169 research outputs found
Increased Incidence of Loco-Regional Recurrences Among African American Women with Terminal Stage Breast Cancer
A prospective analysis of women with terminal breast cancer admitted to CHNE from November 2006âAugust 2007 evaluated anecdotal observations that African American (AA) women are likelier than Caucasian women to evidence loco-regional recurrences (LRR). Women with terminal breast cancer who were admitted to CHNE, a not-for-profit hospice serving over 90% of Northeast Florida hospice patients, were eligible for participation. 134 terminal breast cancer patients were assessed by hospice nurses for LRR presence via chest wall examination. 80% of them (107) were Caucasian, 17% (23) were AA and 3% (4) were of other ethnicities. Evidence of LRR were noted in 13% of the women (17/134). The proportion of patients with LRR was higher in AA women than Caucasian women (26% vs. 10%, 6/23 vs. 11/107, respectively), although this difference was not statistically significant (p = 0.08). The majority of Caucasian women with LRR consented to a medical record review, but a minority of AA women consented (8/11 vs. 2/6, respectively, p = 0.16)
Impacts of stratospheric sulfate geoengineering on global solar photovoltaic and concentrating solar power resource
In recent years, the idea of geoengineering, artificially modifying the climate to reduce global temperatures, has received increasing attention due to the lack of progress in reducing global greenhouse gas emissions. Stratospheric sulfate injection (SSI) is a geoengineering method proposed to reduce planetary warming by reflecting a proportion of solar radiation back into space that would otherwise warm the surface and lower atmosphere. We analyze results from the HadGEM2-CCS climate model with stratospheric emissions of 10 Tg yr-1 of SO2, designed to offset global temperature rise by around 1°C. A reduction in concentrating solar power (CSP) output of 5.9% on average over land is shown under SSI compared to a baseline future climate change scenario (RCP4.5) due to a decrease in direct radiation. Solar photovoltaic (PV) energy is generally less affected as it can use diffuse radiation, which increases under SSI, at the expense of direct radiation. Our results from HadGEM2-CCS are compared to the GEOSCCM chemistry-climate model from the Geoengineering Model Intercomparison Project (GeoMIP), with 5 Tg yr-1 emission of SO2. In many regions, the differences predicted in solar energy output between the SSI and RCP4.5 simulations are robust, as the sign of the changes for both the HadGEM2-CCS and GEOSCCM models agree. Furthermore, the sign of the total and direct annual mean radiation changes evaluated by HadGEM2-CCS agree with the sign of the multi-model mean changes of an ensemble of GeoMIP models over the majority of the world
A âLearning Revolutionâ? Investigating Pedagogic Practices around Interactive Whiteboards in British Primary Classrooms
Interactive whiteboards have been rapidly introduced into all primary schools under UK Government initiatives. These large, touch-sensitive screens, which control a computer connected to a digital projector, seem to be the first type of educational technology particularly suited for whole-class teaching and learning. Strong claims are made for their value by manufacturers and policy makers, but there has been little research on how, if at all, they influence established pedagogic practices, communicative processes and educational goals. This study has been designed to examine this issue, using observations in primary (elementary) school classrooms. It is funded by the UK Economic and Social Research Council and builds on the authorsâ previous research on ICT in educational dialogues and collaborative activities
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Assessment of the representation of West African storm lifecycles in convectionâpermitting simulations
Convectionâpermitting models perform better at representing the diurnal cycle and the intermittency of convective rainfall over land than parameterizedâconvection models. However, most of the previous model assessments have been from an Eulerian point of view, while key impacts of the rainfall depend on a stormârelative perspective of the system lifecycle. Here a stormâtracking algorithm is used to generate stormâcentered Lagrangian lifecycle statistics of precipitation over West Africa from regional climate model simulations and observations. Two versions of the Met Office Unified Model with and without convection parameterization at 4, 12, and 25 km resolution were analyzed. In both of the parameterizedâconvection simulations, storm lifetimes are too short compared to observations, and storms have no preferred propagation direction; the diurnal cycle of initiations and dissipations and the spatial distribution of storms are also inaccurate. The storms in the convectionâpermitting simulations have more realistic diurnal cycles and lifetimes, but are not as large as the largest observed storms. The convectionâpermitting model storms propagate in the correct direction, although not as fast as observed storms, and they have a much improved spatial distribution. The rainfall rate of convectionâpermitting storms is likely too intense compared to observations. The improved representation of the statistics of organized convective lifecycles shows that convectionâpermitting models provide better simulation of a number of aspects of highâimpact weather which are critical to climate impacts in this important geographic region, providing the high rainfall rates can be taken into account
Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers.
