation, and its localisation during mitosis to the centromeres and midzone microtubules is that of a canonical chromosomal passenger protein. In addition to these well-established locations, survivin is also a mitochondrial protein, but how it gets there and its function therein is presently unclear. Here, we show that the first ten amino acids at the N-terminus of survivin are sufficient to target GFP to the mitochondria in vivo, and ectopic expression of this decapeptide decreases cell adhesion and accelerates proliferation. The data <span class="hlt">support</span> a signalling mechanism in which this decapeptide regulates the tyrosine kinase Src, leading to reduced focal adhesion plaques and disruption of F-actin organisation. This strongly suggests that the N-terminus of survivin is a mitochondrial-targeting sequence that regulates Src, and that survivin acts in concert with Src to promote tumorigenesis. PMID:27246243</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/869060','DOE-PATENT-XML'); return false;" href="https://www.osti.gov/servlets/purl/869060"><span>Nuclear reactor having a polyhedral <span class="hlt">primary</span> shield and removable vessel insulation</span></a></p> <p><a target="_blank" href="http://www.osti.gov/doepatents">DOEpatents</a></p> <p>Ekeroth, Douglas E.; Orr, Richard</p> <p>1993-01-01</p> <p>A nuclear reactor is provided having a generally cylindrical reactor vessel disposed within an opening in a <span class="hlt">primary</span> shield. The opening in the <span class="hlt">primary</span> shield is defined by a plurality of generally planar side walls forming a generally polyhedral-shaped opening. The reactor vessel is <span class="hlt">supported</span> within the opening in the <span class="hlt">primary</span> shield by reactor vessel <span class="hlt">supports</span> which are in communication and aligned with central portions of some of the side walls. The reactor vessel is connected to the central portions of the reactor vessel <span class="hlt">supports</span>. A thermal insulation polyhedron formed from a plurality of slidably insertable and removable generally planar insulation panels substantially surrounds at least a portion of the reactor vessel and is disposed between the reactor vessel and the side walls of the <span class="hlt">primary</span> shield. The shape of the insulation polyhedron generally corresponds to the shape of the opening in the <span class="hlt">primary</span> shield. Reactor monitoring instrumentation may be mounted in the corners of the opening in the <span class="hlt">primary</span> shield between the side walls and the reactor vessel such that insulation is not disposed between the instrumentation and the reactor vessel.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://eric.ed.gov/?q=big+AND+6&pg=6&id=ED500314','ERIC'); return false;" href="https://eric.ed.gov/?q=big+AND+6&pg=6&id=ED500314"><span><span class="hlt">Supporting</span> Children's Learning: A Guide for Teaching Assistants</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Overall, Lyn</p> <p>2007-01-01</p> <p>Are you looking for a book that explains all the key ideas on how children learn and how best to <span class="hlt">support</span> children in that learning? Covering all major themes, this book offers: (<span class="hlt">1</span>) An introduction to main theories of learning and development from birth to <span class="hlt">primary</span> including brain and emotional and social development; (2) An introduction to what…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3355015','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3355015"><span>Costs and difficulties of recruiting patients to provide e-health <span class="hlt">support</span>: pilot study in one <span class="hlt">primary</span> care trust</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2012-01-01</p> <p>Background Better use of e-health services by patients could improve outcomes and reduce costs but there are concerns about inequalities of access. Previous research in outpatients suggested that anonymous personal email <span class="hlt">support</span> may help patients with long term conditions to use e-health, but recruiting earlier in their 'journey' may benefit patients more. This pilot study explored the feasibility and cost of recruiting patients for an e-health intervention in one <span class="hlt">primary</span> care trust. Methods The sample comprised 46 practices with total patient population of 250,000. We approached all practices using various methods, seeking collaboration to recruit patients via methods agreed with each practice. A detailed research diary was kept of time spent recruiting practices and patients. Researcher time was used to estimate costs. Patients who consented to participate were offered email <span class="hlt">support</span> for their use of the Internet for health. Results Eighteen practices agreed to take part; we recruited 27 patients, most (23/27) from five practices. Practices agreed to recruit patients for an e-health intervention via waiting room leaflets (16), posters (16), practice nurses (15), doctors giving patients leaflets (5), a study website link (7), inclusion in planned mailshots (2), and a special mailshot to patients selected from practice computers (<span class="hlt">1</span>). After low recruitment response we also recruited directly in five practices through research assistants giving leaflets to patients in waiting rooms. Ten practices recruited no patients. Those practices that were more difficult to recruit were less likely to recruit patients. Leaving leaflets for practice staff to distribute and placing posters in the practice were not effective in recruiting patients. Leaflets handed out by practice nurses and website links were more successful. The practice with lowest costs per patient recruited (£70) used a special mailshot to selected patients. Conclusion Recruitment via general practice was not</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/22458706','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/22458706"><span>Costs and difficulties of recruiting patients to provide e-health <span class="hlt">support</span>: pilot study in one <span class="hlt">primary</span> care trust.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jones, Ray B; O'Connor, Anita; Brelsford, Jade; Parsons, Neil; Skirton, Heather</p> <p>2012-03-29</p> <p>Better use of e-health services by patients could improve outcomes and reduce costs but there are concerns about inequalities of access. Previous research in outpatients suggested that anonymous personal email <span class="hlt">support</span> may help patients with long term conditions to use e-health, but recruiting earlier in their 'journey' may benefit patients more. This pilot study explored the feasibility and cost of recruiting patients for an e-health intervention in one <span class="hlt">primary</span> care trust. The sample comprised 46 practices with total patient population of 250,000. We approached all practices using various methods, seeking collaboration to recruit patients via methods agreed with each practice. A detailed research diary was kept of time spent recruiting practices and patients. Researcher time was used to estimate costs. Patients who consented to participate were offered email <span class="hlt">support</span> for their use of the Internet for health. Eighteen practices agreed to take part; we recruited 27 patients, most (23/27) from five practices. Practices agreed to recruit patients for an e-health intervention via waiting room leaflets (16), posters (16), practice nurses (15), doctors giving patients leaflets (5), a study website link (7), inclusion in planned mailshots (2), and a special mailshot to patients selected from practice computers (<span class="hlt">1</span>). After low recruitment response we also recruited directly in five practices through research assistants giving leaflets to patients in waiting rooms. Ten practices recruited no patients. Those practices that were more difficult to recruit were less likely to recruit patients. Leaving leaflets for practice staff to distribute and placing posters in the practice were not effective in recruiting patients. Leaflets handed out by practice nurses and website links were more successful. The practice with lowest costs per patient recruited (£70) used a special mailshot to selected patients. Recruitment via general practice was not successful and was therefore expensive</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/24758187','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/24758187"><span>Renal impairment as a surgical indication in <span class="hlt">primary</span> hyperparathyroidism: do the data <span class="hlt">support</span> this recommendation?