Diarrhoea risk factors in enterally tube fed critically ill patients : a retrospective audit

Objective: Diarrhoea in the enterally tube fed (ETF) intensive care unit (ICU) patient is a multifactorial problem. Diarrhoeal aetiologies in this patient cohort remain debatable; however, the consequences of diarrhoea have been well established and include electrolyte imbalance, dehydration, bacterial translocation, peri anal wound contamination and sleep deprivation. This study examined the incidence of diarrhoea and explored factors contributing to the development of diarrhoea in the ETF, critically ill, adult patient. ---------- Method: After institutional ethical review and approval, a single centre medical chart audit was undertaken to examine the incidence of diarrhoea in ETF, critically ill patients. Retrospective, non-probability sequential sampling was used of all emergency admission adult ICU patients who met the inclusion/exclusion criteria. ---------- Results: Fifty patients were audited. Faecal frequency, consistency and quantity were considered important criteria in defining ETF diarrhoea. The incidence of diarrhoea was 78%. Total patient diarrhoea days (r = 0.422; p = 0.02) and total diarrhoea frequency (r = 0.313; p = 0.027) increased when the patient was ETF for longer periods of time. Increased severity of illness, peripheral oxygen saturation (Sp02), glucose control, albumin and white cell count were found to be statistically significant factors for the development of diarrhoea. ---------- Conclusion: Diarrhoea in ETF critically ill patients is multi-factorial. The early identification of diarrhoea risk factors and the development of a diarrhoea risk management algorithm is recommended.

Cystine-mediated oxidative defence in Lactobacillus reuteri BR11

Lactobacillus reuteri BR11 possesses an abundant cystine uptake (Cyu) ABC-transporter that was previously found to be involved in a novel mechanism of oxidative defence mediated by cystine. The current study aimed to elucidate this mechanism with a focus on the role of the co-transcribed cystathionine ã-lyase (Cgl). Growth studies of wild-type L. reuteri BR11 and mutants inactivated in cgl and the cystine-binding protein encoding gene cyuC showed that in contrast to the Cyu transporter, whose inactivation led to growth arrest in aerated cultures, Cgl is not crucial for oxidative defence. However, the role of Cgl in oxidative defence became apparent in the presence of severe oxidative damage and cysteine deprivation. Cysteine was found to be protective against oxidative stress, and the action of Cgl in both cysteine biosynthesis and degradation poses a seemingly futile pathway that deprives the intracellular cysteine pool. To further characterise the relationship between Cgl activity and cysteine and their roles in oxidative defence, enzymatic assays were performed on purified Cgl, and intracellular concentrations of cysteine, cystathionine and methionine were determined. Cgl was highly active towards cystine and cystathionine and less active towards cysteine in vitro, suggesting the main function of Cgl to be cysteine biosynthesis. Cysteine was found at high concentrations in the cell, but the levels were not significantly affected by inactivation of cgl or growth under aerobic conditions. It was concluded that both anabolic and catabolic activities of Cgl towards cysteine contribute to oxidative defence, the former by maintaining an intracellular reservoir of thiol analogous to glutathione, and the latter by producing H2S which is readily secreted, thus creating a reducing extracellular environment. The significance of the Cyu transporter to the physiology of L. reuteri BR11 prompted a phylogenetic study to determine its presence in bacteria. Orthologs of the Cyu transporter that are closest matches to the Cyu transporter are only limited to several species of Lactobacillus and Leuconostoc. Outside the Lactobacillales order, the closest matching orthologs belong to Proteobacteria, and there are more orthologs in Proteobacteria than non-Lactobacillales Firmicutes, suggesting that the Cyu transporter locus was present in the ancestor of the Proteobacteria and Firmicutes, and over evolutionary time has been lost or diverged in many Firmicutes. The clustering of the Cyu transporter locus with a gene encoding a Cgl family protein is even rarer. It was only found in L. reuteri, Lactobacillus vaginalis, Weissella paramesenteroides, the Lactobacillus casei group, and several Campylobacter sp. An accompanying phylogenetic study of L. reuteri BR11 using multi-locus sequence analysis showed that L. reuteri BR11 had diverged from more than 100 strains of L. reuteri isolated from various hosts and geographical locations. However, comparison with other Lactobacillus species supported the current classification of BR11 as L. reuteri. The most closely related species to L. reuteri is L. vaginalis or Lactobacillus antri, depending on the housekeeping gene used for analysis. The close evolutionary relationship of L. vaginalis to L. reuteri and the high degree of sequence identity between the cgl-cyuABC loci in both species suggest that the Cyu system is highly likely to perform similar functions in L. vaginalis. In search of other genes that function in oxidative defence, a number of mutants which were inactivated in genes that confer increased resistance to oxidative stress in other bacteria were constructed. The genes targeted were ahpC (peroxidase component of the alkyl hydroperoxide reductase system), tpx (thiol peroxidase), osmC (osmotically induced protein C), mntH (Mn2+/Fe2+ transporter), gshA (ã-glutamylcysteine synthetase) and msrA (methionine sulfoxide reductase). The ahpC and mntH mutants had slightly lower minimum inhibitory concentrations of organic peroxides, suggesting these genes might be involved in resistance to organic peroxides in L. reuteri. However, none of the mutants exhibited growth defects in aerated cultures, in stark contrast to the cyuC mutant. This may be due to compensatory functions of other genes, a hypothesis which cannot be tested until a robust protocol for constructing markerless multiple gene deletion mutants in L. reuteri is developed. These results highlight the importance of the Cyu transporter in oxidative defence and provide a foundation for extending the research of this system in other bacteria.

