6,208 research outputs found
Trends in office internal gains and the impact on space heating and cooling demands
Internal gains from occupants, equipment and lighting contribute a significant proportion of the heat gains in an office space. Looking at trends in Generation-Y, it appears there are two diverging paths for future ICT demand: one where energy demand is carefully regulated and the other where productivity enhancers such as multiple monitors and media walls causes an explosion of energy demand within the space. These internal gains scenarios were simulated on a variety of different building archetypes to test their influence on the space heating and cooling demand. It was demonstrated that in offices with a high quality facade, internal gains are the dominant factor. As a case study, it was shown that natural ventilation is only possible when the ICT demand is carefully regulated
Presence of rd8 mutation does not alter the ocular phenotype of late-onset retinal degeneration mouse model.
PurposeA spontaneous frameshift mutation, c.3481delC, in the Crb1 gene is the underlying cause of dysplasia and retinal degeneration in rd8 mice. The rd8 mutation is found in C57BL/6N but not in C57BL/6J mouse sub-strains. The development of ocular pathology in single knockout Ccl2-/-, Cx3cr1-/- and in double knockout Ccl2-/-, Cx3cr1-/- mice raised on a C57BL/6 background has been reported to depend on the presence of a rd8 mutation. In this study, we investigated the influence of the rd8 mutation on the retinal pathology that we previously described in the late-onset retinal degeneration (L-ORD) mouse model with a heterozygous S163R mutation in the C1q-tumor necrosis factor-related protein-5Ctrp5+/- gene that was generated on a C57BL/6J background.MethodsMouse lines carrying the Ctrp5 S163R and rd8 mutations (Ctrp5+/-;rd8/rd8), corresponding controls without the rd8 mutation (Ctrp5+/-;wt/wt), and wild-type mice with and without the rd8 mutation (Wtrd8/rd8 and Wtwt/wt, respectively) were generated by systematic breeding of mice in our L-ORD mouse colony. Genotyping the mice for the rd8 (del C at nt3481 in Crb1) and Ctrp5 S163R mutations was performed with allelic PCR or sequencing. Retinal morphology was studied with fundus imaging, histology, light microscopy, electron microscopy, and immunohistochemistry.ResultsGenotype analysis of the mice in L-ORD mouse colony detected the rd8 mutation in the homozygous and heterozygous state. Fundus imaging of wild-type mice without the rd8 mutation (Wtwt/wt) revealed no autofluorescence (AF) spots up to 6-8 months and few AF spots at 21 months. However, the accumulation of AF lesions accelerated with age in the Ctrp5+/- mice that lack the rd8 mutation (Ctrp5+/-;wt/wt). The number of AF lesions was significantly increased (p<0.001), and they were small and uniformly distributed throughout the retina in the 21-month-old Ctrp5+/-;wt/wt mice when compared to the age-matched controls. Wild-type and Ctrp5+/- mice with the rd8 mutation (Wtrd8/rd8 and Ctrp5+/-;rd8/rd8, respectively) revealed an integrated retinal architecture with well-defined outer segments/inner segments (OS/IS), outer nuclear layer (ONL), outer plexiform layer (OPL), and inner nuclear layer (INL). The presence of pseudorosette structures reported in the rd8 mice between the ONL and the INL in the ventral quadrant of the retina was not observed in all genotypes studied. Further, the external limiting membrane was continuous in the Ctrp5+/-;rd8/rd8 and Wtrd8/rd8 mice. Evaluation of the retinal phenotype revealed that the Ctrp5+/-;wt/wt mice developed characteristic L-ORD pathology including age-dependent accumulation of AF spots, development of sub-retinal, sub-RPE, and basal laminar deposits, and Bruch's membrane abnormalities at older age, while these changes were not observed in the age-matched littermate WTwt/wt mice.ConclusionsThe Wtrd8/rd8 and Ctrp5+/-;rd8/rd8 mice raised on C57BL/6J did not develop early onset retinal changes that are characteristic of the rd8 phenotype, supporting the hypothesis that manifestation of rd8-associated pathology depends on the genetic background. The retinal pathology observed in mice with the Ctrp5+/-;wt/wt genotype is consistent with the L-ORD phenotype observed in patients and with the phenotype we described previously. The lack of rd8-associated retinal pathology in the Ctrp5+/-;wt/wt mouse model raised on the C57BL/6J background and the development of the L-ORD phenotype in these mice in the presence and absence of the rd8 mutation suggests that the pathology observed in the Ctrp5+/-;wt/wt mice is primarily associated with the S163R mutation in the Ctrp5 gene
Could the Icelandic banking collapse of 2008 have been prevented? The role of economists prior to the crisis
In 2008, the three main banks in Iceland collapsed. There is strong evidence that the banks would have become insolvent even without the subprime crisis. Yet, there was a marked difference in opinion at the time about the viability of the Icelandic banks. A clean bill of health was given by the commissioned reports of Mishkin in 2007 and Portes in 2008, just prior to the collapse, whereas severe reservations about the Icelandic financial system were expressed by Wade, inter alios. These contrasting views were widely debated and may well have influenced both potential and actual foreign depositors in the banks. This paper analyses the disparate arguments put forward and contrasts it with the actual outcome. It considers the influence of economists in public policy debates and draws some methodological conclusions.This is the author accepted manuscript. The final version is available from Edward Elgar Publishing via https://doi.org/10.4337/ejeep.2016.03.0
BACs as tools for the study of genomic imprinting.
