Town or country: which is best for Australia's Indigenous peoples?

The document attached has been archived with permission from the editor of the Medical Journal of Australia. An external link to the publisher’s copy is included.Some commentators suggest that the poor health of Australia's Indigenous population is due to misguided ideology-driven policy that has forced people to live in remote communities, preventing them from benefiting from the mainstream economy. The evidence shows that the poor health status of Indigenous people is found in all areas where they live and that, on some indicators, living in remote areas has health benefits. Government policies aimed at relocating Indigenous people from their traditional lands are not supported by evidence, and may further entrench Indigenous disadvantage

MCL-1 antagonism enhances the anti-invasive effects of dasatinib in pancreatic adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies. It is phenotypically heterogeneous with a highly unstable genome and provides few common therapeutic targets. We found that MCL1, Cofilin1 (CFL1) and SRC mRNA were highly expressed by a wide range of these cancers, suggesting that a strategy of dual MCL-1 and SRC inhibition might be efficacious for many patients. Immunohistochemistry revealed that MCL-1 protein was present at high levels in 94.7% of patients in a cohort of PDACs from Australian Pancreatic Genome Initiative (APGI). High MCL1 and Cofilin1 mRNA expression was also strongly predictive of poor outcome in the TCGA dataset and in the APGI cohort. In culture, MCL-1 antagonism reduced the level of the cytoskeletal remodeling protein Cofilin1 and phosphorylated SRC on the active Y416 residue, suggestive of reduced invasive capacity. The MCL-1 antagonist S63845 synergized with the SRC kinase inhibitor dasatinib to reduce cell viability and invasiveness through 3D-organotypic matrices. In preclinical murine models, this combination reduced primary tumor growth and liver metastasis of pancreatic cancer xenografts. These data suggest that MCL-1 antagonism, while reducing cell viability, may have an additional benefit in increasing the antimetastatic efficacy of dasatinib for the treatment of PDAC

Stellar Coronal and Wind Models: Impact on Exoplanets

Surface magnetism is believed to be the main driver of coronal heating and stellar wind acceleration. Coronae are believed to be formed by plasma confined in closed magnetic coronal loops of the stars, with winds mainly originating in open magnetic field line regions. In this Chapter, we review some basic properties of stellar coronae and winds and present some existing models. In the last part of this Chapter, we discuss the effects of coronal winds on exoplanets.Comment: Chapter published in the "Handbook of Exoplanets", Editors in Chief: Juan Antonio Belmonte and Hans Deeg, Section Editor: Nuccio Lanza. Springer Reference Work

Cyclic Tetrapyrrolic Photosensitisers from the leaves of Phaeanthus ophthalmicus

<p>Abstract</p> <p>Background</p> <p>Twenty-seven extracts from 26 plants were identified as photo-cytotoxic in the course of our bioassay guided screening program for photosensitisers from 128 extracts prepared from 64 terrestrial plants in two different collection sites in Malaysia - Royal Belum Forest Reserve in the State of Perak and Gunung Nuang in the State of Selangor. One of the photo-cytotoxic extracts from the leaves of <it>Phaeanthus ophtalmicus </it>was further investigated.</p> <p>Results</p> <p>The ethanolic extract of the leaves from <it>Phaeanthus ophtalmicus </it>was able to reduce the <it>in vitro </it>viability of leukaemic HL60 cells to < 50% when exposed to 9.6 J/cm²of a broad spectrum light at a concentration of 20 μg/mL. Dereplication of the photo-cytotoxic fractions from <it>P. ophthalmicus </it>extracts based on TLC R_fvalues and HPLC co-injection of reference tetrapyrrolic compounds enabled quick identification of known photosensitisers, pheophorbide-<it>a</it>, pheophorbide-<it>a </it>methyl ester, 13²-hydroxypheophorbide-<it>a </it>methyl ester, pheophytin-<it>a </it>and 15¹-hydroxypurpurin 7-lactone dimethyl ester. In addition, compound <b>1 </b>which was not previously isolated as a natural product was also identified as 7-formyl-15¹-hydroxypurpurin-7-lactone methyl ester using standard spectroscopic techniques.</p> <p>Conclusions</p> <p>Our results suggest that the main photosensitisers in plants are based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in very minor amounts or are not as active as those with the cyclic tetrapyrrole structure.</p

Acceptance and commitment therapy for fatigue interference in advanced gastrointestinal cancer and caregiver burden: protocol of a pilot randomized controlled trial

Background: Fatigue interference with activities, mood, and cognition is one of the most prevalent and bothersome concerns of advanced gastrointestinal (GI) cancer patients. As fatigue interferes with patient functioning, family caregivers often report feeling burdened by increasing responsibilities. Evidence-based interventions jointly addressing cancer patient fatigue interference and caregiver burden are lacking. In pilot studies, acceptance and commitment therapy (ACT) has shown promise for addressing symptom-related suffering in cancer patients. The current pilot trial seeks to test a novel, dyadic ACT intervention for both advanced GI cancer patients with moderate-to-severe fatigue interference and their family caregivers with significant caregiving burden or distress. Methods: A minimum of 40 patient-caregiver dyads will be randomly assigned to either the ACT intervention or an education/support control condition. Dyads in both conditions attend six weekly 50-min telephone sessions. Outcomes are assessed at baseline as well as 2 weeks and 3 months post-intervention. We will evaluate the feasibility, acceptability, and preliminary efficacy of ACT for improving patient fatigue interference and caregiver burden. Secondary outcomes include patient sleep interference and patient and caregiver engagement in daily activities, psychological flexibility, and quality of life. We will also explore the effects of ACT on patient and caregiver physical and mental health service use. Discussion: Findings will inform a large-scale trial of intervention efficacy. Results will also lay the groundwork for further novel applications of ACT to symptom interference with functioning and caregiver burden in advanced cancer

