969 resultados para Marcus, Brian
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The Urban Informatics Research Lab brings together a group of people who focus their research on interdisciplinary topics at the intersection of social, spatial, and technical research domains—that is, people, place, and technology. Those topics are spread across the breadth of urban life—its contemporary issues and its needs, as well as the design opportunities that we have as individuals, groups, communities, and as a whole society. The lab’s current research areas include urban planning and design, civic innovation, mobility and transportation, education and connected learning, environmental sustainability, and food and urban agriculture. The common denominator of the lab’s approach is user-centered design research directed toward understanding, conceptualizing, developing, and evaluating sociotechnical practices as well as the opportunities afforded by innovative digital technology in urban environments.
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Background: Seizures and interictal spikes in mesial temporal lobe epilepsy (MTLE) affect a network of brain regions rather than a single epileptic focus. Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) studies have demonstrated a functional network in which hemodynamic changes are time-locked to spikes. However, whether this reflects the propagation of neuronal activity from a focus, or conversely the activation of a network linked to spike generation remains unknown. The functional connectivity (FC) changes prior to spikes may provide information about the connectivity changes that lead to the generation of spikes. We used EEG-fMRI to investigate FC changes immediately prior to the appearance of interictal spikes on EEG in patients with MTLE. Methods/principal findings: Fifteen patients with MTLE underwent continuous EEG-fMRI during rest. Spikes were identified on EEG and three 10 s epochs were defined relative to spike onset: spike (0–10 s), pre-spike (−10 to 0 s), and rest (−20 to −10 s, with no previous spikes in the preceding 45s). Significant spike-related activation in the hippocampus ipsilateral to the seizure focus was found compared to the pre-spike and rest epochs. The peak voxel within the hippocampus ipsilateral to the seizure focus was used as a seed region for FC analysis in the three conditions. A significant change in FC patterns was observed before the appearance of electrographic spikes. Specifically, there was significant loss of coherence between both hippocampi during the pre-spike period compared to spike and rest states. Conclusion/significance: In keeping with previous findings of abnormal inter-hemispheric hippocampal connectivity in MTLE, our findings specifically link reduced connectivity to the period immediately before spikes. This brief decoupling is consistent with a deficit in mutual (inter-hemispheric) hippocampal inhibition that may predispose to spike generation.
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The prognosis of epithelial ovarian cancer is poor in part due to the high frequency of chemoresistance. Recent evidence points to the Toll-like receptor-4 (TLR4), and particularly its adaptor protein MyD88, as one potential mediator of this resistance. This study aims to provide further evidence that MyD88 positive cancer cells are clinically significant, stem-like and reproducibly detectable for the purposes of prognostic stratification. Expression of TLR4 and MyD88 was assessed immunohistochemically in 198 paraffin-embedded ovarian tissues and in an embryonal carcinoma model of cancer stemness. In parallel, expression of TLR4 and MyD88 mRNA and regulatory microRNAs (miR-21 and miR-146a) was assessed, as well as in a series of chemosensitive and resistant cancer cells lines. Functional analysis of the pathway was assessed in chemoresistant SKOV-3 ovarian cancer cells. TLR4 and MyD88 expression can be reproducibly assessed via immunohistochemistry using a semi-quantitative scoring system. TLR4 expression was present in all ovarian epithelium (normal and neoplastic), whereas MyD88 was restricted to neoplastic cells, independent of tumour grade and associated with reduced progression-free and overall survival, in an immunohistological specific subset of serous carcinomas, p<0.05. MiR-21 and miR-146a expression was significantly increased in MyD88 negative cancers (p<0.05), indicating their participation in regulation. Significant alterations in MyD88 mRNA expression were observed between chemosensitive and chemoresistant cells and tissue. Knockdown of TLR4 in SKOV-3 ovarian cells recovered chemosensitivity. Knockdown of MyD88 alone did not. MyD88 expression was down-regulated in differentiated embryonal carcinoma (NTera2) cells, supporting the MyD88+ cancer stem cell hypothesis. Our findings demonstrate that expression of MyD88 is associated with significantly reduced patient survival and altered microRNA levels and suggest an intact/functioning TLR4/MyD88 pathway is required for acquisition of the chemoresistant phenotype. Ex vivo manipulation of ovarian cancer stem cell (CSC) differentiation can decrease MyD88 expression, providing a potentially valuable CSC model for ovarian cancer.
