Proteomic and other analyses to determine the functional consequences of deregulated kallikrein-related peptidase (KLK) expression in prostate and ovarian cancer

Rapidly developing proteomic tools are improving detection of deregulated kallikrein-related peptidase (KLK) expression, at the protein level, in prostate and ovarian cancer, as well as facilitating the determination of functional consequences downstream. Mass spectrometry (MS)-driven proteomics uniquely allows for the detection, identification and quantification of thousands of proteins in a complex protein pool, and this has served to identify certain KLKs as biomarkers for these diseases. In this review we describe applications of this technology in KLK biomarker discovery, and elucidate MS-based techniques which have been used for unbiased, global screening of KLK substrates within complex protein pools. Although MS-based KLK degradomic studies are limited to date, they helped to discover an array of novel KLK substrates. Substrates identified by MS-based degradomics are reported with improved confidence over those determined by incubating a purified or recombinant substrate and protease of interest, in vitro. We propose that these novel proteomic approaches represent the way forward for KLK research, in order to correlate proteolysis of biological substrates with tissue-related consequences, toward clinical targeting of KLK expression and function for cancer diagnosis, prognosis and therapies.

Disclosure of climate change-related corporate governance practices

Based on a survey of climate change experts in different stakeholder groups and interviews with corporate climate change managers, this study provides insights into the gap between what information stakeholders expect and what Australian corporations disclose. This paper focuses on annual reports and sustainability reports with specific reference to the disclosure of climate change-related corporate governance practices. The findings culminate in the refinement of a best practice index for the disclosure of climate-change-related corporate governance practises. Interview results indicate that the low levels of disclosures made by Australian companies may be due to a number of factors. These include a potential expectations gap, the absence of pressure from powerful stakeholders, a concern for stakeholder information overload, the cost of providing information, limited perceived accountability for climate change, and preferring other media for disclosure.

Assessment of driving-related performance in chronic whiplash using an advanced driving simulator

Driving is often nominated as problematic by individuals with chronic whiplash associated disorders (WAD), yet driving-related performance has not been evaluated objectively. The purpose of this study was to test driving-related performance in persons with chronic WAD against healthy controls of similar age, gender and driving experience to determine if driving-related performance in the WAD group was sufficiently impaired to recommend fitness to drive assessment. Driving-related performance was assessed using an advanced driving simulator during three driving scenarios; freeway, residential and a central business district (CBD). Total driving duration was approximately 15 min. Five driving tasks which could cause a collision (critical events) were included in the scenarios. In addition, the effect of divided attention (identify red dots projected onto side or rear view mirrors) was assessed three times in each scenario. Driving performance was measured using the simulator performance index (SPI) which is calculated from 12 measures. z-Scores for all SPI measures were calculated for each WAD subject based on mean values of the control subjects. The z-scores were then averaged for the WAD group. A z-score of ≤−2 indicated a driving failing grade in the simulator. The number of collisions over the five critical events was compared between the WAD and control groups as was reaction time and missed response ratio in identifying the red dots. Seventeen WAD and 26 control subjects commenced the driving assessment. Demographic data were comparable between the groups. All subjects completed the freeway scenario but four withdrew during the residential and eight during the CBD scenario because of motion sickness. All scenarios were completed by 14 WAD and 17 control subjects. Mean z-scores for the SPI over the three scenarios was statistically lower in the WAD group (−0.3 ± 0.3; P < 0.05) but the score was not below the cut-off point for safe driving. There were no differences in the reaction time and missed response ratio in divided attention tasks between the groups (All P > 0.05). Assessment of driving in an advanced driving simulator for approximately 15 min revealed that driving-related performance in chronic WAD was not sufficiently impaired to recommend the need for fitness to drive assessment.