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hendrickson, Chase D; Castro Pereira, Daniel J; Comi, Richard J</p> <p>2014-08-01</p> <p>Management of <span class="hlt">primary</span> hyperparathyroidism has evolved over the past two decades, yet impaired renal function has consistently been a surgical indication. This recommendation has been based upon the historical association between <span class="hlt">primary</span> hyperparathyroidism and renal impairment, and a review of the literature is needed to determine whether such a recommendation is warranted. PubMed was utilized to identify English-language articles published between January 1990 and February 2014 using keywords related to hyperparathyroidism and renal function. The keywords were "<span class="hlt">primary</span> hyperparathyroidism," "surgery," "parathyroidectomy," "kidney," "renal," "glomerular filtration rate," and "creatinine." Of the 1926 articles obtained with this search, all articles germane to the topic that quantified the relationship between <span class="hlt">primary</span> hyperparathyroidism and renal function were included. All references within these articles were investigated for inclusion. When helpful, data tables were constructed to summarize the results succinctly. A secondary elevation of PTH levels has not been consistently shown to occur at the threshold currently indicated for surgical intervention. While renal impairment is seen with more significant disease, mild asymptomatic <span class="hlt">primary</span> hyperparathyroidism has not been conclusively associated with renal impairment. Furthermore, there is no evidence to suggest that surgically curing <span class="hlt">primary</span> hyperparathyroidism via a parathyroidectomy has any impact upon renal function.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23344833','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23344833"><span>Macrolide-based regimens in absence of bacterial co-infection in critically ill H<span class="hlt">1</span>N<span class="hlt">1</span> patients with <span class="hlt">primary</span> viral pneumonia.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Martín-Loeches, I; Bermejo-Martin, J F; Vallés, J; Granada, R; Vidaur, L; Vergara-Serrano, J C; Martín, M; Figueira, J C; Sirvent, J M; Blanquer, J; Suarez, D; Artigas, A; Torres, A; Diaz, E; Rodriguez, A</p> <p>2013-04-01</p> <p>To determine whether macrolide-based treatment is associated with mortality in critically ill H<span class="hlt">1</span>N<span class="hlt">1</span> patients with <span class="hlt">primary</span> viral pneumonia. Secondary analysis of a prospective, observational, multicenter study conducted across 148 Intensive Care Units (ICU) in Spain. <span class="hlt">Primary</span> viral pneumonia was present in 733 ICU patients with pandemic influenza A (H<span class="hlt">1</span>N<span class="hlt">1</span>) virus infection with severe respiratory failure. Macrolide-based treatment was administered to 190 (25.9 %) patients. Patients who received macrolides had chronic obstructive pulmonary disease more often, lower severity on admission (APACHE II score on ICU admission (13.<span class="hlt">1</span> ± 6.8 vs. 14.4 ± 7.4 points, p < 0.05), and multiple organ dysfunction syndrome less often (23.4 vs. 30.<span class="hlt">1</span> %, p < 0.05). Length of ICU stay in survivors was not significantly different in patients who received macrolides compared to patients who did not (10 (IQR 4-20) vs. 10 (IQR 5-20), p = 0.9). ICU mortality was 24.<span class="hlt">1</span> % (n = 177). Patients with macrolide-based treatment had lower ICU mortality in the univariate analysis (19.2 vs. 28.<span class="hlt">1</span> %, p = 0.02); however, a propensity score analysis showed no effect of macrolide-based treatment on ICU mortality (OR = 0.87; 95 % CI 0.55-<span class="hlt">1</span>.37, p = 0.5). Moreover, the sensitivity analysis revealed very similar results (OR = 0.91; 95 % CI 0.58-<span class="hlt">1</span>.44, p = 0.7). A separate analysis of patients under mechanical ventilation yielded similar results (OR = 0.77; 95 % CI 0.44-<span class="hlt">1</span>.35, p = 0.4). Our results suggest that macrolide-based treatment was not associated with improved survival in critically ill H<span class="hlt">1</span>N<span class="hlt">1</span> patients with <span class="hlt">primary</span> viral pneumonia.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.osti.gov/servlets/purl/989051','SCIGOV-STC'); return false;" href="https://www.osti.gov/servlets/purl/989051"><span>Technical <span class="hlt">Support</span> Document for Version 3.6.<span class="hlt">1</span> of the COMcheck Software</span></a></p> <p><a target="_blank" href="http://www.osti.gov/search">DOE Office of Scientific and Technical Information (OSTI.GOV)</a></p> <p>Bartlett, Rosemarie; Connell, Linda M.; Gowri, Krishnan</p> <p>2009-09-29</p> <p>This technical <span class="hlt">support</span> document (TSD) is designed to explain the technical basis for the COMcheck software as originally developed based on the ANSI/ASHRAE/IES Standard 90.<span class="hlt">1</span>-1989 (Standard 90.<span class="hlt">1</span>-1989). Documentation for other national model codes and standards and specific state energy codes <span class="hlt">supported</span> in COMcheck has been added to this report as appendices. These appendices are intended to provide technical documentation for features specific to the <span class="hlt">supported</span> codes and for any changes made for state-specific codes that differ from the standard features that <span class="hlt">support</span> compliance with the national model codes and standards.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://pubs.er.usgs.gov/publication/70156781','USGSPUBS'); return false;" href="https://pubs.er.usgs.gov/publication/70156781"><span>Methylmercury bioaccumulation in stream food webs declines with increasing <span class="hlt">primary</span> production</span></a></p> <p><a target="_blank" href="http://pubs.er.usgs.gov/pubs/index.jsp?view=adv">USGS Publications Warehouse</a></p> <p>Walters, David; D.F. Raikow,; C.R. Hammerschmidt,; M.G. Mehling,; A. Kovach,; J.T. Oris,</p> <p>2015-01-01</p> <p>Opposing hypotheses posit that increasing <span class="hlt">primary</span> productivity should result in either greater or lesser contaminant accumulation in stream food webs. We conducted an experiment to evaluate <span class="hlt">primary</span> productivity effects on MeHg accumulation in stream consumers. We varied light for 16 artificial streams creating a productivity gradient (oxygen production =0.048–0.71 mg O2 L–<span class="hlt">1</span> d–<span class="hlt">1</span>) among streams. Two-level food webs were established consisting of phytoplankton/filter feeding clam, periphyton/grazing snail, and leaves/shredding amphipod (Hyalella azteca). Phytoplankton and periphyton biomass, along with MeHg removal from the water column, increased significantly with productivity, but MeHg concentrations in these <span class="hlt">primary</span> producers declined. Methylmercury concentrations in clams and snails also declined with productivity, and consumer concentrations were strongly correlated with MeHg concentrations in <span class="hlt">primary</span> producers. Heterotroph biomass on leaves, MeHg in leaves, and MeHg in Hyalella were unrelated to stream productivity. Our results <span class="hlt">support</span> the hypothesis that contaminant bioaccumulation declines with stream <span class="hlt">primary</span> production via the mechanism of bloom dilution (MeHg burden per cell decreases in algal blooms), extending patterns of contaminant accumulation documented in lakes to lotic systems.