187 research outputs found

    Pilbara steer growth evaluation : 1994 - 1996

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    Growth potential of steers in the Pilbara - a summary. The trial was conducted over a range of conditions on three locations. The pasture type at Wyloo, the Ashburton River frontage, which is regarded as one of the most productive pasture types in the area, combined with conservative stocking, a fresh paddock and excellent seasonal conditions during 1995, gives us an indication of the District\u27s potential. In extrapolating any of these data to other cases, consideration must be given to adjustment bas

    The Rostral Migratory Stream Plays a Key Role in Intranasal Delivery of Drugs into the CNS

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    Background: The blood brain barrier (BBB) is impermeable to most drugs, impeding the establishment of novel neuroprotective therapies and strategies for many neurological diseases. Intranasal administration offers an alternative path for efficient drug delivery into the CNS. So far, the anatomical structures discussed to be involved in the transport of intranasally administered drugs into the CNS include the trigeminal nerve, olfactory nerve and the rostral migratory stream (RMS), but the relative contributions are debated. Methods and Findings: In the present study we demonstrate that surgical transection, and the resulting structural disruption of the RMS, in mice effectively obstructs the uptake of intranasally administered radioligands into the CNS. Furthermore, using a fluorescent cell tracer, we demonstrate that intranasal administration in mice allows agents to be distributed throughout the entire brain, including olfactory bulb, hippocampus, cortex and cerebellum. Conclusions: This study provides evidence of the vital role the RMS has in the CNS delivery of intranasally administered agents. The identification of the RMS as the major access path for intranasally administered drugs into the CNS may contribute to the development of treatments that are tailored for efficient transport within this structure. Research into the RMS needs to continue to elucidate its limitations, capabilities, mechanisms of transport and potential hazards before w

    Knowledge acquisition for the internationalization of the smaller firm: content and sources

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    Internationalization process research emphasizes accumulated experience and networks as sources of knowledge for internationalization. Our understanding, however, as to what this knowledge is in practice for smaller firms, the challenges they face in acquiring it, and how they address those challenges is limited. Integrating organizational learning concepts with our theoretical understanding of the small firm internationalization process, we develop a new framework for understanding knowledge acquisition processes, which are examined with a case study of 10 Scottish internationalizing firms. We find smaller firms may not have relevant experience or useful networks, and rely on sources rarely recognised before. Firms used recruitment, government advisors and consultants to acquire indirect experience. Recruitment is a source of market and technological knowledge and government advisors and consultants a source of internationalization knowledge. Accessing internal information is important for firms that have internationalized. Our integrated theoretical framework identifies knowledge content and sources that are critical for internationalization, but that may be absent

    Development of a synthetic phantom for the selection of optimal scanning parameters in CAD-CT colonography

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    The aim of this paper is to present the development of a synthetic phantom that can be used for the selection of optimal scanning parameters in computed tomography (CT) colonography. In this paper we attempt to evaluate the influence of the main scanning parameters including slice thickness, reconstruction interval, field of view, table speed and radiation dose on the overall performance of a computer aided detection (CAD)–CTC system. From these parameters the radiation dose received a special attention, as the major problem associated with CTC is the patient exposure to significant levels of ionising radiation. To examine the influence of the scanning parameters we performed 51 CT scans where the spread of scanning parameters was divided into seven different protocols. A large number of experimental tests were performed and the results analysed. The results show that automatic polyp detection is feasible even in cases when the CAD–CTC system was applied to low dose CT data acquired with the following protocol: 13 mAs/rotation with collimation of 1.5 mm × 16 mm, slice thickness of 3.0 mm, reconstruction interval of 1.5 mm, table speed of 30 mm per rotation. The CT phantom data acquired using this protocol was analysed by an automated CAD–CTC system and the experimental results indicate that our system identified all clinically significant polyps (i.e. larger than 5 mm)

    Deletion of the Candida albicans TLO gene family using CRISPR-Cas9 mutagenesis allows characterisation of functional differences in α-, β- and γ- TLO gene function