Sports participation and health-related behaviors among US youth

Objective To examine the relationship between sports participation and health-related behaviors among high school students. Design Cross-sectional design using data from the 1997 Centers for Disease Control and Prevention Youth Risk Behavior Survey. Participants A nationally representative sample of 14221 US high school students. Main Outcome Measures Prevalence of sports participation among males and females from 3 ethnic groups and its associations with other health behaviors, including diet, tobacco use, alcohol and illegal drug use, sexual activity, violence, and weight loss practices. Results Approximately 70% of male students and 53% of female students reported participating on 1 or more spores teams in school and/or nonschool settings; rates varied substantially by age, sex, and ethnicity. Male sports participants were more likely than male nonparticipants to report fruit and vegetable consumption on the previous day and less likely to report cigarette smelting, cocaine and other illegal drug use, and trying to lose weight. Compared with female nonparticipants, female sports participants were more likely to report consumption of vegetables on the previous day and less likely to report having sexual intercourse in the past 3 months. Among white males and females, several other beneficial health behaviors were associated with sports participation. A few associations with. negative health behaviors were observed in African American and Hispanic subgroups. Conclusion Sports participation is highly prevalent among US high school students, and is associated with numerous positive health behaviors and few negative health behaviors.

On secure multi-party computation in black-box groups

We study the natural problem of secure n-party computation (in the passive, computationally unbounded attack model) of the n-product function f G (x 1,...,x n ) = x 1 ·x 2 ⋯ x n in an arbitrary finite group (G,·), where the input of party P i is x i  ∈ G for i = 1,...,n. For flexibility, we are interested in protocols for f G which require only black-box access to the group G (i.e. the only computations performed by players in the protocol are a group operation, a group inverse, or sampling a uniformly random group element). Our results are as follows. First, on the negative side, we show that if (G,·) is non-abelian and n ≥ 4, then no ⌈n/2⌉-private protocol for computing f G exists. Second, on the positive side, we initiate an approach for construction of black-box protocols for f G based on k-of-k threshold secret sharing schemes, which are efficiently implementable over any black-box group G. We reduce the problem of constructing such protocols to a combinatorial colouring problem in planar graphs. We then give two constructions for such graph colourings. Our first colouring construction gives a protocol with optimal collusion resistance t < n/2, but has exponential communication complexity O(n*2t+1^2/t) group elements (this construction easily extends to general adversary structures). Our second probabilistic colouring construction gives a protocol with (close to optimal) collusion resistance t < n/μ for a graph-related constant μ ≤ 2.948, and has efficient communication complexity O(n*t^2) group elements. Furthermore, we believe that our results can be improved by further study of the associated combinatorial problems.

In Response: "Oral versus IV treatment for catheter-related bloodstream infections - by Burke A. Cunha"

In his letter Cunha suggests that oral antibiotic therapy is safer and less expensive than intravenous therapy via central venous catheters (CVCs) (1). The implication is that costs will fall and increased health benefits will be enjoyed resulting in a gain in efficiency within the healthcare system. CVCs are often used in critically ill patients to deliver antimicrobial therapy, but expose patients to a risk of catheter-related bloodstream infection (CRBSI). Our current knowledge about the efficiency (i.e. costeffectiveness) of allocating resources toward interventions that prevent CRBSI in patients requiring a CVC has already been reviewed (2). If for some patient groups antimicrobial therapy can be delivered orally, instead of through a CVC, then the costs and benefits of this alternate strategy should be evaluated...

Decision support system for age-related macular degeneration using discrete wavelet transform

Age-related macular degeneration (AMD) affects the central vision and subsequently may lead to visual loss in people over 60 years of age. There is no permanent cure for AMD, but early detection and successive treatment may improve the visual acuity. AMD is mainly classified into dry and wet type; however, dry AMD is more common in aging population. AMD is characterized by drusen, yellow pigmentation, and neovascularization. These lesions are examined through visual inspection of retinal fundus images by ophthalmologists. It is laborious, time-consuming, and resource-intensive. Hence, in this study, we have proposed an automated AMD detection system using discrete wavelet transform (DWT) and feature ranking strategies. The first four-order statistical moments (mean, variance, skewness, and kurtosis), energy, entropy, and Gini index-based features are extracted from DWT coefficients. We have used five (t test, Kullback–Lieber Divergence (KLD), Chernoff Bound and Bhattacharyya Distance, receiver operating characteristics curve-based, and Wilcoxon) feature ranking strategies to identify optimal feature set. A set of supervised classifiers namely support vector machine (SVM), decision tree, k -nearest neighbor ( k -NN), Naive Bayes, and probabilistic neural network were used to evaluate the highest performance measure using minimum number of features in classifying normal and dry AMD classes. The proposed framework obtained an average accuracy of 93.70 %, sensitivity of 91.11 %, and specificity of 96.30 % using KLD ranking and SVM classifier. We have also formulated an AMD Risk Index using selected features to classify the normal and dry AMD classes using one number. The proposed system can be used to assist the clinicians and also for mass AMD screening programs.

