Height Systems and Vertical Datums: a Review in the Australian Context

This paper reviews (without equations) the various definitions of height systems and vertical geodetic datum surfaces, together with their practical realisation for users in Australia. Excluding geopotential numbers, a height system is a one-dimensional coordinate system used to express the metric distance (height) of a point from some reference surface. Its definition varies according to the reference surface chosen and the path along which the height is measured. A vertical geodetic datum is the practical realisation of a height system and its reference surface for users, nominally tied to mean sea level. In Australia, the normal-orthometric height system is used, which is embedded in the Australian Height Datum (AHD). The AHD was realised by the adjustment of ~195,000 km of spirit-levelling observations fixed to limited-term observations of mean sea level at multiple tide-gauges. The paper ends by giving some explanation of the problems with the AHD and of the differences between the AHD and the national geoid model, pointing out that it is preferable to recompute the AHD

Cultured fish cells metabolize octadecapentaenoic acid (all-cis delta3,6,9,12,15–18∶5) to octadecatetraenoic acid (all-cis delta6,9,12,15–18∶4) via its 2-trans intermediate (trans delta2, all-cis delta6,9,12,15–18∶5)

Octadecapentaenoic acid (all-cis Δ3,6,9,12,15-18:5; 18:5n-3) is an unusual fatty acid found in marine dinophytes, haptophytes and prasinophytes. It is not present at higher trophic levels in the marine food web but its metabolism by animals ingesting algae is unknown. Here we studied the metabolism of 18:5n-3 in cell lines derived from turbot (Scophthalmus maximus), gilthead sea bream (Sparus aurata) and Atlantic salmon (Salmo salar). Cells were incubated in the presence of approximately 1 μM [U-14C] 18:5n-3 methyl ester or [U-14C] 18:4n-3 (octadecatetraenoic acid; all-cis Δ6,9,12,15-18:4) methyl ester, both derived from the alga Isochrysis galbana grown in H14CO3, and also with 25 μM unlabelled 18:5n-3 or 18:4n-3. Cells were also incubated with 25 μM trans Δ2, all-cis Δ6,9,12,15-18:5 (2-trans 18:5n-3) produced by alkaline isomerization of 18:5n-3 chemically synthesized from docosahexaenoic acid (all-cis Δ4,7,10,13,16,19-22:6; 22:6n-3). Radio- and mass analyses of total fatty acids extracted from cells incubated with 18:5n-3 were consistent with this fatty acid being rapidly metabolized to 18:4n-3 which was then elongated and further desaturated to eicosatetraenoic acid (all-cis Δ8,11,14,17,19-20:4; 20:4n-3) and eicosapentaenoic acid (all-cis Δ5,8,11,14,17-20:5; 20:5n-3). Similar mass increases of 18:4n-3 and its elongation and further desaturation products occurred in cells incubated with 18:5n-3 or 2-trans 18:5n-3. We conclude that 18:5n-3 is readily converted biochemically to 18:4n-3 via a 2-trans 18:5n-3 intermediate generated by a Δ3,Δ2-enoyl-CoA-isomerase acting on 18:5n-3. Thus, 2-trans 18:5n-3 is implicated as a common intermediate in the β-oxidation of both 18:5n-3 and 18:4n-3

The Public Repository of Xenografts enables discovery and randomized phase II-like trials in mice

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease

Search for the Chiral Magnetic Effect in Au+Au collisions at sNN=27\sqrt{s_{_{\rm{NN}}}}=27 GeV with the STAR forward Event Plane Detectors

A decisive experimental test of the Chiral Magnetic Effect (CME) is considered one of the major scientific goals at the Relativistic Heavy-Ion Collider (RHIC) towards understanding the nontrivial topological fluctuations of the Quantum Chromodynamics vacuum. In heavy-ion collisions, the CME is expected to result in a charge separation phenomenon across the reaction plane, whose strength could be strongly energy dependent. The previous CME searches have been focused on top RHIC energy collisions. In this Letter, we present a low energy search for the CME in Au+Au collisions at $\sqrt{s_{_{\rm{NN}}}}=27$ GeV. We measure elliptic flow scaled charge-dependent correlators relative to the event planes that are defined at both mid-rapidity $|\eta|<1.0$ and at forward rapidity $2.1 < |\eta|<5.1$. We compare the results based on the directed flow plane ($\Psi_1$) at forward rapidity and the elliptic flow plane ($\Psi_2$) at both central and forward rapidity. The CME scenario is expected to result in a larger correlation relative to $\Psi_1$ than to $\Psi_2$, while a flow driven background scenario would lead to a consistent result for both event planes[1,2]. In 10-50\% centrality, results using three different event planes are found to be consistent within experimental uncertainties, suggesting a flow driven background scenario dominating the measurement. We obtain an upper limit on the deviation from a flow driven background scenario at the 95\% confidence level. This work opens up a possible road map towards future CME search with the high statistics data from the RHIC Beam Energy Scan Phase-II.Comment: main: 8 pages, 5 figures; supplementary material: 2 pages, 1 figur

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation