The high price of drug patents: Australia, patent law, pharmaceutical drugs and the Trans-Pacific Partnership

This week, the secrecy surrounding an independent Australian report on patent law and pharmaceutical drugs has been lifted, and the work has been published to great acclaim...

Academic stress, parental pressure, anxiety and mental health among Indian high school students

This work investigates the academic stress and mental health of Indian high school students and the associations between various psychosocial factors and academic stress. A total of190 students from grades 11 and 12 (mean age: 16.72 years) from three government-aided and three private schools in Kolkata India were surveyed in the study. Data collection involved using a specially designed structured questionnaire as well as the General Health Questionnaire. Nearly two-thirds (63.5%) of the students reported stress due to academic pressure – with no significant differences across gender, age, grade, and several other personal factors. About two-thirds (66%) of the students reported feeling pressure from their parents for better academic performance. The degree of parental pressure experienced differed significantly across the educational levels of the parents, mother’s occupation, number of private tutors, and academic performance. In particular, children of fathers possessing a lower education level (non-graduates) were found to be more likely to perceive pressure for better academic performance. About one-thirds (32.6%) of the students were symptomatic of psychiatric caseness and 81.6% reported examination-related anxiety. Academic stress was positively correlated with parental pressure and psychiatric problems, while examination-related anxiety also was positively related to psychiatric problems. Academic stress is a serious issue which affects nearly two thirds of senior high school students in Kolkata. Potential methods for combating the challenges of academic pressure are suggested.

Price and trade: World no tobacco day 2015

This special issue of Tobacco Control for World No Tobacco Day is focused on the theme of Price and Trade.

When the price is not right: Technology price gouging in Australia

Apple Inc. has often portrayed itself as the champion of consumers, with its advertising campaigns on “1984”, “Think Different”, and “Rip, Mix, Burn”. However, this reputation has been called into question after Apple refused to appear before the Parliament’s inquiry into IT Pricing in Australia and explain its pricing policies in Australia.

Modelling interregional links in electricity price spikes

Abnormally high price spikes in spot electricity markets represent a significant risk to market participants. As such, a literature has developed that focuses on forecasting the probability of such spike events, moving beyond simply forecasting the level of price. Many univariate time series models have been proposed to dealwith spikes within an individual market region. This paper is the first to develop a multivariate self-exciting point process model for dealing with price spikes across connected regions in the Australian National Electricity Market. The importance of the physical infrastructure connecting the regions on the transmission of spikes is examined. It is found that spikes are transmitted between the regions, and the size of spikes is influenced by the available transmission capacity. It is also found that improved risk estimates are obtained when inter-regional linkages are taken into account.

Manifestations of type 2 diabetes in corneal endothelial cell density, corneal thickness and intraocular pressure

We sought to evaluate central corneal thickness (CCT), corneal endothelial cell density (ECD) and intraocular pressure (IOP) in patients with type 2 diabetes mellitus (DM) and to associate potential differences with diabetes duration and treatment modality in a prospective, randomized study. We measured ECD, CCT and IOP of 125 patients with type 2 DM (mean age 57.1¡11.5 years) and compared them with 90 age-matched controls. Measured parameters were analyzed for association with diabetes duration and glucose control modalities (insulin injection or oral medication) while controlling for age. In the diabetic group, the mean ECD (2511¡252 cells/mm2), mean CCT (539.7¡33.6 mm) and mean IOP (18.3¡2.5 mmHg) varied significantly from those the control group [ECD: 2713¡132 cells/mm2 (P,0.0001), CCT: 525.0¡45.3 mm (P50.003) and IOP: 16.7¡1.8 mmHg (P,0.0001)]. ECD was significantly reduced by about 32 cell/mm2 for diabetics with duration of .10 years when compared with those with duration of ,10 years (P,0.05). CCT was thicker and IOP was higher for diabetics with duration of .10 years than those with duration of ,10 years (P.0.05). None of the measured parameters was significantly associated with diabetes duration and treatment modality (P.0.05). In conclusion, subjects with type 2 DM exhibit significant changes in ECD, IOP and CCT, which, however, are not correlated with disease duration or if the patients receive on insulin injection or oral medications.

