Differential substrate behaviours of ethylene oxide and propylene oxide towards human glutathione transferase theta hGSTT1-1

The transformation of ethylene oxide (EO), propylene oxide (PO) and 1- butylene oxide (1-BuO) by human glutathione transferase theta (hGSTT1-1) was studied comparatively using 'conjugator' (GSTT1 + individuals) erythrocyte lysates. The relative sequence of velocity of enzymic transformation was PO > EO >> 1-BuO. The faster transformation of PO compared to EO was corroborated in studies with human and rat GSTT1-1 (hGSTT1-1 and rGSTT1-1, respectively) expressed by Salmonella typhimurium TA1535. This sequence of reactivities of homologous epoxides towards GSTT1-1 contrasts to the sequence observed in homologous alkyl halides (methyl bromide, MBr; ethyl bromide, EtBr; n-propyl bromide, PrBr) where the relative sequence MeBr >> EtBr > PrBr is observed. The higher reactivity towards GSTT1-1 of propylene oxide compared to ethylene oxide is consistent with a higher chemical reactivity. This is corroborated by experimental data of acid-catalysed hydrolysis of a number of aliphatic epoxides, including ethylene oxide and propylene oxide and consistent with semi-empirical molecular orbital modelings.

Differential effects of monotony versus fatigue on driving performance and the effectiveness of various detection methods : implications for road safety in the ACT

Background Situational driving factors, including fatigue, distraction, inattention and monotony, are recognised killers in Australia, contributing to an estimated 40% of fatal crashes and 34% of all crashes . More often than not the main contributing factor is identified as fatigue, yet poor driving performance has been found to emerge early in monotonous conditions, independent of fatigue symptoms and time on task. This early emergence suggests an important role for monotony. However, much road safety research suggests that monotony is solely a task characteristic that directly causes fatigue and associated symptoms and there remains an absence of consistent evidence explaining the relationship. Objectives We report an experimental study designed to disentangle the characteristics and effects of monotony from those associated with fatigue. Specifically, we examined whether poor driving performance associated with hypovigilance emerges as a consequence of monotony, independent of fatigue. We also examined whether monotony is a multidimensional construct, determined by environmental characteristics and/or task demands that independently moderate sustained attention and associated driving performance. Method Using a driving simulator, participants completed four, 40 minute driving scenarios. The scenarios varied in the degree of monotony as determined by the degree of variation in road design (e.g., straight roads vs. curves) and/or road side scenery. Fatigue, as well as a number of other factors known to moderate vigilance and driving performance, was controlled for. To track changes across time, driving performance was assessed in five minute time periods using a range of behavioural, subjective and physiological measures, including steering wheel movements, lane positioning, electroencephalograms, skin conductance, and oculomotor activity. Results Results indicate that driving performance is worse in monotonous driving conditions characterised by low variability in road design. Critically, performance decrements associated with monotony emerge very early, suggesting monotony effects operate independent of fatigue. Conclusion Monotony is a multi-dimensional construct where, in a driving context, roads containing low variability in design are monotonous and those high in variability are non-monotonous. Importantly, low variability in road side scenery does not appear to exacerbate monotony or associated poor performance. However, high variability in road side scenery can act as a distraction and impair sustained attention and poor performance when driving on monotonous roads. Furthermore, high sensation seekers seem to be more susceptible to distraction when driving on monotonous roads. Implications of our results for the relationship between monotony and fatigue, and the possible construct-specific detection methods in a road safety context, will be discussed.

Saliva as an emerging biofluid for clinical diagnosis and applications of MEMS/NEMS in salivary diagnostics

Saliva as a biological fluid is gaining wider acceptance for diagnosing diseases. The growing interest in saliva as a biological fluid is due to its noninvasiveness, ease of use, cost-effectiveness, and multiple sample collection possibilities as well as minimal risk to health care professionals of contracting infectious organisms such as HIV and Hep B. However, the clinical translation of saliva is hampered by our lack of understanding of the biomolecular transportation from blood into saliva, the diurnal variations of biomolecules present in saliva, and relatively low levels of analytes (100th to a 1000th fold less than in blood). We provide information on the current status of salivary research, salivary diagnostics empowered by nanotechnology, and future prospects in this emerging field of saliva diagnostics.

Optimal HMM filtering and decision feedback equalisation for differential encoded transmission systems

In this paper conditional hidden Markov model (HMM) filters and conditional Kalman filters (KF) are coupled together to improve demodulation of differential encoded signals in noisy fading channels. We present an indicator matrix representation for differential encoded signals and the optimal HMM filter for demodulation. The filter requires O(N3) calculations per time iteration, where N is the number of message symbols. Decision feedback equalisation is investigated via coupling the optimal HMM filter for estimating the message, conditioned on estimates of the channel parameters, and a KF for estimating the channel states, conditioned on soft information message estimates. The particular differential encoding scheme examined in this paper is differential phase shift keying. However, the techniques developed can be extended to other forms of differential modulation. The channel model we use allows for multiplicative channel distortions and additive white Gaussian noise. Simulation studies are also presented.

