18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

To determine whether [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (±6.3) to 8.1 (±2.9) after 1 week of chemoradiation (P = 0.070). In nonresponders (72%), the results were 9.7 (±5.4) and 7.1 (±3.8), respectively (P = 0.003). The MTV in responders fell from 36.6 (±22.7) to 22.3 (±10.4) cm3 (P = 0.180), while in nonresponders, this fell from 35.9 (±36.7) to 31.9 (±52.7) cm3 (P = 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer. © 2006 Cancer Research UK.

Targeting histone deacetylases for the treatment of disease : Epigenetics Review Series

The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular 'code' recognized and used by non-histone proteins to regulate specific chromatin functions. One modification, which has received significant attention, is that of histone acetylation. The enzymes that regulate this modification are described as lysine acetyltransferases or KATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The pro-inflammatory environment is increasingly being recognized as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential and current development of histone deacetylases for the treatment of diseases for which a pro-inflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the pro-inflammatory environment. © 2009 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

Targeting histone deacetylases for the treatment of immune, endocrine and metabolic disorders

The 'histone code' is a well-established hypothesis describing the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as histone acetyltransferases or HATs, and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. The proinflammatory environment is increasingly being recognised as a critical element for both degenerative diseases and cancer. The present review will discuss the current knowledge surrounding the clinical potential & current development of histone deacetylases for the treatment of diseases for which a proinflammatory environment plays important roles, and the molecular mechanisms by which such inhibitors may play important functions in modulating the proinflammatory environment. © 2009 Bentham Science Publishers Ltd.

Outsider board activity, ownership structure and firm value : evidence from Korea

Using a sample of publicly listed firm in Korea from 2002 to 2006, this article examines the impact of board monitoring on firm value and productivity. We use outsider's attendance of board meetings as a proxy for board monitoring. Consistent with the commitment hypothesis, we find that outsider's attendance rate increases firm value, suggesting that attending board meeting itself is a strong signal that reflects outsider's intention to monitor insiders. While ownership of controlling shareholders negatively affects firm value, this relationship is not moderated by increased monitoring by outsiders. Our findings provide further evidence that the outside director system is less effective in chaebol-affiliated firms. Results also indicate that the effect of outsider's board monitoring activity on investor's valuation of the firm is greater than on productivity improvement of the firm. Our conclusions are robust for possible endogeneity in the relationship between firm value and board attendance by outside directors.

The impact of mining and smelting activities on property values : a study of Mount Isa city, Queensland, Australia

Much publicity has been given to the problem of high levels of environmental contaminants, most notably high blood lead concentration levels among children in the city of Mount Isa because of mining and smelting activities. The health impacts from mining-related pollutants are now well documented. This includes published research being discussed in an editorial of the Medical Journal of Australia (see Munksgaard et al. 2010). On the other hand, negative impacts on property prices, although mentioned, have not been examined to date. This study rectifies this research gap. This study uses a hedonic property price approach to examine the impact of mining- and smelting-related pollution on nearby property prices. The hypothesis is that those properties closer to the lead and copper smelters have lower property (house) prices than those farther away. The results of the study show that the marginal willingness to pay to be farther from the pollution source is AUS $13 947 per kilometre within the 4 km radius selected. The study has several policy implications, which are discussed briefly. We used ordinary least squares, geographically weighted regression, spatial error and spatial autoregressive or spatial lag models for this analysis.

The influence of perpetrator and victim intoxication on perceivers' ratings of a sexual perpetrator's own awareness of wrongdoing for his sexually aggressive behaviour

Rape-perception studies have examined the influence of alcohol intoxication on perpetrator blame attributions: However, no studies have examined how intoxication affects perceptions of a sexual perpetrator’s awareness of the wrongfulness of his behaviour despite its relevance to the conceptualisation of responsibility and blame. This experiment investigated the impact of perpetrator and victim intoxication on perceptions of a perpetrator’s own awareness of wrongdoing for acquaintance rape. Undergraduate students (N = 314) read one of four rape-scenarios in which intoxication was manipulated and rated the perpetrator’s awareness of the consequences and wrongfulness of his sexual aggression. Findings supported the hypothesis that participants would assign less awareness of wrongdoing to an intoxicated, compared to sober, perpetrator. Further, males ascribed more awareness of wrongdoing to the perpetrator of an intoxicated, compared to sober, victim. Findings indicate that intoxicated sexual perpetrators are seen as not fully aware of the nature and consequences of their crime.