The role of time pressure and different psychological safety climate referents in the prediction of nurses’ hand hygiene compliance

In this study of 638 Australian nurses, compliance to hand hygiene (HH), as defined by the “five moments” recommended by the World Health Organisation (2009), was examined. Hypotheses focused on the extent to which time pressure reduces compliance and safety climate (operationalised in relation to HH using colleagues, manager, and hospital as referents) increases compliance. It also was proposed that HH climate would interact with time pressure, such that the negative effects of time pressure would be less marked when HH climate is high. The extent to which the three HH climate variables would interact among each other, either in the form of boosting or compensatory effects, was tested in an exploratory manner. A prospective research design was used in which time pressure and the HH climate variables were assessed at Time 1 and compliance was assessed by self-report two weeks later. Compliance was high but varied significantly across the 5 HH Moments, suggesting that nurses make distinctions between inherent and elective HH and also seemed to engage in some implicit rationing of HH. Time pressure dominated the utility of HH climate to have its positive impact on compliance. The most conducive workplace for compliance was one low in time pressure and high in HH climate. Colleagues were very influential in determining compliance, more so than the manager and hospital. Manager and hospital support for HH enhanced the positive effects of colleagues on compliance. Providing training and enhancing knowledge was important, not just for compliance, but for safety climate.

Dynamic, invivo, real-time detection of retinal oxidative status in a model of elevated intraocular pressure using a novel, reversibly responsive, profluorescent nitroxide probe

Changes to the redox status of biological systems have been implicated in the pathogenesis of a wide variety of disorders including cancer, Ischemia-reperfusion (I/R) injury and neurodegeneration. In times of metabolic stress e.g. ischaemia/reperfusion, reactive oxygen species (ROS) production overwhelms the intrinsic antioxidant capacity of the cell, damaging vital cellular components. The ability to quantify ROS changes in vivo, is therefore essential to understanding their biological role. Here we evaluate the suitability of a novel reversible profluorescent probe containing a redox-sensitive nitroxide moiety (methyl ester tetraethylrhodamine nitroxide, ME-TRN), as an in vivo, real-time reporter of retinal oxidative status. The reversible nature of the probe's response offers the unique advantage of being able to monitor redox changes in both oxidizing and reducing directions in real time. After intravitreal administration of the ME-TRN probe, we induced ROS production in rat retina using an established model of complete, acute retinal ischaemia followed by reperfusion. After restoration of blood flow, retinas were imaged using a Micron III rodent fundus fluorescence imaging system, to quantify the redox-response of the probe. Fluorescent intensity declined during the first 60 min of reperfusion. The ROS-induced change in probe fluorescence was ameliorated with the retinal antioxidant, lutein. Fluorescence intensity in non-Ischemia eyes did not change significantly. This new probe and imaging technology provide a reversible and real-time response to oxidative changes and may allow the in vivo testing of antioxidant therapies of potential benefit to a range of diseases linked to oxidative stress

Atmospheric pressure gas plasma-induced colorectal cancer cell death is mediated by Nox2-ASK1 apoptosis pathways and oxidative stress is mitigated by Srx-Nrf2 anti-oxidant system

Atmospheric pressure gas plasma (AGP) generates reactive oxygen species (ROS) that induce apoptosis in cultured cancer cells. The majority of cancer cells develop a ROS-scavenging anti-oxidant system regulated by Nrf2, which confers resistance to ROS-mediated cancer cell death. Generation of ROS is involved in the AGP-induced cancer cell death of several colorectal cancer cells (Caco2, HCT116 and SW480) by activation of ASK1-mediated apoptosis signaling pathway without affecting control cells (human colonic sub-epithelial myofibroblasts; CO18, human fetal lung fibroblast; MRC5 and fetal human colon; FHC). However, the identity of an oxidase participating in AGP-induced cancer cell death is unknown. Here, we report that AGP up-regulates the expression of Nox2 (NADPH oxidase) to produce ROS. RNA interference designed to target Nox2 effectively inhibits the AGP-induced ROS production and cancer cell death. In some cases both colorectal cancer HT29 and control cells showed resistance to AGP treatment. Compared to AGP-sensitive Caco2 cells, HT29 cells show a higher basal level of the anti-oxidant system transcriptional regulator Nrf2 and its target protein sulfiredoxin (Srx) which are involved in cellular redox homeostasis. Silencing of both Nrf2 and Srx sensitized HT29 cells, leads to ROS overproduction and decreased cell viability. This indicates that in HT29 cells, Nrf2/Srx axis is a protective factor against AGP-induced oxidative stress. The inhibition of Nrf2/Srx signaling should be considered as a central target in drug-resistant colorectal cancer treatments.