Effect of the increase in "alcopops" tax on alcohol-related harms in young people : a controlled interrupted time series

Objective: To measure alcohol-related harms to the health of young people presenting to emergency departments (EDs) of Gold Coast public hospitals before and after the increase in the federal government "alcopops" tax in 2008. Design, setting and participants: Interrupted time series analysis over 5 years (28 April 2005 to 27 April 2010) of 15-29-year-olds presenting to EDs with alcohol-related harms compared with presentations of selected control groups. Main outcome measures: Proportion of 15-29-year-olds presenting to EDs with alcohol-related harms compared with (i) 30-49-year-olds with alcohol-related harms, (ii)15-29-year-olds with asthma or appendicitis, and (iii) 15-29-yearolds with any non-alcohol and non-injury related ED presentation. Results: Over a third of 15-29-year-olds presented to ED with alcohol-related conditions, as opposed to around a quarter for all other age groups. There was no significant decrease in alcohol-related ED presentations of 15-29-year-olds compared with any of the control groups after the increase in the tax. We found similar results for males and females, narrow and broad definitions of alcoholrelated harms, under-19s, and visitors to and residents of the Gold Coast. Conclusions: The increase in the tax on al copops was not associated with any reduction in alcohol-related harms in this population in a unique tourist and holiday region. A more comprehensive approach to reducing alcohol harms in young people is needed.

Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Functional magnetic resonance brain imaging of executive cognitive performance in young first-episode schizophrenia patients and age-matched long-term cannabis users

Converging evidence from epidemiological, clinical and neuropsychological research suggests a link between cannabis use and increased risk of psychosis. Long-term cannabis use has also been related to deficit-like “negative” symptoms and cognitive impairment that resemble some of the clinical and cognitive features of schizophrenia. The current functional brain imaging study investigated the impact of a history of heavy cannabis use on impaired executive function in first-episode schizophrenia patients. Whilst performing the Tower of London task in a magnetic resonance imaging scanner, event-related blood oxygenation level-dependent (BOLD) brain activation was compared between four age and gender-matched groups: 12 first-episode schizophrenia patients; 17 long-term cannabis users; seven cannabis using first-episode schizophrenia patients; and 17 healthy control subjects. BOLD activation was assessed as a function of increasing task difficulty within and between groups as well as the main effects of cannabis use and the diagnosis of schizophrenia. Cannabis users and non-drug using first-episode schizophrenia patients exhibited equivalently reduced dorsolateral prefrontal activation in response to task difficulty. A trend towards additional prefrontal and left superior parietal cortical activation deficits was observed in cannabis-using first-episode schizophrenia patients while a history of cannabis use accounted for increased activation in the visual cortex. Cannabis users and schizophrenia patients fail to adequately activate the dorsolateral prefrontal cortex, thus pointing to a common working memory impairment which is particularly evident in cannabis-using first-episode schizophrenia patients. A history of heavy cannabis use, on the other hand, accounted for increased primary visual processing, suggesting compensatory imagery processing of the task.

Age related differences in the validity of the OMNI perceived exertion scale during lifestyle activities

PURPOSE The OMNI Perceived Exertion Scale was developed for children to report perceived effort while performing physical activity; however no studies have formally examined age-related differences in validity. This study evaluated the validity of the OMNI-RPE in four age groups performing a range of lifestyle activities. METHODS 206 participants were stratified into four age groups: 6-8 years (n = 42), 9-10 years (n = 46), 11-12 years (n = 47), and 13-15 years (n = 71). Heart rate and VO2 were measured during 11 activity trials ranging in intensity from sedentary to vigorous. After each trial, participants reported effort from the OMNI walk/run scale. Concurrent validity was assessed by calculating within-subject correlations between OMNI ratings and the two physiological indices. RESULTS The average correlation between OMNI ratings and VO2 was 0.67, 0.77, 0.85 and 0.87 for the 6-8, 9-10, 11-12 and 13-15 y age groups, respectively. CONCLUSION The OMNI RPE scale demonstrated fair to good evidence of validity across a range of lifestyle activities among 6-15 year old children. The validity of the scale appears to be developmentally related with RPE reports closely reflecting physiological responses among children older than 8 years.