Intimate relationship status variations in violence against women : urban, suburban, and rural differences

Woman abuse varies across intimate relationship categories (e.g., marriage, divorce, separation). However, it is unclear whether relationship status variations in violence against women differ across urban, suburban, and rural areas. We test the hypothesis that rural females, regardless of their intimate partner relationship status, are at higher risk of intimate violence than their urban and suburban counterparts. Results indicate that marital status is an important aspect of the relationship between intimate victimization and geographic area and that rural divorced and separated females are victimized at rates exceeding their urban counterparts.

Identification and elimination of a matrix-induced systematic error in LA–ICP–MS 206Pb/238U dating of zircon

Black et al. (2004) identified a systematic difference between LA–ICP–MS and TIMS measurements of 206Pb/238U in zircons, which they correlated with the incompatible trace element content of the zircon. We show that the offset between the LA–ICP–MS and TIMS measured 206Pb/238U correlates more strongly with the total radiogenic Pb than with any incompatible trace element. This suggests that the cause of the 206Pb/238U offset is related to differences in the radiation damage (alpha dose) between the reference and unknowns. We test this hypothesis in two ways. First, we show that there is a strong correlation between the difference in the LA–ICP–MS and TIMS measured 206Pb/238U and the difference in the alpha dose received by unknown and reference zircons. The LA–ICP–MS ages for the zircons we have dated can be as much as 5.1% younger than their TIMS age to 2.1% older, depending on whether the unknown or reference received the higher alpha dose. Second, we show that by annealing both reference and unknown zircons at 850 °C for 48 h in air we can eliminate the alpha-dose-induced differences in measured 206Pb/238U. This was achieved by analyzing six reference zircons a minimum of 16 times in two round robin experiments: the first consisting of unannealed zircons and the second of annealed grains. The maximum offset between the LA–ICP–MS and TIMS measured 206Pb/238U for the unannealed zircons was 2.3%, which reduced to 0.5% for the annealed grains, as predicted by within-session precision based on counting statistics. Annealing unknown zircons and references to the same state prior to analysis holds the promise of reducing the 3% external error for the measurement of 206Pb/238U of zircon by LA–ICP–MS, indicated by Klötzli et al. (2009), to better than 1%, but more analyses of annealed zircons by other laboratories are required to evaluate the true potential of the annealing method.

Correlating flow induced shear stress and chondrocytes activity in micro-porous scaffold using computational fluid dynamics and rapid prototyping

Flow induced shear stress plays an important role in regulating cell growth and distribution in scaffolds. This study sought to correlate wall shear stress and chondrocytes activity for engineering design of micro-porous osteochondral grafts based on the hypothesis that it is possible to capture and discriminate between the transmitted force and cell response at the inner irregularities. Unlike common tissue engineering therapies with perfusion bioreactors in which flow-mediated stress is the controlling parameter, this work assigned the associated stress as a function of porosity to influence in vitro proliferation of chondrocytes. D-optimality criterion was used to accommodate three pore characteristics for appraisal in a mixed level fractional design of experiment (DOE); namely, pore size (4 levels), distribution pattern (2 levels) and density (3 levels). Micro-porous scaffolds (n=12) were fabricated according to the DOE using rapid prototyping of an acrylic-based bio-photopolymer. Computational fluid dynamics (CFD) models were created correspondingly and used on an idealized boundary condition with a Newtonian fluid domain to simulate the dynamic microenvironment inside the pores. In vitro condition was reproduced for the 3D printed constructs seeded by high pellet densities of human chondrocytes and cultured for 72 hours. The results showed that cell proliferation was significantly different in the constructs (p<0.05). Inlet fluid velocity of 3×10-2mms-1 and average shear stress of 5.65×10-2 Pa corresponded with increased cell proliferation for scaffolds with smaller pores in hexagonal pattern and lower densities. Although the analytical solution of a Poiseuille flow inside the pores was found insufficient for the description of the flow profile probably due to the outside flow induced turbulence, it showed that the shear stress would increase with cell growth and decrease with pore size. This correlation demonstrated the basis for determining the relation between the induced stress and chondrocyte activity to optimize microfabrication of engineered cartilaginous constructs.

