Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan-Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment

Submission to KPMG review of the Federal Government Initiative to “analyse dementia program and services funded by the Department of Social Services"

The comments I make are based on my nearly twenty years involvement in the dementia cause at both a national and international level. In preparation, I read two papers namely the Ministerial Dementia Forum – Option Paper produced by KPMG Management Consultants (2014) and Analysis of Dementia Programmes and Services Funded by the Department of Social Services: Conversation Starter prepared by KPMG as a preparation document for those attending a workshop in Brisbane on April 22nd 2015. Dementia is a complex “syndrome” and as is often said, “when you meet one person with dementia, you have met one” meaning that no two persons with dementia are the same. Even in dementia care, Australia is a “lucky country” and there is much to be said for the quality and diversity of dementia care available for people living with dementia. Despite this, I agree with the many views expressed in the material I read that there is scope for improvement, especially in the way that services are coordinated. In saying that, I do not purport to have all the solutions nor claim to have the knowledge required to comment on all the programs covered by this review. If I appear to be a “biased” advocate for Alzheimer’s Australia across the States and Territories, it is because I have seen constant evidence of ordinary people doing extraordinary things with inadequate resources. Dementia care is not cheap and if those funding dementia services are primarily only interested in economic outcomes and benefits, the real purpose of this consultation will be defeated. In addition, nowhere in the material I have read is there any recognition that in many instances program funding is a complex mix of government (at all levels) and private funding. This makes reviewing those programs more complex and less able to be coordinated at a Departmental level. It goes without saying therefore that the Federal Government is not” the only player in this game”. Of all those participating in this review, Alzheimer’s Australia is best placed to comment on programs as it is more connected to people living with dementia and has probably the best record of consulting with them. It would appear however that their role has been reduced to that of a “bit player”. Without wanting to be critical, the Forum Report which deals with the comments made at a gathering of 70 individuals and organisations, only three (3) or 4.28% were actual carers of people living with dementia. Even if it is argued that a number of organisations present represented consumers, the percentage goes up only marginally to 8.57% which is hardly an endorsement of the forum being “consumer driven”. The predominance of those present were service providers, each with their own agenda and each seeking advantage for their “business”. The final point I want to make before commenting on more specific, program related issues, is that many programs being reviewed have a much longer history than is reflected in the material I have read. Their growth and development was pioneered by Alzheimer’s Australia organisations across the country often with no government funding. Attempts to bring about better coordination of programs were often at the behest of Alzheimer’s Australia but in the main were ignored. The opportunity to now put this right is long overdue.

Groundwater balance research to improve the accuracy of drawdown predictions in the Surat Basin, Queensland

Groundwater modelling studies rely on an accurate determination of inputs and outputs that make up the water balance. Often there is large uncertainty associated with estimates of recharge and unmetered groundwater use. This can translate to equivalent uncertainty in the forecasting of sustainable yields, impacts of extraction, and susceptibility of groundwater dependent ecosystems. In the case of Coal Seam Gas, it is important to characterise the temporal and special distribution of depressurisation in the reservoir and how this may or may not extend to the adjacent aquifers. A regional groundwater flow model has been developed by the Queensland Government to predict drawdown impacts due to Coal Seam Gas activities in the Surat basin. This groundwater model is undergoing continued refinement and there is currently scope to address some of the key areas of uncertainty including better quantification of groundwater recharge and unmetered groundwater extractions. Research is currently underway to improve the accuracy of estimates of both of these components of the groundwater balance in order to reduce uncertainty in predicted groundwater drawdowns due to CSG activities.

Costing the Australian National Hand Hygiene Initiative

Background The Australian National Hand Hygiene Initiative (NHHI) is a major patient safety programme co-ordinated by Hand Hygiene Australia (HHA) and funded by the Australian Commission for Safety and Quality in Health Care. The annual costs of running this programme need to be understood to know the cost-effectiveness of a decision to sustain it as part of health services. Aim To estimate the annual health services cost of running the NHHI; the set-up costs are excluded. Methods A health services perspective was adopted for the costing and collected data from the 50 largest public hospitals in Australia that implemented the initiative, covering all states and territories. The costs of HHA, the costs to the state-level infection-prevention groups, the costs incurred by each acute hospital, and the costs for additional alcohol-based hand rub are all included. Findings The programme cost AU$5.56 million each year (US$5.76, £3.63 million). Most of the cost is incurred at the hospital level (65%) and arose from the extra time taken for auditing hand hygiene compliance and doing education and training. On average, each infection control practitioner spent 5 h per week on the NHHI, and the running cost per annum to their hospital was approximately AU$120,000 in 2012 (US$124,000, £78,000). Conclusion Good estimates of the total costs of this programme are fundamental to understanding the cost-effectiveness of implementing the NHHI. This paper reports transparent costing methods, and the results include their uncertainty.

Geochronological (U–Pb, U–Th–total Pb, Sm–Nd) and geochemical (REE, 87Sr/86Sr, δ18O, δ13C) tracing of intraplate tectonism and associated fluid flow in the Warburton Basin, Australia

The Warburton Basin of central Australia has experienced a complex tectonic and fluid-flow history, resulting in the formation of various authigenic minerals. Geochemical and geochronological analyses were undertaken on vein carbonates from core samples of clastic sediments. Results were then integrated with zircon U–Pb dating and uraninite U–Th–total Pb dating from the underlying granite. Stable and radiogenic isotopes (δ18O, Sr and εNd), as well as trace element data of carbonate veins indicate that >200 °C basinal fluids of evolved meteoric origin circulated through the Warburton Basin. Almost coincidental ages of these carbonates (Sm–Nd; 432 ± 12 Ma) with primary zircon (421 ± 3.8 Ma) and uraninite (407 ± 16 Ma) ages from the granitic intrusion point towards a substantial period of active tectonism and an elevated thermal regime during the mid Silurian. We hypothesise that such a thermal regime may have resulted from extensional tectonism and concomitant magmatic activity following regional orogenesis. This study shows that the combined application of geochemical and geochronological analyses of both primary and secondary species may constrain the timing of tectonomagmatic events and associated fluid flow in intraplate sedimentary basins. Furthermore, this work suggests that the Sm–Nd-isotopic system is surprisingly robust and can record geologically meaningful age data from hydrothermal mineral species.

Multifractal analyses of daily rainfall time series in Pearl River basin of China

The multifractal properties of daily rainfall time series at the stations in Pearl River basin of China over periods of up to 45 years are examined using the universal multifractal approach based on the multiplicative cascade model and the multifractal detrended fluctuation analysis (MF-DFA). The results from these two kinds of multifractal analyses show that the daily rainfall time series in this basin have multifractal behavior in two different time scale ranges. It is found that the empirical multifractal moment function K(q)K(q) of the daily rainfall time series can be fitted very well by the universal multifractal model (UMM). The estimated values of the conservation parameter HH from UMM for these daily rainfall data are close to zero indicating that they correspond to conserved fields. After removing the seasonal trend in the rainfall data, the estimated values of the exponent h(2)h(2) from MF-DFA indicate that the daily rainfall time series in Pearl River basin exhibit no long-term correlations. It is also found that K(2)K(2) and elevation series are negatively correlated. It shows a relationship between topography and rainfall variability.

Evidence-based recommendations for the diagnosis of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

• As part of the 3E program, we conducted a systematic literature review and gathered consensus from 23 practising Australian rheumatologists to develop guidelines for early identification of ankylosing spondylitis and specialist referral. • In three rounds of break-out sessions followed by discussion and voting, the specialist panel addressed three questions related to diagnosis of ankylosing spondylitis: In individuals with back pain, what are the early clinical features that suggest ankylosing spondylitis? How useful is imaging in identifying early ankylosing spondylitis? Based on which clinical features should a general practitioner refer a patient to a rheumatologist for further evaluation? • The panel agreed on six recommendations related to the three questions: 1a. Early clinical features to suggest ankylosing spondylitis include inflammatory back pain and age at symptom onset < 45 years. 1b. The absence of symptomatic response to an appropriate course of non-steroidal anti-inflammatory drugs makes the diagnosis of ankylosing spondylitis less likely. 1c. Raised inflammatory markers are supportive, but their absence does not rule out the diagnosis of ankylosing spondylitis. 2a. Despite low sensitivity to detect changes of early ankylosing spondylitis, plain radiographs of the pelvis and spine are appropriate initial imaging techniques. 2b. Magnetic resonance imaging is a useful imaging modality for detecting early changes of ankylosing spondylitis. 3. Individuals with inflammatory back pain should be referred to a rheumatologist for further evaluation. • Effective dissemination and implementation of these recommendations are important to standardise the approach to early diagnosis of ankylosing spondylitis.

