980 resultados para Stephen
Resumo:
Eco-feedback interventions are capable of producing reductions in household energy consumption. Yet less is known about exactly how this reduction is achieved, how to maximise user engagement, or how to effectively translate engagement into energy saving. This paper discusses design opportunities for eco-feedback systems through observations of domestic energy use in both Western and rural developing world contexts. Drawing on case studies from these two contexts including 21 empirical interviews, we present an alternative framework for human-resource interaction, highlighting design opportunities for a transition towards more engaged and sustainable energy consumption among users.
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Background: In sub-tropical and tropical Queensland, a legacy of poor housing design,minimal building regulations with few compliance measures, an absence of post-construction performance evaluation and various social and market factors has led to a high and growing penetration of, and reliance on, air conditioners to provide thermal comfort for occupants. The pervasive reliance on air conditioners has arguably impacted on building forms, changed cultural expectations of comfort and social practices for achieving comfort, and may have resulted in a loss of skills in designing and constructing high performance building envelopes. Aim: The aim of this paper is to report on initial outcomes of a project that sought to determine how the predicted building thermal performance of twenty-five houses in subtropical and tropical Queensland compared with objective performance measures and comfort performance as perceived by occupants. The purpose of the project was to shed light on the role of various supply chain agents in the realisation of thermal performance outcomes. Methodology: The case study methodology embraced a socio-technical approach incorporating building science and sociology. Building simulation was used to model thermal performance under controlled comfort assumptions and adaptive comfort conditions. Actual indoor climate conditions were measured by temperature and relative humidity sensors placed throughout each house, whilst occupants’ expectations of thermal comfort and their self-reported behaviours were gathered through semi-structured interviews and periodic comfort surveys. Thermal imaging and air infiltration tests, along with building design documents, were analysed to evaluate the influence of various supply chain agents on the actual performance outcomes. Results: The results clearly show that in the housing supply chain – from designer to constructor to occupant – there is limited understanding from each agent of their role in contributing to, or inhibiting, occupants’ comfort.
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Climate change is leading to an increased frequency and severity of heat waves. Spells of several consecutive days of unusually high temperatures have led to increased mortality rates for the more vulnerable in the community. The problem is compounded by the escalating energy costs and increasing peak electrical demand as people become more reliant on air conditioning. Domestic air conditioning is the primary determinant of peak power demand which has been a major driver of higher electricity costs. This report presents the findings of multidisciplinary research which develops a national framework to evaluate the potential impacts of heat waves. It presents a technical, social and economic approach to adapt Australian residential buildings to ameliorate the impact of heat waves in the community and reduce the risk of its adverse outcomes. Through the development of a methodology for estimating the impact of global warming on key weather parameters in 2030 and 2050, it is possible to re-evaluate the size and anticipated energy consumption of air conditioners in future years for various climate zones in Australia. Over the coming decades it is likely that mainland Australia will require more cooling than heating. While in some parts the total electricity usage for heating and cooling may remain unchanged, there is an overall significant increase in peak electricity demand, likely to further drive electricity prices. Through monitoring groups of households in South Australia, New South Wales and Queensland, the impact of heat waves on both thermal comfort sensation and energy consumption for air conditioning has been evaluated. The results show that households are likely to be able to tolerate slightly increased temperature levels indoors during periods of high outside temperatures. The research identified that household electricity costs are likely to rise above what is currently projected due to the impact of climate change. Through a number of regulatory changes to both household design and air conditioners, this impact can be minimised. A number of proposed retrofit and design measures are provided, which can readily reduce electricity usage for cooling at minimal cost to the household. Using a number of social research instruments, it is evident that households are willing to change behaviour rather than to spend money. Those on lower income and elderly individuals are the least able to afford the use of air conditioning and should be a priority for interventions and assistance. Increasing community awareness of cost effective strategies to manage comfort and health during heat waves is a high priority recommended action. Overall, the research showed that a combined approach including behaviour change, dwelling modification and improved air conditioner selection can readily adapt Australian households to the impact of heat waves, reducing the risk of heat related deaths and household energy costs.
