92 research outputs found

    A Conversation with Margaret Atwood

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    Evaluating health visitor assessments of mother–infant interactions: a mixed methods study

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    Background: Given the significance of reliably detecting cases where mother–infant relationships are not developing successfully, it is important that initial assessment processes are as sensitive and specific as possible. Objectives: This study sought to examine the processes by which health visitors identify problems in mother–infant relationships in the post-natal period. Design: Mixed methods. Settings: Two universities and two primary care trusts. Participant: In Phase One 17 first-time mothers and their 6- to 16-week-old infants were recruited. In Phase Two, a sample of 12 health visitors participated. Methods: The study incorporated two data collection phases. In Phase One, each mother’s interaction with her baby was video-recorded for 20 min in an observation laboratory. The video-recordings were coded and resultant data were analysed to derive a number of quantitative measures of interaction quality, including mothers’ responsiveness and sensitivity to their infants as rated by the Global Ratings Scales (GRS) of Mother–Infant Interaction. In Phase Two, 12 health visitors rated and assessed 9 clips of the video-recorded mother–infant interactions. The rationales for their ratings were then explored through in-depth interviews. Health visitor ratings of the video clips were compared to the GRS ratings. The relationship between the main focus of each health visitor rating, as reported in the interview, and the consistency of ratings with the GRS ratings were then investigated. Results: Correlations between individual health visitors’ ratings and the GRS ratings ranged from .17 to .83 and were statistically significant in only four cases. There was a weak relationship with health visitors’ years of experience (rs = .47, NS). When explaining their judgements, health visitors tended to comment on the mother’s behaviours or the relationship between the mother and baby and often ignored the behaviour of the baby. There was a highly significant relationship between the consistency of health visitor/GRS ratings and the number of references to the baby in the health visitors’ explanations (rs = .75, p = .005). Conclusion: This study contributes to the understanding of how health visitors make assessments of mother–infant interactions. The frequent lack of attention and reference to the baby’s behaviour suggests an area for further training

    Effect of HER2 Expression on NUPL2 Protein in Cervical Cancer Cells

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    Recurring cervical cancer patients frequently present overexpressed Human Epidermal Growth Factor Receptor 2 (HER2) protein, which promotes the growth of the cancer. Some HER2-expressing cells and cervical cancer patients have enhanced gene expression of Nucleoporin-like 2 (NUPL2). As part of the nuclear pore complex, the NUPL2 protein serves to selectively export substances from the nucleus to the cytoplasm. In this experiment, HER2 was expressed in cervical cancer cells to examine its effect on NUPL2 protein expression and localization. Interestingly, there was no difference in NUPL2 protein levels between HER2-expressing and non-expressing cells. Importantly, consistent instances of NUPL2 protein localization specific to the nucleus occurred in a large sampling of HER2-expressing cells. This is significant because it suggests a mechanism as to how HER2 promotes excessive cell growth, via changes in NUPL2 localization, potentially impacting its function and ability to selectively export substances that modulate cell growth

    Upregulation of xCT by KSHV-Encoded microRNAs Facilitates KSHV Dissemination and Persistence in an Environment of Oxidative Stress

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    Upregulation of xCT, the inducible subunit of a membrane-bound amino acid transporter, replenishes intracellular glutathione stores to maintain cell viability in an environment of oxidative stress. xCT also serves as a fusion-entry receptor for the Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma (KS). Ongoing KSHV replication and infection of new cell targets is important for KS progression, but whether xCT regulation within the tumor microenvironment plays a role in KS pathogenesis has not been determined. Using gene transfer and whole virus infection experiments, we found that KSHV-encoded microRNAs (KSHV miRNAs) upregulate xCT expression by macrophages and endothelial cells, largely through miR-K12-11 suppression of BACH-1—a negative regulator of transcription recognizing antioxidant response elements within gene promoters. Correlative functional studies reveal that upregulation of xCT by KSHV miRNAs increases cell permissiveness for KSHV infection and protects infected cells from death induced by reactive nitrogen species (RNS). Interestingly, KSHV miRNAs simultaneously upregulate macrophage secretion of RNS, and biochemical inhibition of RNS secretion by macrophages significantly reduces their permissiveness for KSHV infection. The clinical relevance of these findings is supported by our demonstration of increased xCT expression within more advanced human KS tumors containing a larger number of KSHV-infected cells. Collectively, these data support a role for KSHV itself in promoting de novo KSHV infection and the survival of KSHV-infected, RNS-secreting cells in the tumor microenvironment through the induction of xCT

    Zebrafish SPI-1 marks a site of myeloid development independent of primitive erythropoiesis: implications for axial patterning.

