The Automated Delimitation of Maritime Boundaries - An Australian Perspective

Determining the accurate location of maritime boundaries and computing the outer limits of the extended continental shelf can be a mathematically demanding and computationally intensive task. This paper considers the relevant issues, particularly from an Australian perspective. An efficient and automated solution to maritime boundary and extended continental shelf delimitation has been designed and implemented in the form of a software package known as MarZone. This paper introduces the MarZone software. In the design of MarZone, emphasis was placed on a geodetically rigorous methodology while at the same time maintaining strict agreement with the relevant provisions of the United Nations Convention on the Law of the Sea. The reasons for such an emphasis are explained in the paper

Planck-LFI: Design and Performance of the 4 Kelvin Reference Load Unit

The LFI radiometers use a pseudo-correlation design where the signal from the sky is continuously compared with a stable reference signal, provided by a cryogenic reference load system. The reference unit is composed by small pyramidal horns, one for each radiometer, 22 in total, facing small absorbing targets, made of a commercial resin ECCOSORB CR (TM), cooled to approximately 4.5 K. Horns and targets are separated by a small gap to allow thermal decoupling. Target and horn design is optimized for each of the LFI bands, centered at 70, 44 and 30 GHz. Pyramidal horns are either machined inside the radiometer 20K module or connected via external electro-formed bended waveguides. The requirement of high stability of the reference signal imposed a careful design for the radiometric and thermal properties of the loads. Materials used for the manufacturing have been characterized for thermal, RF and mechanical properties. We describe in this paper the design and the performance of the reference system.Comment: This is an author-created, un-copyedited version of an article accepted for publication in JINST. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The definitive publisher authenticated version is available online at [10.1088/1748-0221/4/12/T12006]. 14 pages, 34 figure

Imatinib in combination with phosphoinositol kinase inhibitor buparlisib in patients with gastrointestinal stromal tumour who failed prior therapy with imatinib and sunitinib: a Phase 1b, multicentre study

Background The majority of patients with advanced gastrointestinal stromal tumours (GISTs) develop resistance to imatinib and sunitinib, the standard of care for these patients. This study evaluated the combination of buparlisib, an oral phosphoinositide 3-kinase (PI3K) inhibitor, with imatinib in patients with advanced GIST, who have failed prior therapy with imatinib and sunitinib. Methods This Phase 1b, multicentre, open-label study aimed to determine the maximum tolerated dose (MTD) and/or a recommended Phase 2 dose of buparlisib in combination with 400 mg of imatinib through a dose-escalation part and a dose-expansion part, and also evaluated the clinical profile of the combination. Results Sixty patients were enrolled, including 25 in the dose-escalation part and 35 in the dose-expansion part. In the combination, MTD of buparlisib was established as 80 mg. No partial or complete responses were observed. The estimated median progression-free survival was 3.5 months in the expansion phase. Overall, 98.3% of patients had treatment-related adverse events (AEs), including 45% with grade 3 or 4 AEs. Conclusions Buparlisib in combination with imatinib provided no additional benefit compared with currently available therapies. Due to the lack of objective responses, further development of this combination was not pursued for third-line/fourth-line advanced/metastatic GIST.Experimentele farmacotherapi

Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairments observed in drug addicts may reflect drug-induced neuronal dysfunction and neurotoxicity. The drugs of abuse directly or indirectly affect neurotransmitter systems, particularly dopaminergic and glutamatergic neurons. This review explores the literature reporting cellular and molecular alterations reflecting the cytotoxicity induced by amphetamines, cocaine and opiates in neuronal systems. The neurotoxic effects of drugs of abuse are often associated with oxidative stress, mitochondrial dysfunction, apoptosis and inhibition of neurogenesis, among other mechanisms. Understanding the mechanisms that underlie brain dysfunction observed in drug-addicted individuals may contribute to improve the treatment of drug addiction, which may have social and economic consequences.http://www.sciencedirect.com/science/article/B6SYS-4S50K2J-1/1/7d11c902193bfa3f1f57030572f7034