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    The Candida albicans genome contains between ten and fifteen distinct TLO genes that all encode a Med2 subunit of Mediator. In order to investigate the biological role of Med2/Tlo in C. albicans we deleted all fourteen TLO genes using CRISPR-Cas9 mutagenesis. ChIP-seq analysis showed that RNAP II localized to 55% fewer genes in the tloΔ mutant strain compared to the parent, while RNA-seq analysis showed that the tloΔ mutant exhibited differential expression of genes required for carbohydrate metabolism, stress responses, white-opaque switching and filamentous growth. Consequently, the tloΔ mutant grows poorly in glucose- and galactose-containing media, is unable to grow as true hyphae, is more sensitive to oxidative stress and is less virulent in the wax worm infection model. Reintegration of genes representative of the α-, β- and γ-TLO clades resulted in the complementation of the mutant phenotypes, but to different degrees. TLOα1 could restore phenotypes and gene expression patterns similar to wild-type and was the strongest activator of glycolytic and Tye7-regulated gene expression. In contrast, the two γ-TLO genes examined (i.e., TLOγ5 and TLOγ11) had a far lower impact on complementing phenotypic and transcriptomic changes. Uniquely, expression of TLOβ2 in the tloΔ mutant stimulated filamentous growth in YEPD medium and this phenotype was enhanced when Tloβ2 expression was increased to levels far in excess of Med3. In contrast, expression of reintegrated TLO genes in a tloΔ/med3Δ double mutant background failed to restore any of the phenotypes tested, suggesting that complementation of these Tlo-regulated processes requires a functional Mediator tail module. Together, these data confirm the importance of Med2/Tlo in a wide range of C. albicans cellular activities and demonstrate functional diversity within the gene family which may contribute to the success of this yeast as a coloniser and pathogen of humans

    The Solar Particle Acceleration Radiation and Kinetics (SPARK) Mission Concept

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    © 2023by the authors. Licensee MDPI, Basel, Switzerland. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Particle acceleration is a fundamental process arising in many astrophysical objects, including active galactic nuclei, black holes, neutron stars, gamma-ray bursts, accretion disks, solar and stellar coronae, and planetary magnetospheres. Its ubiquity means energetic particles permeate the Universe and influence the conditions for the emergence and continuation of life. In our solar system, the Sun is the most energetic particle accelerator, and its proximity makes it a unique laboratory in which to explore astrophysical particle acceleration. However, despite its importance, the physics underlying solar particle acceleration remain poorly understood. The SPARK mission will reveal new discoveries about particle acceleration through a uniquely powerful and complete combination of γ-ray, X-ray, and EUV imaging and spectroscopy at high spectral, spatial, and temporal resolutions. SPARK’s instruments will provide a step change in observational capability, enabling fundamental breakthroughs in our understanding of solar particle acceleration and the phenomena associated with it, such as the evolution of solar eruptive events. By providing essential diagnostics of the processes that drive the onset and evolution of solar flares and coronal mass ejections, SPARK will elucidate the underlying physics of space weather events that can damage satellites and power grids, disrupt telecommunications and GPS navigation, and endanger astronauts in space. The prediction of such events and the mitigation of their potential impacts are crucial in protecting our terrestrial and space-based infrastructure.Peer reviewe

    Beliefs About Medication and Uptake of Preventive Therapy in Women at Increased Risk of Breast Cancer: Results From a Multicenter Prospective Study

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    Introduction Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy. Patients and Methods Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis. Results Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036). Conclusion Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making

    Level of agreement between frequently used cardiovascular risk calculators in people living with HIV

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    Objectives The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). Methods PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into ‘low’ ( 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland–Altman plots. Results The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49–59] years. The median calculated 10‐year CVD risk was 11.9% (IQR 6.8–18.4%), 8.9% (IQR 4.6–15.0%), 8.5% (IQR 4.8–14.6%) and 6.9% (IQR 4.1–11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50–0.60 range. Conclusions Estimates of predicted 10‐year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone
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