Local anaesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro

Retrospective studies indicate that the use of regional anesthesia can reduce cancer recurrence after surgery which could be due to ranging from immune function preservation to direct molecular mechanisms. This study was to investigate the effects of bupivacaine on ovarian and prostate cancer cell biology and the underlying molecular mechanisms. Cell viability, proliferation and migration of ovarian carcinoma (SKOV-3) and prostate carcinoma (PC-3) were examined following treatment with bupivacaine. Cleaved caspase 3, 8 and 9, and GSK-3β, pGSK-3β(tyr216) and pGSK-3β(ser9) expression were assessed by immunofluorescence. FAS ligand neutralization, caspase and GSK-3 inhibitors and GSK-3β siRNA were applied to further explore underlying mechanisms. Clinically relevant concentrations of bupivacaine reduced cell viability and inhibited cellular proliferation and migration in both cell lines. Caspase 8 and 9 inhibition generated partial cell death reversal in SKOV-3, whilst only caspase 9 was effective in PC-3. Bupivacaine increased the phosphorylation of GSK-3β(Tyr216) in SKOV-3 but without measurable effect in PC3. GSK-3β inhibition and siRNA gene knockdown decreased bupivacaine induced cell death in SKOV-3 but not in PC3. Our data suggests that bupivacaine has direct ‘anti-cancer’ properties through the activation of intrinsic and extrinsic apoptotic pathways in ovarian cancer but only the intrinsic pathway in prostate cancer

Casimir micro-sphere diclusters and three-body effects in fluids

Our previous article [Phys. Rev. Lett. 104, 060401 (2010)] predicted that Casimir forces induced by the material-dispersion properties of certain dielectrics can give rise to stable configurations of objects. This phenomenon was illustrated via a dicluster configuration of non-touching objects consisting of two spheres immersed in a fluid and suspended against gravity above a plate. Here, we examine these predictions from the perspective of a practical experiment and consider the influence of non-additive, three-body, and nonzero-temperature effects on the stability of the two spheres. We conclude that the presence of Brownian motion reduces the set of experimentally realizable silicon/teflon spherical diclusters to those consisting of layered micro-spheres, such as the hollow- core (spherical shells) considered here.Comment: 11 pages, 9 figure

Prevention programmes for children of problem drinkers: a review

It is well established that children of problem drinkers have an increased risk of developing mental health problems, including drinking and drug misuse problems, depression, eating disorders, conduct disorders, and delinquency. However, compared to the hundreds of studies that have examined the effects of parental problem drinking on their children, the genetics of problem drinking, and the physical and mental problems of these children, it is disappointing that so few studies have explored the possibilities of prevention. Despite all the research on children of problem drinkers, we have no usable operationalizations of what problem drinking is, or when a child can be defined as a child of a problem drinker. Furthermore, no valid screening or severity assessment instruments are available; there is no solution for the ethical dilemma of the need to involve parents while these parents are at the same time the problem; very few theory-driven prevention programmes have been developed; very little is known about protective factors that could be the focus of prevention programmes; and we have no programmes that can be considered to be ‘evidence based’. This paper describes these problems, presents an overview of the prevention research in this area, and gives some directions for future research

The Fundamental Diagram of Pedestrian Movement Revisited

The empirical relation between density and velocity of pedestrian movement is not completely analyzed, particularly with regard to the `microscopic' causes which determine the relation at medium and high densities. The simplest system for the investigation of this dependency is the normal movement of pedestrians along a line (single-file movement). This article presents experimental results for this system under laboratory conditions and discusses the following observations: The data show a linear relation between the velocity and the inverse of the density, which can be regarded as the required length of one pedestrian to move. Furthermore we compare the results for the single-file movement with literature data for the movement in a plane. This comparison shows an unexpected conformance between the fundamental diagrams, indicating that lateral interference has negligible influence on the velocity-density relation at the density domain $1 m^{-2}<\rho<5 m^{-2}$. In addition we test a procedure for automatic recording of pedestrian flow characteristics. We present preliminary results on measurement range and accuracy of this method.Comment: 13 pages, 9 figure

Long-lived photoexcited states in polydiacetylenes with different molecular and supramolecular organization