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    The mammalian transcription factor SPI-1 (synonyms: SPI1, PU.1, or Sfpi1) plays a critical role in myeloid development. To examine early myeloid commitment in the zebrafish embryo, we isolated a gene from zebrafish that is a SPI-1 orthologue on the basis of homology and phylogenetic considerations. The zebrafish spi1 (pu1) gene was first expressed at 12 h postfertilization in rostral lateral plate mesoderm (LPM), anatomically isolated from erythroid development in caudal lateral plate mesoderm. Fate-mapping traced rostral LPM cells from the region of initial spi1 expression to a myeloid fate. spi1 expression was lost in the bloodless mutant cloche, but rostral spi1 expression and myeloid development were preserved in the mutant spadetail, despite its complete erythropoietic failure. This dissociation of myeloid and erythroid development was further explored in studies of embryos overexpressing BMP-4, or chordin, in bmp-deficient swirl and snailhouse mutants, and chordin-deficient chordino mutants. These studies demonstrate that, in zebrafish, spi1 marks a rostral population of LPM cells committed to a myeloid fate anatomically separated from and developmentally independent of erythroid commitment in the caudal LPM. Such complete anatomical and developmental dissociation of two hematopoietic lineages adds an interesting complexity to the understanding of vertebrate hematopoietic development and presents significant implications for the mechanisms regulating axial patterning

    Outbreak of Neisseria meningitidis capsular group W among scouts returning from the World Scout Jamboree, Japan, 2015

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    The 23rd World Scout Jamboree was held in Japan from 28 July to 8 August 2015 and was attended by over 33,000 scouts from 162 countries. An outbreak of invasive meningococcal disease capsular group W was investigated among participants, with four confirmed cases identified in Scotland, who were all associated with one particular scout unit, and two confirmed cases in Sweden; molecular testing showed the same strain to be responsible for illness in both countries. The report describes the public health action taken to prevent further cases and the different decisions reached with respect to how wide to extend the offer of chemoprophylaxis in the two countries; in Scotland, chemoprophylaxis was offered to the unit of 40 participants to which the four cases belonged and to other close contacts of cases, while in Sweden chemoprophylaxis was offered to all those returning from the Jamboree. The report also describes the international collaboration and communication required to investigate and manage such multinational outbreaks in a timely manner

    Prevalence of Influenza A viruses in wild migratory birds in Alaska: Patterns of variation in detection at a crossroads of intercontinental flyways

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    <p>Abstract</p> <p>Background</p> <p>The global spread of the highly pathogenic avian influenza H5N1 virus has stimulated interest in a better understanding of the mechanisms of H5N1 dispersal, including the potential role of migratory birds as carriers. Although wild birds have been found dead during H5N1 outbreaks, evidence suggests that others have survived natural infections, and recent studies have shown several species of ducks capable of surviving experimental inoculations of H5N1 and shedding virus. To investigate the possibility of migratory birds as a means of H5N1 dispersal into North America, we monitored for the virus in a surveillance program based on the risk that wild birds may carry the virus from Asia.</p> <p>Results</p> <p>Of 16,797 birds sampled in Alaska between May 2006 and March 2007, low pathogenic avian influenza viruses were detected in 1.7% by rRT-PCR but no highly pathogenic viruses were found. Our data suggest that prevalence varied among sampling locations, species (highest in waterfowl, lowest in passerines), ages (juveniles higher than adults), sexes (males higher than females), date (highest in autumn), and analytical technique (rRT-PCR prevalence = 1.7%; virus isolation prevalence = 1.5%).</p> <p>Conclusion</p> <p>The prevalence of low pathogenic avian influenza viruses isolated from wild birds depends on biological, temporal, and geographical factors, as well as testing methods. Future studies should control for, or sample across, these sources of variation to allow direct comparison of prevalence rates.</p

    The genetic architecture of the human cerebral cortex

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    The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

    Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

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    BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom
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