Paclitaxel resistance and multicellular spheroid formation are induced by kallikrein-related peptidase 4 in serous ovarian cancer cells in an ascites mimicking microenvironment

High tumor kallikrein-related-peptidase 4 (KLK4) levels are associated with a poor outcome for women with serous epithelial ovarian cancer (EOC), for which peritoneal dissemination and chemoresistance are key events. To determine the role of KLK4 in these events, we examined KLK4-transfected SKOV-3 and endogenous KLK4 expressing OVCA432 cells in 3-dimensional (3D) suspension culture to mimic the ascites microenvironment. KLK4-SKOV-3 cells formed multicellular aggregates (MCAs) as seen in ascites, as did SKOV-3 cells treated with active KLK4. MCA formation was reduced by treatment with a KLK4 blocking antibody or the selective active site KLK4 sunflower trypsin inhibitor (SFTI-FCQR). KLK4-MCAs formed larger cancer cell foci in mesothelial cell monolayers than those formed by vector and native SKOV-3 cells, suggesting KLK4-MCAs are highly invasive in the peritoneal microenvironment. A high level of KLK4 is expressed by ascitic EOC cells compared to matched primary tumor cells, further supporting its role in the ascitic microenvironment. Interestingly, KLK4 transfected SKOV-3 cells expressed high levels of the KLK4 substrate, urokinase plasminogen activator (uPA), particularly in 3D-suspension, and high levels of both KLK4 and uPA were observed in patient cells taken from ascites. Importantly, the KLK4-MCAs were paclitaxel resistant which was reversed by SFTI-FCQR and to a lesser degree by the general serine protease inhibitor, Aprotinin, suggesting that in addition to uPA, other as yet unidentified substrates of KLK4 must be involved. Nonetheless, these data suggest that KLK4 inhibition, in conjunction with paclitaxel, may improve the outcome for women with serous epithelial ovarian cancer and high KLK4 levels in their tumors.

A prospective window into medical device-related pressure ulcers in intensive care

Objective: To determine the prevalence, severity, location, etiology, treatment, and healing of medical device-related pressure ulcers in intensive care patients for up to 7 days. Design: Prospective repeated measures study. Setting and participants: Patients in 6 intensive care units of 2 major medical centers, one each in Australia and the United States, were screened 1 day per month for 6 months. Those with device-related ulcers were followed daily up to 7 days. Outcome measures: Device-related ulcer prevalence, pain, infection, treatment, healing. Results: 15/483 patients had device-related ulcers and 9/15 with 11 ulcers were followed beyond screening. Their mean age was 60.5 years, most were men, over-weight, and at increased pressure ulcer risk. Endotracheal and nasogastric tubes were the cause of most device-related ulcers. Repositioning was the most frequent treatment. 4/11 ulcers healed within the 7 day observation period. Conclusion: Device-related ulcer prevalence was 3.1%, similar to that reported in the limited literature available, indicating an ongoing problem. Systematic assessment and repositioning of devices are the mainstays of care. We recommend continued prevalence determination and that nurses remain vigilant to prevent device-related ulcers, especially in patients with nasogastric and endotracheal tubes.

The relationship between CFH and ARMS2 genotypes and neuroretinal function in persons without age-related macular degeneration