Evidence-based recommendations for the monitoring and treatment of ankylosing spondylitis: Results from the Australian 3E initiative in rheumatology

Aim: To develop a set of Australian recommendations for the monitoring and treatment of ankylosing spondylitis (AS) through systematic literature review combined with the opinion of practicing rheumatologists. Methods: A set of eight questions, four in each domain of monitoring and treatment, were formulated by voting and the Delphi method. The results of a systematic literature review addressing each question were presented to the 23 participants of the Australian 3E meeting. All participants were clinical rheumatologists experienced in the daily management of AS. Results: After three rounds of breakout sessions to discuss the findings of the literature review, a set of recommendations was finalized after discussion and voting. The category of evidence and strength of recommendation were determined for each proposal. The level of agreement among participants was excellent (mean 84%, range 64-100%). Conclusions: The 12 recommendations developed from evidence and expert opinion provide guidance for the daily management of AS patients. For most recommendations, we found a paucity of supportive evidence in the literature highlighting the need for additional clinical studies.

Adolescent sexual behavioral intentions measurement: A gender approach in the Colombian Caribbean region [Medición de la Intención en la Actividad Sexual en Adolescentes: una Aproximación de Acuerdo al Género del Caribe Colombiano]

The study of 1777 male and female adolescent students of 11-19 years in the Colombian Caribbean had two objectives: development and validation of two reproductive health intention scales and analyze gender differences. The pilot of the scale consisted of 8 items and was reduced to 6, to check the reliability and validity using factor analysis and principal components with VARIMAX rotation yielded two factors: Intention and Intention Risk Protection, explained between 69.4% and 70% respectively. In the male Protection Intent (M = 3.87 and SD = 1.29) and risk (M = 2.56 and SD = 1.18) obtained an alpha between 0.74 and 0.86, and in Protection of Intent to female (M = 3.49 and SD = 1.35) and risk (M = 1.50 and SD = 0.89) ranged between 0.78 and 086. In conclusion, the reliability and structural stability are adequate and there are gender differences in the scales.

Role of predictors in downscaling surface temperature to river basin in India for IPCC SRES scenarios using support vector machine

In this paper, downscaling models are developed using a support vector machine (SVM) for obtaining projections of monthly mean maximum and minimum temperatures (T-max and T-min) to river-basin scale. The effectiveness of the model is demonstrated through application to downscale the predictands for the catchment of the Malaprabha reservoir in India, which is considered to be a climatically sensitive region. The probable predictor variables are extracted from (1) the National Centers for Environmental Prediction (NCEP) reanalysis dataset for the period 1978-2000, and (2) the simulations from the third-generation Canadian Coupled Global Climate Model (CGCM3) for emission scenarios A1B, A2, B1 and COMMIT for the period 1978-2100. The predictor variables are classified into three groups, namely A, B and C. Large-scale atmospheric variables Such as air temperature, zonal and meridional wind velocities at 925 nib which are often used for downscaling temperature are considered as predictors in Group A. Surface flux variables such as latent heat (LH), sensible heat, shortwave radiation and longwave radiation fluxes, which control temperature of the Earth's surface are tried as plausible predictors in Group B. Group C comprises of all the predictor variables in both the Groups A and B. The scatter plots and cross-correlations are used for verifying the reliability of the simulation of the predictor variables by the CGCM3 and to Study the predictor-predictand relationships. The impact of trend in predictor variables on downscaled temperature was studied. The predictor, air temperature at 925 mb showed an increasing trend, while the rest of the predictors showed no trend. The performance of the SVM models that are developed, one for each combination of predictor group, predictand, calibration period and location-based stratification (land, land and ocean) of climate variables, was evaluated. In general, the models which use predictor variables pertaining to land surface improved the performance of SVM models for downscaling T-max and T-min

