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.

A time series analysis of presentations to Queensland health facilities for alcohol-related conditions, following the increase in 'alcopops' tax

Objective: In response to concerns about the health consequences of high-risk drinking by young people, the Australian Government increased the tax on pre-mixed alcoholic beverages ('alcopops') favoured by this demographic. We measured changes in admissions for alcohol-related harm to health throughout Queensland, before and after the tax increase in April 2008. Methods: We used data from the Queensland Trauma Register, Hospitals Admitted Patients Data Collection, and the Emergency Department Information System to calculate alcohol-related admission rates per 100,000 people, for 15 - 29 year-olds. We analysed data over 3 years (April 2006 - April 2009), using interrupted time-series analyses. This covered 2 years before, and 1 year after, the tax increase. We investigated both mental and behavioural consequences (via F10 codes), and intentional/unintentional injuries (S and T codes). Results: We fitted an auto-regressive integrated moving average (ARIMA) model, to test for any changes following the increased tax. There was no decrease in alcohol-related admissions in 15 - 29 year-olds. We found similar results for males and females, as well as definitions of alcohol-related harms that were narrow (F10 codes only) and broad (F10, S and T codes). Conclusions: The increased tax on 'alcopops' was not associated with any reduction in hospital admissions for alcohol-related harms in Queensland 15 - 29 year-olds.

Letter to Lady Chatterley

A letter written to Lady Chatterley, a fictional character in a novel by D H Lawrence. The topic of the letter is the influence of fictional characters on a reader's sense of self.

Characterization of the tail-specific protease (Tsp) from Legionella

Bacterial tail-specific proteases (Tsps) have been attributed a wide variety of functions including intracellular virulence, cell wall morphology, proteolytic signal cascades and stress response. This study tested the hypothesis that Tsp has a key function for the transmissive form of Legionella pneumophila. A tsp mutant was generated in Legionella pneumophila 130b and the characteristics of this strain and the isogenic wild-type were examined using a range of growth and proteomic analyses. Recombinant Tsp protein was also produced and analyzed. The L. pneumophila tsp mutant showed no defect in growth on rich media or during thermo-osmotic stress conditions. In addition, no defects in cellular morphology were observed when the cells were examined using transmission electron microscopy. Purified recombinant Tsp was found to be an active protease with a narrow substrate range. Proteome analysis using iTRAQ (5% coverage of the proteome) found that, of those proteins detected, only 5 had different levels in the tsp mutant compared to the wild type. ACP (Acyl Carrier Protein), which has a key role for Legionella differentiation to the infectious form, was reduced in the tsp mutant; however, tsp(-) was able to infect and replicate inside macrophages to the same extent as the wild type. Combined, these data demonstrate that Tsp is a protease but is not essential for Legionella growth or cell infection. Thus, Tsp may have functional redundancy in Legionella.

Locality-sensitive hashing for protein classification

Determination of sequence similarity is a central issue in computational biology, a problem addressed primarily through BLAST, an alignment based heuristic which has underpinned much of the analysis and annotation of the genomic era. Despite their success, alignment-based approaches scale poorly with increasing data set size, and are not robust under structural sequence rearrangements. Successive waves of innovation in sequencing technologies – so-called Next Generation Sequencing (NGS) approaches – have led to an explosion in data availability, challenging existing methods and motivating novel approaches to sequence representation and similarity scoring, including adaptation of existing methods from other domains such as information retrieval. In this work, we investigate locality-sensitive hashing of sequences through binary document signatures, applying the method to a bacterial protein classification task. Here, the goal is to predict the gene family to which a given query protein belongs. Experiments carried out on a pair of small but biologically realistic datasets (the full protein repertoires of families of Chlamydia and Staphylococcus aureus genomes respectively) show that a measure of similarity obtained by locality sensitive hashing gives highly accurate results while offering a number of avenues which will lead to substantial performance improvements over BLAST..

