2,364 research outputs found
Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)
Exploring the Potential of Social Media Platforms as Data Collection Methods for Accessing and Understanding Experiences of Youth with Disabilities: A Narrative Review
Purpose: Social media (SM) is a critical component of youth culture, and may provide a useful platform for exploring young people’s authentic voices. This narrative review considers how researchers are exploring the experiences of youth with disabilities using SM.  Methods: Five health and social science databases were searched using terms related to ‘social media’ and ‘data collection’. Articles were reviewed for relevancy. Narrative analysis was undertaken.Results: Searches returned 1524 results, of which 15 articles were included. SM-based data collection methods fell into three categories: 1) observational; 2) interactive; and 3) combined online/offline, each offering unique advantages to data collection. Literature suggests that SM can be used to effectively explore self-care, coping and social experiences of youth with health conditions, however youth with disabilities were notably absent from all three categories.Conclusion: As a prominent component of youth culture, researchers have turned to SM-based data collection methods to understand youths’ real-world experiences. It is imperative, however, that the voices of youth with varied abilities and backgrounds be included in the conversation.
Simulating morphologies of organic semiconductors by exploiting low-frequency vibrational modes
Age-related mitochondrial DNA depletion and the impact on pancreatic beta cell function
Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA) copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes
Overscreening and Underscreening in Solid-Electrolyte Grain Boundary Space-Charge Layers
Polycrystalline solids can exhibit material properties that differ
significantly from those of equivalent single-crystal samples, in part, because
of a spontaneous redistribution of mobile point defects into so-called
space-charge regions adjacent to grain boundaries. The general analytical form
of these space-charge regions is known only in the dilute limit, where
defect-defect correlations can be neglected. Using kinetic Monte Carlo
simulations of a three-dimensional Coulomb lattice gas, we show that
grain-boundary space-charge regions in non-dilute solid electrolytes exhibit
overscreening -- damped oscillatory space-charge profiles -- and underscreening
-- decay lengths that are longer than the corresponding Debye length and that
increase with increasing defect-defect interaction strength. Overscreening and
underscreening are known phenomena in concentrated liquid electrolytes, and the
observation of functionally analogous behaviour in solid electrolyte
space-charge regions suggests that the same underlying physics drives behaviour
in both classes of systems. We therefore expect theoretical approaches
developed to study non-dilute liquid electrolytes to be equally applicable to
future studies of solid electrolytes
Determination of the electron diffusion length in dye-sensitized solar cells by substrate contact patterning
Mixed A-Cation Perovskites for Solar Cells:Atomic-Scale Insights into Structural Distortion, Hydrogen Bonding, and Electronic Properties
Hybrid lead halide
perovskites containing a mixture of A-site cations
such as the formamidinium (CHÂ(NH<sub>2</sub>)<sub>2</sub><sup>+</sup>, FA) and the smaller cesium (Cs<sup>+</sup>) cations have attracted considerable interest due to their
improved stability and solar cell performance. However, the structural
changes at the atomic scale and modifications to the optoelectronic
properties of these mixed cation perovskites are not fully understood.
Here, we investigate the FA<sub>1–<i>x</i></sub>Cs<sub><i>x</i></sub>PbI<sub>3</sub> (<i>x</i> ≤
0.25) system using a combination of static and dynamic <i>ab
initio</i> computational methods. We find that the incorporation
of Cs<sup>+</sup> cations into the parent FAPbI<sub>3</sub> structure
induces a chemical pressure or lattice strain effect through Cs/FA
ion size mismatch resulting in structural distortion and stronger
FA-iodide (N–H···I) hydrogen bonding interactions.
The dynamic tilting of PbI<sub>6</sub> octahedra and the rotational
motion of FA cations are also suppressed, which leads to symmetry-breaking
of the lattice. Such symmetry-breaking distortions of the Pb/I lattice
give rise to a Rashba-type effect, which spin-splits the frontier
electronic bands making the band gap indirect. Our results suggest
that the direct–indirect band gap transition may be a factor
in the reduced charge-carrier recombination rate in these mixed cation
perovskites
Transcriptomic analysis of pathways regulated by toll-like receptor 4 in a murine model of chronic pulmonary inflammation and carcinogenesis
<p>Abstract</p> <p>Background</p> <p>Therapeutic strategies exist for human pulmonary neoplasia, however due to the heterogeneity of the disease, most are not very effective. The innate immunity gene, toll-like receptor 4 (TLR4), protects against chronic pulmonary inflammation and tumorigenesis in mice, but the mechanism is unclear. This study was designed to identify TLR4-mediated gene expression pathways that may be used as prognostic indicators of susceptibility to lung tumorigenesis in mice and provide insight into the mechanism.</p> <p>Methods</p> <p>Whole lung mRNA was isolated from C.C3H-<it>Tlr4</it><sup><it>Lps</it>-<it>d </it></sup>(BALB<sup><it>Lps</it>-<it>d</it></sup>; <it>Tlr4 </it>mutant) and BALB/c (<it>Tlr4 </it>normal) mice following butylated hydroxytoluene (BHT)-treatment (four weekly ip. injections; 150-200 mg/kg/each; "promotion"). mRNA from micro-dissected tumors (adenomas) and adjacent uninvolved tissue from both strains were also compared 27 wks after a single carcinogen injection (3-methylcholanthrene (MCA), 10 μg/g; "control") or followed by BHT (6 weekly ip. injections; 125-200 mg/kg/each; "progression"). Bronchoalveolar lavage fluid was analyzed for inflammatory cell content and total protein determination, a marker of lung hyperpermeability; inflammation was also assessed using immunohistochemical staining for macrophages (F4/80) and lymphocytes (CD3) in mice bearing tumors (progression).