Signaling of receptor tyrosine kinases in the nucleus

Since the discovery of the first receptor tyrosine kinase (RTK) proteins in the late 1970s and early 1980s, many scientists have explored the functions of these important cell signaling molecules. The finding that these proteins are often deregulated or mutated in diseases such as cancers and diabetes, together with their potential as clinical therapeutic targets, has further highlighted the necessity for understanding the signaling functions of these important proteins. The mechanisms of RTK regulation and function have been recently reviewed by Lemmon & Schlessinger (2010) but in this review we instead focus on the results of several recent studies that show receptor tyrosine kinases can function from subcellular localisations, including in particular the nucleus, in addition to their classical plasma membrane location. Nuclear localisation of receptor tyrosine kinases has been demonstrated to be important for normal cell function but is also believed to contribute to the pathogenesis of several human diseases.

Treatment of cannabis use among people with psychotic disorders : critical review of randomised controlled trials

There is growing and converging evidence that cannabis may be a major risk factor in people with psychotic disorders and prodromal psychotic symptoms. The lack of available pharmacological treatments for cannabis use indicates that psychological interventions should be a high priority, especially among people with psychotic disorders. However, there have been few randomised controlled trials (RCTs) of psychological interventions among this group. In the present study we critically overview RCTs of psychological and pharmacologic interventions among people with psychotic disorders, giving particular attention to those studies which report cannabis use outcomes. We then review data regarding treatment preferences among this group. RCTs of interventions within "real world" mental health systems among adults with severe mental disorders suggest that cannabis use is amenable to treatment in real world settings among people with psychotic disorders. RCTs of manual guided interventions among cannabis users indicate that while brief interventions are associated with reductions in cannabis use, longer interventions may be more effective. Additionally, RCTs reviewed suggest treatment with antipsychotic medication is not associated with a worsening of cannabis cravings or use and may be beneficial. The development of cannabinoid agonist medication may be an effective strategy for cannabis dependence and suitable for people with psychotic disorders. The development of cannabis use interventions for people with psychotic disorders should also consider patients' treatment preferences. Initial results indicate face-to-face interventions focussed on cannabis use may be preferred. Further research investigating the treatment preferences of people with psychotic disorders using cannabis is needed.

A spectroscopic comparison of YBCO superconductors synthesised by solid-state and co-precipitation methods

Raman spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM) have been used to compare samples of YBa2Cu3O7 (YBCO) synthesised by the solid-state method and a novel co-precipitation technique. XRD results indicate that YBCO prepared by these two methods are phase pure, however the Raman and SEM results show marked differences between these samples.

Managing the health effects of temperature in response to climate change : challenges ahead

BACKGROUND: Although many studies have shown that high temperatures are associated with an increased risk of mortality and morbidity, there has been little research on managing the process of planned adaptation to alleviate the health effects of heat events and climate change. In particular, economic evaluation of public health adaptation strategies has been largely absent from both the scientific literature and public policy discussion. OBJECTIVES: his paper aims to discuss how public health organizations should implement adaptation strategies, and how to improve the evidence base for policies to protect health from heat events and climate change. DISCUSSION: Public health adaptation strategies to cope with heat events and climate change fall into two categories: reducing the heat exposure and managing the health risks. Strategies require a range of actions, including timely public health and medical advice, improvements to housing and urban planning, early warning systems, and the assurance that health care and social systems are ready to act. Some of these actions are costly, and the implementation should be based on the cost-effectiveness analysis given scarce financial resources. Therefore, research is required not only on the temperature-related health costs, but also on the costs and benefits of adaptation options. The scientific community must ensure that the health co-benefits of climate change policies are recognized, understood and quantified. CONCLUSIONS: The integration of climate change adaptation into current public health practice is needed to ensure they increase future resilience. The economic evaluation of temperature-related health costs and public health adaptation strategies are particularly important for policy decisions.

Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010 : a systematic analysis for the Global Burden of Disease Study 2010