Comparative studies made simple in GPFlow

This work describes recent extensions to the GPFlow scientific workflow system in development at MQUTeR (www.mquter.qut.edu.au), which facilitate interactive experimentation, automatic lifting of computations from single-case to collection-oriented computation and automatic correlation and synthesis of collections. A GPFlow workflow presents as an acyclic data flow graph, yet provides powerful iteration and collection formation capabilities.

Think Sociology

Contents: 1. SOCIOLOGY: An Introduction to the Sociological Imagination. John Carl, Sarah Baker 2. SOCIOLOGICAL THEORY: An Introduction to the Theoretical Foundations of Sociology. John Carl, Sarah Baker 3. SOCIAL CLASS IN AUSTRALIA: Stratification in a Modern Society. John Carl, John Scott 4. RACE AND ETHNIC STRATIFICATION: Is it a Question of Colour? John Carl, John Scott 5. SEX AND GENDER: The Social Side of Sex. John Carl, Wendy Hillman 6. AGE AND AGEING: The Greying of Society. John Carl, Sarah Baker 7. CRIME AND THE LEGAL SYSTEM: How Do Societies Respond to Crime and Deviance? John Carl, John Scott 8. EDUCATION AND EMPLOYMENT: From the Classroom to the Workforce. John Carl, Sarah Baker and Brady Robards 9: MARRIAGE AND FAMILY: How Do Societies Perpetuate Themselves? John Carl, Wendy Hillman 10. THE BODY, HEALTH AND ILLNESS: A Weight on Australia’s Shoulder. John Carl, John Scott 11. GLOBALISATION: The Economy and Society. John Carl, Geoffrey Lawrence 12. CULTURE: A Framework for the Individual. John Carl, Sarah Baker and Brady Robards 13. RELIGION: Is Society Losing Faith? John Carl, Sarah Baker and Brady Robards 14. ENVIRONMENTAL SUSTAINABILITY AND SOCIAL MOVEMENTS: How Do Societies Connect with Nature? John Carl, Geoffrey Lawrence 15. SOCIOLOGICAL RESEARCH: How Do We Learn about Society? John Carl, Wendy Hillman

Head-of-bed elevation improves end-expiratory lung volumes in mechanically ventilated subjects : a prospective observational study

BACKGROUND: Head-of-bed elevation (HOBE) has been shown to assist in reducing respiratory complications associated with mechanical ventilation; however, there is minimal research describing changes in end-expiratory lung volume. This study aims to investigate changes in end-expiratory lung volume in a supine position and 2 levels of HOBE. METHODS: Twenty postoperative cardiac surgery subjects were examined using electrical impedance tomography. End-expiratory lung impedance (EELI) was recorded as a surrogate measurement of end-expiratory lung volume in a supine position and at 20° and then 30°. RESULTS: Significant increases in end-expiratory lung volume were seen at both 20° and 30° HOBE in all lung regions, except the anterior, with the largest changes from baseline (supine) seen at 30°. From baseline to 30° HOBE, global EELI increased by 1,327 impedance units (95% CI 1,080–1,573, P < .001). EELI increased by 1,007 units (95% CI 880–1,134, P < .001) in the left lung region and by 320 impedance units (95% CI 188–451, P < .001) in the right lung. Posterior increases of 1,544 impedance units (95% CI 1,405–1,682, P < .001) were also seen. EELI decreased anteriorly, with the largest decreases occurring at 30° (−335 impedance units, 95% CI −486 to −183, P < .001). CONCLUSIONS: HOBE significantly increases global and regional end-expiratory lung volume; therefore, unless contraindicated, all mechanically ventilated patients should be positioned with HOBE.

