369 research outputs found

    Generation of Sub-nanosecond H Atom Pulses for Scattering from Single-Crystal Epitaxial Graphene

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    Pulsed molecular beams allow high-density gas samples to be cooled to low internal temperatures and to produce narrow speed distributions. They are particularly useful in combination with pulsed-laser-based detection schemes and have also been used as pump pulses in pump–probe experiments with neutral matter. The mechanical response of pulsed valves and chopper wheels limits the duration of these pulses typically to about 10–100 μs. Bunch compression photolysis has been proposed as a means to produce atomic pulses shorter than 1 ns─an experimental capability that would allow new measurements to be made on chemical systems. This technique employs a spatially chirped femtosecond duration photolysis pulse that produced an ensemble of H atom photoproducts that rebunches into a short pulse downstream. To date, this technique could not produce strong enough beams to allow new experiments to be carried out. In this paper, we report production of pulsed H atom beams consistent with a 700 ps pulse duration and with sufficient intensity to carry out differentially resolved inelastic H scattering experiments from a graphene surface. We observe surprisingly narrow angular distributions for H atoms incident normal to the surface. At low incidence energies quasi-elastic scattering dominates, and at high incidence energy we observe a strongly inelastic scattering channel. These results provide the basis for future experiments where the H atoms synchronously collide with a pulsed-laser-excited surface

    Identification of Australian Aboriginal and Torres Strait Islander Cancer Patients in the Primary Health Care Setting.

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    BACKGROUND: Aboriginal and Torres Strait Islander Australians have poorer cancer outcomes and experience 30% higher mortality rates compared to non-Indigenous Australians. Primary health care (PHC) services are increasingly being recognized as pivotal in improving Indigenous cancer patient outcomes. It is currently unknown whether patient information systems and practices in PHC settings accurately record Indigenous and cancer status. Being able to identify Indigenous cancer patients accessing services in PHC settings is the first step in improving outcomes. METHODS: Aboriginal Medical Centres, mainstream (non-Indigenous specific), and government-operated centers in Queensland were contacted and data were collected by telephone during the period from 2014 to 2016. Participants were asked to (i) identify the number of patients diagnosed with cancer attending the service in the previous year; (ii) identify the Indigenous status of these patients and if this information was available; and (iii) advise how this information was obtained. RESULTS: Ten primary health care centers (PHCCs) across Queensland participated in this study. Four centers were located in regional areas, three in remote areas and three in major cities. All participating centers reported ability to identify Indigenous cancer patients attending their service and utilizing electronic Patient Care Information Systems (PCIS) to manage their records; however, not all centers were able to identify Indigenous cancer patients in this way. Indigenous cancer patients were identified by PHCCs using PCIS (n = 8), searching paper records (n = 1), and combination of PCIS and staff recall (n = 1). Six different types of PCIS were being utilized by participating centers. There was no standardized way to identify Indigenous cancer patients across centers. Health service information systems, search functions and capacities of systems, and staff skill in extracting data using PCIS varied between centers. CONCLUSION: It is crucial to be able to easily identify Indigenous cancer patients accessing health services in the PHC setting to monitor progress, improve and evaluate care, and ultimately improve Indigenous cancer outcomes. It is also important for PHC staff to receive adequate training and support to utilize PCISs efficiently and effectively

    Results of a randomized, double-blind phase II clinical trial of NY-ESO-1 vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in participants with high-risk resected melanoma.

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    BACKGROUND: To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence. METHODS: Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity. RESULTS: The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants. CONCLUSIONS: The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse

    Agent-based model of angiogenesis simulates capillary sprout initiation in multicellular networks

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    We developed an agent-based model of endothelial sprout initiations based on time-lapse confocal imaging in vitro that outperforms Monte Carlo simulations, suggesting that sprout location and frequency are not purely stochastic behaviors

    The closest elastic tensor of arbitrary symmetry to an elasticity tensor of lower symmetry

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    The closest tensors of higher symmetry classes are derived in explicit form for a given elasticity tensor of arbitrary symmetry. The mathematical problem is to minimize the elastic length or distance between the given tensor and the closest elasticity tensor of the specified symmetry. Solutions are presented for three distance functions, with particular attention to the Riemannian and log-Euclidean distances. These yield solutions that are invariant under inversion, i.e., the same whether elastic stiffness or compliance are considered. The Frobenius distance function, which corresponds to common notions of Euclidean length, is not invariant although it is simple to apply using projection operators. A complete description of the Euclidean projection method is presented. The three metrics are considered at a level of detail far greater than heretofore, as we develop the general framework to best fit a given set of moduli onto higher elastic symmetries. The procedures for finding the closest elasticity tensor are illustrated by application to a set of 21 moduli with no underlying symmetry.Comment: 48 pages, 1 figur

    Fungal plant pathogen “mutagenomics” reveals tagged and untagged mutations in Zymoseptoria tritici and identifies SSK2 as key morphogenesis and stress-responsive virulence factor