Purpose: To determine whether neuroretinal function differs in healthy persons with and without common risk gene variants for age- related macular degeneration (AMD) and no ophthalmoscopic signs of AMD, and to compare those findings in persons with manifest early AMD. Methods and Participants: Neuroretinal function was assessed with the multifocal electroretinogram (mfERG) (VERIS, Redwood City, CA,) in 32 participants (22 healthy persons with no clinical signs of AMD and 10 early AMD patients). The 22 healthy participants with no AMD were risk genotypes for either the CFH (rs380390) and/or ARMS2 (rs10490920). We used a slow flash mfERG paradigm (3 inserted frames) and a 103 hexagon stimulus array. Recordings were made with DTL electrodes; fixation and eye movements were monitored online. Trough N1 to peak P1 (N1P1) response densities and P1-implicit times (IT) were analysed in 5 concentric rings. Results: N1P1 response densities (mean ± SD) for concentric rings 1-3 were on average significantly higher in at-risk genotypes (ring 1: 17.97 nV/deg2 ± 1.9, ring 2: 11.7 nV/deg2 ±1.3, ring 3: 8.7 nV/deg2 ± 0.7) compared to those without risk (ring 1: 13.7 nV/deg2 ± 1.9, ring 2: 9.2 nV/deg2 ±0.8, ring 3: 7.3 nV/deg2 ± 1.1) and compared to persons with early AMD (ring 1: 15.3 nV/deg2 ± 4.8, ring 2: 9.1 nV/deg2 ±2.3, ring 3 nV/deg2: 7.3± 1.3) (p<0.5). The group implicit times, P1-ITs for ring 1 were on average delayed in the early AMD patients (36.4 ms ± 1.0) compared to healthy participants with (35.1 ms ± 1.1) or without risk genotypes (34.8 ms ±1.3), although these differences were not significant. Conclusion: Neuroretinal function in persons with normal fundi can be differentiated into subgroups based on their genetics. Increased neuroretinal activity in persons who carry AMD risk genotypes may be due to genetically determined subclinical inflammatory and/or histological changes in the retina. Assessment of neuroretinal function in healthy persons genetically susceptible to AMD may be a useful early biomarker before there is clinical manifestation of AMD.

Eyes on 3D-Current 3D biomimetic disease concept models and potential applications in age-related macular degeneration

Three dimensional cellular models that mimic disease are being increasingly investigated and have opened an exciting new research area into understanding pathomechanisms. The advantage of 3D in vitro disease models is that they allow systematic and in-depth studies of physiological and pathophysiological processes with less costs and ethical concerns that have arisen with animal models. The purpose of the 3D approach is to allow crosstalk between cells and microenvironment, and with cues from the microenvironment, cells can assemble their niche similar to in vivo conditions. The use of 3D models for mimicking disease processes such as cancer, osteoarthritis etc., is only emerging and allows multidisciplinary teams consisting of tissue engineers, biologist biomaterial scientists and clinicians to work closely together. While in vitro systems require rigorous testing before they can be considered as replicates of the in vivo model, major steps have been made, suggesting that they will become powerful tools for studying physiological and pathophysiological processes. This paper aims to summarize some of the existing 3D models and proposes a novel 3D model of the eye structures that are involved in the most common cause of blindness in the Western World, namely age-related macular degeneration (AMD).

Consumer product-related injuries in Queensland children : A snapshot of current problem areas for potential action

This report presents a snapshot from work which was funded by the Queensland Injury Prevention Council in 2010-11 titled “Feasibility of Using Health Data Sources to Inform Product Safety Surveillance in Queensland children”. The project provided an evaluation of the current available evidence-base for identification and surveillance of product-related injuries in children in Queensland and Australia. A comprehensive 300 page report was produced (available at: http://eprints.qut.edu.au/46518/) and a series of recommendations were made which proposed: improvements in the product safety data system, increased utilisation of health data for proactive and reactive surveillance, enhanced collaboration between the health sector and the product safety sector, and improved ability of health data to meet the needs of product safety surveillance. At the conclusion of the project, a Consumer Product Injury Research Advisory group (CPIRAG) was established as a working party to the Queensland Injury Prevention Council (QIPC), to prioritise and advance these recommendations and to work collaboratively with key stakeholders to promote the role of injury data to support product safety policy decisions at the Queensland and national level. This group continues to meet monthly and is comprised of the organisations represented on the second page of this report. One of the key priorities of the CPIRAG group for 2012 was to produce a snapshot report to highlight problem areas for potential action arising out of the larger report. Subsequent funding to write this snapshot report was provided by the Institute for Health and Biomedical Innovation, Injury Prevention and Rehabilitation Domain at QUT in 2012. This work was undertaken by Dr Kirsten McKenzie and researchers from QUT's Centre for Accident Research and Road Safety - Queensland. This snapshot report provides an evidence base for potential further action on a range of children’s products that are significantly represented in injury data. Further information regarding injury hazards, safety advice and regulatory responses are available on the Office of Fair Trading (OFT) Queensland website and the Product Safety Australia websites. Links to these resources are provided for each product reviewed.

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...

Nursing a case of the blues : an examination of the role of depression in predicting job-related affective well-being in nurses

The current study explored the effect of depression, optimism, and anxiety on job-related affective well-being in 70 graduate nurses. It was predicted that depression and anxiety would have a significant negative effect on job-related affective well-being, whereas optimism would have a significant positive effect on job-related affective well-being. Questionnaires were completed online or in hard-copy forms. Results revealed that depression, optimism, and anxiety were all significantly correlated to job-related affective well-being in the expected direction however, depression was found to be the only variable that made a significant unique contribution to the prediction of job-related affective well-being. Possible explanations for these findings are explored.