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Sequences with optimal correlation properties are much sought after for applications in communication systems. In 1980, Alltop (\emph{IEEE Trans. Inf. Theory} 26(3):350-354, 1980) described a set of sequences based on a cubic function and showed that these sequences were optimal with respect to the known bounds on auto and crosscorrelation. Subsequently these sequences were used to construct mutually unbiased bases (MUBs), a structure of importance in quantum information theory. The key feature of this cubic function is that its difference function is a planar function. Functions with planar difference functions have been called \emph{Alltop functions}. This paper provides a new family of Alltop functions and establishes the use of Alltop functions for construction of sequence sets and MUBs.
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Currently there are ~3000 known species of Sarcophagidae (Diptera), which are classified into 173 genera in three subfamilies. Almost 25% of sarcophagids belong to the genus Sarcophaga (sensu lato) however little is known about the validity of, and relationships between the ~150 (or more) subgenera of Sarcophaga s.l. In this preliminary study, we evaluated the usefulness of three sources of data for resolving relationships between 35 species from 14 Sarcophaga s.l. subgenera: the mitochondrial COI barcode region, ~800. bp of the nuclear gene CAD, and 110 morphological characters. Bayesian, maximum likelihood (ML) and maximum parsimony (MP) analyses were performed on the combined dataset. Much of the tree was only supported by the Bayesian and ML analyses, with the MP tree poorly resolved. The genus Sarcophaga s.l. was resolved as monophyletic in both the Bayesian and ML analyses and strong support was obtained at the species-level. Notably, the only subgenus consistently resolved as monophyletic was Liopygia. The monophyly of and relationships between the remaining Sarcophaga s.l. subgenera sampled remain questionable. We suggest that future phylogenetic studies on the genus Sarcophaga s.l. use combined datasets for analyses. We also advocate the use of additional data and a range of inference strategies to assist with resolving relationships within Sarcophaga s.l.
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Hitherto, the Malaconothridae contained Malaconothrus Berlese, 1904 and Trimalaconothrus Berlese, 1916, defined by the possession of one pre-tarsal claw (monodactyly) or by three claws (tridactyly) respectively. However, monodactyly is a convergent apomorphy within the Oribatida and an unreliable character for a classification. Therefore we undertook a phylogenetic analysis of 102 species as the basis for a taxonomic review of the Malaconothridae. We identified two major clades, equivalent to the genera Tyrphonothrus Knülle, 1957 and Malaconothrus. These genera are redefined. Trimala-conothrus becomes the junior subjective synonym of Malaconothrus. Some 42 species of Trimalaconothrus are recom-bined to Malaconothrus and 15 species to Tyrphonothrus. Homonyms created by the recombinations are rectified. The replacement name M. hammerae nom. nov. is proposed for M. angulatus Hammer, 1958, the junior homonym of M. an-gulatus (Willmann, 1931) and the replacement name M. luxtoni nom. nov. is proposed for M. scutatus Luxton, 1987, the junior homonym of M. scutatus Mihelč ič, 1959. Trimalaconothrus iteratus Subías, 2004 is an unnecessary replacement name and is a junior objective synonym of Malaconothrus longirostrum (Hammer 1966). Malaconothrus praeoccupatus Subías, 2004 is a junior objective synonym of M. machadoi Balogh & Mahunka, 1969. Malaconothrus obsessus (Subías, 2004), an unnecessary replacement name for Trimalaconothrus albulus Hammer 1966 sensu Tseng 1982, becomes an available name for what is in fact a previously-undescribed species of Malaconothrus. We describe four new species of Tyrphonothrus: T. gnammaensis sp. nov. from Western Australia, T. gringai sp. nov. and T. maritimus sp. nov. from New South Wales, and T. taylori sp. nov. from Queensland. We describe six new species of Malaconothrus: M. beecroftensis sp. nov., M. darwini sp. nov. M. gundungurra sp. nov. and M. knuellei sp. nov. from New South Wales, M. jowettae sp. nov. from Norfolk Island, and M. talaitae sp. nov. from Victoria.