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3037296','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3037296"><span>New insights into HIV-<span class="hlt">1</span>-<span class="hlt">primary</span> skin disorders</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p></p> <p>2011-01-01</p> <p>Since the first reports of AIDS, skin involvement has become a burdensome stigma for seropositive patients and a challenging task for dermatologist and infectious disease specialists due to the severe and recalcitrant nature of the conditions. Dermatologic manifestations in AIDS patients act as markers of disease progression, a fact that enhances the importance of understanding their pathogenesis. Broadly, cutaneous disorders associated with HIV type-<span class="hlt">1</span> infection can be classified as <span class="hlt">primary</span> and secondary. While the pathogenesis of secondary complications, such as opportunistic infections and skin tumours, is directly correlated with a decline in the CD4+ T cell count, the origin of the certain manifestations primarily associated with the retroviral infection itself still remains under investigation. The focus of this review is to highlight the immunological phenomena that occur in the skin of HIV-<span class="hlt">1</span>-seropositive patients, which ultimately lead to skin disorders, such as seborrhoeic dermatitis, atopic dermatitis, psoriasis and eosinophilic folliculitis. Furthermore, we compile the latest data on how shifts in the cytokines milieu, impairments of the innate immune compartment, reactions to xenobiotics and autoimmunity are causative agents in HIV-<span class="hlt">1</span>-driven skin diseases. Additionally, we provide a thorough analysis of the small animal models currently used to study HIV-<span class="hlt">1</span>-associated skin complications, centering on transgenic rodent models, which unfortunately, have not been able to fully unveil the role of HIV-<span class="hlt">1</span> genes in the pathogenesis of their primarily associated dermatological manifestations. PMID:21261982</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/27734632','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/27734632"><span>Is there a role for IGF-<span class="hlt">1</span> in the development of second <span class="hlt">primary</span> cancers?</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Shanmugalingam, Thurkaa; Bosco, Cecilia; Ridley, Anne J; Van Hemelrijck, Mieke</p> <p>2016-11-01</p> <p>Cancer survival rates are increasing, and as a result, more cancer survivors are exposed to the risk of developing a second <span class="hlt">primary</span> cancer (SPC). It has been hypothesized that one of the underlying mechanisms for this risk could be mediated by variations in insulin-like growth factor-<span class="hlt">1</span> (IGF-<span class="hlt">1</span>). This review summarizes the current epidemiological evidence to identify whether IGF-<span class="hlt">1</span> plays a role in the development of SPCs. IGF-<span class="hlt">1</span> is known to promote cancer development by inhibiting apoptosis and stimulating cell proliferation. Epidemiological studies have reported a positive association between circulating IGF-<span class="hlt">1</span> levels and various <span class="hlt">primary</span> cancers, such as breast, colorectal, and prostate cancer. The role of IGF-<span class="hlt">1</span> in increasing SPC risk has been explored less. Nonetheless, several experimental studies have observed a deregulation of the IGF-<span class="hlt">1</span> pathway, which may explain the association between IGF-<span class="hlt">1</span> and SPCs. Thus, measuring serum IGF-<span class="hlt">1</span> may serve as a useful marker in assessing the risk of SPCs, and therefore, more translational experimental and epidemiological studies are needed to further disentangle the role of IGF-<span class="hlt">1</span> in the development of specific SPCs. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/25489416','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/25489416"><span>Arctigenin Increases Hemeoxygenase-<span class="hlt">1</span> Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat <span class="hlt">Primary</span> Astrocytes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun</p> <p>2014-11-01</p> <p>In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat <span class="hlt">primary</span> astrocytes. Since hemeoxygenase-<span class="hlt">1</span> (HO-<span class="hlt">1</span>) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-<span class="hlt">1</span> expression in rat <span class="hlt">primary</span> astrocytes. We found that arctigenin increased HO-<span class="hlt">1</span> mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-<span class="hlt">1</span> promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat <span class="hlt">primary</span> astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-<span class="hlt">1</span> expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-<span class="hlt">1</span> expression by arctigenin via modulation of Nrf2/ARE axis in rat <span class="hlt">primary</span> astrocytes.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li class="active"><span>24</span></li> <li><a href="#" onclick='return showDiv("page_25");'>25</a></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_24 --> <div id="page_25" class="hiddenDiv"> <div class="row"> <div class="col-sm-12"> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div> </div> <div class="row"> <div class="col-sm-12"> <ol class="result-class" start="481"> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4256028','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4256028"><span>Arctigenin Increases Hemeoxygenase-<span class="hlt">1</span> Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat <span class="hlt">Primary</span> Astrocytes</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun</p> <p>2014-01-01</p> <p>In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat <span class="hlt">primary</span> astrocytes. Since hemeoxygenase-<span class="hlt">1</span> (HO-<span class="hlt">1</span>) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-<span class="hlt">1</span> expression in rat <span class="hlt">primary</span> astrocytes. We found that arctigenin increased HO-<span class="hlt">1</span> mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-<span class="hlt">1</span> promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat <span class="hlt">primary</span> astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-<span class="hlt">1</span> expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-<span class="hlt">1</span> expression by arctigenin via modulation of Nrf2/ARE axis in rat <span class="hlt">primary</span> astrocytes. PMID:25489416</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28711522','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28711522"><span>Engaging with <span class="hlt">primary</span> schools: <span class="hlt">Supporting</span> the delivery of the new curriculum in evolution and inheritance.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Kover, Paula X; Hogge, Emily S</p> <p>2017-10-01</p> <p>The official school regulator in England (OFSTED) recently reported that the delivery of science lessons has been significantly diminished in many <span class="hlt">primary</span> schools. There is concern that the lack of good quality science in school can reduce the recruitment of young scientists, and the level of science literacy among the general public. We believe university scientists and undergraduate students can have a significant impact in the delivery of science in <span class="hlt">primary</span> schools. However, a relatively small proportion of scientists engage with young children to improve curricular <span class="hlt">primary</span> school science education. Here, we argue that long term engagement with <span class="hlt">primary</span> schools can produce significant impact for the scientist's research, schools, and society. As an example, we describe our experience developing teaching materials for the topic of "Evolution and inheritance"; highlighting possible pitfalls and perceived benefits, in hope of encouraging and facilitating other scientists to engage with <span class="hlt">primary</span> schools. Copyright © 2017 Elsevier Ltd. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/23167911','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/23167911"><span>REsearch into implementation STrategies to <span class="hlt">support</span> patients of different ORigins and language background in a variety of European <span class="hlt">primary</span> care settings (RESTORE): study protocol.