Continuous appearance-based trajectory SLAM

This paper describes a novel probabilistic approach to incorporating odometric information into appearance-based SLAM systems, without performing metric map construction or calculating relative feature geometry. The proposed system, dubbed Continuous Appearance-based Trajectory SLAM (CAT-SLAM), represents location as a probability distribution along a trajectory, and represents appearance continuously over the trajectory rather than at discrete locations. The distribution is evaluated using a Rao-Blackwellised particle filter, which weights particles based on local appearance and odometric similarity and explicitly models both the likelihood of revisiting previous locations and visiting new locations. A modified resampling scheme counters particle deprivation and allows loop closure updates to be performed in constant time regardless of map size. We compare the performance of CAT-SLAM to FAB-MAP (an appearance-only SLAM algorithm) in an outdoor environment, demonstrating a threefold increase in the number of correct loop closures detected by CAT-SLAM.

The psychological impact of industrial strikes: Does involvement in union activity during strikes make a difference?

The current study investigated the psychological impact of a United Steelworkers of America strike on the steelworkers involved, and the relationship between psychological well-being and individuals' levels of involvement in union activity during the strike. Three hundred and fifty-one steelworkers (302 `strikers' and 49 `non-strikers') completed surveys measuring a range of demographic and psychological well-being variables. Strikers, compared to non-strikers, reported higher levels of depression, anxiety, and irritation, and lower levels of mental health. For strikers, engaging in higher levels of union activity during the strike was associated with better psychological well-being. Jahoda's theory of deprivation during unemployment is used as the lens through which to explain some of the results, supporting the view that latent benefits associated with work are important for psychological well-being. A range of practical implications are offered for unions and their members.

Broadening of transgenic adenocarcinoma of the mouse prostate (TRAMP) model to represent late stage androgen depletion independent cancer