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A loss of function mutation in the TRESK K2P potassium channel (KCNK18), has recently been linked with typical familial migraine with aura. We now report the functional characterisation of additional TRESK channel missense variants identified in unrelated patients. Several variants either had no apparent functional effect, or they caused a reduction in channel activity. However, the C110R variant was found to cause a complete loss of TRESK function, yet is present in both sporadic migraine and control cohorts, and no variation in KCNK18 copy number was found. Thus despite the previously identified association between loss of TRESK channel activity and migraine in a large multigenerational pedigree, this finding indicates that a single non-functional TRESK variant is not alone sufficient to cause typical migraine and highlights the genetic complexity of this disorder. Migraine is a common, disabling neurological disorder with a genetic, environmental and in some cases hormonal component. It is characterized by attacks of severe, usually unilateral and throbbing headache, can be accompanied by nausea, vomiting and photophobia and is clinically divided into two main subtypes, migraine with aura (MA) when a migraine is accompanied by transient and reversible focal neurological symptoms and migraine without aura (MO)1. The multifactorial and clinical heterogeneity of the disorder have considerably hindered the identification of common migraine susceptibility genes and most of our current understanding comes from the studies of familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA2. So far, the three susceptibility genes that have been convincingly identified in FHM families all encode ion channels or transporters: CACNA1A encoding the α1 subunit of the Cav2.1 calcium channel3, SCN1A encoding the Nav1.1 sodium channel4 and ATP1A2 encoding the α2 subunit of the Na+/K+ pump5. It is believed that mutations in these genes may lead to increased efflux of glutamate and potassium in the synapse and thereby cause migraine by rendering the brain more susceptible to cortical spreading depression (CSD)6 which is thought to play a role in initiating a migraine attack7,8. However, these genes have not to date been implicated in common forms of migraine9. Nevertheless, current opinion suggests that typical migraine, like FHM, is also disorder of neuronal excitability, ion homeostasis and neurotransmitter release10,11,12. Mutations in the SLC4A4 gene encoding the sodium-bicarbonate cotransporter NBCe1, have recently been implicated in several different forms of migraine13, and a variety of genes involved in glutamate homeostasis (PGCP, MTDH14 and LRP115) and a cation channel (TRPM8)15 have also recently been implicated in migraine via genome-wide association studies. Ion channels are therefore highly likely to play an important role in the pathogenesis of typical migraine. TRESK (KCNK18), is a member of the two-pore domain (K2P) family of potassium channels involved in the control of cellular electrical excitability16. Regulation of TRESK activity by the calcium-dependent phosphatase calcineurin17, as well as its expression in dorsal root ganglia (DRG)18 and trigeminal ganglia (TG)19,20 has led to a proposed role for this channel in a variety of pain pathways. In a recent study, a frameshift mutation (F139Wfsx24) in TRESK was identified in a large multigenerational pedigree where it co-segregated perfectly with typical MA and a significant genome-wide linkage LOD score of 3.0. Furthermore, functional analysis revealed that this mutation caused a complete loss of TRESK function and that the truncated subunit was also capable of down regulating wild-type channel function. This therefore highlighted KCNK18 as potentially important candidate gene and suggested that TRESK dysfunction might play a possible role in the pathogenesis of familial migraine with visual aura20. Additional screening for KCNK18 mutations in unrelated sporadic migraine and control cohorts also identified a number of other missense variants; R10G, A34V, C110R, S231P and A233V20. The A233V variant was found only in the control cohort, whilst A34V was identified in a single Australian migraine proband for which family samples were not available, but it was not detected in controls. By contrast, the R10G, C110R, and S231P variants were found in both migraineurs and controls in both cohorts. In this study, we have investigated the functional effect of these variants to further probe the potential association of TRESK dysfunction with typical migraine.