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>MacFarlane, Anne; O'Donnell, Catherine; Mair, Frances; O'Reilly-de Brún, Mary; de Brún, Tomas; Spiegel, Wolfgang; van den Muijsenbergh, Maria; van Weel-Baumgarten, Evelyn; Lionis, Christos; Burns, Nicola; Gravenhorst, Katja; Princz, Christine; Teunissen, Erik; van den Driessen Mareeuw, Francine; Saridaki, Aristoula; Papadakaki, Maria; Vlahadi, Maria; Dowrick, Christopher</p> <p>2012-11-20</p> <p>The implementation of guidelines and training initiatives to <span class="hlt">support</span> communication in cross-cultural <span class="hlt">primary</span> care consultations is ad hoc across a range of international settings with negative consequences particularly for migrants. This situation reflects a well-documented translational gap between evidence and practice and is part of the wider problem of implementing guidelines and the broader range of professional educational and quality interventions in routine practice. In this paper, we describe our use of a contemporary social theory, Normalization Process Theory and participatory research methodology--Participatory Learning and Action--to investigate and <span class="hlt">support</span> implementation of such guidelines and training initiatives in routine practice. This is a qualitative case study, using multiple <span class="hlt">primary</span> care sites across Europe. Purposive and maximum variation sampling approaches will be used to identify and recruit stakeholders-migrant service users, general practitioners, <span class="hlt">primary</span> care nurses, practice managers and administrative staff, interpreters, cultural mediators, service planners, and policy makers. We are conducting a mapping exercise to identify relevant guidelines and training initiatives. We will then initiate a PLA-brokered dialogue with stakeholders around Normalization Process Theory's four constructs--coherence, cognitive participation, collective action, and reflexive monitoring. Through this, we will enable stakeholders in each setting to select a single guideline or training initiative for implementation in their local setting. We will prospectively investigate and <span class="hlt">support</span> the implementation journeys for the five selected interventions. Data will be generated using a Participatory Learning and Action approach to interviews and focus groups. Data analysis will follow the principles of thematic analysis, will occur in iterative cycles throughout the project and will involve participatory co-analysis with key stakeholders to enhance the</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/21653233','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/21653233"><span>Protein kinase Cδ is a critical component of Dectin-<span class="hlt">1</span> signaling in <span class="hlt">primary</span> human monocytes.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Elsori, Deena H; Yakubenko, Valentin P; Roome, Talat; Thiagarajan, Praveena S; Bhattacharjee, Ashish; Yadav, Satya P; Cathcart, Martha K</p> <p>2011-09-01</p> <p>Zymosan, a mimic of fungal pathogens, and its opsonized form (ZOP) are potent stimulators of monocyte NADPH oxidase, resulting in the production of O(2)(.-), which is critical for host defense against fungal and bacterial pathogens and efficient immune responses; however, uncontrolled O(2)(.-) production may contribute to chronic inflammation and tissue injury. Our laboratory has focused on characterizing the signal transduction pathways that regulate NADPH oxidase activity in <span class="hlt">primary</span> human monocytes. In this study, we examined the involvement of various pattern recognition receptors and found that Dectin-<span class="hlt">1</span> is the <span class="hlt">primary</span> receptor for zymosan stimulation of O(2)(.-) via NADPH oxidase in human monocytes, whereas Dectin-<span class="hlt">1</span> and CR3 mediate the activation by ZOP. Further studies identified Syk and Src as important signaling components downstream of Dectin-<span class="hlt">1</span> and additionally identified PKCδ as a novel downstream signaling component for zymosan-induced O(2)(.-) as well as phagocytosis. Our results show that Syk and Src association with Dectin-<span class="hlt">1</span> is dependent on PKCδ activity and expression and demonstrate direct binding between Dectin-<span class="hlt">1</span> and PKCδ. Finally, our data show that PKCδ and Syk but not Src are required for Dectin-<span class="hlt">1</span>-mediated phagocytosis. Taken together, our data identify Dectin-<span class="hlt">1</span> as the major PRR for zymosan in <span class="hlt">primary</span> human monocytes and identify PKCδ as a novel downstream signaling kinase for Dectin-<span class="hlt">1</span>-mediated regulation of monocyte NADPH oxidase and zymosan phagocytosis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.gpo.gov/fdsys/pkg/CFR-2010-title48-vol1/pdf/CFR-2010-title48-vol1-sec19-705-1.pdf','CFR'); return false;" href="https://www.gpo.gov/fdsys/pkg/CFR-2010-title48-vol1/pdf/CFR-2010-title48-vol1-sec19-705-1.pdf"><span>48 CFR 19.705-<span class="hlt">1</span> - General <span class="hlt">support</span> of the program.</span></a></p> <p><a target="_blank" href="http://www.gpo.gov/fdsys/browse/collectionCfr.action?selectedYearFrom=2010&page.go=Go">Code of Federal Regulations, 2010 CFR</a></p> <p></p> <p>2010-10-01</p> <p>... 48 Federal Acquisition Regulations System <span class="hlt">1</span> 2010-10-01 2010-10-01 false General <span class="hlt">support</span> of the program. 19.705-<span class="hlt">1</span> Section 19.705-<span class="hlt">1</span> Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... any contractual incentive provision based upon rewarding the contractor monetarily for exceeding goals...</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4108511','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4108511"><span>Inhibition of CRM<span class="hlt">1</span>-dependent nuclear export sensitizes malignant cells to cytotoxic and targeted agents</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Turner, Joel G.; Dawson, Jana; Cubitt, Christopher L.; Baz, Rachid; Sullivan, Daniel M.</p> <p>2014-01-01</p> <p>Nuclear-cytoplasmic trafficking of proteins is a significant factor in the development of cancer and drug resistance. Subcellular localization of exported proteins linked to cancer development include those involved in cell growth and proliferation, apoptosis, cell cycle regulation, transformation, angiogenesis, cell adhesion, invasion, and metastasis. Here, we examined the basic mechanisms involved in the export of proteins from the nucleus to the cytoplasm. All proteins over 40 kDa use the nuclear pore complex to gain entry or exit from the nucleus, with the <span class="hlt">primary</span> nuclear export molecule involved in these processes being chromosome region maintenance <span class="hlt">1</span> (CRM<span class="hlt">1</span>, exportin <span class="hlt">1</span> or <span class="hlt">XPO</span><span class="hlt">1</span>). Proteins exported from the nucleus must possess a hydrophobic nuclear export signal (NES) peptide that binds to a hydrophobic groove containing an active-site Cys528 in the CRM<span class="hlt">1</span> protein. CRM<span class="hlt">1</span> inhibitors function largely by covalent modification of the active site Cys528 and prevent binding to the cargo protein NES. In the absence of a CRM<span class="hlt">1</span> inhibitor, CRM<span class="hlt">1</span> binds cooperatively to the NES of the cargo protein and RanGTP, forming a trimer that is actively transported out of the nucleus by facilitated diffusion. Nuclear export can be blocked by CRM<span class="hlt">1</span> inhibitors, NES peptide inhibitors or by preventing post-translational modification of cargo proteins. Clinical trials using the classic CRM<span class="hlt">1</span> inhibitor leptomycin B proved too toxic for patients; however, a new generation of less toxic small molecule inhibitors are being used in clinical trials in patients with both hematological malignancies and solid tumors. Additional trials are being initiated using small-molecule CRM<span class="hlt">1</span> inhibitors in combination with chemotherapeutics such as pegylated