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    “Mutagenomics” is the combination of random mutagenesis, phenotypic screening, and whole-genome re-sequencing to uncover all tagged and untagged mutations linked with phenotypic changes in an organism. In this study, we performed a mutagenomics screen on the wheat pathogenic fungus Zymoseptoria tritici for altered morphogenetic switching and stress sensitivity phenotypes using Agrobacterium-mediated “random” T-DNA mutagenesis (ATMT). Biological screening identified four mutants which were strongly reduced in virulence on wheat. Whole genome re-sequencing defined the positions of the T-DNA insertion events and revealed several unlinked mutations potentially affecting gene functions. Remarkably, two independent reduced virulence mutant strains, with similarly altered stress sensitivities and aberrant hyphal growth phenotypes, were found to have a distinct loss of function mutations in the ZtSSK2 MAPKKK gene. One mutant strain had a direct T-DNA insertion affecting the predicted protein’s N-terminus, while the other possessed an unlinked frameshift mutation towards the C-terminus. We used genetic complementation to restore both strains’ wild-type (WT) function (virulence, morphogenesis, and stress response). We demonstrated that ZtSSK2 has a non-redundant function with ZtSTE11 in virulence through the biochemical activation of the stress-activated HOG1 MAPK pathway. Moreover, we present data suggesting that SSK2 has a unique role in activating this pathway in response to specific stresses. Finally, dual RNAseq-based transcriptome profiling of WT and SSK2 mutant strains revealed many HOG1-dependent transcriptional changes in the fungus during early infection and suggested that the host response does not discriminate between WT and mutant strains during this early phase. Together these data define new genes implicated in the virulence of the pathogen and emphasise the importance of a whole genome sequencing step in mutagenomic discovery pipelines

    Maternal Alcohol Consumption During Pregnancy and Physical Outcomes up to 5 Years of Age: A Longitudinal Study

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    Aim To examine whether alcohol exposure in pregnancy affects weight and head circumference (HC) at birth and 5 years, and whether these effects are independent of cigarette exposure in pregnancy and social disadvantage. Study design The Mater-University Study of Pregnancy (MUSP) involves a prospective cohort of 8556 mothers who were enrolled at first antenatal visit. The quantity and frequency of alcohol consumption in early and late pregnancy and a measure of binge drinking in early pregnancy were recorded. Weight and HC were measured on children seen at birth and at 5 years. Level of cigarette use in early pregnancy and maternal age and level of education and family income were also measured. Results Light and moderate alcohol consumption in early or later pregnancy had no independent effects on weight or HC at birth or 5 years. Binge drinking in early pregnancy was not associated with restricted HC, and there was no effect modification by concurrent cigarette use in early pregnancy. An apparent effect of alcohol in late pregnancy on birth weight was due to confounding by cigarette use, with social risk being an independent predictor. Conclusion Alcohol ingestion up to moderate levels in pregnancy was not associated with deficits in either weight or HC at birth or at 5 years

    Multi-omic features of oesophageal adenocarcinoma in patients treated with preoperative neoadjuvant therapy

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    Oesophageal adenocarcinoma is a poor prognosis cancer and the molecular features underpinning response to treatment remain unclear. We investigate whole genome, transcriptomic and methylation data from 115 oesophageal adenocarcinoma patients mostly from the DOCTOR phase II clinical trial (Australian New Zealand Clinical Trials Registry-ACTRN12609000665235), with exploratory analysis pre-specified in the study protocol of the trial. We report genomic features associated with poorer overall survival, such as the APOBEC mutational and RS3-like rearrangement signatures. We also show that positron emission tomography non-responders have more sub-clonal genomic copy number alterations. Transcriptomic analysis categorises patients into four immune clusters correlated with survival. The immune suppressed cluster is associated with worse survival, enriched with myeloid-derived cells, and an epithelial-mesenchymal transition signature. The immune hot cluster is associated with better survival, enriched with lymphocytes, myeloid-derived cells, and an immune signature including CCL5, CD8A, and NKG7. The immune clusters highlight patients who may respond to immunotherapy and thus may guide future clinical trials.Marjan M. Naeini, Felicity Newell, LaurenG. Aoude, Vanessa F. Bonazzi, Kalpana Patel, Guy Lampe, Lambros T. Koufariotis, Vanessa Lakis, Venkateswar Addala, Olga Kondrashova, Rebecca L. Johnston, Sowmya Sharma, Sandra Brosda, Oliver Holmes, Conrad Leonard, Scott Wood, Qinying Xu, Janine Thomas, Euan Walpole, G. Tao Mai, Stephen P. Ackland, Jarad Martin, Matthew Burge, Robert Finch, Christos S. Karapetis, Jenny Shannon, Louise Nott, Robert Bohmer, Kate Wilson, Elizabeth Barnes, John R. Zalcberg, B. Mark Smithers, John Simes, Timothy Price, Val Gebski, Katia Nones, David I. Watson, John V. Pearson, Andrew P. Barbour, Nicola Waddel
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