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Background: Multiple sclerosis (MS) is the most common cause of chronic neurologic disability beginning in early to middle adult life. Results from recent genome-wide association studies (GWAS) have substantially lengthened the list of disease loci and provide convincing evidence supporting a multifactorial and polygenic model of inheritance. Nevertheless, the knowledge of MS genetics remains incomplete, with many risk alleles still to be revealed. Methods: We used a discovery GWAS dataset (8,844 samples, 2,124 cases and 6,720 controls) and a multi-step logistic regression protocol to identify novel genetic associations. The emerging genetic profile included 350 independent markers and was used to calculate and estimate the cumulative genetic risk in an independent validation dataset (3,606 samples). Analysis of covariance (ANCOVA) was implemented to compare clinical characteristics of individuals with various degrees of genetic risk. Gene ontology and pathway enrichment analysis was done using the DAVID functional annotation tool, the GO Tree Machine, and the Pathway-Express profiling tool. Results: In the discovery dataset, the median cumulative genetic risk (P-Hat) was 0.903 and 0.007 in the case and control groups, respectively, together with 79.9% classification sensitivity and 95.8% specificity. The identified profile shows a significant enrichment of genes involved in the immune response, cell adhesion, cell communication/ signaling, nervous system development, and neuronal signaling, including ionotropic glutamate receptors, which have been implicated in the pathological mechanism driving neurodegeneration. In the validation dataset, the median cumulative genetic risk was 0.59 and 0.32 in the case and control groups, respectively, with classification sensitivity 62.3% and specificity 75.9%. No differences in disease progression or T2-lesion volumes were observed among four levels of predicted genetic risk groups (high, medium, low, misclassified). On the other hand, a significant difference (F = 2.75, P = 0.04) was detected for age of disease onset between the affected misclassified as controls (mean = 36 years) and the other three groups (high, 33.5 years; medium, 33.4 years; low, 33.1 years). Conclusions: The results are consistent with the polygenic model of inheritance. The cumulative genetic risk established using currently available genome-wide association data provides important insights into disease heterogeneity and completeness of current knowledge in MS genetics.
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microRNAs are small, non-coding RNAs that influence gene expression on a post-transcriptional level. They participate in diverse biological pathways and may act as either tumor suppressor genes or oncogenes. As they may have an effect on thousands of target mRNAs, single-nucleotide polymorphisms in microRNA genes might have major functional consequences, because the microRNA's properties and/or maturation may change. miR-196a has been reported to be aberrantly expressed in breast cancer tissue. Additionally, the SNP rs11614913 in hsa-mir-196a-2 has been found to be associated with breast cancer risk in some studies although not in others. This study evaluated the association between rs11614913 and breast cancer risk in a Caucasian case-control cohort in Queensland, Australia. Results do not support an association of the tested hsa-mir-196a-2 polymorphism with breast cancer susceptibility in this cohort. As there is a discrepancy between our results and previous findings, it is important to assess the role of rs11614913 in breast cancer by further larger studies investigating different ethnic groups.
A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura
Resumo:
Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.
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Objectives – To describe the development of an educational workshop to develop procedural skills in undergraduate Paramedic students using fresh frozen cadavers and to report the student’s assessment of the program. Methods – A six-hour anatomy based workshop was developed using fresh frozen cadavers to teach a range of airway and invasive procedural skills to second year undergraduate paramedic students. Embedded QUAN (qual) methodology will be utilised to evaluate the student’s satisfaction, perception and quality of teaching as compared to other existing clinical teaching techniques such as high fidelity simulation. Students will be asked to complete an anonymous validated survey (10 questions formulated on a 5 point Likert scale) and provide a qualitative feedback pre and post the six-hour workshop. Results – This is a prospective study planned for September 2013. Low-risk human research ethics are being sought. Teaching evaluation results from the inaugural 2012 workshop (undergraduate and postgraduate Paramedic students) and interim results for 2013 will be presented. Conclusions – Clinical teaching using fresh frozen cadavers thus far has predominately been used in the education of medical and surgical trainees. A number of studies have found them to be effective and in some cases superior to traditional high fidelity simulation teaching strategies. Fresh frozen cadavers are said to provide perfect anatomy, normal tissue consistency and a realistic operative training experience (Lloyd, Maxwell-Armstrong et al. 2011). The authors believe that this study will show that the use of fresh frozen cadavers offers a safe and effective mode to teach procedural skills to student paramedics that will help bridge the skills gap and increase confidence prior to students undertaking such interventions on living patients. A modified training program may be formulated for general practitioners undertaking Emergency Medicine Advanced Rural Skills.
