1,659 research outputs found

    Uncertainty quantification in non-rigid image registration via stochastic gradient Markov chain Monte Carlo

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    We develop a new Bayesian model for non-rigid registration of three-dimensional medical images, with a focus on uncertainty quantification. Probabilistic registration of large images with calibrated uncertainty estimates is difficult for both computational and modelling reasons. To address the computational issues, we explore connections between the Markov chain Monte Carlo by backpropagation and the variational inference by backpropagation frameworks, in order to efficiently draw samples from the posterior distribution of transformation parameters. To address the modelling issues, we formulate a Bayesian model for image registration that overcomes the existing barriers when using a dense, high-dimensional, and diffeomorphic transformation parametrisation. This results in improved calibration of uncertainty estimates. We compare the model in terms of both image registration accuracy and uncertainty quantification to VoxelMorph, a state-of-the-art image registration model based on deep learning

    Ancestral and derived attributes of the dlx gene repertoire, cluster structure and expression patterns in an African cichlid fish

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    <p>Abstract</p> <p>Background</p> <p>Cichlid fishes have undergone rapid, expansive evolutionary radiations that are manifested in the diversification of their trophic morphologies, tooth patterning and coloration. Understanding the molecular mechanisms that underlie the cichlids' unique patterns of evolution requires a thorough examination of genes that pattern the neural crest, from which these diverse phenotypes are derived. Among those genes, the homeobox-containing <it>Dlx </it>gene family is of particular interest since it is involved in the patterning of the brain, jaws and teeth.</p> <p>Results</p> <p>In this study, we characterized the <it>dlx </it>genes of an African cichlid fish, <it>Astatotilapia burtoni</it>, to provide a baseline to later allow cross-species comparison within Cichlidae. We identified seven <it>dlx </it>paralogs (<it>dlx1a</it>, <it>-2a</it>, <it>-4a</it>, <it>-3b</it>, <it>-4b</it>, <it>-5a </it>and <it>-6a</it>), whose orthologies were validated with molecular phylogenetic trees. The intergenic regions of three <it>dlx </it>gene clusters (<it>dlx1a-2a</it>, <it>dlx3b-4b</it>, and <it>dlx5a-6a</it>) were amplified with long PCR. Intensive cross-species comparison revealed a number of conserved non-coding elements (CNEs) that are shared with other percomorph fishes. This analysis highlighted additional lineage-specific gains/losses of CNEs in different teleost fish lineages and a novel CNE that had previously not been identified. Our gene expression analyses revealed overlapping but distinct expression of <it>dlx </it>orthologs in the developing brain and pharyngeal arches. Notably, four of the seven <it>A. burtoni dlx </it>genes, <it>dlx2a</it>, <it>dlx3b</it>, <it>dlx4a </it>and <it>dlx5a</it>, were expressed in the developing pharyngeal teeth.</p> <p>Conclusion</p> <p>This comparative study of the <it>dlx </it>genes of <it>A. burtoni </it>has deepened our knowledge of the diversity of the <it>Dlx </it>gene family, in terms of gene repertoire, expression patterns and non-coding elements. We have identified possible cichlid lineage-specific changes, including losses of a subset of <it>dlx </it>expression domains in the pharyngeal teeth, which will be the targets of future functional studies.</p

    Seeing is believing: the nocturnal malarial mosquito Anopheles coluzzii responds to visual host-cues when odour indicates a host is nearby