The mycotoxins 4-deoxynivalenol, zearalenone and aflatoxin in weather-damaged wheat harvested 1983-1985 in south-east Queensland

A survey for various mycotoxins was carried out on samples of all wheat delivered to nine storage and marketing depots in south-eastern Queensland, selected as most likely to receive mycotoxin-contaminated grain. All wheat was surveyed during 1983, when the degree of weather damage was high. Samples of the poorest grade of wheat from these depots were also surveyed in 1984 and 1985. The surveys included all regions where head scab of wheat caused by Fusariurn graminearurn Schwabe Group 2 had been reported to occur at significant levels. 4-Deoxynivalenol was detected in nearly all pooled samples representing bulk wheat at concentrations ranging from traces of <0.01 up to 1.7 mg kg-1. The highest concentration of zearlenone detected in a pooled wheat sample was 0.04 mg kg-1. In a few samples representing individual wheat deliveries and with up to 2.8% by weight of pink grains, 4-deoxynivalenol concentrations ranged up to 11.7 mg kg-' and zearalenone up to 0.43 mg kg-l. Aflatoxins B,, B2, G1 and G2 were detected in only one pooled sample of wheat, at a total aflatoxin concentration of 0.003 mg kg-'. Ochratoxin A, sterigmatocystin and T-2 toxin were not detected. Higher concentrations of mycotoxins were found in the poorer grades of wheat.

Predicting wood value in Queensland Caribbean pine plantations using a decision support system

A decision support system has been developed in Queensland to evaluate how changes in silvicultural regimes affect wood quality, and specifically the graded recovery of structural timber. Models of tree growth, branch architecture and wood properties were developed from data collected in routine Caribbean pine plantations and specific silvicultural experiments. These models were incorporated in software that simulates the conversion of standing trees into logs, and the logs into boards, and generates detailed data on knot location and basic density distribution. The structural grade of each board was determined by simulating the machine stress-grading process, and the predicted graded recovery provided an indicator of wood value. The decision support system improves the basis of decision-making by simulating the performance of elite genetic material under specified silvicultural regimes and by predicting links between wood quality and general stand attributes such as stocking and length of rotation.