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We have previously reported a preliminary taxonomy of patient error. However, approaches to managing patients' contribution to error have received little attention in the literature. This paper aims to assess how patients and primary care professionals perceive the relative importance of different patient errors as a threat to patient safety. It also attempts to suggest what these groups believe may be done to reduce the errors, and how. It addresses these aims through original research that extends the nominal group analysis used to generate the error taxonomy. Interviews were conducted with 11 purposively selected groups of patients and primary care professionals in Auckland, New Zealand, during late 2007. The total number of participants was 83, including 64 patients. Each group ranked the importance of possible patient errors identified through the nominal group exercise. Approaches to managing the most important errors were then discussed. There was considerable variation among the groups in the importance rankings of the errors. Our general inductive analysis of participants' suggestions revealed the content of four inter-related actions to manage patient error: Grow relationships; Enable patients and professionals to recognise and manage patient error; be Responsive to their shared capacity for change; and Motivate them to act together for patient safety. Cultivation of this GERM of safe care was suggested to benefit from 'individualised community care'. In this approach, primary care professionals individualise, in community spaces, population health messages about patient safety events. This approach may help to reduce patient error and the tension between personal and population health-care.
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Utilising archival human breast cancer biopsy material we examined the stromal/epithelial interactions of several matrix metalloproteinases (MMPs) using in situ-RT-PCR (IS-RT-PCR). In breast cancer, the stromal/epithelial interactions that occur, and the site of production of these proteases, are central to understanding their role in invasive and metastatic processes. We examined MT1-MMP (MMP-14, membrane type-1-MMP), MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) for their localisation profile in progressive breast cancer biopsy material (poorly differentiated invasive breast carcinoma (PDIBC), invasive breast carcinomas (IBC) and lymph node metastases (LNM)). Expression of MT1-MMP, MMP-1 and MMP-3 was observed in both the tumour epithelial and surrounding stromal cells in most tissue sections examined. MT1-MMP expression was predominantly localised to the tumour component in the pre-invasive lesions. MMP-1 gene expression was relatively well distributed between both tissue compartments, while MMP-3 demonstrated highest expression levels in the stromal tissue surrounding the epithelial tumour cells. The results demonstrate the ability to distinguish compartmental gene expression profiles using IS-RT-PCR. Further, we suggest a role for MT1-MMP in early tumour progression, expression of MMP-1 during metastasis and focal expression pattern of MMP-3 in areas of expansion. These expression profiles may provide markers for early breast cancer diagnoses and present potential therapeutic targets.
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Our laboratory has previously found that anti-mitogenic nuclear receptor mRNA is elevated in late stage tumours and this study was performed to scrutinize the possibility of cancer-stroma crosstalk using hormone signaling in these tissues. RNA levels in stromal tissue were examined for the estrogen α, estrogen β, androgen, progesterone and glucocorticoid nuclear receptors by a semi-quantitative PCR. Significant differences in expression between the cancer stroma and control tissue were seen, analyzing for both cancer grade and estrogen receptor status. Stroma and control tissue were significantly different for the progesterone and glucocorticoid nuclear receptors (p = 5.908 × 10−7 and 2.761 × 10−5, respectively). Glucocorticoid receptor also showed a significant increase to mRNA levels in the stroma of estrogen receptor negative tumours (p = 5.85 × 10−5). By contrast, the estrogen receptors α and β, those most closely associated with breast tissue growth, showed no significant change in mRNA (p = 0.372 and 0.655, respectively). Androgen receptor mRNA also remained unaffected (p = 0.174).
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Molecular and morphological data indicate that the pest thrips damaging Myoporum species in California and Hawai'i, Klambothrips myoporiMound and Morris, originated in Tasmania, Australia. This trans-Pacific dispersal presumably resulted from the international horticultural trade in Myoporum species. The data distinguish the pest from K. adelaideae sp.n. that induces leaf deformation on M. insulare along the coast of mainland Australia that is separated by ∼300km from Tasmania by the Bass Strait. K. myopori is more damaging to its non-native hosts in California and Hawai'i than to M. insulare in Tasmania, and further research is needed to determine if this is the result of release from its natural enemies. However, in certain areas of California, some Myoporum species are invasive weeds, and K. myopori may be considered an example of an accidental but beneficial introduction in this instance because of its detrimental impact on the plant species.