BACKGROUND The transgenic adenocarcinoma of the mouse prostate (TRAMP) model closely mimics PC-progression as it occurs in humans. However, the timing of disease incidence and progression (especially late stage) makes it logistically difficult to conduct experiments synchronously and economically. The development and characterization of androgen depletion independent (ADI) TRAMP sublines are reported. METHODS Sublines were derived from androgen-sensitive TRAMP-C1 and TRAMP-C2 cell lines by androgen deprivation in vitro and in vivo. Epithelial origin (cytokeratin) and expression of late stage biomarkers (E-cadherin and KAI-1) were evaluated using immunohistochemistry. Androgen receptor (AR) status was assessed through quantitative real time PCR, Western blotting, and immunohistochemistry. Coexpression of AR and E-cadherin was also evaluated. Clonogenicity and invasive potential were measured by soft agar and matrigel invasion assays. Proliferation/survival of sublines in response to androgen was assessed by WST-1 assay. In vivo growth of subcutaneous tumors was assessed in castrated and sham-castrated C57BL/6 mice. RESULTS The sublines were epithelial and displayed ADI in vitro and in vivo. Compared to the parental lines, these showed (1) significantly faster growth rates in vitro and in vivo independent of androgen depletion, (2) greater tumorigenic, and invasive potential in vitro. All showed substantial downregulation in expression levels of tumor suppressor, E-cadherin, and metastatis suppressor, KAI-1. Interestingly, the percentage of cells expressing AR with downregulated E-cadherin was higher in ADI cells, suggesting a possible interaction between the two pathways. CONCLUSIONS The TRAMP model now encompasses ADI sublines potentially representing different phenotypes with increased tumorigenicity and invasiveness.

Ocular characteristics of anisometropia

Animal models of refractive error development have demonstrated that visual experience influences ocular growth. In a variety of species, axial anisometropia (i.e. a difference in the length of the two eyes) can be induced through unilateral occlusion, image degradation or optical manipulation. In humans, anisometropia may occur in isolation or in association with amblyopia, strabismus or unilateral pathology. Non-amblyopic myopic anisometropia represents an interesting anomaly of ocular growth, since the two eyes within one visual system have grown to different endpoints. These experiments have investigated a range of biometric, optical and mechanical properties of anisometropic eyes (with and without amblyopia) with the aim of improving our current understanding of asymmetric refractive error development. In the first experiment, the interocular symmetry in 34 non-amblyopic myopic anisometropes (31 Asian, 3 Caucasian) was examined during relaxed accommodation. A high degree of symmetry was observed between the fellow eyes for a range of optical, biometric and biomechanical measurements. When the magnitude of anisometropia exceeded 1.75 D, the more myopic eye was almost always the sighting dominant eye. Further analysis of the optical and biometric properties of the dominant and non-dominant eyes was conducted to determine any related factors but no significant interocular differences were observed with respect to best-corrected visual acuity, corneal or total ocular aberrations during relaxed accommodation. Given the high degree of symmetry observed between the fellow eyes during distance viewing in the first experiment and the strong association previously reported between near work and myopia development, the aim of the second experiment was to investigate the symmetry between the fellow eyes of the same 34 myopic anisometropes following a period of near work. Symmetrical changes in corneal and total ocular aberrations were observed following a short reading task (10 minutes, 2.5 D accommodation demand) which was attributed to the high degree of interocular symmetry for measures of anterior eye morphology, and corneal biomechanics. These changes were related to eyelid shape and position during downward gaze, but gave no clear indication of factors associated with near work that might cause asymmetric eye growth within an individual. Since the influence of near work on eye growth is likely to be most obvious during, rather than following near tasks, in the third experiment the interocular symmetry of the optical and biometric changes was examined during accommodation for 11 myopic anisometropes. The changes in anterior eye biometrics associated with accommodation were again similar between the eyes, resulting in symmetrical changes in the optical characteristics. However, the more myopic eyes exhibited slightly greater amounts of axial elongation during accommodation which may be related to the force exerted by the ciliary muscle. This small asymmetry in axial elongation we observed between the eyes may be due to interocular differences in posterior eye structure, given that the accommodative response was equal between eyes. Using ocular coherence tomography a reduced average choroidal thickness was observed in the more myopic eyes compared to the less myopic eyes of these subjects. The interocular difference in choroidal thickness was correlated with the magnitude of spherical equivalent and axial anisometropia. The symmetry in optics and biometrics between fellow eyes which have undergone significantly different visual development (i.e. anisometropic subjects with amblyopia) is also of interest with respect to refractive error development. In the final experiment the influence of altered visual experience upon corneal and ocular higher-order aberrations was investigated in 21 amblyopic subjects (8 refractive, 11 strabismic and 2 form deprivation). Significant differences in aberrations were observed between the fellow eyes, which varied according to the type of amblyopia. Refractive amblyopes displayed significantly higher levels of 4th order corneal aberrations (spherical aberration and secondary astigmatism) in the amblyopic eye compared to the fellow non-amblyopic eye. Strabismic amblyopes exhibited significantly higher levels of trefoil, a third order aberration, in the amblyopic eye for both corneal and total ocular aberrations. The results of this experiment suggest that asymmetric visual experience during development is associated with asymmetries in higher-order aberrations, proportional to the magnitude of anisometropia and dependent upon the amblyogenic factor. This suggests a direct link between the development of higher-order optical characteristics of the human eye and visual feedback. The results from these experiments have shown that a high degree of symmetry exists between the fellow eyes of non-amblyopic myopic anisometropes for a range of biomechanical, biometric and optical parameters for different levels of accommodation and following near work. While a single specific optical or biomechanical factor that is consistently associated with asymmetric refractive error development has not been identified, the findings from these studies suggest that further research into the association between ocular dominance, choroidal thickness and higher-order aberrations with anisometropia may improve our understanding of refractive error development.

Long-evans rats acquire operant self-administration of 20% ethanol without sucrose fading

A major obstacle in the development of new medications for the treatment of alcohol use disorders (AUDs) has been the lack of preclinical, oral ethanol consumption paradigms that elicit high consumption. We have previously shown that rats exposed to 20% ethanol intermittently in a two-bottle choice paradigm will consume two times more ethanol than those given continuous access without the use of water deprivation or sucrose fading (5-6 g/kg every 24 h vs 2-3 g/kg every 24 h, respectively). In this study, we have adapted the model to an operant self-administration paradigm. Long-Evans rats were given access to 20% ethanol in overnight sessions on one of two schedules: (1) intermittent (Monday, Wednesday, and Friday) or (2) daily (Monday through Friday). With the progression of the overnight sessions, both groups showed a steady escalation in drinking (3-6 g/kg every 14 h) without the use of a sucrose-fading procedure. Following the acquisition phase, the 20% ethanol groups consumed significantly more ethanol than did animals trained to consume 10% ethanol with a sucrose fade (1.5 vs 0.7 g/kg every 30 min) and reached significantly higher blood ethanol concentrations. In addition, training history (20% ethanol vs 10% ethanol with sucrose fade) had a significant effect on the subsequent self-administration of higher concentrations of ethanol. Administration of the pharmacological stressor yohimbine following extinction caused a significant reinstatement of ethanol-seeking behavior. Both 20% ethanol models show promise and are amenable to the study of maintenance, motivation, and reinstatement. Furthermore, training animals to lever press for ethanol without the use of sucrose fading removes a potential confound from self-administration studies. © 2010 Nature Publishing Group All rights reserved.

Safeguarding rural Australia: addressing masculinity and violence in rural settings : intentional violent harm to others in an Australian rural context: analysis of secondary data analysis

This report is an update of an earlier one produced in January 2010 (see Carrington et al. 2010) which remains as an ePrint through the project’s home page. This report focuses on our examination of extant data which have been sourced with respect to intentional violence perpetrated or experienced by males living in regional and remote Australia . and which were available in public data bases at production. The nature of intentional violent acts can be physical, sexual or psychological or involve deprivation or neglect.

The role of near adaptation in myopia development

Prolonged near work is associated with myopia development in children and young adults but the reason underlying this association is unknown. Two potentially important factors are the near work induced ocular adaptations of contrast and accommodative adaptation. This study measured the degrees of contrast and accommodative adaptation during and following reading in myopic and emmetropic children and young adults in Singapore, where myopia is highly prevalent. Reading caused significantly greater contrast and accommodative adaptations in myopic children and myopic young adults compared to that measured in emmetropes of comparable ages. The adaptations were greater in magnitude in children than young adults, suggesting that children are more susceptible to ocular changes induced by reading and thus are potentially at greater risk of adverse refractive outcomes from these adaptations. In addition to the magnitude of the adaptations the regression time of these adaptations, (i.e. their durations) are also important. Longer accommodative adaptation regression times were measured for myopic children than for emmetropic children. Although the regression of contrast adaptation was not measured, its duration may likewise be important. The refractive effects of both of these adaptations are likely to be cumulative across the day and this could promote myopia in susceptible individuals performing considerable amounts of near work. Whether the type of text read affected the magnitude of the adaptations was also explored. Given the high prevalence of myopia in Chinese children and the fact that Chinese text is more complicated to write than English text, it was hypothesized that Chinese text would induce greater adaptation. However, both Chinese and English text produced similar amounts of accommodative and contrast adaptation in young adult subjects. We propose that children who spend prolonged periods reading at a young age are most vulnerable to near work induced adaptations and hence near work induced myopia. Both Chinese and English texts produce these effects and we propose that these adaptations are likely to occur for all types of common reading texts.

The role of insulin and IGF2 signalling on metabolic pathways in prostate cancer progression

Prostate cancer (CaP) is the most commonly diagnosed cancer in males in Australia, North America, and Europe. If found early and locally confined, CaP can be treated with radical prostatectomy or radiation therapy; however, 25-40% patients will relapse and go on to advanced disease. The most common therapy in these cases is androgen deprivation therapy (ADT), which suppresses androgen production from the testis. Lack of the testicular androgen supply causes cells of the prostate to undergo apoptosis. However, in some cases the regression initially seen with ADT eventually gives way to a growth of a population of cancerous cells that no longer require testicular androgens. This phenotype is essentially fatal and is termed castrate resistant prostate cancer (CRPC). In addition to eventual regression, there are many undesirable side effects which accompany ADT, including development of a metabolic syndrome, which is defined by the U.S. National Library of Medicine as “a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes.” This project will focus on the effect of ADT induced hyperinsulinemia, as mimicked by treating androgen receptor positive CaP cells with insulin in a serum (hormone) deprived environment. While this side effect is not widely explored, in this thesis it is demonstrated for the first time that insulin upregulates pathways important to CaP progression. Our group has previously shown that during CaP progression, the enzymes necessary for de novo steroidogenesis are upregulated in the LNCaP xenograft model, total steroid levels are increased in tumours compared to pre castrate levels, and de novo steroidogenesis from radio-labelled acetate has been demonstrated. Because of the CaP dependence on AR for survival, we and other groups believe that CaP cells carry out de novo steroidogenesis to survive in androgen deprived conditions. Because (a) men on ADT often develop metabolic syndrome, and (b) men with lifestyle-induced obesity and hyperinsulinemia have worse prognosis and faster disease progression, and because (c) insulin causes steroidogenesis in other cell lines, the hypothesis that insulin may contribute to CaP progression through upregulation of steroidogenesis was explored. Insulin upregulates steroidogenesis enzymes at the mRNA level in three AR positive cell lines, as well as upregulating these enzymes at the protein level in two cell lines. It has also been demonstrated that insulin increases mitochondrial (functional) levels of steroid acute regulatory protein (StAR). Furthermore, insulin causes increased levels of total steroids in and induction of de novo steroid synthesis by insulin has been demonstrated at levels induced sufficient to activate AR. The effect of insulin analogs on CaP steroidogenesis in LNCaP and VCaP cells has also been investigated because epidemiological studies suggest that some of the analogs developed may have more cancer stimulatory effects than normal insulin. In this project, despite the signalling differences between glargine, X10, and insulin, these analogs did not appear to induce steroidogenesis any more potently that normal insulin. The effect of insulin of MCF7breast cancer cells was also investigated with results suggesting that breast cancer cells may be capable of de novo steroidogenesis, and that increase in estradiol production may be exacerbated by insulin. Insulin has also been long known to stimulate lipogenesis in the liver and adipocytes, and has been demonstrated to increase lipogenesis in breast cancer cells; therefore, investigation of the effect of insulin on lipogenesis, which is a hallmark of aggressive cancers, was investigated. In CaP progression sterol regulatory element binding protein (SREBP) is dysregulated and upregulates fatty acid synthase (FASN), acetyl CoA-carboxylase, and other lipogenesis genes. SREBP is important for steroidogenesis and in this project has been shown to be upregulated by insulin in CaP cells. Fatty acid synthesis provides building blocks of membrane growth, provides substrates for acid oxidation, the main energy source for CaP cells, provides building blocks for anti-apoptotic and proinflammatory molecules, and provides molecules that stimulate steroidogenesis. In this project it has been shown that insulin upregulates FASN and ACC, which synthesize fatty acids, as well as upregulating hormone sensitive lipase (HSL), diazepam-binding inhibitor (DBI), and long-chain acyl-CoA synthetase 3 (ACSL3), which contribute to lipid activation of steroidogenesis. Insulin also upregulates total lipid levels and de novo lipogenesis, which can be suppressed by inhibition of the insulin receptor (INSR). The fatty acids synthesized after insulin treatment are those that have been associated with CaP; furthermore, microarray data suggests insulin may upregulate fatty acid biosynthesis, metabolism and arachidonic acid metabolism pathways, which have been implicated in CaP growth and survival. Pharmacological agents used to treat patients with hyperinsulinemia/ hyperlipidemia have gained much interest in regards to CaP risk and treatment; however, the scientific rationale behind these clinical applications has not been examined. This thesis explores whether the use of metformin or simvastatin would decrease either lipogenesis or steroidogenesis or both in CaP cells. Simvastatin is a 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) inhibitor, which blocks synthesis of cholesterol, the building block of steroids/ androgens. It has also been postulated to down regulate SREBP in other metabolic disorders. It has been shown in this thesis, in LNCaP cells, that simvastatin inhibited and decreased insulin induced steroidogenesis and lipogenesis, respectively, but increased these pathways in the absence of insulin. Conversely, metformin, which activates AMP-activated protein kinase (AMPK) to shut down lipogenesis, cholesterol synthesis, and protein synthesis, highly suppresses both steroidogenesis and lipogenesis in the presence and absence of insulin. Lastly, because it has been demonstrated to increase steroidogenesis in other cell lines, and because the elucidation of any factors affecting steroidogenesis is important to understanding CaP, the effect of IGF2 on steroidogenesis in CaP cells was investigated. In patient samples, as men progress to CRPC, IGF2 mRNA and the protein levels of the receptors it may signal through are upregulated. It has also been demonstrated that IGF2 upregulates steroidogenic enzymes at both the mRNA and protein levels in LNCaP cells, increases intracellular and secreted steroid/androgen levels in LNCaPs to levels sufficient to stimulate the AR, and upregulated de novo steroidogenesis in LNCaPs and VCaPs. As well, inhibition of INSR and insulin-like growth factor 1 receptor (IGF1R), which IGF2 signals through, suggests that induction of steroidogenesis may be occurring predominantly through IGF1R. In summary, this project has illuminated for the first time that insulin is likely to play a large role in cancer progression, through upregulation of the steroidogenesis and lipogenesis pathways at the mRNA and protein levels, and production levels, and demonstrates a novel role for IGF-II in CaP progression through stimulation of steroidogenesis. It has also been demonstrated that metformin and simvastatin drugs may be useful in suppressing the insulin induction of these pathways. This project affirms the pathways by which ADT- induced metabolic syndrome may exacerbate CaP progression and strongly suggests that the monitoring and modulation of the metabolic state of CaP patients could have a strong impact on their therapeutic outcomes.

CAT-SLAM : probabilistic localisation and mapping using a continuous appearance-based trajectory

This paper describes a new system, dubbed Continuous Appearance-based Trajectory Simultaneous Localisation and Mapping (CAT-SLAM), which augments sequential appearance-based place recognition with local metric pose filtering to improve the frequency and reliability of appearance-based loop closure. As in other approaches to appearance-based mapping, loop closure is performed without calculating global feature geometry or performing 3D map construction. Loop-closure filtering uses a probabilistic distribution of possible loop closures along the robot’s previous trajectory, which is represented by a linked list of previously visited locations linked by odometric information. Sequential appearance-based place recognition and local metric pose filtering are evaluated simultaneously using a Rao–Blackwellised particle filter, which weights particles based on appearance matching over sequential frames and the similarity of robot motion along the trajectory. The particle filter explicitly models both the likelihood of revisiting previous locations and exploring new locations. A modified resampling scheme counters particle deprivation and allows loop-closure updates to be performed in constant time for a given environment. We compare the performance of CAT-SLAM with FAB-MAP (a state-of-the-art appearance-only SLAM algorithm) using multiple real-world datasets, demonstrating an increase in the number of correct loop closures detected by CAT-SLAM.

Stop and revive? : the effectiveness of nap and active rest breaks for reducing driver sleepiness

The incidence of sleep-related crashes has been estimated to account for approximately 20% of all fatal and severe crashes. The use of sleepiness countermeasures by drivers is an important component to reduce the incidence rates of sleep-related crashes. Taking a brief nap and stopping for a rest break are two highly publicised countermeasures for driver sleepiness and are also believed by drivers to be the most effective countermeasures. Despite this belief, there is scarce evidence to support the utility of these countermeasures for reducing driver sleepiness levels. Therefore, determining the effectiveness of these countermeasures is an important road safety concern. The current study utilised a young adult sample (N = 20) to investigate the effectiveness of a nap and an active rest break. The countermeasures effects were evaluated by physiological, behavioural (hazard perception skill), and subjective measures previously found sensitive to sleepiness. Participants initially completed two hours of a simulated driving task followed by a 15 minute nap opportunity or a 15 minute active rest break that included 10 minutes of brisk walking. After the break, participants completed one final hour of the simulated driving task. A within-subjects design was used so that each participant completed both the nap and the active rest break conditions on separate occasions. The analyses revealed that only the nap break provided any meaningful reduction in physiological sleepiness, reduced subjective sleepiness levels, and maintained hazard perception performance. In contrast, the active rest break had no effect for reducing physiological sleepiness and resulted in a decrement in hazard perception performance (i.e., an increase of reaction time latencies), with a transient reduction in subjective sleepiness levels. A number of theoretical, empirical and practical issues were identified by the current study.

The role of insulin in advanced prostate cancer

Advanced prostate cancer is a common and generally incurable disease. Androgen deprivation therapy is used to treat advanced prostate cancer with good benefits to quality of life and regression of disease. Prostate cancer invariably progresses however despite ongoing treatment, to a castrate resistant state. Androgen deprivation is associated with a form of metabolic syndrome, which includes insulin resistance and hyperinsulinaemia. The mitogenic and anti-apoptotic properties of insulin acting through the insulin and hybrid insulin/IGF-1 receptors seem to have positive effects on prostate tumour growth. This pilot study was designed to assess any correlation between elevated insulin levels and progression to castrate resistant prostate cancer. Methods: 36 men receiving ADT for advanced prostate cancer were recruited, at various stages of their treatment, along with 47 controls, men with localised prostate cancer pre-treatment. Serum measurements of C-peptide (used as a surrogate marker for insulin production) were performed and compared between groups. Correlation between serum C-peptide level and time to progression to castrate resistant disease was assessed. Results: There was a significant elevation of C-peptide levels in the ADT group (mean = 1639pmol/L)) compared to the control group (mean = 1169pmol/L), with a p-value of 0.025. In 17 men with good initial response to androgen deprivation, a small negative trend towards earlier progression to castrate resistance with increasing C-peptide level was seen in the ADT group (r = -0.050), however this did not reach statistical significance (p>0.1). Conclusions: This pilot study confirms an increase in serum C-peptide levels in men receiving ADT for advance prostate cancer. A non-significant, but negative trend towards earlier progression to castrate resistance with increasing C-peptide suggests the need for a formal prospective study assessing this hypothesis.

Friedman Economic Policies, Social Exclusion and Crime: Toward a Gendered Left Realist Subcultural Theory.