With the aim of determining the importance of the molecular and supramolecular organization on the excited states of polydiacetylenes, we have studied the photoinduced absorption spectra of the red form of poly[1,6-bis(3,6-didodecyl-N-carbazolyl)-2,4-hexadiyne] (polyDCHD-S) and the results compared with those of the blue form of the same polymer. An interpretation of the data is given in terms of both the conjugation length and the interbackbone separation also in relation to the photoinduced absorption spectra of both blue and red forms of poly[1,6-bis(N-carbazolyl)-2,4-hexadiyne] (polyDCHD), which does not carry the alkyl substituents on the carbazolyl side groups. Information on the above properties is derived from the analysis of the absorption and Raman spectra of this class of polydiacetylenes

Temporally varying natural mortality: Sensitivity of a virtual population analysis and an exploration of alternatives

Cohort reconstructions (CR) currently applied in Pacific salmon management estimate temporally variant exploitation, maturation, and juvenile natural mortality rates but require an assumed (typically invariant) adult natural mortality rate (dA), resulting in unknown biases in the remaining vital rates. We explored the sensitivity of CR results to misspecification of the mean and/or variability of dA, as well as the potential to estimate dA directly using models that assumed separable year and age/cohort effects on vital rates (separable cohort reconstruction, SCR). For CR, given the commonly assumed dA = 0.2, the error (RMSE) in estimated vital rates is generally small (? 0.05) when annual values of dA are low to moderate (? 0.4). The greatest absolute errors are in maturation rates, with large relative error in the juvenile survival rate. The ability of CR estimates to track temporal trends in the juvenile natural mortality rate is adequate (Pearson's correlation coefficient > 0.75) except for high dA (? 0.6) and high variability (CV > 0.35). The alternative SCR models allowing estimation of time-varying dA by assuming additive effects in natural mortality, fishing mortality, and/or maturation rates did not outperform CR across all simulated scenarios, and are less accurate when additivity assumptions are violated. Nevertheless an SCR model assuming additive effects on fishing and natural (juvenile and adult) mortality rates led to nearly unbiased estimates of all quantities estimated using CR, along with borderline acceptable estimates of the mean dA under multiple sets of conditions conducive to CR. Adding an assumption of additive effects on the maturation rates allowed nearly unbiased estimates of the mean dA as well. The SCR models performed slightly better than CR when the vital rates covaried as assumed. These separable models could serve as a partial check on the validity of CR assumptions about the adult natural mortality rate, or even a preferred alternative if there is strong reason to believe the vital rates, including juvenile and adult natural mortality rates, covary strongly across years or age classes as assumed

Enhanced empirical data for the fundamental diagram and the flow through bottlenecks

In recent years, several approaches for modelling pedestrian dynamics have been proposed and applied e.g. for design of egress routes. However, so far not much attention has been paid to their 'quantitative' validation. This unsatisfactory situation belongs amongst others on the uncertain and contradictory experimental data base. The fundamental diagram, i.e. the density-dependence of the flow or velocity, is probably the most important relation as it connects the basic parameter to describe the dynamic of crowds. But specifications in different handbooks as well as experimental measurements differ considerably. The same is true for the bottleneck flow. After a comprehensive review of the experimental data base we give an survey of a research project, including experiments with up to 250 persons performed under well controlled laboratory conditions. The trajectories of each person are measured in high precision to analyze the fundamental diagram and the flow through bottlenecks. The trajectories allow to study how the way of measurement influences the resulting relations. Surprisingly we found large deviation amongst the methods. These may be responsible for the deviation in the literature mentioned above. The results are of particular importance for the comparison of experimental data gained in different contexts and for the validation of models.Comment: A contribution to: Pedestrian and Evacuation Dynamics 2008 (Springer) 12 pages, 7 figure

Using machine learning to infer reasoning provenance from user interaction log data: based on the data/frame theory of sensemaking

The reconstruction of analysts’ reasoning processes (reasoning provenance) during complex sensemaking tasks can support reflection and decision making. One potential approach to such reconstruction is to automatically infer reasoning from low-level user interaction logs. We explore a novel method for doing this using machine learning. Two user studies were conducted in which participants performed similar intelligence analysis tasks. In one study, participants used a standard web browser and word processor; in the other, they used a system called INVISQUE (Interactive Visual Search and Query Environment). Interaction logs were manually coded for cognitive actions based on captured think-aloud protocol and posttask interviews based on Klein, Phillips, Rall, and Pelusos’s data/frame model of sensemaking as a conceptual framework. This analysis was then used to train an interaction frame mapper, which employed multiple machine learning models to learn relationships between the interaction logs and the codings. Our results show that, for one study at least, classification accuracy was significantly better than chance and compared reasonably to a reported manual provenance reconstruction method. We discuss our results in terms of variations in feature sets from the two studies and what this means for the development of the method for provenance capture and the evaluation of sensemaking systems