Clinical and neuropathological characteristics associated with G4C2 repeat expansions in chromosome 9 open reading frame 72 (C9ORF72), the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, are highly variable. To gain insight on the molecular basis for the heterogeneity among C9ORF72 mutation carriers, we evaluated associations between features of disease and levels of two abundantly expressed "c9RAN proteins" produced by repeat-associated non-ATG (RAN) translation of the expanded repeat. For these studies, we took a departure from traditional immunohistochemical approaches and instead employed immunoassays to quantitatively measure poly(GP) and poly(GA) levels in cerebellum, frontal cortex, motor cortex, and/or hippocampus from 55 C9ORF72 mutation carriers [12 patients with ALS, 24 with frontotemporal lobar degeneration (FTLD) and 19 with FTLD with motor neuron disease (FTLD-MND)]. We additionally investigated associations between levels of poly(GP) or poly(GA) and cognitive impairment in 15 C9ORF72 ALS patients for whom neuropsychological data were available. Among the neuroanatomical regions investigated, poly(GP) levels were highest in the cerebellum. In this same region, associations between poly(GP) and both neuropathological and clinical features were detected. Specifically, cerebellar poly(GP) levels were significantly lower in patients with ALS compared to patients with FTLD or FTLD-MND. Furthermore, cerebellar poly(GP) associated with cognitive score in our cohort of 15 patients. In the cerebellum, poly(GA) levels similarly trended lower in the ALS subgroup compared to FTLD or FTLD-MND subgroups, but no association between cerebellar poly(GA) and cognitive score was detected. Both cerebellar poly(GP) and poly(GA) associated with C9ORF72 variant 3 mRNA expression, but not variant 1 expression, repeat size, disease onset, or survival after onset. Overall, these data indicate that cerebellar abnormalities, as evidenced by poly(GP) accumulation, associate with neuropathological and clinical phenotypes, in particular cognitive impairment, of C9ORF72 mutation carriers
Expression of SORL1 and a novel SORL1 splice variant in normal and Alzheimers disease brain
<p>Abstract</p> <p>Background</p> <p>Variations in sortilin-related receptor (SORL1) expression and function have been implicated in Alzheimers Disease (AD). Here, to gain insights into SORL1, we evaluated SORL1 expression and splicing as a function of AD and AD neuropathology, neural gene expression and a candidate single nucleotide polymorphism (SNP).</p> <p>Results</p> <p>To identify SORL1 splice variants, we scanned each of the 46 internal SORL1 exons in human brain RNA samples and readily found SORL1 isoforms that lack exon 2 or exon 19. Quantification in a case-control series of the more abundant isoform lacking exon 2 (delta-2-SORL1), as well as the "full-length" SORL1 (FL-SORL1) isoform containing exon 2 showed that expression of FL-SORL1 was reduced in AD individuals. Moreover, FL-SORL1 was reduced in cognitively intact individuals with significant AD-like neuropathology. In contrast, the expression of the delta-2-SORL1 isoform was similar in AD and non-AD brains. The expression of FL-SORL1 was significantly associated with synaptophysin expression while delta-2-SORL1 was modestly enriched in white matter. Lastly, FL-SORL1 expression was associated with rs661057, a SORL1 intron one SNP that has been associated with AD risk. A linear regression analysis found that rs661057, synaptophysin expression and AD neuropathology were each associated with FL-SORL1 expression.</p> <p>Conclusion</p> <p>These results confirm that FL-SORL1 expression declines in AD and with AD-associated neuropathology, suggest that FL-SORL1 declines in cognitively-intact individuals with AD-associated neuropathology, identify a novel SORL1 splice variant that is expressed similarly in AD and non-AD individuals, and provide evidence that an AD-associated SNP is associated with SORL1 expression. Overall, these results contribute to our understanding of SORL1 expression in the human brain.</p
In vivo silencing of alpha-synuclein using naked siRNA