Helsingin galleriakenttä, kentän muutokset ja positiot vuosina 1983-2009

Tutkielman aiheena on Helsingin taidegalleriat ja niiden muodostama galleriakenttä. Tutkielmassa tarkastellaan galleriakenttää, galleriakentän ja galleriatoiminnan muutoksia sekä gallerioiden asemia ja asemien muutoksia kentän sisällä vuosina 1983–2009. Tutkielman tavoitteena on toimia Helsingin galleriakentän ja sen lähihistorian perustutkimuksena ja galleriakentän sisäisten asemien rakentumisen analyysina. Tutkimuskysymykset ovat seuraavat: Millaisia muutoksia Helsingin taidegalleriakentässä, sen toimijajoukossa ja gallerioiden toiminnassa on tapahtunut 1980-luvun alkupuolelta 2000-luvun ensimmäisen vuosikymmenen loppuun tultaessa? Mitkä ja millaiset galleriat ovat tutkittavan ajanjakson eri vaiheissa muodostaneet keskeisten gallerioiden joukon, mihin tämä asema on perustunut ja miten galleriakentän sisäiset asemat ovat muuttuneet? Galleriakenttää analysoidaan ja tarkastellaan yhdistäen taidehistoriallisen perustutkimuksen menetelmiä taiteensosiologiseen analyysiin. Tutkielman teoreettinen näkökulma perustuu sosiologi Pierre Bourdieun kenttää koskevaan teoriaan. Teorian rooli on toimia työkaluna tutkittavan kentän ja sen toimijoiden asemien havainnoinnissa ja analyysissa. Tutkielman empiirinen aineisto muodostuu tutkielman tekijän laatimien 28 galleristin ja muun galleriakentän toimijan haastattelujen muodostamasta haastatteluaineistosta. Haastatellut edustavat 22 galleriaa. Niiden muodostama joukko koostuu yksityisistä gallerioista, taiteilijaliittojen gallerioista ja vaihtoehtoisiksi tai taiteilijavetoisiksi määriteltävissä olevista tutkitulla ajanjaksolla eri tavoin keskeisinä pidetyistä gallerioista. Haastattelujen ohella tärkeänä aineistona toimii tutkittavan ajanjakson lehtikirjoittelu. Sen osalta lähteenä on käytetty Helsingin galleriakenttää ja gallerioita koskevaa lehtikirjoittelua, joka on tallennettu Kuvataiteen keskusarkiston leikearkistoon. Lisäksi lähteinä ovat Taide-lehden vuosikerrat tutkittavalta ajalta. Galleriakentän lähihistorian tarkastelun pohjaksi tutkielmassa analysoidaan gallerioiden roolia kuvataiteen kentän portinvartijoina, galleriakentän toimijoiden näkemyksiä keskeisen gallerian aseman rakentumisesta ja gallerioita koskevia luokituksia ja ryhmityksiä. Tutkielman ytimen muodostaa luku, jossa käydään kronologisesti läpi galleriakentän muutoksia ja keskeisiä toimijoita tutkielmassa tarkastellulla ajanjaksolla. Lopuksi syvennetään kentän kronologisen kuvauksen pohjalta galleriakentän muutosten analyysia Bourdieun teorian ja käsitteiden avulla. Tutkielman yhtenä tuloksena on tutkittavan kentän ajanjakson hahmottuminen seuraaviksi jaksoiksi: vuodet 1983–1990, vuodet 1990–1997, vuodet 1997–2002 ja vuodesta 2002 alkanut kentän nykytilanteeseen sidostuva jakso. Jaksot hahmottuvat tarkastellun kentän, galleriatoiminnan ja kentällä kulloinkin keskeisten toimijoiden joukon muutosten pohjalta. Jaksojen liitoskohdat ovat muutosten tihentymiä kentän keskeisten toimijoiden joukossa. Jaksot liittyvät osittain myös yleisen taloustilanteen muutoksiin siltä osin kuin ne ovat vaikuttaneet galleriatoimintaan ja siihen, millainen galleriatoiminta ja mitkä toimijat kulloinkin ovat nousseet keskeisiksi. Tutkielman ydinluvussa tarkasteltava ja analysoitava kentän muutosten ja gallerioiden asemien kronologinen kuvaus muodostaa kokonaisuudessaan tutkielman tärkeimmät perustutkimukselliset tulokset. Tulosten loppupäätelminä tutkielmassa päädytään seuraavaan analyysiin. Galleriakentän muutokset sidostuvat kuvataiteen muutoksiin ja talouden nousu- ja laskukausiin, ne eivät kuitenkaan ole tämänkaltaisista ulkoisista tekijöistä johdettavissa. Gallerioiden asemien rakentuminen ja muutokset ovat kytköksissä kentän sisäisiin muutoksiin siten, että kentän toimijajoukon muutokset joko sidostuvat toisiinsa tai asettuvat samanaikaisiksi. Kentän asemien tila vaikuttaa siihen, millaisen aseman uusi galleria pyrkii ottamaan sekä millaisen aseman se saa kentällä ja mediassa. Kenttä näyttäytyy tilana, jossa toisen toimijan poistuminen kentältä luo aukkoja ja tilauksia toisten toimijoiden synnylle. Kentän asemien rakentuminen ja muutokset syntyvät toisaalta gallerioiden toiminnan ja niiden esittämän taiteen ja taiteilijoiden perusteella sekä toisaalta myös suhteessa gallerioiden jaotteluihin ja luokitteluihin. Kentän rakenteen muodostuessa kentän voimasuhteiden tilan kautta muodostuvat keskeisiksi koettujen gallerioiden joukon muutokset erityisen oleellisiksi sille, miten asemat kentällä ovat kulloinkin rakentuneet