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    Background: The immediate aim of our study was to analyse the behaviour of the malarial mosquito Anopheles coluzzii (An. gambiae species complex) near a human host with the ultimate aim of contributing to our fundamental understanding of mosquito host-seeking behaviour and the overall aim of identifying behaviours that could be exploited to enhance sampling and control strategies. Results: Based on 3D video recordings of individual host-seeking females in a laboratory wind-tunnel, we found that despite being a nocturnal species, An. coluzzii is highly responsive to a visually conspicuous object, but only in the presence of host-odour. Female mosquitoes approached and abruptly veered away from a dark object, which suggests attraction to visual cues plays a role in bringing mosquitoes to the source of host odour. It is worth noting that the majority of our recorded flight tracks consisted of highly stereotyped ‘dipping’ sequences near the ground, which have been mentioned in the literature, but never before quantified. Conclusions: Our quantitative analysis of female mosquito flight patterns within ~1.5 m of a host has revealed highly relevant information about responsiveness to visual objects and flight height that could revolutionise the efficacy of sampling traps; the capturing device of a trap should be visually conspicuous and positioned near the ground where the density of host-seeking mosquitoes would be greatest. These characteristics are not universally present in current traps for malarial mosquitoes. The characterisation of a new type of flight pattern that is prevalent in mosquitoes suggests that there is still much that is not fully understood about mosquito flight behaviour

    Profile of visual impairment in older adult patients attending primary eye care optometry clinic : a retrospective study

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    With an aging population, prevalence of visual impairment (VI) is expected to increase as well. A retrospective study was conducted involving the files of older adult patients aged 60 years and above from the Primary Eye Care (PEC) Optometry Clinic Universiti Kebangsaan Malaysia (UKM). This study was aimed to determine the prevalence and causes of VI among older adults. This retrospective study was conducted by reviewing files of older adult patients aged 60 years and above who had visited PEC Optometry Clinic UKM from 2009 to 2019. Socio-demographic, health status, status of visual acuity (VA), refractive error, prevalence and causes of VI before and after refractive correction were analysed by using descriptive statistic. Habitual distance VA was measured monocularly using the Snellen chart and recorded in decimal unit. The mean habitual distance VA in the better eye was 0.72+0.31, ranging from 0.41 to 1.03 while the mean VA after subjective refraction in the better eye was 0.88+0.28 which ranging from 0.60 to 1.16. The prevalence of VI based on habitual VA were 16.0%. The main cause of VI based on habitual VA was cataract (53.4%). The refractive status after subjective refraction showed highest percentage of hyperopia (41.9%), followed by emmetropia (32.4%) and myopia (25.7%). The findings of this study emphasise the importance of increased patient education and further expansion of optometric services are required to reduce avoidable blindness

    Fast Gate-Based Readout of Silicon Quantum Dots Using Josephson Parametric Amplification

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    Spins in silicon quantum devices are promising candidates for large-scale quantum computing. Gate-based sensing of spin qubits offers a compact and scalable readout with high fidelity, however, further improvements in sensitivity are required to meet the fidelity thresholds and measurement timescales needed for the implementation of fast feedback in error correction protocols. Here, we combine radio-frequency gate-based sensing at 622 MHz with a Josephson parametric amplifier, that operates in the 500–800 MHz band, to reduce the integration time required to read the state of a silicon double quantum dot formed in a nanowire transistor. Based on our achieved signal-to-noise ratio, we estimate that singlet-triplet single-shot readout with an average fidelity of 99.7% could be performed in 1     μ s , well below the requirements for fault-tolerant readout and 30 times faster than without the Josephson parametric amplifier. Additionally, the Josephson parametric amplifier allows operation at a lower radio-frequency power while maintaining identical signal-to-noise ratio. We determine a noise temperature of 200 mK with a contribution from the Josephson parametric amplifier (25%), cryogenic amplifier (25%) and the resonator (50%), showing routes to further increase the readout speed

    Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

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    Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

    Migraine aura: retracting particle-like waves in weakly susceptible cortex

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    Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]&#x3c;1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]&#x3e;&#x3e;1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

    Response of lymphocyte subsets and cytokines to Shenyang prescription in Sprague-Dawley rats with tongue squamous cell carcinomas induced by 4NQO