Left realists contend that people lacking legitimate means of solving the problem of relative deprivation may come into contact with other frustrated disenfranchised people and form subcultures, which in turn, encourage criminal behaviors. Absent from this theory is an attempt to address how, today, subcultural development in North America and elsewhere is heavily shaped simultaneously by the recent destructive consequences of right-wing Friedman or Chicago School economic policies and marginalized men's attempts to live up to the principles of hegemonic masculinity. The purpose of this paper, then, is to offer a new left realist theory that emphasizes the contribution of these two key determinants.

The influence of smoking status on malnutrition risk and 1-year mortality in outpatients with chronic obstructive pulmonary disease.

Introduction:  Smoking status in outpatients with chronic obstructive pulmonary disease (COPD) has been associated with a low body mass index (BMI) and reduced mid-arm muscle circumference (Cochrane & Afolabi, 2004). Individuals with COPD identified as malnourished have also been found to be twice as likely to die within 1 year compared to non-malnourished patients (Collins et al., 2010). Although malnutrition is both preventable and treatable, it is not clear what influence current smoking status, another modifiable risk factor, has on malnutrition risk. The current study aimed to establish the influence of smoking status on malnutrition risk and 1-year mortality in outpatients with COPD. Methods:  A prospective nutritional screening survey was carried out between July 2008 and May 2009 at a large teaching hospital (Southampton General Hospital) and a smaller community hospital within Hampshire (Lymington New Forest Hospital). In total, 424 outpatients with a diagnosis of COPD were routinely screened using the ‘Malnutrition Universal Screening Tool’, ‘MUST’ (Elia, 2003); 222 males, 202 females; mean (SD) age 73 (9.9) years; mean (SD) BMI 25.9 (6.4) kg m−2. Smoking status on the date of screening was obtained for 401 of the outpatients. Severity of COPD was assessed using the GOLD criteria, and social deprivation determined using the Index of Multiple Deprivation (Nobel et al., 2008). Results:  The overall prevalence of malnutrition (medium + high risk) was 22%, with 32% of current smokers at risk (who accounted for 19% of the total COPD population). In comparison, 19% of nonsmokers and ex-smokers were likely to be malnourished [odds ratio, 1.965; 95% confidence interval (CI), 1.133–3.394; P = 0.015]. Smoking status remained an independent risk factor for malnutrition even after adjustment for age, social deprivation and disease-severity (odds ratio, 2.048; 95% CI, 1.085–3.866; P = 0.027) using binary logistic regression. After adjusting for age, disease severity, social deprivation, smoking status, malnutrition remained a significant predictor of 1-year mortality [odds ratio (medium + high risk versus low risk), 2.161; 95% CI, 1.021–4.573; P = 0.044], whereas smoking status did not (odds ratio for smokers versus ex-smokers + nonsmokers was 1.968; 95% CI, 0.788–4.913; P = 0.147). Discussion:  This study highlights the potential importance of combined nutritional support and smoking cessation in order to treat malnutrition. The close association between smoking status and malnutrition risk in COPD suggests that smoking is an important consideration in the nutritional management of malnourished COPD outpatients. Conclusions:  Smoking status in COPD outpatients is a significant independent risk factor for malnutrition and a weaker (nonsignificant) predictor of 1-year mortality. Malnutrition significantly predicted 1 year mortality. References:  Cochrane, W.J. & Afolabi, O.A. (2004) Investigation into the nutritional status, dietary intake and smoking habits of patients with chronic obstructive pulmonary disease. J. Hum. Nutr. Diet.17, 3–11. Collins, P.F., Stratton, R.J., Kurukulaaratchym R., Warwick, H. Cawood, A.L. & Elia, M. (2010) ‘MUST’ predicts 1-year survival in outpatients with chronic obstructive pulmonary disease. Clin. Nutr.5, 17. Elia, M. (Ed) (2003) The ‘MUST’ Report. BAPEN. http://www.bapen.org.uk (accessed on March 30 2011). Nobel, M., McLennan, D., Wilkinson, K., Whitworth, A. & Barnes, H. (2008) The English Indices of Deprivation 2007. http://www.communities.gov.uk (accessed on March 30 2011).