Portfolio selection using artificial intelligence

The application of artificial intelligence in finance is relatively new area of research. This project employed artificial neural networks (ANNs) that use both fundamental and technical inputs to predict future prices of widely held Australian stocks and use these predicted prices for stock portfolio selection over a long investment horizon. The research involved the creation and testing of a large number of possible network configurations and draws conclusions about ANN architectures and their overall suitability for the purpose of stock portfolio selection.

Developing a model of links between general and workplace belongingness and depressive symptoms

Given the high prevalence of depression in the community there is urgent need to understand the interpersonal predictors of this disorder. Data from large community samples indicates that a diminished sense of belonging appears to be the most salient and immediate antecedent of a rapid depressive response. Belongingness in the workplace is also very important and associated with depressive symptoms over and above associations attributable to general or community belongingness. Finally it appears that the personality factor of interpersonal sensitivity moderates the relationship between belongingness and depressive symptoms. Results have extensive future implications for the prevention and treatment of depression.

Testing second order cyclostationarity in the squared envelope spectrum of non-white vibration signals

Cyclostationary models for the diagnostic signals measured on faulty rotating machineries have proved to be successful in many laboratory tests and industrial applications. The squared envelope spectrum has been pointed out as the most efficient indicator for the assessment of second order cyclostationary symptoms of damages, which are typical, for instance, of rolling element bearing faults. In an attempt to foster the spread of rotating machinery diagnostics, the current trend in the field is to reach higher levels of automation of the condition monitoring systems. For this purpose, statistical tests for the presence of cyclostationarity have been proposed during the last years. The statistical thresholds proposed in the past for the identification of cyclostationary components have been obtained under the hypothesis of having a white noise signal when the component is healthy. This need, coupled with the non-white nature of the real signals implies the necessity of pre-whitening or filtering the signal in optimal narrow-bands, increasing the complexity of the algorithm and the risk of losing diagnostic information or introducing biases on the result. In this paper, the authors introduce an original analytical derivation of the statistical tests for cyclostationarity in the squared envelope spectrum, dropping the hypothesis of white noise from the beginning. The effect of first order and second order cyclostationary components on the distribution of the squared envelope spectrum will be quantified and the effectiveness of the newly proposed threshold verified, providing a sound theoretical basis and a practical starting point for efficient automated diagnostics of machine components such as rolling element bearings. The analytical results will be verified by means of numerical simulations and by using experimental vibration data of rolling element bearings.

The effect of nitroxides on swarming motility and biofilms, multicellular behaviors in Pseudomonas aeruginosa

The ability of NO to induce biofilm dispersion has been well established. Here we investigated the effect of nitroxides (sterically hindered nitric oxide analogues) on biofilm formation and swarming motility in Pseudomonas aeruginosa. A transposon mutant unable to produce nitric oxide endogenously (nirS) was deficient in swarming motility relative to wild type and the complemented strain. Moreover, expression of the nirS gene was up-regulated by 9.65-fold in wild type swarming cells when compared to planktonic cells. Wild type swarming levels were substantially restored upon exogenous addition of nitroxide containing compounds, consistent with the hypothesis that NO is necessary for swarming motility. Here, we showed that nitroxides not only mimicked the dispersal activity of NO, but also prevented biofilms from forming in flow cell chambers. In addition, a nirS transposon mutant was deficient in biofilm formation relative to wild type and the complemented strain, thus implicating NO in the formation of biofilms. Intriguingly despite its stand alone action in inhibiting biofilm formation and promoting dispersal, a nitroxide partially restored the ability of a nirS mutant to form biofilms.