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This article focusses on the two libel cases arising from Brian Penton's review of Vivian Crockett's novel Mezzomorto for the Bulletin in 1934, viewing them as points of entry into Australian literary politics in the 1930s, and as windows on to one of the most enduring and interesting feuds in Australian literary culture, that between P.R. 'Inky' Stephensen, self-styled 'Bunyip Critic,' and Brian Penton, arch exponent of 'destructive criticism' and scourge of parochial pretension. The cases are particularly interesting for what they reveal about the evolving positions of two influential figures in Australian writing of the 1930s and 1940s. They also play in to contemporary debates about the state and status of 'literature' in Australia. And while Penton's biographer Patrick Buckridge avers that the cases did not impact on any of the larger contemporary literary issues (meaning censorship and free speech), a case may be made for the significance of the libel actions in the context of attempts to establish an industrial and cultural presence for a diverse range of Australian writing.
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Recent years have seen global food prices rise and become more volatile. Price surges in 2008 and 2011 held devastating consequences for hundreds of millions of people and negatively impacted many more. Today one billion people are hungry. The issue is a high priority for many international agencies and national governments. At the Cannes Summit in November 2011, the G20 leaders agreed to implement five objectives aiming to mitigate food price volatility and protect vulnerable persons. To succeed, the global community must now translate these high level policy objectives into practical actions. In this paper, we describe challenges and unresolved dilemmas before the global community in implementing these five objectives. The paper describes recent food price volatility trends and an evaluation of possible causes. Special attention is given to climate change and water scarcity, which have the potential to impact food prices to a much greater extent in coming decades. We conclude the world needs an improved knowledge base and new analytical capabilities, developed in parallel with the implementation of practical policy actions, to manage food price volatility and reduce hunger and malnutrition. This requires major innovations and paradigm shifts by the global community.
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Social marketers and governments have often targeted hard to reach or vulnerable groups (Gordon et al., 2006) such as young adults and low income earners. Past research has shown that low-income earners are often at risk of poor health outcomes and diminished lifestyle (Hampson et al., 2009; Scott et al., 2012). Young adults (aged 18 to 35) are in a transition phase of their life where lifestyle preferences are still being formed and are thus a useful target for long-term sustainable change. An area of focus for all levels of government is the use of energy with an aim to reduce consumption. There is little research to date that combines both of these groups and in particular in the context of household energy usage. Research into financially disadvantaged consumers is challenging the notion that that low income consumer purchasing and usage of products and services is based upon economic status (Sharma et al., 2012). Prior research shows higher income earners view items such as televisions and computers as necessities rather than non-essential (Karlsson et al., 2004). Consistent with this is growing evidence that low income earners purchase non-essential, energy intensive electronic appliances such as multiple big screen TV sets and additional refrigerators. With this in mind, there is a need for knowledge about how psychological and economic factors influence the energy consumption habits (e.g. appliances on standby power, leaving appliances turned on, running multiple devices at one time) of low income earners. Thus, our study sought to address the research question of: What are the factors that influence young adult low-income earners energy habits?
