More light at the end of the tunnel – apixaban in atrial fibrillation

Introduction: Subjects with atrial fibrillation are at risk of thromboembolic events. The vitamin K antagonists (e.g., warfarin) are useful at preventing coagulation in atrial fibrillation, but are difficult to use. One of the FXa inhibitors, oral apixaban, has been tested as an anticoagulant in atrial fibrillation. Areas covered: In ARISTOTLE (Apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation) apixaban was compared to warfarin in subjects with atrial fibrillation, and shown to cause a lower rate of stroke or systemic embolism and of major bleeding, than warfarin. In the AVERROES (Apixaban versus acetylsalicylic acid [ASA] to prevent stroke in atrial fibrillations patients who have failed or are unsuitable for vitamin K antagonist treatment) trial, stroke or systemic embolism occurred less often with apixaban than aspirin, whereas the occurrence of major bleeding was similar in the groups. Expert opinion: Apixaban is much easier for subjects with atrial fibrillation to use than warfarin, as it does not require regular monitoring by a health professional, with dosage adjustment. In addition to replacing warfarin in subjects with atrial fibrillation who are unable or not prepared to use warfarin, apixaban has the potential to replace warfarin more widely in the prevention of thromboembolism in subjects with atrial fibrillation.

Assessment of daily light and ultraviolet exposure in young adults

Purpose: There are some limited reports, based on questionnaire data, which suggest that outdoor activity decreases the risk of myopia in children and may offset the myopia risk associated with prolonged near work. The aim of this study was to explore the relationship between near work, indoor illumination, daily sunlight and ultraviolet (UV) exposure in emmetropic and myopic University students, given that University students perform significant amounts of near work and as a group have a high prevalence of myopia. Methods: Participants were 35 students, aged 17 to 25 years who were classified as being emmetropic (n=13), or having stable (n=12) or progressing myopia (n=10). During waking hours on three separate days participants wore a light sensor data logger (HOBO) and a polysulphone UV dosimeter; these devices measured daily illuminance and accumulative UV exposure respectively; participants also completed a daily activity log. Results: No significant between group differences were observed for average daily illuminance (p=0.732), number of hours per day spent in sunlight (p=0.266), outdoor shade (p=0.726), bright indoor/dim outdoor light (p=0.574) or dim room illumination (p=0.484). Daily UV exposure was significantly different across the groups (p=0.003); with stable myopes experiencing the greatest UV exposure (versus emmetropes p=0.002; versus progressing myopes p=0.004). Conclusions: The current literature suggests there is a link between myopia protection and spending time outdoors in children. Our data provides some evidence of this relationship in young adults and highlights the need for larger studies to further investigate this relationship longitudinally.

Risk factors to predict the incidence of surgical adverse events following open or laparoscopic surgery for apparent early stage endometrial cancer: results from a randomised controlled trial

Aims: To identify risk factors for major Adverse Events (AEs) and to develop a nomogram to predict the probability of such AEs in individual patients who have surgery for apparent early stage endometrial cancer. Methods: We used data from 753 patients who were randomized to either total laparoscopic hysterectomy or total abdominal hysterectomy in the LACE trial. Serious adverse events that prolonged hospital stay or postoperative adverse events (using common terminology criteria 3+, CTCAE V3) were considered major AEs. We analyzed pre-surgical characteristics that were associated with the risk of developing major AEs by multivariate logistic regression. We identified a parsimonious model by backward stepwise logistic regression. The six most significant or clinically important variables were included in the nomogram to predict the risk of major AEs within 6 weeks of surgery and the nomogram was internally validated. Results: Overall, 132 (17.5%) patients had at least one major AE. An open surgical approach (laparotomy), higher Charlson’s medical co-morbidities score, moderately differentiated tumours on curettings, higher baseline ECOG score, higher body mass index and low haemoglobin levels were associated with AE and were used in the nomogram. The bootstrap corrected concordance index of the nomogram was 0.63 and it showed good calibration. Conclusions: Six pre-surgical factors independently predicted the risk of major AEs. This research might form the basis to develop risk reduction strategies to minimize the risk of AEs among patients undergoing surgery for apparent early stage endometrial cancer.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early stage endometrial cancer