liposomal doxorubicin. In this review, we present evidence that combining the new CRM<span class="hlt">1</span> inhibitors with other classes of therapeutics may prove effective in the treatment of cancer. Potential combinatorial therapies discussed include the use of CRM<span class="hlt">1</span> inhibitors</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5125481','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5125481"><span>Standing on the Precipice: Evaluating Final-Year Physiotherapy Students' Perspectives of Their Curriculum as Preparation for <span class="hlt">Primary</span> Health Care Practice</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>O'Donoghue, Grainne; Doody, Catherine; O'Neill, Geraldine; Barrett, Terry; Cusack, Tara</p> <p>2016-01-01</p> <p>Purpose: To explore final-year physiotherapy students' perceptions of <span class="hlt">primary</span> health care practice to determine (<span class="hlt">1</span>) aspects of their curriculum that <span class="hlt">support</span> their learning, (2) deficiencies in their curriculum, and (3) areas that they believe should be changed to adequately equip them to make the transition from student to <span class="hlt">primary</span> health care professional. Methods: Framework analysis methodology was used to analyze group opinion obtained using structured group feedback sessions. Sixty-eight final-year physiotherapy students from the four higher education institutions in Ireland participated. Results: The students identified several key areas that (<span class="hlt">1</span>) <span class="hlt">supported</span> their learning (exposure to evidence-based practice, opportunities to practise with problem-based learning, and interdisciplinary learning experiences); (2) were deficient (<span class="hlt">primary</span> health care placements, additional active learning sessions, and further education and practice opportunities for communication and health promotion), and (3) required change (practice placements in <span class="hlt">primary</span> health care, better curriculum organization to accommodate <span class="hlt">primary</span> health care throughout the programme with the suggestion of a specific <span class="hlt">primary</span> health care module). Conclusion: This study provides important insights into physiotherapy students' perceptions of <span class="hlt">primary</span> health care. It also provides important indicators of the curriculum changes needed to increase graduates' confidence in their ability to take up employment in <span class="hlt">primary</span> health care. PMID:27909366</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://ntrs.nasa.gov/search.jsp?R=20040087913&hterms=primary+function&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D30%26Ntt%3Dprimary%2Bfunction','NASA-TRS'); return false;" href="https://ntrs.nasa.gov/search.jsp?R=20040087913&hterms=primary+function&qs=Ntx%3Dmode%2Bmatchall%26Ntk%3DAll%26N%3D0%26No%3D30%26Ntt%3Dprimary%2Bfunction"><span>Polycystins <span class="hlt">1</span> and 2 mediate mechanosensation in the <span class="hlt">primary</span> cilium of kidney cells</span></a></p> <p><a target="_blank" href="http://ntrs.nasa.gov/search.jsp">NASA Technical Reports Server (NTRS)</a></p> <p>Nauli, Surya M.; Alenghat, Francis J.; Luo, Ying; Williams, Eric; Vassilev, Peter; Li, Xiaogang; Elia, Andrew E H.; Lu, Weining; Brown, Edward M.; Quinn, Stephen J.; <a style="text-decoration: none; " href="javascript:void(0); " onClick="displayelement('author_20040087913'); toggleEditAbsImage('author_20040087913_show'); toggleEditAbsImage('author_20040087913_hide'); "> <img style="display:inline; width:12px; height:12px; " src="images/arrow-up.gif" width="12" height="12" border="0" alt="hide" id="author_20040087913_show"> <img style="width:12px; height:12px; display:none; " src="images/arrow-down.gif" width="12" height="12" border="0" alt="hide" id="author_20040087913_hide"></p> <p>2003-01-01</p> <p>Several proteins implicated in the pathogenesis of polycystic kidney disease (PKD) localize to cilia. Furthermore, cilia are malformed in mice with PKD with mutations in TgN737Rpw (encoding polaris). It is not known, however, whether ciliary dysfunction occurs or is relevant to cyst formation in PKD. Here, we show that polycystin-<span class="hlt">1</span> (PC<span class="hlt">1</span>) and polycystin-2 (PC2), proteins respectively encoded by Pkd<span class="hlt">1</span> and Pkd2, mouse orthologs of genes mutated in human autosomal dominant PKD, co-distribute in the <span class="hlt">primary</span> cilia of kidney epithelium. Cells isolated from transgenic mice that lack functional PC<span class="hlt">1</span> formed cilia but did not increase Ca(2+) influx in response to physiological fluid flow. Blocking antibodies directed against PC2 similarly abolished the flow response in wild-type cells as did inhibitors of the ryanodine receptor, whereas inhibitors of G-proteins, phospholipase C and InsP(3) receptors had no effect. These data suggest that PC<span class="hlt">1</span> and PC2 contribute to fluid-flow sensation by the <span class="hlt">primary</span> cilium in renal epithelium and that they both function in the same mechanotransduction pathway. Loss or dysfunction of PC<span class="hlt">1</span> or PC2 may therefore lead to PKD owing to the inability of cells to sense mechanical cues that normally regulate tissue morphogenesis.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/20150937','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/20150937"><span>Evidence of true genotype-phenotype correlation in <span class="hlt">primary</span> hyperoxaluria type <span class="hlt">1</span>.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hoppe, Bernd</p> <p>2010-03-01</p> <p>A genotype-phenotype correlation in patients with <span class="hlt">primary</span> hyperoxaluria type <span class="hlt">1</span> and specific AGXT mutations has supposedly been found, at least for sensitivity to medication and long-term outcome. Nevertheless, other determinants, such as environmental factors or modifier genes, must play an essential role in the intra- and interfamilial heterogeneity of this disease. Harambat and co-workers report on this situation, presenting data on a major population of genotyped patients.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5780671','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5780671"><span>Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H<span class="hlt">1</span>N<span class="hlt">1</span> pneumonia: <span class="hlt">primary</span> influenza pneumonia versus concomitant/secondary bacterial pneumonia</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Song, Joon Y.; Cheong, Hee J.; Heo, Jung Y.; Noh, Ji Y.; Yong, Hwan S.; Kim, Yoon K.; Kang, Eun Y.; Choi, Won S.; Jo, Yu M.; Kim, Woo J.</p> <p>2011-01-01</p> <p>Please cite this paper as: Song et al. (2011). Clinical, laboratory and radiologic characteristics of 2009 pandemic influenza A/H<span class="hlt">1</span>N<span class="hlt">1</span> pneumonia: <span class="hlt">primary</span> influenza pneumonia versus concomitant/secondary bacterial pneumonia. Influenza and Other Respiratory Viruses 5(6), e535–e543. Background  Although influenza virus usually involves the upper respiratory tract, pneumonia was seen more frequently with the 2009 pandemic influenza A/H<span class="hlt">1</span>N<span class="hlt">1</span> than with seasonal influenza. Methods  From September <span class="hlt">1</span>, 2009, to January 31, 2010, a specialized clinic for patients (aged ≥15 years) with ILI was operated in Korea University Guro Hospital. RT‐PCR assay was performed to diagnose 2009 pandemic influenza A/H<span class="hlt">1</span>N<span class="hlt">1</span>. A retrospective case–case–control study was performed to determine the predictive factors for influenza pneumonia and to discriminate concomitant/secondary bacterial pneumonia from <span class="hlt">primary</span> influenza pneumonia during the 2009–2010 pandemic. Results  During the study period, the proportions of fatal cases and pneumonia development were 0·12% and <span class="hlt">1</span>·59%, respectively. Patients with pneumonic influenza were less likely to have nasal symptoms and extra‐pulmonary symptoms (myalgia, headache, and diarrhea) compared to patients with non‐pneumonic influenza. Crackle was audible in just about half of the patients with pneumonic influenza (38·5% of patients with <span class="hlt">primary</span> influenza pneumonia and 53·3% of patients with concomitant/secondary bacterial pneumonia). Procalcitonin, C‐reactive protein (CRP), and lactate dehydrogenase were markedly increased in patients with influenza pneumonia. Furthermore, procalcitonin (cutoff value 0·35 ng/ml, sensitivity 81·8%, and specificity 66·7%) and CRP (cutoff value 86·5 mg/IU, sensitivity 81·8%, and specificity 59·3%) were discriminative between patients with concomitant/secondary bacterial pneumonia and patients with <span class="hlt">primary</span> influenza pneumonia. Conclusions  Considering the subtle manifestations of 2009 pandemic</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15871643','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15871643"><span>Twelve-month drug cost savings related to use of an electronic prescribing system with integrated decision <span class="hlt">support</span> in <span class="hlt">primary</span> care.