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Purpose There is a suggestion that the long wavelength-sensitive (LWS)-to-middle wavelength-sensitive (MWS) cone ratio in the retina is associated with myopia. The aim was to measure the LWS/MWS amplitude modulation ratio, an estimate of the LWS/MWS cone ratio, in young adult emmetropes and myopes. Methods Multifocal visual evoked potentials were measured when the LWS and MWS cone systems were excited separately using the method of silent substitution. The 30 young adult participants (22 to 33 years) included 10 emmetropes (mean [±SD] refraction, +0.3 [±0.4] diopters [D]) and 20 myopes (mean [±SD] refraction, -3.4 [±1.7] D). Results The LWS/MWS amplitude modulation ratios ranged from 0.56 to 1.80 in the central 3- to 13-degree diameter ring and from 0.94 to 1.91 in the peripheral 13- to 30-degree diameter ring. Within the central ring, the mean (±SD) ratios were 1.20 (±0.26) and 1.20 (±0.33) for the emmetropic and the myopic groups, respectively. For the peripheral ring, the mean (±SD) ratios were 1.48 (±0.27) and 1.30 (±0.27), respectively. There were no significant differences in the ratios between the emmetropic and myopic groups for either the central (p = 0.99) or peripheral (p = 0.08) rings. For the latter, more myopic refractive error was associated with lower LWS/MWS amplitude modulation ratio; the refraction explained 16% (p = 0.02) of variation in ratio. Conclusions The relationship between the LWS/MWS amplitude modulation ratios and refraction at 13 to 30 degrees indicates that a large longitudinal study of changes in refraction in persons with known cone ratio is required to determine if a low LWS/MWS cone ratio is associated with myopia development.
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The deployment of high speed broadband around Australia offers opportunities to extend digital participation among and between regional and rural communities. Full realisation of these opportunities requires a greater understanding about community members’ current digital participation and development needs, to underpin innovative community-driven initiatives. This paper outlines the Fostering Digital Participation Project’s initial undertakings to determine current digital participation and the future digital aspirations of a number of regional and rural communities.
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In the last few decades payday loans have mushroomed in many developed countries. The arguments for and against an industry which provides small, short-term loans at very high interest rates have also blossomed. This article presents findings from an Australian study to contribute to the international policy and practice debate about a sector which orients to those on a low income. At the heart of this debate lies a conundrum: Borrowing from payday lenders exacerbates poverty, yet many low-income households rely on these loans. We argue that the key problem is the restricted framework within which the debate currently oscillates.
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Occupational stress research has consistently demonstrated negative effects for employees. Research also describes potential moderators of this relationship. While research has revealed some positive effects of emotional intelligence (EI) on employee adjustment, it has neglected investigation of their potential stress buffering effects. Based on the Job-Demand Resources model, it was predicted that higher trait emotional intelligence would act as a buffer to the potential negative effects of stressors on employee adjustment. Hierarchical multiple regression analyses with a sample of 306 nurses found no main effects of EI but revealed eight moderating effects. While some interactions support the buffering hypothesis, others revealed buffering for those with low EI. Findings are discussed in terms of theoretical and practical implications.
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Leptospirosis outbreaks have been associated with many common water events including water consumption, water sports, environmental disasters and occupational exposure. The ability of leptospires to survive in moist environments makes them a high risk agent for infection following contact with any contaminated water source. Water treatment processes reduce the likelihood of leptospirosis or other microbial agents causing infection provided they do not malfunction and the distribution networks are maintained. Notably, there are many differences in water treatment systems around the world, particularly between developing and developed countries. Detection of leptospirosis in water samples is uncommonly performed by molecular methods.
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Large concentrations of magnetite in sedimentary deposits and soils with igneous parent material have been reported to affect geophysical sensor performance. We have undertaken the first systematic experimental effort to understand the effects of magnetite for ground-penetrating radar (GPR) characterization of the shallow subsurface. Laboratory experiments were conducted to study how homogeneous magnetite-sand mixtures and magnetite concentrated in layers affect the propagation behavior (velocity, attenuation) of high-frequency GPR waves and the reflection characteristics of a buried target. Important observations were that magnetite had a strong effect on signal velocity and reflection, at magnitudes comparable to what has been observed in small-scale laboratory experiments that measured electromagnetic properties of magnetite-silica mixtures. Magnetite also altered signal attenuation and affected the reflection characteristics of buried targets. Our results indicated important implications for several fields, including land mine detection, Martian exploration, engineering, and moisture mapping using satellite remote sensing and radiometers.