Genomic imprinting in mammals results in the expression of genes from only one parental allele. Imprinting occurs as a consequence of epigenetic marks set down either in the father's or the mother's germ line and affects a very specific category of mammalian gene. A greater understanding of this distinctive phenomenon can be gained from studies using large genomic clones, called bacterial artificial chromosomes (BACs). Here, we review the important applications of BACs to imprinting research, covering physical mapping studies and the use of BACs as transgenes in mice to study gene expression patterns, to identify imprinting centres, and to isolate the consequences of altered gene dosage. We also highlight the significant and unique advantages that rapid BAC engineering brings to genomic imprinting research
Institutional Effects in a Simple Model of Educational Production
This paper presents a model of educational production that tries to make sense of recent evidence on effects of institutional arrangements on student performance. In a simple principal-agent framework, students choose their learning effort to maximize their net benefits, while the government chooses educational spending to maximize its net benefits. In the jointly determined equilibrium, schooling quality is shown to depend on several institutionally determined parameters. The impact on student performance of institutions such as central examinations, centralization versus school autonomy, teachers\u27 influence, parental influence, and competition from private schools is analyzed. Furthermore, the model can rationalize why positive resource effects may be lacking in educational production
Transformation Pathways of Silica under High Pressure
Concurrent molecular dynamics simulations and ab initio calculations show
that densification of silica under pressure follows a ubiquitous two-stage
mechanism. First, anions form a close-packed sub-lattice, governed by the
strong repulsion between them. Next, cations redistribute onto the interstices.
In cristobalite silica, the first stage is manifest by the formation of a
metastable phase, which was observed experimentally a decade ago, but never
indexed due to ambiguous diffraction patterns. Our simulations conclusively
reveal its structure and its role in the densification of silica.Comment: 14 pages, 4 figure
Quality of Life of People Living with HIV in Australia: The Role of Stigma, Social Disconnection and Mental Health.
HIV is a manageable chronic illness, due to advances in biomedical management. However, many people living with HIV (PLHIV) continue to experience psychosocial challenges, which have been associated with poorer quality of life (QoL). This study aimed to explore how psychosocial factors contributed to the QoL of PLHIV in Australia; specifically, the relationship between HIV-related stigma, social connectedness, mental health, and QoL. Participants were 122 PLHIV attending The Albion Centre (a tertiary HIV clinic in Sydney, Australia), who completed questionnaires which measured HIV-related stigma, social support, mental health symptomology and QoL. Results indicated that HIV-related stigma predicted poorer QoL, as did mental health symptomology. Conversely, social connectedness improved QoL. Additionally, social connectedness was found to mediate the relationship between HIV-related stigma and QoL, whereas the hypothesized moderating role of mental health symptomology on this model was not significant. These findings provide insight into the impact of psychosocial factors on QoL, offering practitioners various points of clinical intervention
A new composite measure of colonoscopy: the Performance Indicator of Colonic Intubation (PICI)
Abstract
Background and study aim Cecal intubation rate (CIR) is an established performance indicator of colonoscopy. In some patients, cecal intubation with acceptable tolerance is only achieved with additional sedation. This study proposes a composite Performance Indicator of Colonic Intubation (PICI), which combines CIR, comfort, and sedation.
Methods Data from 20 085 colonoscopies reported in the 2011 UK national audit were analyzed. PICI was defined as the percentage of procedures achieving cecal intubation with median dose (2 mg) of midazolam or less, and nurse-assessed comfort score of 1 – 3/5. Multivariate logistic regression analysis evaluated possible associations between PICI and patient, unit, colonoscopist, and diagnostic factors.
Results PICI was achieved in 54.1 % of procedures. PICI identified factors affecting performance more frequently than single measures such as CIR and polyp detection, or CIR + comfort alone. Older age, male sex, adequate bowel preparation, and a positive fecal occult blood test as indication were associated with a higher PICI. Unit accreditation, the presence of magnetic imagers in the unit, greater annual volume, fewer years’ experience, and higher training/trainer status were associated with higher PICI rates. Procedures in which PICI was achieved were associated with significantly higher polyp detection rates than when PICI was not achieved.
Conclusions PICI provides a simpler picture of performance of colonoscopic intubation than separate measures of CIR, comfort, and sedation. It is associated with more factors that are amenable to change that might improve performance and with higher likelihood of polyp detection. It is proposed that PICI becomes the key performance indicator for intubation of the colon in colonoscopy quality improvement initiatives.</jats:p
Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.
BACKGROUND: Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression. METHOD: A diagnosis of depression during pregnancy was recorded from Manchester cohort participants' medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression. RESULTS: In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively). CONCLUSIONS: This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.The Manchester cohort
was supported by Manchester National Institute
for Health Research (NIHR) Biomedical Research.
The Queen Charlotte’s cohort was supported by the
Medical Research Council (MRC) (Eurostress),
National Institutes of Health (R01MH073842) and the
Genesis Research Trust. The MBAM cohort was supported
by the Genesis Research Trust. A.B.J. was supported
by a Biotechnology and Biological Sciences
Research Council (BBSRC) Doctoral Training Grants
(DTG) studentship and subsequently MRC project
grant MR/M013960/1. S.J.T. was supported by BBSRC
project grant BB/J015156/1. L.E.C. was supported by
an Imperial College London Ph.D. studentship and
both L.E.C. and P.G.R were supported by the NIHR
Imperial Biomedical Research Centre
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