Planck Early Results. VII. The Early Release Compact Source Catalogue

A brief description of the methodology of construction, contents and usage of the Planck Early Release Compact Source Catalogue (ERCSC), including the Early Cold Cores (ECC) and the Early Sunyaev-Zeldovich (ESZ) cluster catalogue is provided. The catalogue is based on data that consist of mapping the entire sky once and 60% of the sky a second time by Planck, thereby comprising the first high sensitivity radio/submillimetre observations of the entire sky. Four source detection algorithms were run as part of the ERCSC pipeline. A Monte-Carlo algorithm based on the injection and extraction of artificial sources into the Planck maps was implemented to select reliable sources among all extracted candidates such that the cumulative reliability of the catalogue is ≥90%. There is no requirement on completeness for the ERCSC. As a result of the Monte-Carlo assessment of reliability of sources from the different techniques, an implementation of the PowellSnakes source extraction technique was used at the five frequencies between 30 and 143 GHz while the SExtractor technique was used between 217 and 857GHz. The 10σ photometric flux density limit of the catalogue at |b| > 30◦ is 0.49, 1.0, 0.67, 0.5, 0.33, 0.28, 0.25, 0.47 and 0.82 Jy at each of the nine frequencies between 30 and 857 GHz. Sources which are up to a factor of ∼2 fainter than this limit, and which are present in “clean” regions of the Galaxy where the sky background due to emission from the interstellar medium is low, are included in the ERCSC if they meet the high reliability criterion. The Planck ERCSC sources have known associations to stars with dust shells, stellar cores, radio galaxies, blazars, infrared luminous galaxies and Galactic interstellar medium features. A significant fraction of unclassified sources are also present in the catalogs. In addition, two early release catalogs that contain 915 cold molecular cloud core candidates and 189 SZ cluster candidates that have been generated using multifrequency algorithms are presented. The entire source list, with more than 15000 unique sources, is ripe for follow-up characterisation with Herschel, ATCA, VLA, SOFIA, ALMA and other ground-based observing facilities

Comparing Presenting Clinical Features in 48 Children With Microscopic Polyangiitis to 183 Children Who Have Granulomatosis With Polyangiitis (Wegener's) : an ARChiVe Cohort Study

OBJECTIVE: To uniquely classify children with microscopic polyangiitis (MPA), to describe their demographic characteristics, presenting clinical features, and initial treatments in comparison to patients with granulomatosis with polyangiitis (Wegener's) (GPA). METHODS: The European Medicines Agency (EMA) classification algorithm was applied by computation to categorical data from patients recruited to the ARChiVe (A Registry for Childhood Vasculitis: e-entry) cohort, with the data censored to November 2015. The EMA algorithm was used to uniquely distinguish children with MPA from children with GPA, whose diagnoses had been classified according to both adult- and pediatric-specific criteria. Descriptive statistics were used for comparisons. RESULTS: In total, 231 of 440 patients (64% female) fulfilled the classification criteria for either MPA (n\u2009=\u200948) or GPA (n\u2009=\u2009183). The median time to diagnosis was 1.6 months in the MPA group and 2.1 months in the GPA group (ranging to 39 and 73 months, respectively). Patients with MPA were significantly younger than those with GPA (median age 11 years versus 14 years). Constitutional features were equally common between the groups. In patients with MPA compared to those with GPA, pulmonary manifestations were less frequent (44% versus 74%) and less severe (primarily, hemorrhage, requirement for supplemental oxygen, and pulmonary failure). Renal pathologic features were frequently found in both groups (75% of patients with MPA versus 83% of patients with GPA) but tended toward greater severity in those with MPA (primarily, nephrotic-range proteinuria, requirement for dialysis, and end-stage renal disease). Airway/eye involvement was absent among patients with MPA, because these GPA-defining features preclude a diagnosis of MPA within the EMA algorithm. Similar proportions of patients with MPA and those with GPA received combination therapy with corticosteroids plus cyclophosphamide (69% and 78%, respectively) or both drugs in combination with plasmapheresis (19% and 22%, respectively). Other treatments administered, ranging in decreasing frequency from 13% to 3%, were rituximab, methotrexate, azathioprine, and mycophenolate mofetil. CONCLUSION: Younger age at disease onset and, perhaps, both gastrointestinal manifestations and more severe kidney disease seem to characterize the clinical profile in children with MPA compared to those with GPA. Delay in diagnosis suggests that recognition of these systemic vasculitides is suboptimal. Compared with adults, initial treatment regimens in children were comparable, but the complete reversal of female-to-male disease prevalence ratios is a provocative finding