</p> <p>Results</p> <p>During promotion, the majority of genes identified in the BALB<sup><it>Lps</it>-<it>d </it></sup>compared to BALB/c mice (P < 0.05) were involved in epithelial growth factor receptor (EGFR) signaling (e.g. epiregulin (<it>Ereg</it>)), secreted phosphoprotein 1(<it>Spp1</it>)), which can lead to cell growth and eventual tumor development. Inflammation was significantly higher in BALB<sup><it>Lps</it>-<it>d </it></sup>compared to BALB/c mice during progression, similar to the observed response during tumor promotion in these strains. Increases in genes involved in signaling through the EGFR pathway (e.g. <it>Ereg</it>, <it>Spp1</it>) were also observed during progression in addition to continued inflammation, chemotactic, and immune response gene expression in the BALB<sup><it>Lps</it>-<it>d </it></sup>versus BALB/c mice (<it>P </it>< 0.05), which appears to provide more favorable conditions for cell growth and tumor development. In support of these findings, the BALB/c mice also had significantly reduced expression of many immune response and inflammatory genes in both the tumors and uninvolved tissue.</p> <p>Conclusion</p> <p>This transcriptomic study determined the protective effect of TLR4 in lung carcinogenesis inhibition of multiple pathways including EGFR (e.g. <it>Ereg</it>), inflammatory response genes (e.g. <it>Cxcl5)</it>, chemotaxis (e.g. <it>Ccr1</it>) and other cell proliferation genes (e.g. <it>Arg1</it>, <it>Pthlh</it>). Future studies will determine the utility of these pathways as indicators of immune system deficiencies and tumorigenesis.</p
Targeted Deletion of Nrf2 Reduces Urethane-Induced Lung Tumor Development in Mice
Nrf2 is a key transcription factor that regulates cellular redox and defense responses. However, permanent Nrf2 activation in human lung carcinomas promotes pulmonary malignancy and chemoresistance. We tested the hypothesis that Nrf2 has cell survival properties and lack of Nrf2 suppresses chemically-induced pulmonary neoplasia by treating Nrf2+/+ and Nrf2-/- mice with urethane. Airway inflammation and injury were assessed by bronchoalveolar lavage analyses and histopathology, and lung tumors were analyzed by gross and histologic analysis. We used transcriptomics to assess Nrf2-dependent changes in pulmonary gene transcripts at multiple stages of neoplasia. Lung hyperpermeability, cell death and apoptosis, and inflammatory cell infiltration were significantly higher in Nrf2-/- mice compared to Nrf2+/+ mice 9 and 11 wk after urethane. Significantly fewer lung adenomas were found in Nrf2-/- mice than in Nrf2+/+ mice at 12 and 22 wk. Nrf2 modulated expression of genes involved cell-cell signaling, glutathione metabolism and oxidative stress response, and immune responses during early stage neoplasia. In lung tumors, Nrf2-altered genes had roles in transcriptional regulation of cell cycle and proliferation, carcinogenesis, organismal injury and abnormalities, xenobiotic metabolism, and cell-cell signaling genes. Collectively, Nrf2 deficiency decreased susceptibility to urethane-induced lung tumorigenesis in mice. Cell survival properties of Nrf2 were supported, at least in part, by reduced early death of initiated cells and heightened advantage for tumor cell expansion in Nrf2+/+ mice relative to Nrf2-/- mice. Our results were consistent with the concept that Nrf2 over-activation is an adaptive response of cancer conferring resistance to anti-cancer drugs and promoting malignancy
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Survey of women׳s experiences of care in a new freestanding midwifery unit in an inner city area of London, England: 2. Specific aspects of care
Objective
to describe and compare women׳s experiences of specific aspects of maternity care before and after the opening of the Barkantine Birth Centre, a new freestanding midwifery unit in an inner city area.
Design
telephone surveys undertaken in late pregnancy and about six weeks after birth. Two separate waves of interviews were conducted, Phase 1 before the birth centre opened and Phase 2 after it had opened.
Setting
Tower Hamlets, a deprived inner city borough in east London, 2007–2010.
Participants
620 women who were resident in Tower Hamlets and who satisfied the Barts and the London Trust’s eligibility criteria for using the birth centre. Of these, 259 women were recruited to Phase 1 and 361 to Phase 2.
Measurements and findings
the replies women gave show marked differences between the model of care in the birth centre and that at the obstetric unit at the Royal London Hospital with respect to experiences of care and specific practices. Women who initially booked for birth centre care were more likely to attend antenatal classes and find them useful and were less likely to be induced. Women who started labour care at the birth centre in spontaneous labour were more likely to use non-pharmacological methods of pain relief, most notably water and less likely to use pethidine than women who started care at the hospital. They were more likely to be able to move around in labour and less likely to have their membranes ruptured or have continuous CTG. They were more likely to be told to push spontaneously when they needed to rather than under directed pushing and more likely to report that they had been able to choose their position for birth and deliver in places other than the bed, in contrast to the situation at the hospital. The majority of women who had a spontaneous onset of labour delivered vaginally, with 28.6 per cent of women at the birth centre but no one at the hospital delivering in water. Primiparous women who delivered at the birth centre were less likely to have an episiotomy. Most women who delivered at the birth centre reported that they had chosen whether or not to have a physiological third stage, whereas a worrying proportion at the hospital reported that they had not had a choice. A higher proportion of women at the birth centre reported skin to skin contact with their baby in the first two hours after birth.
Key conclusions and implications for practice
significant differences were reported between the hospital and the birth centre in practices and information given to the women, with lower rates of intervention, more choice and significant differences in women’s experiences. This case study of a single inner-city freestanding midwifery unit, linked to the Birthplace in England Research Programme, indicates that this model of care also leads to greater choice and a better experience for women who opted for it
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