<p>Abstract</p> <p>Background</p> <p>Overexpression of α-synuclein (SNCA) in families with multiplication mutations causes parkinsonism and subsequent dementia, characterized by diffuse Lewy Body disease <it>post-mortem</it>. Genetic variability in <it>SNCA </it>contributes to risk of idiopathic Parkinson's disease (PD), possibly as a result of overexpression. <it>SNCA </it>downregulation is therefore a valid therapeutic target for PD.</p> <p>Results</p> <p>We have identified human and murine-specific siRNA molecules which reduce <it>SNCA in vitro</it>. As a proof of concept, we demonstrate that direct infusion of chemically modified (naked), murine-specific siRNA into the hippocampus significantly reduces <it>SNCA </it>levels. Reduction of <it>SNCA </it>in the hippocampus and cortex persists for a minimum of 1 week post-infusion with recovery nearing control levels by 3 weeks post-infusion.</p> <p>Conclusion</p> <p>We have developed naked gene-specific siRNAs that silence expression of <it>SNCA in vivo</it>. This approach may prove beneficial toward our understanding of the endogenous functional equilibrium of <it>SNCA</it>, its role in disease, and eventually as a therapeutic strategy for α-synucleinopathies resulting from <it>SNCA </it>overexpression.</p
Synchronous online CPD: empirical support for the value of webinars in career settings
The careers profession in England is facing unprecedented challenges. Initiatives to improve service delivery while keeping costs low are attractive and online training holds the promise of high impact at low cost. The present study employs a qualitative methodology to evaluate a series of online âwebinarsâ conducted with 15 careers advisers. Results showed that the technology itself could impede learning, and participants missed out on the peer-to-peer interaction that takes place in a âbricks and mortarâ setting, but overall participants found that access to relevant, good quality training from the convenience of their workplace more than compensated for the challenges. The article offers conceptual support for the viability of online learning through the theory of equivalency, andragogy and transactional distance theory, and makes recommendations for practice
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Impact of the MaddenâJulian oscillation and equatorial waves on tracked mesoscale convective systems over southeast Asia
Southeast Asia is a region dominated by high-impact weather, but numerical weather prediction here is a challenge owing to the complex orography and interactions between small- and large-scale phenomena. Localised mesoscale convective systems (MCSs) can produce intense precipitation. Here, we track MCSs over a 5-year period in Himawari satellite data, characterise the distribution of MCSs in the region, and investigate how they are modulated by the MaddenâJulian oscillation (MJO) and equatorial waves. Between 10°S and 10°N in southeast Asia, MCSs account for 45â70% of the precipitation during boreal extended winter (NovemberâApril). Over most of the region, the fractional MCS contribution to rainfall is higher than average on days with extreme rainfall (>55%). Long-lived (>12âhr) MCSs contribute disproportionately, providing 85% of the rainfall despite comprising only 34% of all MCSs. Variability in MCS rainfall accounts for >50% of the total rainfall variability during an MJO cycle, mostly due to larger numbers of MCSs in convectively active MJO phases. Variations in MCS size and mean rain rate due to shifts in the stratiform proportion provide compensating effects. In the west of the region, a shift to faster moving MCSs in active MJO phases and slower moving MCSs in inactive phases resulted in fast-moving MCSs having the greatest impact on the MJO-associated variability. Variability is larger in the west than in the east. Equatorial Kelvin waves modulate MCS rainfall, with MCSs accounting for 20â50% of local rainfall anomalies. This variability is again enhanced in the west. By contrast, rainfall anomalies due to westward-propagating mixed Rossbyâgravity waves and Rossby-1 waves are dominated by tropical-cyclone-related rainfall. Skill at local scales may be extracted from forecasts of subseasonal drivers such as the MJO and Kelvin waves, by understanding how these modulate the number and characteristics of MCSs
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