Objectives: To evaluate the clinical value of pre-operative serum CA125 in predicting the presence of extra-uterine disease in patients with apparent early stage endometrial cancer. Methods: Between October 6, 2005 and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. This study is based on data from 657 patients with endometrial adenocarcinoma who had a pre-operative serum CA125 value, and was undertaken to correlate pre-operative serum CA125 with final stage. Results: Using a pre-operative CA-125 cutpoint of 30U/ml was associated with the smallest misclassification error (14.5%) using a multiple cross-validation method. Median pre-operative serum CA-125 was 14U/ml, and using a cutpoint of 30U/ml, 14.9% of patients had elevated CA-125 levels. Of 98 patients with elevated CA-125 level, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had elevated CA-125 level. In univariate and multivariate logistic regression analysis, only pre-operative CA-125 level was found to be associated with extra-uterine spread of disease. Utilising a cutpoint of 30U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0%, 88.5%, 36.7% and 85.7% respectively. Overall, 326/657 (49.6%) of patients had full surgical staging involving lymph node dissection. When analysis was limited to patients that had undergone full surgical staging, the outcomes remained essentially unchanged. Conclusions: Elevated CA-125 above 30U/ml in patients with apparent early stage disease is associated with a sensitivity of 31.0% and specificity of 88.5% in detecting extra-uterine disease. Pre-operative identification of this risk factor may assist to triage patients to tertiary centres and comprehensive surgical staging.

Improved surgical safety after laparoscopic compared to open surgery for apparent early stage endometrial cancer : results from a randomised controlled trial

AIM: To compare Total Laparoscopic Hysterectomy (TLH) and Total Abdominal Hysterectomy (TAH) with regard to surgical safety. METHODS: Between October 2005 and June 2010, 760 patients with apparent early stage endometrial cancer were enroled in a multicentre, randomised clinical trial (LACE) comparing outcomes following TLH or TAH. The main study end points for this analysis were surgical adverse events (AE), hospital length of stay, conversion from laparoscopy to laparotomy, including 753 patients who completed at least 6 weeks of follow-up. Postoperative AEs were graded according to Common Toxicity Criteria (V3), and those immediately life-threatening, requiring inpatient hospitalisation or prolonged hospitalisation, or resulting in persistent or significant disability/incapacity were regarded as serious AEs. RESULTS: The incidence of intra-operative AEs was comparable in either group. The incidence of post-operative AE CTC grade 3+ (18.6% in TAH, 12.9% in TLH, p 0.03) and serious AE (14.3% in TAH, 8.2% in TLH, p 0.007) was significantly higher in the TAH group compared to the TLH group. Mean operating time was 132 and 107 min, and median length of hospital stay was 2 and 5 days in the TLH and TAH group, respectively (p<0.0001). The decline of haemoglobin from baseline to day 1 postoperatively was 2g/L less in the TLH group (p 0.006). CONCLUSIONS: Compared to TAH, TLH is associated with a significantly decreased risk of major surgical AEs. A laparoscopic surgical approach to early stage endometrial cancer is safe.

A method for systematically pooling data in very early stage construction price forecasting

Client owners usually need an estimate or forecast of their likely building costs in advance of detailed design in order to confirm the financial feasibility of their projects. Because of their timing in the project life cycle, these early stage forecasts are characterized by the minimal amount of information available concerning the new (target) project to the point that often only its size and type are known. One approach is to use the mean contract sum of a sample, or base group, of previous projects of a similar type and size to the project for which the estimate is needed. Bernoulli’s law of large numbers implies that this base group should be as large as possible. However, increasing the size of the base group inevitably involves including projects that are less and less similar to the target project. Deciding on the optimal number of base group projects is known as the homogeneity or pooling problem. A method of solving the homogeneity problem is described involving the use of closed form equations to compare three different sampling arrangements of previous projects for their simulated forecasting ability by a cross-validation method, where a series of targets are extracted, with replacement, from the groups and compared with the mean value of the projects in the base groups. The procedure is then demonstrated with 450 Hong Kong projects (with different project types: Residential, Commercial centre, Car parking, Social community centre, School, Office, Hotel, Industrial, University and Hospital) clustered into base groups according to their type and size.