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    BACKGROUND: The study was designed to investigate immunocompetence in relation to cancer progression in rat and to assess the effect of the traditional Chinese anti-cancer medicine, "Shenyang" prescription, on immunity. METHODS: 4-Nitroquinoline-1-oxide (4NQO) was administered to 80 Sprague-Dawley (SD) rats via the drinking water for up to 36 weeks. Tongue squamous cell carcinoma (SCC) was confirmed by pathological examination in 61 rats. "Shenyang" prescription was administered to subgroups of these rats, and blood samples were taken before and after treatment. Lymphocyte subsets were determined by flow cytometry. Serum Th1 and Th2-type cytokines were assessed by an enzyme-linked immunosorbent assay. RESULTS: As the cancer progressed at the tongue root, the percentage of CD3+CD4+ T lymphocytes and NK cells and the levels of IFN-γ and IL-2 decreased gradually, while the percentage of CD3+CD8+ T lymphocytes and the levels of IL-4 and IL-10 increased. The CD4+/CD8+ ratios were lower in the cancer groups than in the control group. However, after administering "Shenyang" prescription, the levels of CD3+CD4+ T lymphocytes, NK cells, IFN-γ and IL-2 increased, while the CD3+CD8+ T lymphocyte counts and the levels of IL-4 and IL-10 decreased. CONCLUSION: 4NQO-induced lesions were good models for exploring oral cavity carcinogenesis. The rats with 4NQO-induced SCC demonstrated abnormalities in lymphocyte subsets and a shift from Th1-type to Th2-type, which were good models for assessing the effect of anticancer agent on immunity. Oral cancer progression was associated with an aggressive disturbance of immune function. "Shenyang" prescription has the ability to improve the disturbance of immune function

    Sugar-fermenting yeast as an organic source of carbon dioxide to attract the malaria mosquito Anopheles gambiae s.s.

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    <p>Abstract</p> <p>Background</p> <p>Carbon dioxide (CO<sub>2</sub>) plays an important role in the host-seeking process of opportunistic, zoophilic and anthropophilic mosquito species and is, therefore, commonly added to mosquito sampling tools. The African malaria vector <it>Anopheles gambiae sensu stricto </it>is attracted to human volatiles augmented by CO<sub>2</sub>. This study investigated whether CO<sub>2</sub>, usually supplied from gas cylinders acquired from commercial industry, could be replaced by CO<sub>2 </sub>derived from fermenting yeast (yeast-produced CO<sub>2</sub>).</p> <p>Methods</p> <p>Trapping experiments were conducted in the laboratory, semi-field and field, with <it>An. gambiae s.s</it>. as the target species. MM-X traps were baited with volatiles produced by mixtures of yeast, sugar and water, prepared in 1.5, 5 or 25 L bottles. Catches were compared with traps baited with industrial CO<sub>2</sub>. The additional effect of human odours was also examined. In the laboratory and semi-field facility dual-choice experiments were conducted. The effect of traps baited with yeast-produced CO<sub>2 </sub>on the number of mosquitoes entering an African house was studied in the MalariaSphere. Carbon dioxide baited traps, placed outside human dwellings, were also tested in an African village setting. The laboratory and semi-field data were analysed by a χ<sup>2</sup>-test, the field data by GLM. In addition, CO<sub>2 </sub>concentrations produced by yeast-sugar solutions were measured over time.</p> <p>Results</p> <p>Traps baited with yeast-produced CO<sub>2 </sub>caught significantly more mosquitoes than unbaited traps (up to 34 h post mixing the ingredients) and also significantly more than traps baited with industrial CO<sub>2</sub>, both in the laboratory and semi-field. Adding yeast-produced CO<sub>2 </sub>to traps baited with human odour significantly increased trap catches. In the MalariaSphere, outdoor traps baited with yeast-produced or industrial CO<sub>2 </sub>+ human odour reduced house entry of mosquitoes with a human host sleeping under a bed net indoors. <it>Anopheles gambiae s.s</it>. was not caught during the field trials. However, traps baited with yeast-produced CO<sub>2 </sub>caught similar numbers of <it>Anopheles arabiensis </it>as traps baited with industrial CO<sub>2</sub>. Addition of human odour increased trap catches.</p> <p>Conclusions</p> <p>Yeast-produced CO<sub>2 </sub>can effectively replace industrial CO<sub>2 </sub>for sampling of <it>An. gambiae s.s</it>.. This will significantly reduce costs and allow sustainable mass-application of odour-baited devices for mosquito sampling in remote areas.</p
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