Background Non-fatal health outcomes from diseases and injuries are a crucial consideration in the promotion and monitoring of individual and population health. The Global Burden of Disease (GBD) studies done in 1990 and 2000 have been the only studies to quantify non-fatal health outcomes across an exhaustive set of disorders at the global and regional level. Neither effort quantified uncertainty in prevalence or years lived with disability (YLDs). Methods Of the 291 diseases and injuries in the GBD cause list, 289 cause disability. For 1160 sequelae of the 289 diseases and injuries, we undertook a systematic analysis of prevalence, incidence, remission, duration, and excess mortality. Sources included published studies, case notification, population-based cancer registries, other disease registries, antenatal clinic serosurveillance, hospital discharge data, ambulatory care data, household surveys, other surveys, and cohort studies. For most sequelae, we used a Bayesian meta-regression method, DisMod-MR, designed to address key limitations in descriptive epidemiological data, including missing data, inconsistency, and large methodological variation between data sources. For some disorders, we used natural history models, geospatial models, back-calculation models (models calculating incidence from population mortality rates and case fatality), or registration completeness models (models adjusting for incomplete registration with health-system access and other covariates). Disability weights for 220 unique health states were used to capture the severity of health loss. YLDs by cause at age, sex, country, and year levels were adjusted for comorbidity with simulation methods. We included uncertainty estimates at all stages of the analysis. Findings Global prevalence for all ages combined in 2010 across the 1160 sequelae ranged from fewer than one case per 1 million people to 350 000 cases per 1 million people. Prevalence and severity of health loss were weakly correlated (correlation coefficient −0·37). In 2010, there were 777 million YLDs from all causes, up from 583 million in 1990. The main contributors to global YLDs were mental and behavioural disorders, musculoskeletal disorders, and diabetes or endocrine diseases. The leading specific causes of YLDs were much the same in 2010 as they were in 1990: low back pain, major depressive disorder, iron-deficiency anaemia, neck pain, chronic obstructive pulmonary disease, anxiety disorders, migraine, diabetes, and falls. Age-specific prevalence of YLDs increased with age in all regions and has decreased slightly from 1990 to 2010. Regional patterns of the leading causes of YLDs were more similar compared with years of life lost due to premature mortality. Neglected tropical diseases, HIV/AIDS, tuberculosis, malaria, and anaemia were important causes of YLDs in sub-Saharan Africa. Interpretation Rates of YLDs per 100 000 people have remained largely constant over time but rise steadily with age. Population growth and ageing have increased YLD numbers and crude rates over the past two decades. Prevalences of the most common causes of YLDs, such as mental and behavioural disorders and musculoskeletal disorders, have not decreased. Health systems will need to address the needs of the rising numbers of individuals with a range of disorders that largely cause disability but not mortality. Quantification of the burden of non-fatal health outcomes will be crucial to understand how well health systems are responding to these challenges. Effective and affordable strategies to deal with this rising burden are an urgent priority for health systems in most parts of the world. Funding Bill & Melinda Gates Foundation.

Ideas to improve the selection of NHMRC Project Grants

The starting point for this presentation is that applicants provide a large surplus of information when submitting a NHMRC Project Grant proposal for funding. This is costly in their time, attracts high administration costs, makes the task appear daunting for peer reviewers and may reduce the quality of the peer review leading to less than perfect reliability in decision making. We are currently experimenting with alternate models to see whether similar reliability in funding outcomes are achieved at less cost. We will compare traditional NHMRC Grant Review Panels (GRPs) with panels that use less information and journal style panels. By way of background to this experimental work, we will show some results on current levels of reliability for GRPs, the costs incurred by all who participate in Project Grant selection, and the level of reliability acceptable to researchers. By experimenting in this way and building an evidence base for how research funding should be allocated, the NHMRC is showing international leadership in this important field.

Nature and genesis of clay minerals of the Rustler Formation in the vicinity of the Waste Isolation Pilot Plant in Souteastern New Mexico

Detailed mineralogical studies of the matrix and fracture-fill materials of a large number of samples from the Rustler Formation have been carried out using x-ray diffraction, high-resolution transmission electron microscopy, electron microprobe analysis, x-ray fluorescence, and atomic absorption spectrophotometry. These analyses indicate the presence of four clay minerals: interstratified chlorite/saponite, illite, chlorite, and serpentine. Corrensite (regularly stratified chlorite/saponite) is the dominant clay mineral in samples from the Culebra dolomite and two shale layers of the lower unnamed member of the Rustler Formation. Within other layers of the Rustler Formation, disordered mixed chlorite/saponite is usually the most abundant clay mineral. Studies of the morphology and composition of clay crystallites suggest that the corrensite was formed by the alteration of detrital dioctahedral smectite in magnesium-rich pore fluids during early diagenesis of the Rustler Formation. This study provides initial estimates of the abundance and nature of the clay minerals in the Culebra dolomite in the vicinity of the Waste Isolation Pilot Plant.

Funding : Australia’s grant system wastes time

We found that scientists in Australia spent more than five centuries' worth of time preparing research-grant proposals for consideration by the largest funding scheme of 2012. Because just 20.5% of these applications were successful, the equivalent of some four centuries of effort returned no immediate benefit to researchers and wasted valuable research time. The system needs reforming and alternative funding processes should be investigated...

Does 2-wheeler experience affect behaviours and attitudes to 2-wheelers as a car driver?

• Car-bicycle and car-motorcycle crashes often serious • Car driver mostly at fault, often because of failure to see (Schramm et al, 2010) • Car drivers with motorcycling experience less likely to be involved in motorcycle crashes or be at fault (Brooks & Guppy, 1990; Magazzu et al., 2006) and hold more positive beliefs about motorcyclists (Crundall et al., 2008) • Does bicycle riding experience have the same benefits?

Does experience with one type of two-wheeler affect behaviours and attitudes to other types?