Regulation of land access for resource development: A coal seam gas case study from Queensland

A number of regulatory statutes provide for agreements with landowners which are given extended effect, that is, are binding upon the landowner’s successors (‘statutory agreements’). Several Queensland statutes require a project proponent to enter into a statutory agreement with a landowner before a resource development activity can be carried out on private land or by accessing private land. Provisions of Queensland’s Petroleum and Gas (Production and Safety) Act 2004 make certain types of statutory agreements binding upon successors and assigns of the landowner, but do not clearly prescribe the nature and contents of an agreement, nor require that the agreement be recorded on the land title or petroleum register. If statutory agreements are to be used for such purposes, their purpose and content should be more clearly defined by statute and they should be recorded on a searchable register.

Coal seam gas waters - their geochemical signature and potential environmental implications

Coal Seam Gas (CSG) is a form of natural gas (mainly methane) sorbed in underground coal beds. To mine this gas, wells are drilled directly into an underground coal seam and groundwater (CSG water) is pumped out to the surface. This lowers the downhole piezometric pressure and enables gas desporption from the coal matrix. In the United States, this gas has been extracted commercially since the 1980s. The economic success of US CSG projects has inspired exploration and development in Australia and New Zealand. In Australia, Queensland’s Bowen and Surat basins have been the subject of increased CSG development over the last decade. CSG growth in other Australian basins has not matured to the same level but exploration and development are taking place at an accelerated pace in the Sydney Basin (Illawarra and the Hunter Valley, NSW) and in the Gunnedah Basin. Similarly, CSG exploration in New Zealand has focused in the Waikato region (Maramarua and Huntly), in the West Coast region (Buller, Reefton, and Greymouth), and in Southland (Kaitangata, Mataura, and Ohai). Figure 1 shows a Shcoeller diagram with CSG samples from selected basins in Australia, New Zealand, and the USA. CSG water from all of these basins exhibit the same geochemical signature – low calcium, low magnesium, high bicarbonate, low sulphate and, sometimes, high chloride. This water quality is a direct result of specific biological and geological processes that have taken part in the formation of CSG. In general, these processes include the weathering of rocks (carbonates, dolomite, and halite), cation exchange with clays (responsible for enhanced sodium and depleted calcium and magnesium), and biogenic processes (accounting for the presence of high bicarbonate concentrations). The salinity of CSG waters tends to be brackish (TDS < 30000 mg/l) with a fairly neutral pH. These particular characteristics need to be taken into consideration when assessing water management and disposal alternatives. Environmental issues associated with CSG water disposal have been prominent in developed basins such as the Powder River Basin (PRB) in the United States. When disposed on the land or used for irrigation, water having a high dissolved salts content may reduce water availability to crops thus affecting crop yield. In addition, the high sodium, low calcium and low magnesium concentrations increase the potential to disperse soils and significantly reduce the water infiltration rate. Therefore, CSG waters need to be properly characterised, treated, and disposed to safeguard the environment without compromising other natural resources.

Exploring the information practices of people with end stage kidney disease

This small exploratory study sought to understand how people with End Stage Kidney Disease (ESKD) experience the information environment and what information practices they employ in order to inform the decisions they make in relation to treatment and care. Using a constructivist methodology, in-depth interviews were conducted with five people who were receiving haemodialysis in two small satellite dialysis units located in regional and rural communities in New South Wales, Australia. Thematic analysis revealed two types of patients. The first type appears to adopt a received view of information, who do not question their condition; and passively accept information. In the other type, patients were found to be engaged; they actively identified their information needs and quickly learned what that they needed to ask and who to ask. Knowing the information practices of people with ESKD is useful for nephrology nurses when providing patient education.

Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis

Paraffin sections from 190 epithelial ovarian tumours, including 159 malignant and 31 benign epithelial tumours, were analysed immunohistochemically for expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product p16INK4A (p16). Most benign tumours showed no p16 expression in the tumour cells, whereas only 11% of malignant cancers were p16 negative. A high proportion of p16-positive tumour cells was associated with advanced stage and grade, and with poor prognosis in cancer patients. For FIGO stage 1 tumours, a high proportion of p16-positive tumour cells was associated with poorer survival, suggesting that accumulation of p16 is an early event of ovarian tumorigenesis. In contrast to tumour cells, high expression of p16 in the surrounding stromal cells was not associated with the stage and grade, but was associated with longer survival. When all parameters were combined in multivariate analysis, high p16 expression in stromal cells was not an independent predictor for survival, indicating that low p16 expression in stromal cells is associated with other markers of tumour progression. High expression of p16 survival in the stromal cells of tumours from long-term survivors suggests that tumour growth is limited to some extent by factors associated with p16 expression in the matrix.