Ghrelin O-acyltransferase (GOAT) is expressed in prostate cancer tissues and cell lines and expression is differentially regulated in vitro by ghrelin

Background Ghrelin is a 28 amino acid peptide hormone that is expressed in the stomach and a range of peripheral tissues, where it frequently acts as an autocrine/paracrine growth factor. Ghrelin is modified by a unique acylation required for it to activate its cognate receptor, the growth hormone secretagogue receptor (GHSR), which mediates many of the actions of ghrelin. Recently, the enzyme responsible for adding the fatty acid residue (octanoyl/acyl group) to the third amino acid of ghrelin, GOAT (ghrelin O-acyltransferase), was identified. Methods We used cell culture, quantitative real-time reverse transcription (RT)-PCR and immunohistochemistry to demonstrate the expression of GOAT in prostate cancer cell lines and tissues from patients. Real-time RT-PCR was used to demonstrate the expression of prohormone convertase (PC)1/3, PC2 and furin in prostate cancer cell lines. Prostate-derived cell lines were treated with ghrelin and desacyl ghrelin and the effect on GOAT expression was measured using quantitative RT-PCR. Results We have demonstrated that GOAT mRNA and protein are expressed in the normal prostate and human prostate cancer tissue samples. The RWPE-1 and RWPE-2 normal prostate-derived cell lines and the LNCaP, DU145, and PC3 prostate cancer cell lines express GOAT and at least one other enzyme that is necessary to produce mature, acylated ghrelin from proghrelin (PC1/3, PC2 or furin). Finally, ghrelin, but not desacyl ghrelin (unacylated ghrelin), can directly regulate the expression of GOAT in the RWPE-1 normal prostate derived cell line and the PC3 prostate cancer cell line. Ghrelin treatment (100nM) for 6 hours significantly decreased GOAT mRNA expression two-fold (P < 0.05) in the PC3 prostate cancer cell line, however, ghrelin did not regulate GOAT expression in the DU145 and LNCaP prostate cancer cell lines. Conclusions This study demonstrates that GOAT is expressed in prostate cancer specimens and cell lines. Ghrelin regulates GOAT expression, however, this is likely to be cell-type specific. The expression of GOAT in prostate cancer supports the hypothesis that the ghrelin axis has autocrine/paracrine roles. We propose that the RWPE-1 prostate cell line and the PC3 prostate cancer cell line may be useful for investigating GOAT regulation and function.

Is recovery driven by central or peripheral factors? A role for the brain in recovery following intermittent-sprint exercise

Prolonged intermittent-sprint exercise (i.e., team sports) induce disturbances in skeletal muscle structure and function that are associated with reduced contractile function, a cascade of inflammatory responses, perceptual soreness, and a delayed return to optimal physical performance. In this context, recovery from exercise-induced fatigue is traditionally treated from a peripheral viewpoint, with the regeneration of muscle physiology and other peripheral factors the target of recovery strategies. The direction of this research narrative on post-exercise recovery differs to the increasing emphasis on the complex interaction between both central and peripheral factors regulating exercise intensity during exercise performance. Given the role of the central nervous system (CNS) in motor-unit recruitment during exercise, it too may have an integral role in post-exercise recovery. Indeed, this hypothesis is indirectly supported by an apparent disconnect in time-course changes in physiological and biochemical markers resultant from exercise and the ensuing recovery of exercise performance. Equally, improvements in perceptual recovery, even withstanding the physiological state of recovery, may interact with both feed-forward/feed-back mechanisms to influence subsequent efforts. Considering the research interest afforded to recovery methodologies designed to hasten the return of homeostasis within the muscle, the limited focus on contributors to post-exercise recovery from CNS origins is somewhat surprising. Based on this context, the current review aims to outline the potential contributions of the brain to performance recovery after strenuous exercise.