Orexin/hypocretin role in reward: implications for opioid and other addictions

Addiction is a devastating disorder that affects 15.3 million people worldwide. While prevalent, few effective treatments exist. Orexin receptors have been proposed as a potential target for anti-craving medications. Orexins, also known as hypocretins, are neuropeptides produced in neurons of the lateral and dorsomedial hypothalamus and perifornical area, which project widely throughout the brain. The absence of orexins in rodents and humans leads to narcolepsy. However, orexins also have an established role in reward seeking. This review will discuss some of the original studies describing the roles of the orexins in reward seeking as well as specific works that were presented at the 2013 International Narcotics Research Conference. Orexin signalling can promote drug-induced plasticity of glutamatergic synapses onto dopamine neurons of the ventral tegmental area (VTA), a brain region implicated in motivated behaviour. Additional evidence suggests that orexin signalling can also promote drug seeking by initiating an endocannabinoid-mediated synaptic depression of GABAergic inputs to the VTA, and thereby disinhibiting dopaminergic neurons. Orexin neurons co-express the inhibitory opioid peptide dynorphin. It has been proposed that orexin in the VTA may not mediate reward per se, but rather occludes the ‘anti-reward’ effects of dynorphin. Finally, orexin signalling in the prefrontal cortex and the central amygdala is implicated in reinstatement of reward seeking. This review will highlight recent work describing the role of orexin signalling in cellular processes underlying addiction-related behaviours and propose novel hypotheses for the mechanisms by which orexin signalling may impart drug seeking.

Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells

Prostate-specific antigen (PSA) and the related kallikrein family of serine proteases are current or emerging biomarkers for prostate cancer detection and progression. Kallikrein 4 (KLK4/hK4) is of particular interest, as KLK4 mRNA has been shown to be elevated in prostate cancer. In this study, we now show that the comparative expression of hK4 protein in prostate cancer tissues, compared with benign glands, is greater than that of PSA and kallikrein 2 (KLK2/hK2), suggesting that hK4 may play an important functional role in prostate cancer progression in addition to its biomarker potential. To examine the roles that hK4, as well as PSA and hK2, play in processes associated with progression, these kallikreins were separately transfected into the PC-3 prostate cancer cell line, and the consequence of their stable transfection was investigated. PC-3 cells expressing hK4 had a decreased growth rate, but no changes in cell proliferation were observed in the cells expressing PSA or hK2. hK4 and PSA, but not hK2, induced a 2.4-fold and 1.7-fold respective increase, in cellular migration, but not invasion, through Matrigel, a synthetic extracellular matrix. We hypothesised that this increase in motility displayed by the hK4 and PSA-expressing PC-3 cells may be related to the observed change in structure in these cells from a typical rounded epithelial-like cell to a spindle-shaped, more mesenchymal-like cell, with compromised adhesion to the culture surface. Thus, the expression of E-cadherin and vimentin, both associated with an epithelial-mesenchymal transition (EMT), was investigated. E-cadherin protein was lost and mRNA levels were significantly decreased in PC-3 cells expressing hK4 and PSA (10-fold and 7-fold respectively), suggesting transcriptional repression of E-cadherin, while the expression of vimentin was increased in these cells. The loss of E-cadherin and associated increase in vimentin are indicative of EMT and provides compelling evidence that hK4, in particular, and PSA have a functional role in the progression of prostate cancer through their promotion of tumour cell migration.

Learning the learning rate for prediction with expert advice

Most standard algorithms for prediction with expert advice depend on a parameter called the learning rate. This learning rate needs to be large enough to fit the data well, but small enough to prevent overfitting. For the exponential weights algorithm, a sequence of prior work has established theoretical guarantees for higher and higher data-dependent tunings of the learning rate, which allow for increasingly aggressive learning. But in practice such theoretical tunings often still perform worse (as measured by their regret) than ad hoc tuning with an even higher learning rate. To close the gap between theory and practice we introduce an approach to learn the learning rate. Up to a factor that is at most (poly)logarithmic in the number of experts and the inverse of the learning rate, our method performs as well as if we would know the empirically best learning rate from a large range that includes both conservative small values and values that are much higher than those for which formal guarantees were previously available. Our method employs a grid of learning rates, yet runs in linear time regardless of the size of the grid.