Conductometric gas sensors based on nanostructured WO3 thin films

Nanostructured WO3 thin films have been prepared by thermal evaporation to detect hydrogen at low temperatures. The influence of heat treatment on the physical, chemical and electronic properties of these films has been investigated. The films were annealed at 400oC for 2 hours in air. AFM and TEM analysis revealed that the as-deposited WO3 film is high amorphous and made up of cluster of particles. Annealing at 400oC for 2 hours in air resulted in very fine grain size of the order of 5 nm and porous structure. GIXRD and Raman analysis revealed that annealing improved the crystallinity of WO3 film. Gas sensors based on annealed WO3 films have shown a high response towards various concentrations (10-10000 ppm) H2 at an operating temperature of 150oC. The improved sensing performance at low operating temperature is due to the optimum physical, chemical and electronic properties achieved in the WO3 film through annealing.

Kaolinite particle sizes in the <2 µM range using laser scattering

The Clay Minerals Society Source Clay kaolinites, Georgia KGa-1 and KGa-2, have been subjected to particle size determinations by 1) conventional sedimentation methods, 2) electron microscopy and image analysis, and 3) laser scattering using improved algorithms for the interaction of light with small particles. Particle shape, size distribution, and crystallinity vary considerably for each kaolinite. Replicate analyses of separated size fractions showed that in the <2 µm range, the sedimentation/centrifugation method of Tanner and Jackson (1947) is reproducible for different kaolinite types and that the calculated size ranges are in reasonable agreement with the size bins estimated from laser scattering. Particle sizes determined by laser scattering must be calculated using Mie theory when the dominant particle size is less than ∼5 µm. Based on this study of two well-known and structurally different kaolinites, laser scattering, with improved data reduction algorithms that include Mie theory, should be considered an internally consistent and rapid technique for clay particle sizing.

Selective reductions using visible light photocatalysts of supported gold nanoparticles

Photocatalytic synthesis using visible light is a desirable chemical process because of its potential to utilize sunlight. Supported gold nanoparticles (Au-NPs) were found to be efficient photocatalysts and the effects of the supports were identified including CeO2, TiO2, ZrO2, Al2O3, and zeolite Y. In particular Au/CeO2 exhibited the high catalytic activity to reduce nitroaromatics to azo compounds, hydrogenate azobenzene to hydroazobenzene, reduce ketones to alcohols, and deoxygenate epoxides to alkenes at ambient temperatures, under irradiation of visible light (or simulated sunlight). The reac-tive efficiency depends on two primary factors: one is the light adsorption of catalysts and another is the driving ability of catalysts corresponding to the reactants. The light absorption by Au-NPs is due to surface plasmon resonance effect or inter-band electron transition; this is related to the reduction ability of the photocatalysts. Irradiation with shorter wavelengths can excite the conduction electrons in Au-NPs to higher energy levels and as a result, induce reduction with more negative reduction potentials. It is known when irradiated with light the Au-NPs can abstract hydrogen from isopropanol forming Au-H species on the Au-NP surface. Hence, we proposed that the active Au-H species will react with the N=O, N=N, C=O double bonds or epoxide bonds, which are weakened by the interaction with the excited electrons in the Au-NPs, and yield the final reductive products. The reacting power of the Au-H species depends on the energy of the excited electrons in Au-NPs: the higher the electronic energy, the stronger the reduction ability of the Au-H species. This finding demonstrates that we can tune the reduction ability of the photocatalysts by manipulating the irradiation wavelength.

An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria : implications for ex vivo drug susceptibility testing

The emergence of highly chloroquine (CQ) resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT), originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC50) values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC50 for CQ. Our findings indicate that EC50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

Stage brothers slow to resurrect a Ned Kelly myth

JUST like the man, Ned Kelly dramas have had a chequered history. A century ago they were banned from the stage and screen. Following censorship law changes, Douglas Stewart's 4 1/2-hour long 1942 radio play was a hit on the airwaves but a flop onstage. Stewart's Ned was a menacing hero/villain. Little has been seen of Ned in mainstage plays since. Matthew Ryan's Kelly breaks the drought.