2nd ESMO consensus conference on lung cancer : early-stage non-small-cell lung cancer consensus on diagnosis, treatment and follow-up

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, earlystage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on early-stage disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Prevalence, predictors, and correlates of supportive care needs among women 3–5 years after a diagnosis of endometrial cancer

Purpose The purpose of this study is to examine the prevalence, sociodemographic and clinical predictors, and physical and psychosocial correlates of unmet needs among women 3–5 years following treatment for endometrial cancer. Methods Women with endometrial cancer completed a survey around the time of diagnosis and again 3–5 years later. The follow-up survey asked women about their physical and psychosocial functioning and supportive care needs (CaSUN). Multivariable-adjusted logistic regression identified the predictors and correlates of women’s unmet needs 3–5 years after diagnosis. Results Of the 629 women who completed the cancer survivors’ unmet needs measure (CaSUN), 24 % (n = 153) women reported one or more unmet supportive care needs in the last month. Unmet needs at 3–5 years post-diagnosis were predicted by younger age (OR = 4.47; 95 % CI: 2.09–9.56) and advanced disease stage at diagnosis (OR = 2.47; 95 % CI: 1.38–4.45) and correlated with greater cancer symptoms (OR = 1.78; 95 % CI: 1.05–3.02), lower limb swelling (OR = 2.50; 95 % CI: 1.51–4.15), symptoms of anxiety (OR = 2.21; 95 % CI: 1.31–3.72), and less availability of social support (OR = 3.42; 95 % CI: 1.92–6.11). Women with a history of comorbidities (OR = 0.47; 95 % CI: 0.27–0.82) and those living in a rural area at the time of diagnosis (OR = 0.56; 95 % CI: 0.34–0.92) were less likely to report unmet needs. Conclusions Sociodemographic, health, and psychosocial factors seem important for identifying women who will or will not have unmet needs several years following endometrial cancer. Longitudinal assessments of people’s needs over the course of their cancer trajectory may be an effective way to identify areas that should receive further attention by health providers.

Women’s perceptions of their lifestyle and quality of life several years after a diagnosis of endometrial cancer

Background Few studies have examined the long-term changes experienced by women treated for endometrial cancer. Objective The objectives of this study were to describe what women perceived important to their lifestyle and quality of life in the years following their diagnosis and to provide new insights that might inform healthcare practice. Methods This was a thematic analysis of 237 open-ended comments from Australian women diagnosed with endometrial cancer 3 to 5 years previously. Results We identified 3 main themes: (1) personal change, in which women spoke about cancer as permanently altering their lives in mostly negative but sometimes positive ways; (2) continuity of former life, which described both the minimal impact of cancer on women's lives and identities and the difficulties negotiating this within the dominant "cancer survivorship" culture; (3) social support, where women wrote about how the quality of their relationships shaped their cancer trajectory. Conclusions While typical "survivorship" issues exist for many women with endometrial cancer (eg, physical, emotional, sexual health changes), a proportion of women will not be focused on their cancer and can be encouraged to form lives and identities that are not situated within the "cancer survivorship" culture. Implications for Practice A network of support, sensitive to women's responses to having cancer, may benefit women's long-term adjustment. Regular standardized assessment of women's needs may facilitate appropriate support for those with concerns, whereas those without concerns could be reassured by health professionals that their experience is normal and shared by other people with cancer. This may encourage women to form lives that are personally meaningful.

Differential effects of refractive blur on day and night-time driving performance

Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.

Differential effects of tissue culture coating substrates on prostate cancer cell adherence, morphology and behavior

Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common problem and presents technical limitations to the design of experiments. To overcome this problem, various surface coating protocols have been developed. However, a comparative and precise real-time measurement of their impact on cell behavior has not been conducted. The prostate cancer cell line LNCaP, derived from a patient lymph node metastasis, is a commonly used model system in prostate cancer research. However, the cells’ characteristically weak attachment to the surface of tissue culture vessels and cover slips has impeded their manipulation and analysis and use in high throughput screening. To improve the adherence of LNCaP cells to the culture surface, we compared different coating reagents (poly-L-lysine, poly-L-ornithine, collagen type IV, fibronectin, and laminin) and culturing conditions and analyzed their impact on cell proliferation, adhesion, morphology, mobility and gene expression using real-time technologies. The results showed that fibronectin, poly-L-lysine and poly-L-ornithine improved LNCaP cells adherence and provoked cell morphology alterations, such as increase of nuclear and cellular area. These coating reagents also induced a higher expression of F-actin and reduced cell mobility. In contrast, laminin and collagen type IV did not improve adherence but promoted cell aggregation and affected cell morphology. Cells cultured in the presence of laminin displayed higher mobility than control cells. All the coating conditions significantly affected cell viability; however, they did not affect the expression of androgen receptor-regulated genes. Our comparative findings provide important insight for the selection of the ideal coating reagent and culture conditions for the cancer cell lines with respect to their effect on proliferation rate, attachment, morphology, migration, transcriptional response and cellular cytoskeleton arrangement.