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>McMullin, S Troy; Lonergan, Thomas P; Rynearson, Charles S</p> <p>2005-05-01</p> <p>We reported previously the results of a 6-month controlled trial in which the use of a commercially available electronic prescribing system with integrated clinical decision <span class="hlt">support</span> and evidence-based message capability was associated with significantly lower <span class="hlt">primary</span> care drug costs. The original study focused on new prescriptions, defined as claims for a medication that the patient had not received in the previous 12 months. The main objectives of this follow-up report were to (a) determine if the 6-month savings on new prescriptions were sustained during 12 months of follow-up, (b) evaluate the impact of the computerized decision <span class="hlt">support</span> system (CDSS) on all pharmacy claims and per-member-per-month (PMPM) expenditures, and (c) evaluate the prescribing behaviors within 8 high-cost therapeutic categories that were frequently targeted by the electronic messages to prescribers to help verify that the drug cost savings were due to the recommendations in the electronic prescribing system. Two database queries were performed to identify additional pharmacy claims data for all Network Health Plan patients who were cared for by the 38 <span class="hlt">primary</span> care clinicians (32 physicians, 4 nurse practitioners, and 2 physician assistants) included in our original 6-month study. This follow-up analysis (a) identified all new prescription claims for the 2 groups of clinicians throughout the 12-month follow-up period (June 2002 through May 2003) and (b) assessed all pharmacy claims during the same 12-month period to provide more complete savings estimates and to examine between-group differences in PMPM expenditures. During 12 months of follow-up, clinicians using the electronic prescribing system continued to have lower prescription costs than the controls. Clinicians using the electronic prescribing system had average costs for 26,674 new prescriptions that were dollar 4.12 lower (95% confidence interval, dollar <span class="hlt">1</span>.53-dollar 6.71; P=0.003) and PMPM expenditures that were dollar 0.57 lower</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4735126','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=4735126"><span>Theory-driven group-based complex intervention to <span class="hlt">support</span> self-management of osteoarthritis and low back pain in <span class="hlt">primary</span> care physiotherapy: protocol for a cluster randomised controlled feasibility trial (SOLAS)</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Hurley, Deirdre A; Hall, Amanda M; Currie-Murphy, Laura; Pincus, Tamar; Kamper, Steve; Maher, Chris; McDonough, Suzanne M; Lonsdale, Chris; Walsh, Nicola E; Guerin, Suzanne; Segurado, Ricardo; Matthews, James</p> <p>2016-01-01</p> <p>Introduction International clinical guidelines consistently endorse the promotion of self-management (SM), including physical activity for patients with chronic low back pain (CLBP) and osteoarthritis (OA). Patients frequently receive individual treatment and advice to self-manage from physiotherapists in <span class="hlt">primary</span> care, but the successful implementation of a clinical and cost-effective group SM programme is a key priority for health service managers in Ireland to maximise long-term outcomes and efficient use of limited and costly resources. Methods/analysis This protocol describes an assessor-blinded cluster randomised controlled feasibility trial of a group-based education and exercise intervention underpinned by self-determination theory designed to <span class="hlt">support</span> an increase in SM behaviour in patients with CLBP and OA in <span class="hlt">primary</span> care physiotherapy. The <span class="hlt">primary</span> care clinic will be the unit of randomisation (cluster), with each clinic randomised to <span class="hlt">1</span> of 2 groups providing the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention or usual individual physiotherapy. Patients are followed up at 6 weeks, 2 and 6 months. The <span class="hlt">primary</span> outcomes are the (<span class="hlt">1</span>) acceptability and demand of the intervention to patients and physiotherapists, (2) feasibility and optimal study design/procedures and sample size for a definitive trial. Secondary outcomes include exploratory analyses of: point estimates, 95% CIs, change scores and effect sizes in physical function, pain and disability outcomes; process of change in target SM behaviours and selected mediators; and the cost of the intervention to inform a definitive trial. Ethics/dissemination This feasibility trial protocol was approved by the UCD Human Research Ethics—Sciences Committee (LS-13-54 Currie-Hurley) and research access has been granted by the Health Services Executive <span class="hlt">Primary</span> Care Research Committee in January 2014. The study findings will be disseminated to the research</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26801470','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26801470"><span>Theory-driven group-based complex intervention to <span class="hlt">support</span> self-management of osteoarthritis and low back pain in <span class="hlt">primary</span> care physiotherapy: protocol for a cluster randomised controlled feasibility trial (SOLAS).</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Hurley, Deirdre A; Hall, Amanda M; Currie-Murphy, Laura; Pincus, Tamar; Kamper, Steve; Maher, Chris; McDonough, Suzanne M; Lonsdale, Chris; Walsh, Nicola E; Guerin, Suzanne; Segurado, Ricardo; Matthews, James</p> <p>2016-01-21</p> <p>International clinical guidelines consistently endorse the promotion of self-management (SM), including physical activity for patients with chronic low back pain (CLBP) and osteoarthritis (OA). Patients frequently receive individual treatment and advice to self-manage from physiotherapists in <span class="hlt">primary</span> care, but the successful implementation of a clinical and cost-effective group SM programme is a key priority for health service managers in Ireland to maximise long-term outcomes and efficient use of limited and costly resources. This protocol describes an assessor-blinded cluster randomised controlled feasibility trial of a group-based education and exercise intervention underpinned by self-determination theory designed to <span class="hlt">support</span> an increase in SM behaviour in patients with CLBP and OA in <span class="hlt">primary</span> care physiotherapy. The <span class="hlt">primary</span> care clinic will be the unit of randomisation (cluster), with each clinic randomised to <span class="hlt">1</span> of 2 groups providing the Self-management of Osteoarthritis and Low back pain through Activity and Skills (SOLAS) intervention or usual individual physiotherapy. Patients are followed up at 6 weeks, 2 and 6 months. The <span class="hlt">primary</span> outcomes are the (<span class="hlt">1</span>) acceptability and demand of the intervention to patients and physiotherapists, (2) feasibility and optimal study design/procedures and sample size for a definitive trial. Secondary outcomes include exploratory analyses of: point estimates, 95% CIs, change scores and effect sizes in physical function, pain and disability outcomes; process of change in target SM behaviours and selected mediators; and the cost of the intervention to inform a definitive trial. This feasibility trial protocol was approved by the UCD Human Research Ethics-Sciences Committee (LS-13-54 Currie-Hurley) and research access has been granted by the Health Services Executive <span class="hlt">Primary</span> Care Research Committee in January 2014. The study findings will be disseminated to the research, clinical and health service communities through publication in</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/15983282','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/15983282"><span><span class="hlt">Support</span> of evidence-based guidelines for the annual physical examination: a survey of <span class="hlt">primary</span> care providers.