Paleomagnetic data support Early Permian age for the Abor Volcanics in the lower Siang Valley, NE India; significance for Gondwana-related break-up models

Confusion exists as to the age of the Abor Volcanics of NE India. Some consider the unit to have been emplaced in the Early Permian, others the Early Eocene, a difference of ∼230 million years. The divergence in opinion is significant because fundamentally different models explaining the geotectonic evolution of India depend on the age designation of the unit. Paleomagnetic data reported here from several exposures in the type locality of the formation in the lower Siang Valley indicate that steep dipping primary magnetizations (mean = 72.7 ± 6.2°, equating to a paleo-latitude of 58.1°) are recorded in the formation. These are only consistent with the unit being of Permian age, possibly Artinskian based on a magnetostratigraphic argument. Plate tectonic models for this time consistently show the NE corner of the sub-continent >50°S; in the Early Eocene it was just north of the equator, which would have resulted in the unit recording shallow directions. The mean declination is counter-clockwise rotated by ∼94°, around half of which can be related to the motion of the Indian block; the remainder is likely due local Himalayan-age thrusting in the Eastern Syntaxis. Several workers have correlated the Abor Volcanics with broadly coeval mafic volcanic suites in Oman, NE Pakistan–NW India and southern Tibet–Nepal, which developed in response to the Cimmerian block peeling-off eastern Gondwana in the Early-Middle Permian, but we believe there are problems with this model. Instead, we suggest that the Abor basalts relate to India–Antarctica/India–Australia extension that was happening at about the same time. Such an explanation best accommodates the relevant stratigraphical and structural data (present-day position within the Himalayan thrust stack), as well as the plate tectonic model for Permian eastern Gondwana.

Is chrysocolla (Cu,Al)2H2Si2O5(OH)4·nH2O related to spertiniite Cu(OH)2? - a vibrational spectroscopic study

Chrysocolla (Cu, Al)2H2Si2O5(OH)4·nH2O is a hydrated copper hydroxy silicate and is commonly known as a semi-precious jewel. The mineral has an ill defined structure but is said to be orthorhombic, although this remains unproven. Thus, one of the few methods of studying the molecular structure of chrysocolla is to use vibrational spectroscopy. Chrysocolla may be defined as a colloidal mineral. The question arises as to whether chrysocolla is a colloidal system of spertiniite and amorphous silica. The main question addressed by this study is whether chrysocolla is (1) a mesoscopic assemblage of spertiniite, Cu(OH)2, silica, and water, (2) represents a colloidal gel or (3) is composed of microcrystals with a distinct structure. Considerable variation in the vibrational spectra is observed between chrysocolla samples. The Raman spectrum of chrysocolla is characterised by an intense band at 3624 cm−1 assigned to the OH stretching vibrations. Intense Raman bands found at 674, 931 and 1058 cm−1 are assigned to SiO3 vibrations. The Raman spectrum of spertiniite does not correspond to the spectrum of chrysocolla and it is concluded that the two minerals are not related. The spectra of chrysocolla correspond to a copper silicate colloidal gel.

Reducing alcohol-related driving on China's roads : Traffic police officers' perceptions and practice