The radiological diagnosis of pneumonia in children

Despite the importance of paediatric pneumonia as a cause of short and long-term morbidity and mortality worldwide, a reliable gold standard for its diagnosis remains elusive. The utility of clinical, microbiological and radiological diagnostic approaches varies widely within and between populations and is heavily dependent on the expertise and resources available in various settings. Here we review the role of radiology in the diagnosis of paediatric pneumonia. Chest radiographs (CXRs) are the most widely employed test, however, they are not indicated in ambulatory settings, cannot distinguish between viral and bacterial infections and have a limited role in the ongoing management of disease. A standardised definition of alveolar pneumonia on a CXR exists for epidemiological studies targeting bacterial pneumonias but it should not be extrapolated to clinical settings. Radiography, computed tomography and to a lesser extent ultrasonography and magnetic resonance imaging play an important role in complicated pneumonias but there are limitations that preclude their use as routine diagnostic tools. Large population-based studies are needed in different populations to address many of the knowledge gaps in the radiological diagnosis of pneumonia in children, however, the feasibility of such studies is an important barrier.

Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry

Glycerophospholipids (GPs) that differ in the relative position of the two fatty acyl chains on the glycerol backbone (i.e., sn-positional isomers) can have distinct physicochemical properties. The unambiguous assignment of acyl chain position to an individual GP represents a significant analytical challenge. Here we describe a workflow where phosphatidylcholines (PCs) are subjected to ESI for characterization by a combination of differential mobility spectrometry and MS (DMS-MS). When infused as a mixture, ions formed from silver adduction of each phospholipid isomer {e.g., [PC (16:0/18:1) + Ag]+ and [PC (18:1/16:0) + Ag]+} are transmitted through the DMS device at discrete compensation voltages. Varying their relative amounts allows facile and unambiguous assignment of the sn-positions of the fatty acyl chains for each isomer. Integration of the well-resolved ion populations provides a rapid method (< 3 min) for relative quantification of these lipid isomers. The DMS-MS results show excellent agreement with established, but time-consuming, enzymatic approaches and also provide superior accuracy to methods that rely on MS alone. The advantages of this DMS-MS method in identification and quantification of GP isomer populations is demonstrated by direct analysis of complex biological extracts without any prior fractionation.

Natural convection due to differential heating of inclined walls and heat source placed on bottom wall of an attic shaped space

Numerical investigation of free convection heat transfer in an attic shaped enclosure with differentially heated two inclined walls and filled with air is performed in this study. The left inclined surface is uniformly heated whereas the right inclined surface is uniformly cooled. There is a heat source placed on the right side of the bottom surface. Rest of the bottom surface is kept as adiabatic. Finite volume based commercial software ANSYS 15 (Fluent) is used to solve the governing equations. Dependency of various flow parameters of fluid flow and heat transfer is analyzed including Rayleigh number, Ra ranging from 103 to 106, heater size from 0.2 to 0.6, heater position from 0.3 to 0.7 and aspect ratio from 0.2 to 1.0 with a fixed Prandtl number of 0.72. Outcomes have been reported in terms of temperature and stream function contours and local Nusselt number for various Ra, heater size, heater position, and aspect ratio. Grid sensitivity analysis is performed and numerically obtained results have been compared with those results available in the literature and found good agreement.

Echolocation calls, wing shape, diet and phylogenetic diagnosis of the endemic Chinese bat Myotis pequinius

We describe the echolocation calls, flight morphology and diet of the endemic Chinese bat Myotis pequinius Thomas, 1908. Orientation calls are broadband, and reach low terminal frequencies. Diet comprised 80% beetles by volume. Wing shape and call design suggest that the bats fly in cluttered habitats, and the possession of moderately long ears and the dietary composition imply they forage at least sometimes by gleaning. Myotis pequinius resembles a larger Oriental version of the western Palaearctic species M. nattereri. Phylogenetic analysis based on sequences of the cytochrome b gene of mitochondrial DNA (1,140 base pairs) from a range of Palaearctic Myotis species confirmed that M. pequinius is close to the nattereri group, and is a sister-species to the eastern Palaearctic M. bombinus. One bat sequenced from China could not be identified from available species descriptions. It was smaller than M. pequinius, and also differed from it in sequence divergence by 6.7%, suggesting the existence of additional, cryptic taxonomic diversity in this group. Our phylogenetic analysis also supports the recognition of M. schaubi as a species distinct from M. nattereri in Transcaucasia and south-western Asia. Myotis nattereri tschuliensis is more closely related to M. schaubi than to M. nattereri, and is best considered either as a subspecies of M. schaubi, or possibly as a distinct species.