Failure to give way by motor vehicles is a factor in many collisions with both powered and unpowered two wheelers (TWs). Motor vehicle drivers often report that they did not see the TW, but research has shown that motor vehicle drivers who have experience riding a motorcycle are less likely to fail to detect motorcycles. The research reported here examines whether this phenomenon extends to detection of bicycles and whether car drivers who have experience with one mode of TW show improved detection of the other mode. A driving simulator study was conducted in an Australian urban setting which incorporated some of the most common car-TW crash scenarios. Participants with car-only, car plus motorcycle, car plus bicycle, and car plus bicycle plus motorcycle experience operated a car simulator. Their interactions with both types of TWs were measured in terms of visual detection, lateral distance and speed when approaching and passing. The effects of different levels of colour and lighting of the TWs on driver responses were also examined. The attitudes of participants towards TWs were measured in a questionnaire.

Sources of ultrafine particles and chemical species along a traffic corridor : comparison of the results from two receptor models

Particulate matter is common in our environment and has been linked to human health problems particularly in the ultrafine size range. A range of chemical species have been associated with particulate matter and of special concern are the hazardous chemicals that can accentuate health problems. If the sources of such particles can be identified then strategies can be developed for the reduction of air pollution and consequently, the improvement of the quality of life. In this investigation, particle number size distribution data and the concentrations of chemical species were obtained at two sites in Brisbane, Australia. Source apportionment was used to determine the sources (or factors) responsible for the particle size distribution data. The apportionment was performed by Positive Matrix Factorisation (PMF) and Principal Component Analysis/Absolute Principal Component Scores (PCA/APCS), and the results were compared with information from the gaseous chemical composition analysis. Although PCA/APCS resolved more sources, the results of the PMF analysis appear to be more reliable. Six common sources identified by both methods include: traffic 1, traffic 2, local traffic, biomass burning, and two unassigned factors. Thus motor vehicle related activities had the most impact on the data with the average contribution from nearly all sources to the measured concentrations higher during peak traffic hours and weekdays. Further analyses incorporated the meteorological measurements into the PMF results to determine the direction of the sources relative to the measurement sites, and this indicated that traffic on the nearby road and intersection was responsible for most of the factors. The described methodology which utilised a combination of three types of data related to particulate matter to determine the sources could assist future development of particle emission control and reduction strategies.

Linking scientific evidence and decision making : A case study of hand hygiene interventions

We consider how data from scientific research should be used for decision making in health services. Whether a hand hygiene intervention to reduce risk of nosocomial infection should be widely adopted is the case study. Improving hand hygiene has been described as the most important measure to prevent nosocomial infection. 1 Transmission of microorganisms is reduced, and fewer infections arise, which leads to a reduction in mortality2 and cost savings.3 Implementing a hand hygiene program is itself costly, so the extra investment should be tested for cost-effectiveness.4,5 The first part of our commentary is about cost-effectiveness models and how they inform decision making for health services. The second part is about how data on the effectiveness of hand hygiene programs arising from scientific studies are used, and 2 points are made: the threshold for statistical inference of .05 used to judge effectiveness studies is not important for decision making,6,7 and potentially valuable evidence about effectiveness might be excluded by decision makers because it is deemed low quality.8 The ideas put forward will help researchers and health services decision makers to appraise scientific evidence in a more powerful way.

Performance configurations over time: implications for growth-and profit-oriented strategies

Entrepreneurship research and practice places emphasis on company growth as a measure of entrepreneurial success. In many cases, there has been a tendency to give growth a very central role, with some researchers even seeing growth as the very essence of entrepreneurship (Cole, 1949; Sexton, 1997; Stevenson & Gumpert, 1991). A large number of empirical studies of the performance of young and/or small firms use growth as the dependent variable (see reviews by Ardishvili, Cardozo, Harmon, & Vadakath, 1998; Delmar, 1997; Wiklund, 1998). By contrast, the two most prominent views of strategic management – strategic positioning (Porter, 1980) and the resource-based view (Barney, 1991; Wernerfelt, 1984) – are both concerned with achieving competitive advantage and regard achieving economic rents and profitability relative to other competitors as the central measures of firm performance. Strategic entrepreneurship integrates these two perspectives and is simultaneously concerned with opportunity seeking and advantage seeking (Hitt, Ireland, Camp, & Sexton, 2002; Ireland, Hitt, & Sirmon, 2003). Consequently, both company growth and relative profitability are together relevant measures of firm performance in the domain of strategic entrepreneurship.

Working for a better life : longitudinal evidence on the predictors of employment among recently arrived refugee migrant men living in Australia

Although a number of studies have investigated the predictors of employment among refugee migrants, there is a dearth of evidence from longitudinal data. This study investigated the cross-sectional and longitudinal predictors of employment among 233 adult refugee men living in South-East Queensland, Australia. Participants were interviewed four times at six-month intervals between 2008 and 2010. Using a conceptual model developed from the literature, Generalised Estimating Equations were used to model the predictors of employment. Over time, the employment rate increased from 44 percent to 56 percent. Region of birth, length of time in Australia, seeking employment through job service providers and informal networks, and owning a car were significant predictors of employment. Contrary to previous research, English language proficiency was not a significant predictor when other variables were controlled for. Recognition of overseas skills and qualifications decreased the chances of finding employment. The policy and program implications are discussed.