Larvicidal, antimicrobial and brine shrimp activities of extracts from Cissampelos mucronata and Tephrosia villosa from coast region, Tanzania

<p>Abstract</p> <p>Background</p> <p>The leaves and roots of <it>Cissampelos mucronata </it>A. Rich (Menispermaceae) are widely used in the tropics and subtropics to manage various ailments such as gastro-intestinal complaints, menstrual problems, venereal diseases and malaria. In the Coast region, Tanzania, roots are used to treat wounds due to extraction of jigger. Leaves of <it>Tephrosia villosa </it>(L) Pers (Leguminosae) are reported to be used in the treatment of diabetes mellitus in India. In this study, extracts from the roots and aerial parts of <it>C. mucronata </it>and extracts from leaves, fruits, twigs and roots of <it>T. villosa </it>were evaluated for larvicidal activity, brine shrimps toxicity and antimicrobial activity.</p> <p>Methods</p> <p>Powdered materials from <it>C. mucronata </it>were extracted sequentially by dichloromethane followed by ethanol while materials from <it>T.villosa </it>were extracted by ethanol only. The extracts obtained were evaluated for larvicidal activity using <it>Culex quinquefasciatus </it>Say larvae, cytotoxicity using brine shrimp larvae and antimicrobial activity using bacteria and fungi.</p> <p>Results</p> <p>Extracts from aerial parts of <it>C. Mucronata </it>exhibited antibacterial activity against <it>Staphylococcus aureus</it>, <it>Escherichia coli</it>, <it>Pseudomonas aeruginosa</it>, <it>Salmonella typhi</it>, <it>Vibrio cholera</it>, <it>Bacillus anthracis</it>, <it>Streptococcus faecalis </it>and antifungal activity against <it>Candida albicans </it>and <it>Cryptococcus neoformans</it>. They exhibited very low toxicity to brine shrimps and had no larvicidal activity. The root extracts exhibited good larvicidal activity but weak antimicrobial activity. The root dichloromethane extracts from <it>C. mucronata </it>was found to be more toxic with an LC₅₀value of 59.608 μg/mL while ethanolic extracts from root were not toxic with LC₅₀>100 μg/mL). Ethanol extracts from fruits and roots of <it>T. villosa </it>were found to be very toxic with LC₅₀values of 9.690 μg/mL and 4.511 μg/mL, respectively, while, ethanol extracts from leaves and twigs of <it>T. villosa </it>were found to be non toxic (LC₅₀>100 μg/mL).</p> <p>Conclusion</p> <p>These results support the use of <it>C. mucronata </it>in traditional medicine for treatment of wounds. Extracts of <it>C. mucronata </it>have potential to yield active antimicrobial and larvicidal compounds. The high brine shrimp toxicity of <it>T. villosa </it>corroborates with literature reports that the plant is toxic to both livestock and fish. The results further suggest that <it>T. villosa </it>extracts have potential to yield larvicidal and possibly cytotoxic compounds. Further studies to investigate the bioactive compounds responsible for the observed biological effects are suggested.</p

Limits on WWZ and WW\gamma couplings from p\bar{p}\to e\nu jj X events at \sqrt{s} = 1.8 TeV

We present limits on anomalous WWZ and WW-gamma couplings from a search for WW and WZ production in p-bar p collisions at sqrt(s)=1.8 TeV. We use p-bar p -> e-nu jjX events recorded with the D0 detector at the Fermilab Tevatron Collider during the 1992-1995 run. The data sample corresponds to an integrated luminosity of 96.0+-5.1 pb^(-1). Assuming identical WWZ and WW-gamma coupling parameters, the 95% CL limits on the CP-conserving couplings are -0.33<lambda<0.36 (Delta-kappa=0) and -0.43<Delta-kappa<0.59 (lambda=0), for a form factor scale Lambda = 2.0 TeV. Limits based on other assumptions are also presented.Comment: 11 pages, 2 figures, 2 table

Search for New Physics in e mu X Data at D0 Using Sleuth: A Quasi-Model-Independent Search Strategy for New Physics

We present a quasi-model-independent search for the physics responsible for electroweak symmetry breaking. We define final states to be studied, and construct a rule that identifies a set of relevant variables for any particular final state. A new algorithm ("Sleuth") searches for regions of excess in those variables and quantifies the significance of any detected excess. After demonstrating the sensitivity of the method, we apply it to the semi-inclusive channel e mu X collected in 108 pb^-1 of ppbar collisions at sqrt(s) = 1.8 TeV at the D0 experiment during 1992-1996 at the Fermilab Tevatron. We find no evidence of new high p_T physics in this sample.Comment: 23 pages, 12 figures. Submitted to Physical Review

Search For Heavy Pointlike Dirac Monopoles

We have searched for central production of a pair of photons with high transverse energies in $p\bar p$ collisions at $\sqrt{s} = 1.8$ TeV using $70 pb^{-1}$ of data collected with the D\O detector at the Fermilab Tevatron in 1994--1996. If they exist, virtual heavy pointlike Dirac monopoles could rescatter pairs of nearly real photons into this final state via a box diagram. We observe no excess of events above background, and set lower 95% C.L. limits of $610, 870, or 1580 GeV/c^2$ on the mass of a spin 0, 1/2, or 1 Dirac monopole.Comment: 12 pages, 4 figure