Alcohol-related driving is a longstanding, serious problem in China (Li, Xie, Nie, & Zhang, 2012). On 1st May, 2011 a national law was introduced to criminalize drunk driving, and imposed serious penalties including jail for driving with a blood alcohol level of above 80mg/100ml. This pilot study, undertaken a year after introduction of the law, sought traffic police officers’ perceptions of drink driving and the practice of breath alcohol testing (BAT) in a large city in Guangdong Province, southern China. A questionnaire survey and semi-structured interviews were used to gain an in-depth understanding of issues relevant to alcohol-related driving. Fifty-five traffic police officers were recruited for the survey and six traffic police officers with a variety of working experience including roadside alcohol breath testing, traffic crash investigation and police resourcing were interviewed individually. The officers were recruited by the first author with the assistance of the staff from Guangdong Institute of Public Health, Centre for Disease Control and Prevention (CDC). Interview participants reported three primary reasons why people drink and drive: 1) being prepared to take the chance of not being apprehended by police; 2) the strong traditional Chinese drinking culture; and 3) insufficient public awareness about the harmfulness of drink driving. Problems associated with the process of breath alcohol testing (BAT) were described and fit broadly into two categories: resourcing and avoiding detection. It was reported that there were insufficient traffic police officers to conduct routine traffic policing, including alcohol testing. Police BAT equipment was considered sufficient for routine traffic situations but not highway traffic operations. Local media and posters are used by the Public Security Bureau which is responsible for education about safe driving but participants thought that the education campaigns are limited in scope. Participants also described detection avoidance strategies used by drivers including: changing route; ignoring a police instruction to stop; staying inside the vehicle with windows and doors locked to avoid being tested; intentionally not performing breath tests correctly; and arguing with officers. This pilot study provided important insights from traffic police in one Chinese city which suggest there may be potential unintended effects of introducing more severe penalties including a range of strategies reportedly used by drivers to avoid detection. Recommendations for future research include a larger study to confirm these findings and examine the training and education of drivers; the focus and reach of publicity; and possible resource needs to support police enforcement.

Scanning electron microscopy of condensation related minerals : the Bjurbole meteorite

Filamentary single crystals, blades, sheets, euhedral crystals and powders may form by vapor phase condensation depending on the supersauration conditions in the vapor with respect to the condensing species [1]. Filamentary crystal growth requires the operation of an axial screw dislocation [2]. A Vapor-Liquid-Solid (VLS) mechanism may also produce filamentary single crystals, ribbons and blades. The latter two morphologies are typically twinned. Crystals grown by this mechanism do not require the presence of an axial screw dislocation. Impurities may either promote or inhibit crystal growth [3]. The VLS mechanism allows crystals to grow at small supersaturation of the vapor. Thin enstatite blades, ribbons and sheets have been observed in chondritic porous Interplanetary Dust Partics (IDP's) [4, 5]. The requisite screw dislocation for vapor phase condensation [1] has been observed in these enstatite blades [4]. Bradley et al. [4] suggest that these crystals are primary vapor phase condensates which could have formed either in the solar nebula or in presolar environments. These observations [4,5] are significant in that they may provide a demonstrable link to theoretical predictions: viz. that in the primordial solar nebula filamentary condensates could cluster into 'lint balls' and form the predecessors to comets [6].

The role of, and key considerations for, advertising campaigns and educational awareness workshops within the work-related road safety context

Australian and international evidence suggests that, in the work-related driving context, road crashes account for a substantial number of occupational incidents. In the attempt to reduce injury and improve safety, organisations may implement an array of strategies and interventions ranging from policy development and implementation, vehicle selection and incident monitoring through to education and awareness-raising. This conceptual paper discusses aspects relating to the latter collection of interventions and, in particular, the role, and some key considerations with respect to the content and dissemination, of advertising campaigns and educational awareness workshops. In relation to advertising campaigns, this paper discusses how some of the overarching principles associated with advertising in the broader general community road safety strategy also apply within the work-related road safety context. Specifically, advertising campaigns/materials should be viewed as a key component within a dedicated organisational approach to road (driver) safety. This dedicated approach would need to comprise of a number, and varied array, of strategies. In addition, the content of, and medium/s (e.g., posters) by which to deliver such advertising campaigns, cannot be addressed by a one-size-fits all approach but, rather, requires careful consideration of the needs as well as characteristics of specific organisations and their driver fleet. The paper provides a summary of some key considerations when devising an advertising campaign, including the nature of campaign/message content as well as the processes by which to devise and refine such content. In relation to driver education awareness workshops, this paper outlines the key considerations for delivering a series of workshops specifically aimed at occupational driving within the organisational context. A case study approach will be utilised to demonstrate the manner in which educational awareness workshops can compliment successful advertising campaigns promoting safer work related driving through better risk management practice. Research underpinning the development of driver behaviour modification tools incorporated within the workshops will also be discussed along with the mechanisms utilised to encourage improvements in driver monitoring and behaviour. In an effort to assist organisations with their continual search for cost-effective approaches which may, ultimately, contribute to improvements in driver behaviour and safety, the current paper offers some clear and practical suggestions in relation to the development and dissemination of two types of interventions, advertising campaigns and education awareness workshops.