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Prochazka, Allan V; Lundahl, Kristy; Pearson, Wesley; Oboler, Sylvia K; Anderson, Robert J</p> <p>2005-06-27</p> <p>Current evidence does not <span class="hlt">support</span> an annual screening physical examination for asymptomatic adults, but little is known about <span class="hlt">primary</span> care provider (PCP) attitudes and practices regarding an annual physical examination. We conducted a postal survey (32 items) of attitudes and practices regarding the annual physical examination (in asymptomatic patients 18 years or older) of a random sample of PCPs (specializing in internal medicine, family practice, and obstetrics/gynecology) from 3 geographic areas (Boston, Mass; Denver, Colo; and San Diego, Calif). Respondents included 783 (47%) of 1679 PCPs. Overall, 430 (65%) of 664 agreed that an annual physical examination is necessary. Three hundred ninety-three (55%) of 712 disagreed with the statement that national organizations do not recommend an annual physical examination, and 641 (88%) of 726 perform such examinations. Most PCPs agreed that an annual physical examination provides time to counsel patients about preventive health services (696/739 [94%]), improves patient-physician relationships (693/737 [94%]), and is desired by most patients (572/737 [78%]). Most also believe that an annual physical examination improves detection of subclinical illness (545/738 [74%]) and is of proven value (461/736 [63%]). Many believed that tests should be part of an annual physical examination, including mammography (44%), a lipid panel (48%), urinalysis (44%), testing of blood glucose level (46%), and complete blood cell count (39%). Despite contrary evidence, most PCPs believe an annual physical examination detects subclinical illness, and many report performing unproven screening laboratory tests. <span class="hlt">Primary</span> care providers do not appear to accept recommendations that annual physical examinations be abandoned in favor of a more selective approach to preventing health problems.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5152826','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=5152826"><span><span class="hlt">Primary</span> Health Care: care coordinator in regionalized networks?</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>de Almeida, Patty Fidelis; dos Santos, Adriano Maia</p> <p>2016-01-01</p> <p>RESUMO OBJECTIVE To analyze the breadth of care coordination by <span class="hlt">Primary</span> Health Care in three health regions. METHODS This is a quantitative and qualitative case study. Thirty-one semi-structured interviews with municipal, regional and state managers were carried out, besides a cross-sectional survey with the administration of questionnaires to physicians (74), nurses (127), and a representative sample of users (<span class="hlt">1</span>,590) of Estratégia Saúde da Família (Family Health Strategy) in three municipal centers of health regions in the state of Bahia. RESULTS <span class="hlt">Primary</span> Health Care as first contact of preference faced strong competition from hospital outpatient and emergency services outside the network. Issues related to access to and provision of specialized care were aggravated by dependence on the private sector in the regions, despite progress observed in institutionalizing flows starting out from <span class="hlt">Primary</span> Health Care. The counter-referral system was deficient and interprofessional communication was scarce, especially concerning services provided by the contracted network. CONCLUSIONS Coordination capacity is affected both by the fragmentation of the regional network and intrinsic problems in <span class="hlt">Primary</span> Health Care, which poorly <span class="hlt">supported</span> in its essential attributes. Although the health regions have common problems, <span class="hlt">Primary</span> Health Care remains a subject confined to municipal boundaries. PMID:28099663</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/26795953','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/26795953"><span>PDGF-BB induces PRMT<span class="hlt">1</span> expression through ERK<span class="hlt">1</span>/2 dependent STAT<span class="hlt">1</span> activation and regulates remodeling in <span class="hlt">primary</span> human lung fibroblasts.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Sun, Qingzhu; Liu, Li; Mandal, Jyotshna; Molino, Antonio; Stolz, Daiana; Tamm, Michael; Lu, Shemin; Roth, Michael</p> <p>2016-04-01</p> <p>Tissue remodeling of sub-epithelial mesenchymal cells is a major pathology occurring in chronic obstructive pulmonary disease (COPD) and asthma. Fibroblasts, as a major source of interstitial connective tissue extracellular matrix, contribute to the fibrotic and inflammatory changes in these airways diseases. Previously, we described that protein arginine methyltransferase-<span class="hlt">1</span> (PRMT<span class="hlt">1</span>) participates in airway remodeling in a rat model of pulmonary inflammation. In this study we investigated the mechanism by which PDGF-BB regulates PRMT<span class="hlt">1</span> in <span class="hlt">primary</span> lung fibroblasts, isolated from human lung biopsies. Fibroblasts were stimulated with PDGF-BB for up-to 48h and the regulatory and activation of signaling pathways controlling PRMT<span class="hlt">1</span> expression were determined. PRMT<span class="hlt">1</span> was localized by immuno-histochemistry in human lung tissue sections and by immunofluorescence in isolated fibroblasts. PRMT<span class="hlt">1</span> activity was suppressed by the pan-PRMT inhibitor AMI<span class="hlt">1</span>. ERK<span class="hlt">1</span>/2 mitogen activated protein kinase (MAPK) was blocked by PD98059, p38 MAPK by SB203580, and STAT<span class="hlt">1</span> by small interference (si) RNA treatment. The results showed that PDGF-BB significantly increased PRMT<span class="hlt">1</span> expression after <span class="hlt">1</span>h lasting over 48h, through ERK<span class="hlt">1</span>/2 MAPK and STAT<span class="hlt">1</span> signaling. The inhibition of ERK<span class="hlt">1</span>/2 MAPK or of PRMT<span class="hlt">1</span> activity decreased PDGF-BB induced fibroblast proliferation, COX2 production, collagen-<span class="hlt">1</span>A<span class="hlt">1</span> secretion, and fibronectin production. These findings suggest that PRMT<span class="hlt">1</span> is a central regulator of tissue remodeling and that the signaling sequence controlling its expression in <span class="hlt">primary</span> human lung fibroblast is PDGF-ERK-STAT<span class="hlt">1</span>. Therefore, PRMT<span class="hlt">1</span> presents a novel therapeutic and diagnostic target for the control of airway wall remodeling in chronic lung diseases. Copyright © 2016 Elsevier Inc. All rights reserved.</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2607805','PMC'); return false;" href="https://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2607805"><span><span class="hlt">Primary</span> malignant small bowel tumors: an atypical abdominal emergency.</span></a></p> <p><a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pmc">PubMed Central</a></p> <p>Mitchell, K. J.; Williams, E. S.; Leffall, L. D.