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Background Understanding the progression of prostate cancer to androgen-independence/castrate resistance and development of preclinical testing models are important for developing new prostate cancer therapies. This report describes studies performed 30 years ago, which demonstrate utility and shortfalls of xenografting to preclinical modeling. Methods We subcutaneously implanted male nude mice with small prostate cancer fragments from transurethral resection of the prostate (TURP) from 29 patients. Successful xenografts were passaged into new host mice. They were characterized using histology, immunohistochemistry for marker expression, flow cytometry for ploidy status, and in some cases by electron microscopy and response to testosterone. Two xenografts were karyotyped by G-banding. Results Tissues from 3/29 donors (10%) gave rise to xenografts that were successfully serially passaged in vivo. Two, (UCRU-PR-1, which subsequently was replaced by a mouse fibrosarcoma, and UCRU-PR-2, which combined epithelial and neuroendocrine features) have been described. UCRU-PR-4 line was a poorly differentiated prostatic adenocarcinoma derived from a patient who had undergone estrogen therapy and bilateral castration after his cancer relapsed. Histologically, this comprised diffusely infiltrating small acinar cell carcinoma with more solid aggregates of poorly differentiated adenocarcinoma. The xenografted line showed histology consistent with a poorly differentiated adenocarcinoma and stained positively for prostatic acid phosphatase (PAcP), epithelial membrane antigen (EMA) and the cytokeratin cocktail, CAM5.2, with weak staining for prostate specific antigen (PSA). The line failed to grow in female nude mice. Castration of three male nude mice after xenograft establishment resulted in cessation of growth in one, growth regression in another and transient growth in another, suggesting that some cells had retained androgen sensitivity. The karyotype (from passage 1) was 43–46, XY, dic(1;12)(p11;p11), der(3)t(3:?5)(q13;q13), -5, inv(7)(p15q35) x2, +add(7)(p13), add(8)(p22), add(11)(p14), add(13)(p11), add(20)(p12), -22, +r4[cp8]. Conclusions Xenografts provide a clinically relevant model of prostate cancer, although establishing serially transplantable prostate cancer patient derived xenografts is challenging and requires rigorous characterization and high quality starting material. Xenografting from advanced prostate cancer is more likely to succeed, as xenografting from well differentiated, localized disease has not been achieved in our experience. Strong translational correlations can be demonstrated between the clinical disease state and the xenograft model
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The current study sought to explore whether the subcutaneous administration of lymph-targeted dendrimers, conjugated with a model chemotherapeutic (methotrexate, MTX), was able to enhance anticancer activity against lymph node metastases. The lymphatic pharmacokinetics and antitumour activity of PEGylated polylysine dendrimers conjugated to MTX [D-MTX(OH)] via a tumour-labile hexapeptide linker was examined in rats and compared to a similar system where MTX was α-carboxyl O-tert-butylated [D-MTX(OtBu)]. The latter has previously been shown to exhibit longer plasma circulation times. D-MTX(OtBu) was well absorbed from the subcutaneous injection site via the lymph, and 3 to 4%/g of the dose was retained by sentinel lymph nodes. In contrast, D-MTX(OH) showed limited absorption from the subcutaneous injection site, but absorption was almost exclusively via the lymph. The retention of D-MTX(OH) by sentinel lymph nodes was also significantly elevated (approximately 30% dose/g). MTX alone was not absorbed into the lymph. All dendrimers displayed lower lymph node targeting after intravenous administration. Despite significant differences in the lymph node retention of D-MTX(OH) and D-MTX(OtBu) after subcutaneous and intravenous administration, the growth of lymph node metastases was similarly inhibited. In contrast, the administration of MTX alone did not significantly reduce lymph node tumour growth. Subcutaneous administration of drug-conjugated dendrimers therefore provides an opportunity to improve drug deposition in downstream tumour-burdened lymph nodes. In this case, however, increased lymph node biodistribution did not correlate well with antitumour activity, possibly suggesting constrained drug release at the site of action.