Improved nutritional status is related to improved quality of life in Parkinson’s disease

Background: Quality of life is poorer in Parkinson’s disease than in other conditions and in the general population without Parkinson’s disease. Malnutrition also results in poorer quality of life. This study aimed at determining the relationship between quality of life and nutritional status. Methods: Community-dwelling people with Parkinson’s disease >18 years old were recruited. The Patient-Generated Subjective Global Assessment (PG-SGA) assessed nutritional status. The Parkinson’s Disease Questionnaire 39 (PDQ-39) measured quality of life. Phase I was cross-sectional. The malnourished in Phase I were eligible for a nutrition intervention phase, randomised into 2 groups: standard care (SC) with provision of nutrition education materials only and intervention (INT) with individualised dietetic advice and regular weekly follow-up. Data were collected at baseline, 6 weeks, and 12 weeks. Results: Phase I consisted of 120 people who completed the PDQ-39. Phase II consisted of 9 in the SC group and 10 in the INT group. In Phase I, quality of life was poorer in the malnourished, particularly for mobility and activities of daily living domains. There was a significant correlation between PG-SGA and PDQ-39 scores (Phase I, rs = 0.445, p = .000; Phase II, rs = .426, p = .002). In Phase II, no significant difference in the PDQ-39 total or sub-scores was observed between the INT and SC groups; however, there was significant improvement in the emotional well-being domain for the entire group, X2(2) = 8.84, p = .012. Conclusions: Malnourished people with Parkinson’s disease had poorer quality of life than the well-nourished, and improvements in nutritional status resulted in quality of life improvements. Attention to nutritional status is an important component of quality of life and therefore the total care of people with Parkinson’s disease.

Ineffective cerebral perfusion related to increased intracranial pressure secondary to subarachnoid haemorrhage : An examination of nursing interventions

Considered a condition of the elderly population, stroke will soon be the leading cause of death globally. In Singapore it is the fourth leading cause of death after cancer and heart disease. Subarachnoid haemorrhage, when compared with an embolic stroke, has a more devastating outcome because of the deleterious complications associated with it. Vasospam, re-bleeding and global cerebral ischemia are three of the most prominent complications. Therefore, nursing care and interventions developed to reduce the incidence of complications and optimise neurological function are critical in the acute phase of this condition. Using a casestudy approach this article will discuss and offer a rationale to a number of key nursing interventions based around a nursing care plan designed to reduce the incidence of complications.

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.

The effect of the ecstasy 'come-down' on the diagnosis of ecstasy dependence

Background: The existence of an ecstasy dependence syndrome is controversial. We examined whether the acute after-effects of ecstasy use (i.e., the “come-down”) falsely lead to the identification of ecstasy withdrawal and the subsequent diagnosis of ecstasy dependence. Methods: The Structured Clinical Interview for DSM-IV-TR Disorders: Research Version (SCID-RV) was administered to 214 Australian ecstasy users. Ecstasy withdrawal was operationalized in three contrasting ways: (i) as per DSM-IV criteria; (ii) as the expected after effects of ecstasy (a regular come-down); or (iii) as a substantially greater or longer come-down than on first use (intense come-down). These definitions were validated against frequency of ecstasy use, readiness to change and ability to resist the urge to use ecstasy. Confirmatory factor analyses were used to see how they aligned with the overall dependence syndrome. Results: Come-down symptoms increased the prevalence of withdrawal from 1% (DSM-IV criterion) to 11% (intense come-downs) and 75% (regular come-downs). Past year ecstasy dependence remained at 31% when including the DSM-IV withdrawal criteria and was 32% with intense come-downs, but increased to 45% with regular come-downs. Intense come-downs were associated with lower ability to resist ecstasy use and loaded positively on the dependence syndrome. Regular come-downs did not load positively on the ecstasy dependence syndrome and were not related to other indices of dependence. Conclusion: The acute after-effects of ecstasy should be excluded when assessing ecstasy withdrawal as they can lead to a false diagnosis of ecstasy dependence. Worsening of the ecstasy come-down may be a marker for dependence.