</p> <p>1995-01-01</p> <p><span class="hlt">Primary</span> malignant tumors of the small bowel are uncommon in the United States. They comprise less than <span class="hlt">1</span>% of all gastrointestinal malignancies, with an incidence of 2200 cases per year. The clinical presentation of small bowel tumors is frequently insidious and often overlooked by physicians. The low incidence and lack of pathognomonic symptoms are the reasons that the early diagnosis of malignant small bowel tumor is uncommon. To better understand the clinical presentation, diagnostic evaluation, management, and outcome, a review of Howard University patients with <span class="hlt">primary</span> malignant small bowel tumors between 1970 and 1990 was conducted. Our experience concurs with the reported literature and <span class="hlt">supports</span> the conclusion that a high index of suspicion is necessary. The diagnosis of a malignant small bowel tumor should be considered in patients with vague chronic abdominal complaints. Images Figure <span class="hlt">1</span> Figure 2 PMID:7752280</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28042947','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28042947"><span>Efficient Transduction of Human and Rhesus Macaque <span class="hlt">Primary</span> T Cells by a Modified Human Immunodeficiency Virus Type <span class="hlt">1</span>-Based Lentiviral Vector.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>He, Huan; Xue, Jing; Wang, Weiming; Liu, Lihong; Ye, Chaobaihui; Cong, Zhe; Kimata, Jason T; Qin, Chuan; Zhou, Paul</p> <p>2017-03-01</p> <p>Human immunodeficiency virus type <span class="hlt">1</span> (HIV-<span class="hlt">1</span>)-based lentiviral vectors efficiently transduce genes to human, but not rhesus, <span class="hlt">primary</span> T cells and hematopoietic stem cells (HSCs). The poor transduction of HIV-<span class="hlt">1</span> vectors to rhesus cells is mainly due to species-specific restriction factors such as rhesus TRIM5α. Previously, several strategies to modify HIV-<span class="hlt">1</span> vectors were developed to overcome rhesus TRIM5α restriction. While the modified HIV-<span class="hlt">1</span> vectors efficiently transduce rhesus HSCs, they remain suboptimal for rhesus <span class="hlt">primary</span> T cells. Recently, HIV-<span class="hlt">1</span> variants that encode combinations of LNEIE mutations in capsid (CA) protein and SIVmac239 Vif were found to replicate efficiently in rhesus <span class="hlt">primary</span> T cells. Thus, the present study tested whether HIV-<span class="hlt">1</span> vectors packaged by a packaging construct containing these CA substitutions could efficiently transduce both human and rhesus <span class="hlt">primary</span> CD4 T cells. To accomplish this, LNEIE mutations were made in the packaging construct CEMΔ8.9, and recombinant HIV-<span class="hlt">1</span> vectors packaged by Δ8.9 WT or Δ8.9 LNEIE were generated. Transduction rates, CA stability, and vector integration in CEMss-CCR5 and CEMss-CCR5-rhTRIM5α/green fluorescent protein cells, as well as transduction rates in human and rhesus <span class="hlt">primary</span> CD4 T cells by Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-<span class="hlt">1</span> vectors, were compared. Finally, the influence of rhesus TRIM5α variations in transduction rates to <span class="hlt">primary</span> CD4 T cells from a cohort of 37 Chinese rhesus macaques was studied. While it maintains efficient transduction for human T-cell line and <span class="hlt">primary</span> CD4 T cells, Δ8.9 LNEIE-packaged HIV-<span class="hlt">1</span> vector overcomes rhesus TRIM5α-mediated CA degradation, resulting in significantly higher transduction efficiency of rhesus <span class="hlt">primary</span> CD4 T cells than Δ8.9 WT-packaged HIV-<span class="hlt">1</span> vector. Rhesus TRIM5α variations strongly influence transduction efficiency of rhesus <span class="hlt">primary</span> CD4 T cells by both Δ8.9 WT or Δ8.9 LNEIE-packaged HIV-<span class="hlt">1</span> vectors. Thus, it is concluded that Δ8.9 LNEIE-packaged HIV-<span class="hlt">1</span></p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('http://files.eric.ed.gov/fulltext/EJ1098113.pdf','ERIC'); return false;" href="http://files.eric.ed.gov/fulltext/EJ1098113.pdf"><span>Science That Matters: Exploring Science Learning and Teaching in <span class="hlt">Primary</span> Schools</span></a></p> <p><a target="_blank" href="http://www.eric.ed.gov/ERICWebPortal/search/extended.jsp?_pageLabel=advanced">ERIC Educational Resources Information Center</a></p> <p>Fitzgerald, Angela; Smith, Kathy</p> <p>2016-01-01</p> <p>To help <span class="hlt">support</span> <span class="hlt">primary</span> school students to better understand why science matters, teachers must first be <span class="hlt">supported</span> to teach science in ways that matter. In moving to this point, this paper identifies the dilemmas and tensions <span class="hlt">primary</span> school teachers face in the teaching of science. The balance is then readdressed through a research-based…</p> </li> <li> <p><a target="_blank" onclick="trackOutboundLink('https://www.ncbi.nlm.nih.gov/pubmed/28461633','PUBMED'); return false;" href="https://www.ncbi.nlm.nih.gov/pubmed/28461633"><span>Should Dental Schools Train Dentists to Routinely Provide Limited Preventive <span class="hlt">Primary</span> Medical Care? Two Viewpoints: Viewpoint <span class="hlt">1</span>: Dentists Should Be Trained to Routinely Provide Limited Preventive <span class="hlt">Primary</span> Care and Viewpoint 2: Dentists Should Be Trained in <span class="hlt">Primary</span> Care Medicine to Enable Comprehensive Patient Management Within Their Scope of Practice.</span></a></p> <p><a target="_blank" href="https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed">PubMed</a></p> <p>Giddon, Donald B; Donoff, R Bruce; Edwards, Paul C; Goldblatt, Lawrence I</p> <p>2017-05-01</p> <p>This Point/Counterpoint acknowledges the transformation of dental practice from a predominantly technically based profession with <span class="hlt">primary</span> emphasis on restoration of the tooth and its <span class="hlt">supporting</span> structures to that of a more medically based specialty focusing on the oral and maxillofacial complex. While both viewpoints accept the importance of this transformation, they differ on the ultimate desired outcome and how changes should be implemented during training of dentists as oral health professionals. Viewpoint <span class="hlt">1</span> argues that, in response to a shortage of both <span class="hlt">primary</span> care providers and access to affordable oral health care, dentists need to be able and willing to provide limited preventive <span class="hlt">primary</span> care (LPPC), and dental educators should develop and implement training models to prepare them. Among changes proposed are consideration of three types of practitioners: oral physicians with sufficient training to provide LPPC; dentists with excellent technical proficiency but minimal medical and surgical training; and mid-level providers to provide simple restorative and uncomplicated surgical care. Viewpoint 2 argues that the objective of dentists' education in <span class="hlt">primary</span> care medicine is to help them safely and effectively provide all aspects of oral health care, including appropriate preventive medical care, that already fall within their scope of knowledge and practice. Dental educators should encourage students to use this knowledge to take full ownership of non-tooth-related pathologic conditions of the oral and maxillofacial complex not currently managed in the dental setting, but encouraging graduates to expand into non-dental LPPC outside the recognized scope of practice will only further exacerbate fragmentation of care.</p> </li> </ol> <div class="pull-right"> <ul class="pagination"> <li><a href="#" onclick='return showDiv("page_1");'>«</a></li> <li><a href="#" onclick='return showDiv("page_21");'>21</a></li> <li><a href="#" onclick='return showDiv("page_22");'>22</a></li> <li><a href="#" onclick='return showDiv("page_23");'>23</a></li> <li><a href="#" onclick='return showDiv("page_24");'>24</a></li> <li class="active"><span>25</span></li> <li><a href="#" onclick='return showDiv("page_25");'>»</a></li> </ul> </div> </div><!-- col-sm-12 --> </div><!-- row --> </div><!-- page_25 --> <div class="footer-extlink text-muted" style="margin-bottom:1rem; text-align:center;">Some links on this page may take you to non-federal websites. 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