Plantar pressure in diabetic peripheral neuropathy patients with active foot ulceration, previous ulceration and no history of ulceration: A meta-analysis of observational studies

Aims Elevated dynamic plantar pressures are a consistent finding in diabetes patients with peripheral neuropathy with implications for plantar foot ulceration. This meta-analysis aimed to compare the plantar pressures of diabetes patients that had peripheral neuropathy and those with neuropathy with active or previous foot ulcers. Methods Published articles were identified from Medline via OVID, CINAHL, SCOPUS, INFORMIT, Cochrane Central EMBASE via OVID and Web of Science via ISI Web of Knowledge bibliographic databases. Observational studies reporting barefoot dynamic plantar pressure in adults with diabetic peripheral neuropathy, where at least one group had a history of plantar foot ulcers were included. Interventional studies, shod plantar pressure studies and studies not published in English were excluded. Overall mean peak plantar pressure (MPP) and pressure time integral (PTI) were primary outcomes. The six secondary outcomes were MPP and PTI at the rear foot, mid foot and fore foot. The protocol of the meta-analysis was published with PROPSERO, (registration number CRD42013004310). Results Eight observational studies were included. Overall MPP and PTI were greater in diabetic peripheral neuropathy patients with foot ulceration compared to those without ulceration (standardised mean difference 0.551, 95% CI 0.290–0.811, p<0.001; and 0.762, 95% CI 0.303–1.221, p = 0.001, respectively). Sub-group analyses demonstrated no significant difference in MPP for those with neuropathy with active ulceration compared to those without ulcers. A significant difference in MPP was found for those with neuropathy with a past history of ulceration compared to those without ulcers; (0.467, 95% CI 0.181– 0.753, p = 0.001). Statistical heterogeneity between studies was moderate. Conclusions Plantar pressures appear to be significantly higher in patients with diabetic peripheral neuropathy with a history of foot ulceration compared to those with diabetic neuropathy without a history of ulceration. More homogenous data is needed to confirm these findings.

Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.

Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Estimating the parameters of stochastic volatility models using option price data

This article describes a maximum likelihood method for estimating the parameters of the standard square-root stochastic volatility model and a variant of the model that includes jumps in equity prices. The model is fitted to data on the S&P 500 Index and the prices of vanilla options written on the index, for the period 1990 to 2011. The method is able to estimate both the parameters of the physical measure (associated with the index) and the parameters of the risk-neutral measure (associated with the options), including the volatility and jump risk premia. The estimation is implemented using a particle filter whose efficacy is demonstrated under simulation. The computational load of this estimation method, which previously has been prohibitive, is managed by the effective use of parallel computing using graphics processing units (GPUs). The empirical results indicate that the parameters of the models are reliably estimated and consistent with values reported in previous work. In particular, both the volatility risk premium and the jump risk premium are found to be significant.

The measurement of intraocular pressure over positive soft contact lenses by rebound tonometry [Medición de la presión intraocular sobre lentes de contacto blandas positivas, mediante tonometría de rebote]

Purpose To investigate if the accuracy of intraocular pressure (IOP) measurements using rebound tonometry over disposable hydrogel (etafilcon A) contact lenses (CL) is affected by the positive power of the CLs. Methods The experimental group comprised 26 subjects, (8 male, 18 female). IOP measurements were undertaken on the subjects’ right eyes in random order using a Rebound Tonometer (ICare). The CLs had powers of +2.00D and +6.00D. Measurements were taken over each contact lens and also before and after the CLs had been worn. Results The IOP measure obtained with both CLs was significantly lower compared to the value without CLs (t test; p<0.001) but no significant difference was found between the two powers of CLs. Conclusions Rebound tonometry over positive hydrogel CLs leads to a certain degree of IOP underestimation. This result didn’t change for the two positive lenses used in the experiment, despite their large difference in power and therefore in lens thickness. Optometrists should bear this in mind when measuring IOP with the rebound tonometer over plus power contact lenses.

High-Pressure Kinetics of Vinyl Polyperoxides

This is the first report on studies carried out in detail on high-pressure oxygen copolymerization (> 50 psi) of the vinyl monomers styrene and alpha-methylstyrene (AMS). The saturation pressure of oxygen for AMS oxidation, hitherto obscure, is found to be 300 psi. Whereas the ease of oxidation is more favorable for styrene, the rate and yield of polyperoxide formation are higher for AMS. This is explained on the basis of the reactivity of the corresponding alkyl and peroxy radicals. Below 50 degrees C, degradation of the poly(styrene peroxide) formed is about 2.5 times less than that observed above 50 degrees C, so much so that it gives a break in the rate curve, and thereafter the rate is lowered. Normal free radical kinetics is followed before the break point, after which the monomer and initiator exponents become unusually high. This is interpreted on the basis of chain transfer to the degradation products. The low molecular weight of polyperoxides has been attributed to the (i) low reactivity of RO(2)(.) toward the monomer, (ii) chain transfer to degradation products, (iii) facile cleavage of O-O bond, followed by unzipping to nonradical products, and (iv) higher stability of the reinitiating radicals. At lower temperatures, (i) predominates, whereas at higher temperatures, chiefly (ii)-(iv) are the case.